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1.
PLoS Negl Trop Dis ; 18(7): e0012291, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39012845

RESUMEN

BACKGROUND: Understanding and mapping the distribution of sandflies and sandfly-associated pathogens (SAPs) is crucial for guiding the surveillance and control effort. However, their distribution and the related risk burden in China remain poorly understood. METHODS: We mapped the distribution of sandflies and SAPs using literature data from 1940 to 2022. We also mapped the human visceral leishmaniasis (VL) cases using surveillance data from 2014 to 2018. The ecological drivers of 12 main sandfly species and VL were identified by applying machine learning, and their distribution and risk were predicted in three time periods (2021-2040, 2041-2060, and 2061-2080) under three scenarios of climate and socioeconomic changes. RESULTS: In the mainland of China, a total of 47 sandfly species have been reported, with the main 12 species classified into three clusters according to their ecological niches. Additionally, 6 SAPs have been identified, which include two protozoa, two bacteria, and two viruses. The incidence risk of different VL subtypes was closely associated with the distribution risk of specific vectors. The model predictions also revealed a substantial underestimation of the current sandfly distribution and VL risk. The predicted areas affected by the 12 major species of sandflies and the high-risk areas for VL were found to be 37.9-1121.0% and 136.6% larger, respectively, than the observed range in the areas. The future global changes were projected to decrease the risk of mountain-type zoonotic VL (MT-ZVL), but anthroponotic VL (AVL) and desert-type zoonotic VL (DT-ZVL) could remain stable or slightly increase. CONCLUSIONS: Current field observations underestimate the spatial distributions of main sandfly species and VL in China. More active surveillance and field investigations are needed where high risks are predicted, especially in areas where the future risk of VL is projected to remain high or increase.


Asunto(s)
Insectos Vectores , Psychodidae , Animales , China/epidemiología , Psychodidae/parasitología , Humanos , Insectos Vectores/parasitología , Leishmaniasis Visceral/epidemiología , Leishmaniasis Visceral/transmisión , Distribución Animal
2.
Food Chem X ; 22: 101523, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38911916

RESUMEN

Engineered bacterial magnetic nanoparticles (BMPs) fused with protein A (BMP-PA) can bind antibodies, creating immunomagnetic beads that offer an attractive tool for targets screening. In the study, BMP-PA-IgG was formed by attaching broad-spectrum monoclonal antibodies against glucocorticoids (GCs) to BMP-PA. Immunomagnetic assay was developed for analysis of GCs, using the BMP-PA-IgG and hydrocortisone-horseradish peroxidase. The developed assay exhibited broad specificity for GCs, including hydrocortisone (HCS), betamethasone (BMS), dexamethasone (DMS), prednisolone (PNS), beclomethasone (BCMS), cortisone (CS), 6-α-methylprednisone (6-α-MPNS), and fludrocortisone acetate (HFCS), with half inhibitory concentrations (IC50) ranging from 0.88 to 6.57 ng/mL. The proposed assay showed average recoveries of HCS and DMS ranging from 75.6% to 105.2% in chicken and pork samples, which were correlated well with those obtained by LC-MS/MS. This study indicated that the integration of engineered immunomagnetic beads into immunoassay systems offer possibilities for the sensitive and selective detection of GCs.

