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1.
J Am Chem Soc ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39267445

RESUMEN

Iron-nitrogen-carbon (Fe-N-C) materials have been identified as a promising class of platinum (Pt)-free catalysts for the oxygen reduction reaction (ORR). However, the dissolution and oxidation of Fe atoms severely restrict their long-term stability and performance. Modulating the active microstructure of Fe-N-C is a feasible strategy to enhance the ORR activity and stability. Compared with common 3d transition metals (Co, Ni, etc.), the 4d transition metal atom Nb has fewer d electrons and more unoccupied orbitals, which could potentially forge a more robust interaction with the Fe site to optimize the binding energy of the oxygen-containing intermediates while maintaining stability. Herein, an asymmetric Fe-Nb diatomic site catalyst (FeNb/c-SNC) was synthesized, which exhibited superior ORR performance and stability compared with those of Fe single-atom catalysts (SACs). The strong interaction within the Fe-Nb diatomic sites optimized the desorption energy of key intermediates (*OH), so that the adsorption energy of Fe-*OH approaches the apex of the volcano plot, thus exhibiting optimal ORR activity. More importantly, introducing Nb atoms could effectively strengthen the Fe-N bonding and suppress Fe demetalation, causing an outstanding stability. The zinc-air battery (ZAB) and hydroxide exchange membrane fuel cell (HEMFC) equipped with our FeNb/c-SNC could deliver high peak power densities of 314 mW cm-2 and 1.18 W cm-2, respectively. Notably, the stable operation time for ZAB and HEMFC increased by 9.1 and 5.8 times compared to Fe SACs, respectively. This research offers further insights into developing stable Fe-based atomic-level catalytic materials for the energy conversion process.

2.
Artículo en Inglés | MEDLINE | ID: mdl-39254371

RESUMEN

PURPOSE: To objectively quantify posterior capsule opacification (PCO) using swept-source anterior segment optical coherence tomography (SS-ASOCT) in pseudophakic eyes. SETTING: Zhongshan Ophthalmic Center, Guangzhou, China. DESIGN: Prospective cross-sectional study. METHODS: One hundred and eighty eyes with PCO (37 multifocal intraocular lenses [MfIOLs] and 143 monofocal intraocular lenses [MoIOLs]) were enrolled. The PCO Irregular Degree (PID), defined to evaluate the surface irregularity of PCO, the average and maximum thickness of PCO (AT-PCO, MT-PCO) were applied to quantify PCO based on SS-ASOCT (CASIA2) images. Corrected distance visual acuity (CDVA), high order aberrations (HOAs), modulation transfer function (MTF) and Strehl ratio were recorded. The associations between SS-ASOCT parameters and visual function parameters were assessed by Spearman's correlation analysis. RESULTS: PID, AT-PCO and MT-PCO showed significant correlations with CDVA, Strehl ratio and HOAs (CDVA: r = 0.702, 0.741, 0.736; Strehl ratio: r = -0.746, -0.719, -0.740; HOAs: r = 0.762, 0.734, 0.752). The correlations of these three parameters with Strehl ratio and HOAs were significantly higher than those of clinical PCO grading with Strehl ratio and HOAs (all P < 0.05). Particularly, PID demonstrated notable correlations with Strehl ratio and HOAs. In addition, patients with MfIOLs presented worse Strehl ratio and HOAs than those with MoIOLs after matching age, PID, AT-PCO and MT-PCO. CONCLUSIONS: This study provides a novel method for objectively quantifying PCO using successive cross-sectional SS-ASOCT images. AT-PCO, MT-PCO and PID are presented as new indicators to document PCO severity, with PID offering a unique perspective by considering the irregularity aspect of PCO.

3.
Sci Total Environ ; 953: 176054, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39245388

RESUMEN

This study provides the first systematic data on the distribution of short- (SCCPs) and medium chlorinated paraffins (MCCPs) in the atmosphere and surface soils of Lahore, Pakistan. The spatial distribution of SCCPs and MCCPs in air (n = 12) and soil (n = 15) was investigated from industrial, residential, commercial, conventional e-waste burning and background areas of Lahore. The concentrations ranged from below the limit of detection (