3.
Artículo en Inglés | MEDLINE | ID: mdl-38861446

RESUMEN

This paper presents a digital edge neuromorphic spiking neural network (SNN) processor chip for a variety of edge intelligent cognitive applications. This processor allows high-speed, high-accuracy and fully on-chip spike-timing-based multi-layer SNN learning. It is characteristic of hierarchical multi-core architecture, event-driven processing paradigm, meta-crossbar for efficient spike communication, and hybrid and reconfigurable parallelism. A prototype chip occupying an active silicon area of 7.2 mm2 was fabricated using a 65-nm 1P9M CMOS process. when running a 256-256-256-256-200 4-layer fully-connected SNN on downscaled 16 × 16 MNIST images. it typically achieved a high-speed throughput of 802 and 2270 frames/s for on-chip learning and inference, respectively, with a relatively low power dissipation of around 61 mW at a 100 MHz clock rate under a 1.0V core power supply, Our on-chip learning results in comparably high visual recognition accuracies of 96.06%, 83.38%, 84.53%, 99.22% and 100% on the MNIST, Fashion-MNIST, ETH-80, Yale-10 and ORL-10 datasets, respectively. In addition, we have successfully applied our neuromorphic chip to demonstrate high-resolution satellite cloud image segmentation and non-visual tasks including olfactory classification and textural news categorization. These results indicate that our neuromorphic chip is suitable for various intelligent edge systems under restricted cost, energy and latency budgets while requiring in-situ self-adaptative learning capability.

4.
Nat Commun ; 15(1): 4764, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38834561

RESUMEN

Bacteriophage are sophisticated cellular parasites that can not only parasitize bacteria but are increasingly recognized for their direct interactions with mammalian hosts. Phage adherence to mucus is known to mediate enhanced antimicrobial effects in vitro. However, little is known about the therapeutic efficacy of mucus-adherent phages in vivo. Here, using a combination of in vitro gastrointestinal cell lines, a gut-on-a-chip microfluidic model, and an in vivo murine gut model, we demonstrated that a E. coli phage, øPNJ-6, provided enhanced gastrointestinal persistence and antimicrobial effects. øPNJ-6 bound fucose residues, of the gut secreted glycoprotein MUC2, through domain 1 of its Hoc protein, which led to increased intestinal mucus production that was suggestive of a positive feedback loop mediated by the mucus-adherent phage. These findings extend the Bacteriophage Adherence to Mucus model into phage therapy, demonstrating that øPNJ-6 displays enhanced persistence within the murine gut, leading to targeted depletion of intestinal pathogenic bacteria.


Asunto(s)
Infecciones por Escherichia coli , Escherichia coli , Mucosa Intestinal , Mucina 2 , Animales , Escherichia coli/virología , Ratones , Mucosa Intestinal/microbiología , Mucosa Intestinal/virología , Mucina 2/metabolismo , Humanos , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/terapia , Terapia de Fagos/métodos , Adhesión Bacteriana , Femenino , Moco/metabolismo , Moco/virología , Colifagos/fisiología , Fucosa/metabolismo , Ratones Endogámicos C57BL
5.
PLoS One ; 19(6): e0302663, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38833640

RESUMEN

BACKGROUND AND PURPOSE: Clinical studies showed that prolonged infusion of methotrexate (MTX) leads to more severe adverse reactions than short infusion of MTX at the same dose. We hypothesized that it is the saturation of folate polyglutamate synthetase (FPGS) at high MTX concentration that limits the intracellular synthesis rate of methotrexate polyglutamate (MTX-PG). Due to a similar accumulation rate, a longer infusion duration may increase the concentration of MTX-PG and, result in more serious adverse reactions. In this study, we validated this hypothesis. EXPERIMENTAL APPROACH: A549, BEL-7402 and MHCC97H cell lines were treated with MTX at gradient concentrations. Liquid chromatograph-mass spectrometer (UPLC-MS/MS) was used to quantify the intracellular concentration of MTX-PG and the abundance of FPGS and γ-glutamyl hydrolase (GGH). High quality data were used to fit the cell pharmacokinetic model. KEY RESULTS: Both cell growth inhibition rate and intracellular MTX-PG concentration showed a nonlinear relationship with MTX concentration. The parameter Vmax in the model, which represents the synthesis rate of MTX-PG, showed a strong correlation with the abundance of intracellular FPGS. CONCLUSION AND IMPLICATIONS: According to the model fitting results, it was confirmed that the abundance of FPGS is a decisive factor limiting the synthesis rate of MTX-PG. The proposed hypothesis was verified in this study. In addition, based on the intracellular metabolism, a reasonable explanation was provided for the correlation between the severity of adverse reactions of MTX and infusion time. This study provides a new strategy for the individualized treatment and prediction of efficacy/side effects of MTX.


Asunto(s)
Metotrexato , Péptido Sintasas , Ácido Poliglutámico , gamma-Glutamil Hidrolasa , Metotrexato/farmacocinética , Metotrexato/análogos & derivados , gamma-Glutamil Hidrolasa/metabolismo , Péptido Sintasas/metabolismo , Humanos , Línea Celular Tumoral , Ácido Poliglutámico/análogos & derivados , Espectrometría de Masas en Tándem , Proliferación Celular/efectos de los fármacos , Antimetabolitos Antineoplásicos/farmacocinética , Antimetabolitos Antineoplásicos/farmacología
6.
J Transl Med ; 22(1): 564, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38872164

RESUMEN

BACKGROUND/PURPOSE(S): The gut microbiota and its metabolites play crucial roles in pathogenesis of arthritis, highlighting gut microbiota as a promising avenue for modulating autoimmunity. However, the characterization of the gut virome in arthritis patients, including osteoarthritis (OA) and gouty arthritis (GA), requires further investigation. METHODS: We employed virus-like particle (VLP)-based metagenomic sequencing to analyze gut viral community in 20 OA patients, 26 GA patients, and 31 healthy controls, encompassing a total of 77 fecal samples. RESULTS: Our analysis generated 6819 vOTUs, with a considerable proportion of viral genomes differing from existing catalogs. The gut virome in OA and GA patients differed significantly from healthy controls, showing variations in diversity and viral family abundances. We identified 157 OA-associated and 94 GA-associated vOTUs, achieving high accuracy in patient-control discrimination with random forest models. OA-associated viruses were predicted to infect pro-inflammatory bacteria or bacteria associated with immunoglobulin A production, while GA-associated viruses were linked to Bacteroidaceae or Lachnospiraceae phages. Furthermore, several viral functional orthologs displayed significant differences in frequency between OA-enriched and GA-enriched vOTUs, suggesting potential functional roles of these viruses. Additionally, we trained classification models based on gut viral signatures to effectively discriminate OA or GA patients from healthy controls, yielding AUC values up to 0.97, indicating the clinical utility of the gut virome in diagnosing OA or GA. CONCLUSION: Our study highlights distinctive alterations in viral diversity and taxonomy within gut virome of OA and GA patients, offering insights into arthritis etiology and potential treatment and prevention strategies.


Asunto(s)
Artritis Gotosa , Microbioma Gastrointestinal , Osteoartritis , Viroma , Humanos , Artritis Gotosa/virología , Artritis Gotosa/microbiología , Masculino , Osteoartritis/virología , Osteoartritis/microbiología , Femenino , Persona de Mediana Edad , Estudios de Casos y Controles , Anciano , Metagenómica , Heces/virología , Heces/microbiología
7.
Antiviral Res ; 228: 105943, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38909959

RESUMEN

Poxviruses gained international attention due to the sharp rise in monkeypox cases in recent years, highlighting the urgent need for the development of a secure and reliable vaccine. This study involved the development of an innovative combined subunit vaccine (CSV) targeting poxviruses, with lumpy skin disease virus (LSDV) serving as the model virus. To this end, the potential sites for poxvirus vaccines were fully evaluated to develop and purify four recombinant proteins. These proteins were then successfully delivered to the dermis in a mouse model by utilizing dissolvable microneedle patches (DMPs). This approach simplified the vaccination procedure and significantly mitigated the associated risk. CSV-loaded DMPs contained four recombinant proteins and a novel adjuvant, CpG, which allowed DMPs to elicit the same intensity of humoral and cellular immunity as subcutaneous injection. Following immunization with SC and DMP, the mice exhibited notable levels of neutralizing antibodies, albeit at a low concentration. It is noteworthy that the CSV loaded into DMPs remained stable for at least 4 months at room temperature, effectively addressing the storage and transportation challenges. Based on the study findings, CSV-loaded DMPs are expected to be utilized worldwide as an innovative technique for poxvirus inoculation, especially in underdeveloped regions. This novel strategy is crucial for the development of future poxvirus vaccines.