4.
Waste Manag ; 188: 48-59, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39098272

RESUMEN

Ensuring the interpretability of machine learning models in chemical engineering remains challenging due to inherent limitations and data quality issues, hindering their reliable application. In this study, a qualitatively implicit knowledge-guided machine learning framework is proposed to improve plasma gasification modelling. Starting with a pre-trained machine learning model, parameters are further optimized by integrating the heuristic algorithm to minimize the data fitting errors and resolving implicit monotonic inconsistencies. The latter is comprehensively quantified through Monte Carlo simulations. This framework is adaptive to different machine learning techniques, exemplified by artificial neural network (ANN) and support vector machine (SVM) in this study. Validated by a case study on plasma gasification, the results reveal that the improved models achieve better generalizability and scientific interpretability in predicting syngas quality. Specifically, for ANN, the root mean square error (RMSE) and knowledge-based error (KE) reduce by 36.44% and 83.22%, respectively, while SVM displays a decrease of 2.58% in RMSE and a remarkable 100% in KE. Importantly, the improved models successfully capture all desired implicit monotonicity relationships between syngas quality and feedstock characteristics/operating parameters, addressing a limitation that traditional machine learning struggles with.


Asunto(s)
Aprendizaje Automático , Redes Neurales de la Computación , Máquina de Vectores de Soporte , Gases , Algoritmos , Método de Montecarlo , Modelos Teóricos
5.
Invest Ophthalmol Vis Sci ; 65(10): 8, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39102262

RESUMEN

Purpose: Neuroinflammation is a characteristic feature of neurodegenerative diseases. Mesenchymal stem cell-derived exosomes (MSC-exo) have shown neuroprotective effects through immunoregulation, but the therapeutic efficacy remains unsatisfactory. This study aims to enhance the neuroprotective capacity of MSC-exo through IL-23 priming for treating retinal degeneration in mice. Methods: MSC were primed with IL-23 stimulation in vitro, and subsequently, exosomes (MSC-exo and IL-23-MSC-exo) were isolated and characterized. Two retinal degenerative disease models (NaIO3-induced mice and rd10 mice) received intravitreal injections of these exosomes. The efficacy of exosomes was assessed by examining retinal structural and functional recovery. Furthermore, exosomal microRNA (miRNA) sequencing was conducted, and the effects of exosomes on the M1 and M2 microglial phenotype shift were evaluated. Results: IL-23-primed MSC-derived exosomes (IL-23-MSC-exo) exhibited enhanced capability in protecting photoreceptor cells and retinal pigment epithelium (RPE) cells against degenerative damage and fostering the restoration of retinal neural function in both NaIO3-induced retinal degeneration mice and rd10 mice when compared with MSC-exo. The exosomal miRNA suppression via Drosha knockdown in IL-23-primed MSC would abolish the neuroprotective role of IL-23-MSC-exo, highlighting the miRNA-dependent mechanism. Bioinformatic analysis, along with further in vivo biological studies, revealed that IL-23 priming induced a set of anti-inflammatory miRNAs in MSC-exo, prompting the transition of M1 to M2 microglial polarization. Conclusions: IL-23 priming presents as a potential avenue for amplifying the immunomodulatory and neuroprotective effects of MSC-exo in treating retinal degeneration.


Asunto(s)
Modelos Animales de Enfermedad , Exosomas , Interleucina-23 , Células Madre Mesenquimatosas , Ratones Endogámicos C57BL , Degeneración Retiniana , Animales , Exosomas/metabolismo , Exosomas/trasplante , Degeneración Retiniana/terapia , Degeneración Retiniana/metabolismo , Degeneración Retiniana/prevención & control , Ratones , Células Madre Mesenquimatosas/metabolismo , Interleucina-23/metabolismo , MicroARNs/genética , Inyecciones Intravítreas , Fármacos Neuroprotectores , Epitelio Pigmentado de la Retina/metabolismo , Epitelio Pigmentado de la Retina/patología , Yodatos/toxicidad , Células Cultivadas , Microglía/metabolismo , Masculino
6.
Front Med (Lausanne) ; 11: 1405261, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39144652