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Infecciones por Poxviridae , Poxviridae , Vacunas de Subunidad , Animales , Vacunas de Subunidad/inmunología , Vacunas de Subunidad/administración & dosificación , Ratones , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Infecciones por Poxviridae/prevención & control , Infecciones por Poxviridae/inmunología , Femenino , Poxviridae/inmunología , Vacunas Virales/inmunología , Vacunas Virales/administración & dosificación , Ratones Endogámicos BALB C , Virus de la Dermatosis Nodular Contagiosa/inmunología , Vacunación , Inmunidad Celular , Inmunidad Humoral , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/administración & dosificación , Adyuvantes de Vacunas/administración & dosificación , Adyuvantes Inmunológicos/administración & dosificación
8.
Front Public Health ; 12: 1381754, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38873317

RESUMEN

Background: The population with chronic kidney disease (CKD) has significantly heightened risk of fall accidents. The aim of this study was to develop a validated risk prediction model for fall accidents among CKD in the community. Methods: Participants with CKD from the China Health and Retirement Longitudinal Study (CHARLS) were included. The study cohort underwent a random split into a training set and a validation set at a ratio of 70 to 30%. Logistic regression and LASSO regression analyses were applied to screen variables for optimal predictors in the model. A predictive model was then constructed and visually represented in a nomogram. Subsequently, the predictive performance was assessed through ROC curves, calibration curves, and decision curve analysis. Result: A total of 911 participants were included, and the prevalence of fall accidents was 30.0% (242/911). Fall down experience, BMI, mobility, dominant handgrip, and depression were chosen as predictor factors to formulate the predictive model, visually represented in a nomogram. The AUC value of the predictive model was 0.724 (95% CI 0.679-0.769). Calibration curves and DCA indicated that the model exhibited good predictive performance. Conclusion: In this study, we constructed a predictive model to assess the risk of falls among individuals with CKD in the community, demonstrating good predictive capability.


Asunto(s)
Accidentes por Caídas , Insuficiencia Renal Crónica , Humanos , Insuficiencia Renal Crónica/epidemiología , Masculino , Femenino , Accidentes por Caídas/estadística & datos numéricos , Anciano , China/epidemiología , Estudios Longitudinales , Persona de Mediana Edad , Factores de Riesgo , Medición de Riesgo/métodos , Modelos Logísticos , Nomogramas , Curva ROC
9.
BMC Vet Res ; 20(1): 258, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38877537

RESUMEN

BACKGROUND: Senecavirus A (SVA), identified in 2002, is known to cause porcine idiopathic vesicular disease (PIVD), which presents with symptoms resembling other vesicular diseases. This similarity complicates field diagnosis. Conventional molecular diagnostic techniques are limited by their cost, sensitivity, and requirement for complicated instrumentation. Therefore, developing an effective and accurate diagnostic method is crucial for timely identification and isolation of affected pigs, thereby preventing further disease spread. METHODS: In this study, we developed a highly-specific and ultra-sensitive SVA detection method powered by CRISPR/Cas12a. To enhance the availability in laboratories with varied equipment conditions, microplate reader and ultraviolet light transilluminator were introduced. Moreover, PCR amplification has also been incorporated into this method to improve sensitivity. The specificity and sensitivity of this method were determined following the preparation of the recombinant Cas12a protein and optimization of the CRISPR/Cas12a-based trans-cleavage system. RESULTS: The method demonstrated no cross-reactivity with ten kinds of viruses of swine. The minimum template concentration required to activate substantial trans-cleavage activity was determined to be 106 copies/µL of SVA templates. However, when PCR amplification was incorporated, the method achieved a detection limit of one copy of SVA templates per reaction. It also exhibited 100% accuracy in simulated sample testing. The complete testing process does not exceed three hours. CONCLUSIONS: Importantly, this method utilizes standard laboratory equipment, making it accessible for use in resource-limited settings and facilitating widespread and ultra-sensitive screening during epidemics. Overall, the development of this method not only broadens the array of tools available for detecting SVA but also holds significant promise for controlling the spread of PIVD.


Asunto(s)
Sistemas CRISPR-Cas , Picornaviridae , Sensibilidad y Especificidad , Enfermedades de los Porcinos , Animales , Porcinos , Picornaviridae/aislamiento & purificación , Picornaviridae/genética , Enfermedades de los Porcinos/virología , Enfermedades de los Porcinos/diagnóstico , Infecciones por Picornaviridae/veterinaria , Infecciones por Picornaviridae/diagnóstico , Infecciones por Picornaviridae/virología , Reacción en Cadena de la Polimerasa/veterinaria , Reacción en Cadena de la Polimerasa/métodos , Proteínas Asociadas a CRISPR/genética
10.
Insects ; 15(5)2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38786916

RESUMEN

Odontotermes formosanus (Shiraki) is a subterranean termite species known for causing severe damage to trees and structures such as dams. During the synergistic evolution of O. formosanus with pathogenic bacteria, the termite has developed a robust innate immunity. Termicin is a crucial antimicrobial peptide in termites, significantly contributing to the defense against external infections. Building upon the successful construction and expression of the dsRNA-HT115 engineering strains of dsOftermicin1 and dsOftermicin2 in our laboratory, this work employs the ultrasonic breaking method to establish an inactivated dsOftermicins-HT115 technological system capable of producing a substantial quantity of dsRNA. This approach also addresses the limitation of transgenic strains which cannot be directly applied. Treatment of O. formosanus with dsOftermicins produced by this method could enhance the virulence of both Bt and Bb to the termites. This study laid the theoretical groundwork for the development of novel termite immunosuppressants and for the advancement and application of termite biological control strategies.

11.
Virol J ; 21(1): 120, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38816738

RESUMEN

BACKGROUND: The Porcine Epidemic Diarrhea Virus (PEDV) has caused significant economic losses in the global swine industry. As a potential drug for treating diarrhea, the antiviral properties of attapulgite deserve further study. METHODS: In this study, various methods such as RT-qPCR, Western blot, viral titer assay, Cytopathic Effect, immunofluorescence analysis and transmission electron microscopy were used to detect the antiviral activity of attapulgite and to assess its inhibitory effect on PEDV. RESULTS: When exposed to the same amount of virus, there was a significant decrease in the expression of the S protein, resulting in a viral titer reduction from 10-5.613 TCID50/mL to 10-2.90 TCID50/mL, which represents a decrease of approximately 102.6 folds. Results of cytopathic effect and indirect immunofluorescence also indicate a notable decrease in viral infectivity after attapulgite treatment. Additionally, it was observed that modified materials after acidification had weaker antiviral efficacy compared to powdered samples that underwent ultrasonic disintegration, which showed the strongest antiviral effects. CONCLUSION: As a result, Attapulgite powders can trap and adsorb viruses to inhibit PEDV in vitro, leading to loss of viral infectivity. This study provides new materials for the development of novel disinfectants and antiviral additives.