RESUMEN

Background: The intraocular injections of anti-vascular endothelial growth factor (anti-VEGF) demonstrates significant efficacy in inhibiting the formation of ocular neovascularization in neovascular glaucoma (NVG). Ahmed glaucoma valve implantation (AGVI) is extensively employed for the management of diverse glaucoma types. Objective: To further evaluate the efficacy and safety of anti-VEGF combined with AGVI in the treatment of neovascular glaucoma. Methods: A thorough search for randomized controlled trials (RCTs) was conducted across eight databases: PubMed, EMBASE, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang, SinoMed, and VIP. The search period was set from the inception of each database until March 2, 2024, to identify RCTs investigating the effectiveness and safety of combining AGVI with anti-VEGF therapy for NVG. We used the Cochrane Risk of Bias Assessment Tool to evaluate the quality of the literature and performed statistical analysis using Stata 15.0 software. Results: Fourteen RCTs were included in this study. Compared with AGVI alone, the combination of anti-VEGF drugs and AGVI can reduce postoperative intraocular pressure (IOP) at 1 week [WMD = -4.03, 95% CI (-5.73, -2.34), p < 0.001], 1 month [WMD = -5.39, 95% CI (-7.05, -3.74), p < 0.001], 3 months [WMD = -6.59, 95% CI (-7.85, -5.32), p < 0.001], 6 months [WMD = -4.99, 95% CI (-9.56, -0.43), p = 0.032], and more than 12 months [WMD = -3.86, 95% CI (-6.82, -0.90), p = 0.011], with a higher Effective rate [RR = 1.27, 95% CI (1.18, 1.37), p < 0.001], decreased incidence of postoperative hyphema [RR = 0.24, 95% CI (0.15, 0.39), p < 0.001], reduced use of postoperative antiglaucoma medications [WMD = -0.48, 95% CI (-0.61, -0.35), p < 0.001], and decreased aqueous humor VEGF levels [SMD = -2.84, 95% CI (-4.37, -1.31), p < 0.001]. Conclusion: In comparison to AGVI alone, the combination of AGVI with anti-VEGF therapy has better effects in reducing IOP at various time intervals, diminishing postoperative antiglaucoma medication requirements and reducing aqueous humor VEGF levels. Furthermore, it effectively minimizes the incidence of postoperative hyphema. Nevertheless, due to the variability in the quality of the trials included, further high-quality experiments will be required in the future to substantiate this conclusion. Systematic review registration: PROSPERO, identifier CRD42024519862, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024519862.

7.
Sci Rep ; 14(1): 17946, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39095410

RESUMEN

For fractured gas reservoirs with strong water drive, gas phase trapping affects the gas recovery significantly. The recovery may be less than 50% for some reservoirs while it is only 12% for Beaver River gas field. The gas phase trapping mechanism has been revealed by the results of depletion experimental test. The residual pressure of the trapped gas is as high as 11.75 MPa with a 12.8 cm imbibition layer resulting in gas recovery deceased 49.5% compared with that without imbibition layer. A mathematical model is built to calculate the imbibition thickness based on capillary pressure and relative permeability of the matrix. The gas phase trapping are analyzed by two representative wells in Weiyuan gas field, the intermittent production reinforces the imbibition thickness and result in gas trapped in the matrix block with high residual pressure for the low performace gas wells, the extremely low gas recovery can be explained more rationally. That lays a foundation of improving the gas recovery for fractured reservoirs.

8.
J Hazard Mater ; 476: 135130, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-38991639

RESUMEN

During the COVID-19 pandemic, one of Australia's biggest cities, Melbourne, experienced three major isolation ("lockdown") periods in 2020 (160 days) and in 2021 (111 days) which makes it one of the most locked down cities world-wide. This study assessed how the pandemic affected temporal trends in methamphetamine, MDMA and cocaine consumption using wastewater-based epidemiology. Daily samples were collected for most of 2020 and 2021 (n = 660 days). Concentrations were measured using direct-injection LC-MS/MS and back-calculated to consumption estimates. Results indicate that methamphetamine use was increasing before the first lockdown and decreased after the end of the first lockdown in 2020. Methamphetamine trends appeared to have remained steady throughout the second lockdown period before increasing steeply after it ended. For most of 2020, cocaine use remained steady, with an increase after the second lockdown. MDMA use decreased after the start of the first lockdown and remained steady throughout most of 2020 and 2021. In comparison to 2020, trends in 2021 were less variable and stimulant use did not appear to be as associated with COVID-19 restrictions. Overall, this study was able to show the impact of lockdown periods and the related social restrictions on illicit stimulant use. ENVIRONMENTAL IMPLICATION: Illicit drugs are hazardous chemicals, of concern both to humans and the environment. While studies have been undertaken to understand their temporal trends, this work utilizes wastewater-based epidemiology and daily sampling to provide a comprehensive understanding of the impact of the COVID-19 pandemic on the use of methamphetamine, MDMA and cocaine on one of the most locked-down cities in the world. Understanding the consequences of this significant intervention on illicit drug use could provide valuable insights into its potential environmental impact.