Asunto(s)
Antivirales , Virus de la Diarrea Epidémica Porcina , Compuestos de Silicona , Virus de la Diarrea Epidémica Porcina/efectos de los fármacos , Virus de la Diarrea Epidémica Porcina/genética , Virus de la Diarrea Epidémica Porcina/fisiología , Animales , Antivirales/farmacología , Compuestos de Silicona/farmacología , Compuestos de Silicona/química , Chlorocebus aethiops , Compuestos de Magnesio/farmacología , Porcinos , Células Vero , Carga Viral/efectos de los fármacos , Efecto Citopatogénico Viral/efectos de los fármacos , Enfermedades de los Porcinos/virología , Infecciones por Coronavirus/virología , Infecciones por Coronavirus/veterinaria , Microscopía Electrónica de Transmisión
12.
Br J Ophthalmol ; 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38729765

RESUMEN

BACKGROUND/AIMS: To evaluate the diagnostic accuracy of spectral-domain optical coherence tomography (SD OCT) combined with OCT angiography (OCTA) for myopic myopic macular neovascularisation (MNV) activity. METHODS: Both eyes of patients with myopic MNV diagnosed with fluorescein angiography (FA), SD OCT and OCTA were assessed by unmasked investigators. The images were deidentified and randomised before graded by masked investigators, who determined the presence of active myopic MNV by using SD OCT together with OCTA without FA and by FA alone, respectively. The findings of masked investigators were compared with unmasked investigators. RESULTS: 213 eyes of 110 patients comprising 499 imaging episodes were eligible for grading. For diagnosing new-onset myopic MNV without FA, combined use of SD OCT and OCTA had a sensitivity of 0.94, specificity of 0.84 and area under the curve (AUC) of 0.92. FA had a sensitivity of 0.52 (p<0.01), specificity of 0.80 (p=0.38) and AUC of 0.66 (p<0.01). For recurrent myopic MNV, the combination of SD OCT and OCTA had a sensitivity of 0.98, specificity of 0.78 and AUC of 0.88. FA had a sensitivity of 0.50 (p=0.04), specificity of 0.76 (p=0.85) and AUC of 0.63 (p=0.01). Myopic traction maculopathy was more frequently associated with recurrent myopic MNV (p<0.01). CONCLUSION: SD OCT with dense volumetric scan was highly sensitive for diagnosing myopic MNV. The addition of OCTA improved the diagnostic specificity without FA. Monitoring of the longitudinal changes on SD OCT and judicious use of FA is a reliable surveillance strategy for myopic MNV.

13.
Funct Plant Biol ; 512024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38739736

RESUMEN

The forage quality of alfalfa (Medicago sativa ) stems is greater than the leaves. Sucrose hydrolysis provides energy for stem development, with starch being enzymatically converted into sucrose to maintain energy homeostasis. To understand the physiological and molecular networks controlling stem development, morphological characteristics and transcriptome profiles in the stems of two alfalfa cultivars (Zhungeer and WL168) were investigated. Based on transcriptome data, we analysed starch and sugar contents, and enzyme activity related to starch-sugar interconversion. Zhungeer stems were shorter and sturdier than WL168, resulting in significantly higher mechanical strength. Transcriptome analysis showed that starch and sucrose metabolism were significant enriched in the differentially expressed genes of stems development in both cultivars. Genes encoding INV , bglX , HK , TPS and glgC downregulated with the development of stems, while the gene encoding was AMY upregulated. Weighted gene co-expression network analysis revealed that the gene encoding glgC was pivotal in determining the variations in starch and sucrose contents between the two cultivars. Soluble carbohydrate, sucrose, and starch content of WL168 were higher than Zhungeer. Enzyme activities related to sucrose synthesis and hydrolysis (INV, bglX, HK, TPS) showed a downward trend. The change trend of enzyme activity was consistent with gene expression. WL168 stems had higher carbohydrate content than Zhungeer, which accounted for more rapid growth and taller plants. WL168 formed hollow stems were formed during rapid growth, which may be related to the redistribution of carbohydrates in the pith tissue. These results indicated that starch and sucrose metabolism play important roles in the stem development in alfalfa.


Asunto(s)
Medicago sativa , Tallos de la Planta , Almidón , Sacarosa , Medicago sativa/genética , Medicago sativa/metabolismo , Medicago sativa/crecimiento & desarrollo , Almidón/metabolismo , Tallos de la Planta/metabolismo , Tallos de la Planta/crecimiento & desarrollo , Tallos de la Planta/genética , Sacarosa/metabolismo , Regulación de la Expresión Génica de las Plantas , Transcriptoma , Metabolismo de los Hidratos de Carbono/genética , Perfilación de la Expresión Génica
14.
Front Pharmacol ; 15: 1379338, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38738180

RESUMEN

Background: Chinese patent medicine is commonly used in China as an important treatment mechanism to thwart the progression of chronic kidney disease (CKD) stages 3-5, among which Niaoduqing granules are a representative Chinese patent medicine; however, its long-term efficacy on CKD prognosis remains unclear. Methods: Patients were grouped according to Niaoduqing granule prescription duration (non-Niaoduqing granule (non-NDQ) group vs Niaoduqing granule (NDQ) group). Serum creatinine (SCr) variation was compared using a generalized linear mixed model (GLMM). Multivariate Cox regression models were constructed, adjusting for confounding factors, to explore the risk of composite outcomes (receiving renal replacement therapy (RRT) or having an estimated glomerular filtration rate (eGFR)<5 mL/min/1.73 m2, ≥50% decline in the eGFR from the baseline, and doubling of SCr) in individuals consuming Niaoduqing granules. Results: A total of 1,271 patients were included, with a median follow-up duration of 29.71 (12.10, 56.07) months. The mean SCr Z-scores for the non-NDQ group and NDQ group were -0.175 and 0.153, respectively, at baseline (p = 0.015). The coefficients of the NDQ group from visit 1 to visit 5 were -0.207 (95% CI: -0.346, -0.068, p = 0.004), -0.214 (95% CI: 0.389, -0.039, p = 0.017), -0.324 (95% CI: 0.538, -0.109, p = 0.003), -0.502 (95% CI: 0.761, -0.243, p = 0.000), and -0.252 (95% CI: 0.569, 0.065, p = 0.119), respectively. The survival probability was significantly higher in the NDQ group (p = 0.0039). Taking Niaoduqing granules was a significant protective factor for thwarting disease progression (model 1: HR 0.654 (95% CI 0.489-0.875, p = 0.004); model 2: HR 0.646 (95% CI 0.476, 0.877, p = 0.005); and model 3: HR 0.602 (95% CI 0.442, 0.820, p = 0.001)). Conclusion: The long-term use of Niaoduqing granules improved SCr variation and lowered the risk of CKD progression by 39.8%.

15.
Br J Ophthalmol ; 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38777389

RESUMEN

Myopia has long been a global threat to public health. Timely interventions are likely to reduce the risk of vision-threatening complications. There are both established and rapidly evolving therapeutic approaches to slow myopia progression and/or delay its onset. The effective methods for slowing myopia progression include atropine eye-drops, defocus incorporated multiple segments (DIMS) spectacle lenses, spectacle lenses with highly aspherical lenslets target (HALT), diffusion optics technology (DOT) spectacle lenses, red light therapy (RLT), multifocal soft contact lenses and orthokeratology. Among these, 0.05% atropine, HALT lenses, RLT and +3.00 peripheral addition soft contact lenses yield over 60% reduction in myopia progression, whereas DIMS, DOT and MiSight contact lenses demonstrate at least 50% myopia control efficacy. 0.05% atropine demonstrates a more optimal balance of efficacy and safety than 0.01%. The efficacy of 0.01% atropine has not been consistent and requires further validation across diverse ethnicities. Combining atropine 0.01% with orthokeratology or DIMS spectacles yields better outcomes than using these interventions as monotherapies. Increased outdoor time is an effective public health strategy for myopia prevention while recent studies suggest that 0.05% low-concentration atropine and RLT therapy have promising potential as clinical myopia prevention interventions for high-risk groups. Myopia control spectacle lenses, being the least invasive, are safe for long-term use. However, when considering other approaches, it is essential to ensure proper instruction and regular follow-ups to maintain safety and monitor any potential complications. Ultimately, significant advances have been made in myopia control strategies, many of which have shown meaningful clinical outcomes. However, regular use and adequate safety monitoring over extended durations are imperative to foster confidence that can only come from extensive clinical experience.