Asunto(s)
COVID-19 , Cocaína , Metanfetamina , Aguas Residuales , COVID-19/epidemiología , Humanos , Cocaína/análisis , Metanfetamina/análisis , Australia/epidemiología , N-Metil-3,4-metilenodioxianfetamina/análisis , Trastornos Relacionados con Sustancias/epidemiología , Contaminantes Químicos del Agua/análisis , Monitoreo Epidemiológico Basado en Aguas Residuales , Detección de Abuso de Sustancias/métodos , Ciudades , Drogas Ilícitas/análisis , SARS-CoV-2
9.
Comb Chem High Throughput Screen ; 27(13): 1984-1998, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38963027

RESUMEN

BACKGROUND: BLCA is a common urothelial malignancy characterized by a high recurrence rate. Despite its prevalence, the molecular mechanisms underlying its development remain unclear. AIMS: This study aimed to explore new prognostic biomarkers and investigate the underlying mechanism of bladder cancer (BLCA). OBJECTIVE: The objective of this study is to identify key prognostic biomarkers for BLCA and to elucidate their roles in the disease. METHODS: We first collected the overlapping DEGs from GSE42089 and TCGA-BLCA samples for the subsequent weighted gene co-expression network analysis (WGCNA) to find a key module. Then, key module genes were analyzed by the MCODE algorithm, prognostic risk model, expression and immunohistochemical staining to identify the prognostic hub gene. Finally, the hub gene was subjected to clinical feature analysis, as well as cellular function assays. RESULTS: In WGCNA on 1037 overlapping genes, the blue module was the key module. After a series of bioinformatics analyses, POLE2 was identified as a prognostic hub gene in BLCA from potential genes (TROAP, POLE2, ANLN, and E2F8). POLE2 level was increased in BLCA and related to different clinical features of BLCA patients. Cellular assays showed that si-POLE2 inhibited BLCA proliferation, and si-POLE2+ 740Y-P in BLCA cells up-regulated the PI3K and AKT protein levels. CONCLUSION: In conclusion, POLE2 was identified to be a promising prognostic biomarker as an oncogene in BLCA. It was also found that POLE2 exerts a promoting function by the PI3K/AKT signaling pathway in BLCA.


Asunto(s)
Proliferación Celular , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Neoplasias de la Vejiga Urinaria , Humanos , Fosfatidilinositol 3-Quinasas/metabolismo , Pronóstico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/metabolismo
10.
Fish Physiol Biochem ; 50(4): 1667-1682, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38963582

RESUMEN

The present study, as one part of a larger project that aimed to investigate the effects of dietary berberine (BBR) on fish growth and glucose regulation, mainly focused on whether miRNAs involve in BBR's modulation of glucose metabolism in fish. Blunt snout bream Megalobrama amblycephala (average weight of 20.36 ± 1.44 g) were exposed to the control diet (NCD, 30% carbohydrate), the high-carbohydrate diet (HCD, 43% carbohydrate) and the berberine diet (HCB, HCD supplemented with 50 mg/kg BBR). After 10 weeks' feeding trial, intraperitoneal injection of glucose was conducted, and then, the plasma and liver were sampled at 0 h, 1 h, 2 h, 6 h, and 12 h. The results showed the plasma glucose levels in all groups rose sharply and peaked at 1 h after glucose injection. Unlike the NCD and HCB groups, the plasma glucose in the HCD group did not decrease after 1 h, while remained high level until at 2 h. The NCD group significantly increased liver glycogen content at times 0-2 h compared to the other two groups and then liver glycogen decreased sharply until at times 6-12 h. To investigate the role of BBR that may cause the changes in plasma glucose and liver glycogen, miRNA high-throughput sequencing was performed on three groups of liver tissues at 2 h time point. Eventually, 20 and 12 differentially expressed miRNAs (DEMs) were obtained in HCD vs NCD and HCB vs HCD, respectively. Through function analyzing, we found that HCD may affect liver metabolism under glucose loading through the NF-κB pathway; and miRNAs regulated by BBR mainly play roles in adipocyte lipolysis, niacin and nicotinamide metabolism, and amino acid transmembrane transport. In the functional exploration of newly discovered novel:Chr12_18892, we found its target gene, adenylate cyclase 3 (adcy3), was widely involved in lipid decomposition, amino acid metabolism, and other pathways. Furthermore, a targeting relationship of novel:Chr12_18892 and adcy3 was confirmed by double luciferase assay. Thus, BBR may promote novel:Chr12_18892 to regulate the expression of adcy3 and participate in glucose metabolism.


Asunto(s)
Berberina , Cyprinidae , Glucosa , Hígado , MicroARNs , Animales , MicroARNs/genética , MicroARNs/metabolismo , Berberina/farmacología , Cyprinidae/genética , Cyprinidae/metabolismo , Glucosa/metabolismo , Hígado/metabolismo , Hígado/efectos de los fármacos , Glucemia , Dieta/veterinaria , Alimentación Animal/análisis
11.
Animals (Basel) ; 14(13)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38998060

RESUMEN

Oral melanomas are the most common oral malignancies in dogs and are characterized by an aggressive nature, invasiveness, and poor prognosis. With biological and genetic similarities to human oral melanomas, they serve as a valuable spontaneous comparative model. Primary cell cultures are widely used in human medicine and, more recently, in veterinary medicine to study tumorigenesis, cancer progression, and innovative therapeutic approaches. This study aims to establish two- and three-dimensional primary cell lines from oral canine melanomas using fine-needle aspiration as a minimally invasive sampling method. For this study, samples were collected from six dogs, represented by four primary oral melanomas and five lymph nodal metastases. The cells were digested to obtain single-cell suspensions, seeded in flasks, or processed with Matrigel® to form organoids. The cell cultures were characterized through flow cytometry using antibodies against Melan-A, PNL2, and Sox-10. This technique offers a minimally invasive means to obtain cell samples, particularly beneficial for patients that are ineligible for surgical procedures, and enables the establishment of in vitro models crucial for comparative studies in mucosal melanoma oncology. To the best of our knowledge, this is the first work establishing neoplastic primary cell cultures via fine-needle aspiration in dogs.

12.
Materials (Basel) ; 17(13)2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38998136

RESUMEN

A three-dimensional porous bacterial cellulose/graphene oxide (BC/GO) composite hydrogel (BC/GO) was synthesized with multi-layer graphene oxide (GO) as the modifier and bacterial cellulose as the skeleton via an ultrasonic shaking process to absorb lead ions effectively. The characteristics of BC/GO were investigated through TEM, SEM, FT-IR, NMR and Zeta potential experiments. Compared to bacterial cellulose, the ultrasonic method and the carboxyl groups stemming from GO helped to enhance the availability of O(3)H of BC, in addition to the looser three-dimensional structure and enriched oxygen-containing groups, leading to a significantly higher adsorption capacity for Pb(II). In this paper, the adsorption behavior of BC/GO is influenced by the GO concentration, adsorption time, and initial concentration. The highest adsorption capacity for Pb(II) on BC/GO found in this study was 224.5 mg/g. The findings implied that the pseudo-second-order model explained the BC/GO adsorption dynamics and that the data of its adsorption isotherm fit the Freundlich model. Because of the looser three-dimensional structure, the complexation of carboxyl groups, and the enhanced availability of O(3)H, bacterial cellulose exhibited a much better adsorption capacity.

13.
Foods ; 13(13)2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38998652

RESUMEN

Morchella importuna polysaccharide (MIP) has been proven to have obvious hypoglycemic effects on mice with type 2 diabetes (T2DM). This study looked at the functional and rheological characteristics of MIP, and investigated the effects of MIP on the human fecal microbiota through in vitro fermentation experiments. The outcomes demonstrate the excellent oil-holding capacity, emulsifying, foaming, and rheological characteristics of MIP. After salivary gastrointestinal digestion, the Mw of MIP decreased from 398.2 kDa and 21.5 kDa to 21.9 kDa and 11.7 kDa. By 16S rRNA sequencing of bacteria fermented in vitro, it was found that MIP did not improve the richness and diversity of intestinal microorganisms, but it may exert an anti-T2DM function by significantly increasing the relative abundance of Firmicutes and promoting Ruminococcaceae_UCG_014, Bacteroides, and Blautia proliferation. Escherichia-Shigella could also be inhibited to improve the intestinal microenvironment. In addition, the fermentation of MIP increased the total short-chain fatty acid (SCFA) concentration from 3.23 mmol/L to 39.12 mmol/L, and the propionic acid content increased significantly. In summary, MIP has excellent processing performance and is expected to exert potential anti-T2DM activity through the human intestinal microbiota, which has broad market prospects.

14.
Sensors (Basel) ; 24(13)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-39001058

RESUMEN

Compelling evidence has shown that geomagnetic disturbances in vertical intensity polarization before great earthquakes are promising precursors across diverse rupture conditions. However, the geomagnetic vertical intensity polarization method uses the spectrum of smooth signals, and the anomalous waveforms of seismic electromagnetic radiation, which are basically nonstationary, have not been adequately considered. By combining pulse amplitude analysis and an experimental study of the cumulative frequency of anomalies, we found that the pulse amplitudes before the 2022 Luding M6.8 earthquake show characteristics of multiple synchronous anomalies, with the highest (or higher) values occurring during the analyzed period. Similar synchronous anomalies were observed before the 2021 Yangbi M6.4 earthquake, the 2022 Lushan M6.1 earthquake and the 2022 Malcolm M6.0 earthquake, and these anomalies indicate migration from the periphery toward the epicenters over time. The synchronous changes are in line with the recognition of previous geomagnetic anomalies with characteristics of high values before an earthquake and gradual recovery after the earthquake. Our study suggests that the pulse amplitude is effective for extracting anomalies in geomagnetic vertical intensity polarization, especially in the presence of nonstationary signals when utilizing observations from multiple station arrays. Our findings highlight the importance of incorporating pulse amplitude analysis into earthquake prediction research on geomagnetic disturbances.

15.
Sci Rep ; 14(1): 16885, 2024 07 23.
Artículo en Inglés | MEDLINE | ID: mdl-39043809

RESUMEN

There is no reliable causal evidence for the effect of statins on diabetic nephropathy (DN) and diabetic retinopathy (DR), and the results of previous observational studies are contradictory. Genetic variants linked to low-density lipoprotein cholesterol (LDL-C) from a UK biobank genome-wide association study and located within a 100kb window around HMGCR were used to proxy statins, comparing with PCSK9 inhibitors (control). DN and DR genome-wide association study summary statistics were obtained from the FinnGen study. Secondary MR analyses and NHANES cross-sectional data were used for validation. Drug-target Mendelian randomization (MR) was applied to investigate the association between the genetically proxied inhibition of HMGCR and PCSK9 with DN and DR, p < 0.0125 was considered significant after Bonferroni Correction. To triangulate the findings, genetic variants of whole blood-derived targets gene expression (cis-eQTL) and plasma-derived protein (cis-pQTL) levels were used to perform secondary MR analyses and data from the National Health and Nutrition Examination Survey were used for cross-sectional analysis. Genetically proxied inhibition of HMGCR was associated with higher risks of DN and DR (DN: OR = 1.79, p = 0.01; DR: OR = 1.41, p = 0.004), while no such association was found for PCSK9. Secondary MR analyses confirmed these associations. Cross-sectional analysis revealed a positive link between statin use and DR incidence (OR = 1.26, p = 0.03) and a significant negative association with glomerular filtration rate (Beta = - 1.9, p = 0.03). This study provides genetic evidence that genetically proxied inhibition of HMGCR is associated with increased risks of DN/DR, and this effect may not be attributed to their LDL-C-lowering properties. For patients with diabetic dyslipidemia, PCSK9 inhibitors may be a preferable alternative.


Asunto(s)
Nefropatías Diabéticas , Retinopatía Diabética , Estudio de Asociación del Genoma Completo , Hidroximetilglutaril-CoA Reductasas , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Análisis de la Aleatorización Mendeliana , Proproteína Convertasa 9 , Humanos , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Retinopatía Diabética/genética , Retinopatía Diabética/tratamiento farmacológico , Hidroximetilglutaril-CoA Reductasas/genética , Proproteína Convertasa 9/genética , Estudios Transversales , Masculino , LDL-Colesterol/sangre , Polimorfismo de Nucleótido Simple , Femenino , Persona de Mediana Edad
16.
Sci Rep ; 14(1): 16044, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38992223

RESUMEN

With the high yield of many wells represented by Well JT1 in the Maokou Formation, has catalyzed a surge in exploration activities along the platform margin facies of the Maokou Formation in central Sichuan and further showed the significant exploration potential of the Maokou Formation in the northern slope. However, the fracture cave body of the Maokou Formation exhibits a high degree of development, strong longitudinal and horizontal heterogeneity, large formation pressure differences, and drilling events such as gas kicks and lost circulation occur frequently, which seriously affects the efficient implementation of drilling. Understanding the spatial distribution of the three-pressure in the formation can help better deal with and solve the above problems. Therefore, in order to help the safe, high-quality and rapid drilling of the Maokou Formation in the study area, and enhance the efficiency of oil and gas development, this paper explores the research on the prediction method of the three-pressure of jointing well-seismic data based on the geomechanical experimental data and the actual drilling data. In the process of prediction of pore pressure, this study found that the pore pressure and formation velocity in the study area have an exponential relationship. In order to enhance the applicability of the Filippone's method in the study area and improve the prediction accuracy of pore pressure, the linear relationship between pore pressure and formation velocity in the Filippone's method is modified to an exponential relationship, and a pore pressure prediction model suitable for the work area was established. Based on the Mohr-Coulomb criterion and Huang's model, the prediction models of collapse pressure and fracture pressure applicable to the study area were established, respectively. Then, the elastic parameters were obtained through pre-stack inversion, and the three-pressure bodies were calculated based on the elastic parameter bodies. The results indicate that: (1) The three-pressure prediction method of the jointing well-seismic data in this paper can predict the formation's longitudinal and transverse pressure anomaly zones in advance. (2) The Maokou Formation in the study area is characterized by abnormally high pressure, to balance the pressure of the high-ground formation, high-density drilling fluid is necessary. (3) The prediction results of three-pressure in this paper are highly consistent with the actual drilling engineering events, which verifies the reliability of the three-pressure prediction results presented in this study. The results of the study can provide a basis for decision-making in drilling geological design, such as the determination of drilling fluid density, the evaluation of borehole stability and other engineering problems that require support from three-pressure data.

17.
Front Vet Sci ; 11: 1347083, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38952805

RESUMEN

A 3-month-old kitten was presented after successful cardiopulmonary resuscitation, including a presumed intracardial injection by its primary care veterinarian. Throughout the subsequent hospitalization in the intensive care unit, the cat exhibited recurrent hemorrhagic pericardial effusions, along with concurrent pleural and abdominal effusions, resulting in multiple clinical deteriorations, necessitating pericardiocentesis and thoracocentesis. Despite more than 3 days of intensive care, the cat experienced another cardiopulmonary arrest with unsuccessful attempts to achieve the return of spontaneous circulation. Necropsy and histopathological findings revealed diffuse chronic-active pericarditis and hemorrhagic pericardial effusion, a condition that has not been documented in the context of cardiopulmonary resuscitation or pericardiocentesis.

18.
J Neuroinflammation ; 21(1): 164, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38918759

RESUMEN

The microglia-mediated neuroinflammation have been shown to play a crucial role in the ocular pathological angiogenesis process, but specific immunotherapies for neovascular ocular diseases are still lacking. This study proposed that targeting GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) might be a novel immunotherapy for these angiogenesis diseases. We found a significant upregulation of CGAS and STING genes in the RNA-seq data derived from retinal tissues of the patients with proliferative diabetic retinopathy. In experimental models of ocular angiogenesis including laser-induced choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR), the cGAS-STING pathway was activated as angiogenesis progressed. Either genetic deletion or pharmacological inhibition of STING resulted in a remarkable suppression of neovascularization in both models. Furthermore, cGAS-STING signaling was specifically activated in myeloid cells, triggering the subsequent RIP1-RIP3-MLKL pathway activation and leading to necroptosis-mediated inflammation. Notably, targeted inhibition of the cGAS-STING pathway with C-176 or SN-011 could significantly suppress pathological angiogenesis in CNV and OIR. Additionally, the combination of C-176 or SN-011 with anti-VEGF therapy led to least angiogenesis, markedly enhancing the anti-angiogenic effectiveness. Together, our findings provide compelling evidence for the importance of the cGAS-STING-necroptosis axis in pathological angiogenesis, highlighting its potential as a promising immunotherapeutic target for treating neovascular ocular diseases.


Asunto(s)
Proteínas de la Membrana , Ratones Endogámicos C57BL , Enfermedades Neuroinflamatorias , Nucleotidiltransferasas , Nucleotidiltransferasas/metabolismo , Nucleotidiltransferasas/genética , Nucleotidiltransferasas/antagonistas & inhibidores , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/antagonistas & inhibidores , Animales , Humanos , Ratones , Enfermedades Neuroinflamatorias/metabolismo , Neovascularización Coroidal/metabolismo , Neovascularización Coroidal/patología , Neovascularización Coroidal/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Ratones Noqueados , Retinopatía Diabética/metabolismo
19.
Zhongguo Gu Shang ; 37(6): 6095-15, 2024 Jun 25.
Artículo en Chino | MEDLINE | ID: mdl-38910385

RESUMEN

OBJECTIVE: To explore clinical effect of vancomycin calcium sulfate combined with internal fixation on calcaneal beak-like fracture secondary to calcaneal osteomyelitis caused by diabetic foot. METHODS: From April 2018 to October 2021, a retrospective analysis was performed on 5 patients with calcaneal bone osteomyelitis secondary to diabetic foot, including 2 males and 3 females, aged from 48 to 60 years old;diabetes course ranged from 5 to 13 years;the courses of diabetic foot disease ranged from 18 to 52 days;5 patients were grade Ⅲ according to Wagner classification. All patients were treated with debridement, vancomycin bone cement implantation, negative pressure aspiration at stageⅠ, vancomycin calcium sulfate and internal fixation at stageⅡfor calcaneal beak-like fracture. Surgical incision and fracture healing time were recorded, and the recurrence of osteomyelitis was observed. American Orthopedic Foot Andankle Society (AOFAS) score and exudation at 12 months after operation were evaluated. RESULTS: Five patients were successfully completed operation without lower extremity vascular occlusion, and were followed up for 16 to 36 months. The wound healing time after internal fixation ranged from 16 to 26 days, and healing time of fractures ranged from 16 to 27 weeks. AOFAS score ranged from 65 to 91 at 12 months after operation, and 2 patients got excellent result, 2 good and 1 fair. Among them, 1 patient with skin ulcer on the back of foot caused by scalding at 5 months after operation (non-complication), was recovered after treatment;the wound leakage complication occurred in 2 patients, and were recovered after dressing change. No osteomyelitis or fracture occurred in all patients. CONCLUSION: Vancomycin calcium sulfate with internal fixation in treating calcaneal osteomyelitis secondary to calcaneal osteomyelitis caused by diabetic foot could not only control infection, but also promote fracture healing, and obtain good clinical results.


Asunto(s)
Calcáneo , Pie Diabético , Fijación Interna de Fracturas , Osteomielitis , Humanos , Masculino , Persona de Mediana Edad , Femenino , Osteomielitis/cirugía , Osteomielitis/tratamiento farmacológico , Osteomielitis/etiología , Pie Diabético/cirugía , Calcáneo/lesiones , Calcáneo/cirugía , Estudios Retrospectivos , Fijación Interna de Fracturas/métodos , Fracturas Óseas/complicaciones , Fracturas Óseas/cirugía
20.
Ann Thorac Surg ; 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38823757

RESUMEN

BACKGROUND: Recent randomized trial data showed fewer strokes with left atrial appendage occlusion (LAAO) following cardiac surgery in patients with atrial fibrillation. We developed a quality initiative to increase LAAO adoption. METHODS: Among 11,099 patients undergoing isolated CABG between January 2019-March 2021 at 33 hospitals in Michigan, those with atrial fibrillation undergoing first-time, on-pump CABG were eligible (n=1,241). A goal LAAO rate of 75% was selected as a quality improvement target through a statewide collaborative. An interrupted time series analysis evaluated the change in LAAO rate before (January-December 2019) versus after (January 2020-March 2021) implementation. RESULTS: Implementation of the quality metric improved LAAO rate from 61% (357/581) before to 79% (520/660) after implementation (p<0.001). Compared to patients not undergoing concomitant LAAO, LAAO patients (71%, 877/1,241) were older, more frequently male, and had a lower STS-PROM (2.9±3.5% vs. 3.7±5.7%, p=0.003), while other baseline characteristics including CHA2DS2-VASc scores were similar. Mean bypass and cross-clamp times were 7 and 6 minutes longer, respectively, in the LAAO group among those who did not undergo concomitant ablation. Operative mortality, major morbidity, blood product administration, and thromboembolic events were similar between groups. Interrupted time series analysis showed a significant increase in LAAO rate after implementation (p=0.009). CONCLUSIONS: LAAO in patients with atrial fibrillation undergoing isolated CABG did not add operative risk versus isolated CABG without LAAO. A statewide quality improvement initiative was successful in increasing the rate of concomitant LAAO and could be further evaluated as a potential quality metric in cardiac surgery.

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