16.
Int Immunopharmacol ; 133: 112041, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38636373

RESUMEN

Although the pathogenesis of rheumatoid arthritis (RA) remains unclear, an increasing number of studies have confirmed that pyroptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) is an important factor affecting the progression of RA. Periplogenin (PPN) is a natural cardiac glycoside; reportedly, it exerts anti-inflammatory and analgesic effects in diseases by inhibiting cell growth and migration. This study aimed to determine the effect of PPN on the growth, migration, and invasion of RA-FLS and the potential mechanism of pyroptosis regulation. We discovered that PPN could inhibit the migration and invasion abilities of RA-FLS and block their growth cycle, down-regulate the secretion and activation of NLRP3, Caspase-1, GSDMD, IL-1ß, and IL-18, and reduce the number of pyroptosis. In summary, PPN inhibited pyroptosis, reduced the release of inflammatory factors, and improved RA-FLS inflammation by regulating the NLRP3/Caspase-1/GSDMD signaling pathway.


Asunto(s)
Artritis Reumatoide , Fibroblastos , Piroptosis , Transducción de Señal , Sinoviocitos , Humanos , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/metabolismo , Artritis Reumatoide/patología , Caspasa 1/metabolismo , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Fibroblastos/efectos de los fármacos , Gasderminas , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteínas de Unión a Fosfato/metabolismo , Piroptosis/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Sinoviocitos/efectos de los fármacos , Sinoviocitos/metabolismo , Sinoviocitos/patología
17.
Pestic Biochem Physiol ; 201: 105864, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38685240

RESUMEN

MicroRNAs (miRNAs) are noncoding small regulatory RNAs involved in diverse biological processes. Odontotermes formosanus (Shiraki) is a polyphagous pest that causes economic damage to agroforestry. Serratia marcescens is a bacterium with great potential for controlling this insect. However, knowledge about the miRNA pathway and the role of miRNAs in O. formosanus defense against SM1 is limited. In this study, OfAgo1, OfDicer1 and OfDrosha were differentially expressed in different castes and tissues. SM1 infection affected the expression of all three genes in O. formosanus. Then, we used specific double-stranded RNAs to silence OfAgo1, OfDicer1 and OfDrosha. Knockdown of these genes enhanced the virulence of SM1 to O. formosanus, suggesting that miRNAs were critical in the defense of O. formosanus against SM1. Furthermore, we sequenced miRNAs from SM1-infected and uninfected O. formosanus. 33 differentially expressed (DE) miRNAs were identified, whereby 22 were upregulated and 11 were downregulated. Finally, the miRNA-mRNA networks were constructed, which further suggested the important role of miRNAs in the defense of O. formosanus against SM1. Totally, O. formosanus miRNA core genes defend against SM1 infection by regulating miRNA expression. This study elucidates the interactions between O. formosanus and SM1 and provides new theories for biological control.


Asunto(s)
MicroARNs , Serratia marcescens , MicroARNs/genética , MicroARNs/metabolismo , Serratia marcescens/genética , Serratia marcescens/patogenicidad , Animales , Escarabajos/microbiología , Escarabajos/genética
18.
Sci Total Environ ; 928: 172494, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38631642

RESUMEN

Environmental factors significantly impact grain mycobiome assembly and mycotoxin contamination. However, there is still a lack of understanding regarding the wheat mycobiome and the role of fungal communities in the interaction between environmental factors and mycotoxins. In this study, we collected wheat grain samples from 12 major wheat-producing provinces in China during both the harvest and storage periods. Our aim was to evaluate the mycobiomes in wheat samples with varying deoxynivalenol (DON) contamination levels and to confirm the correlation between environmental factors, the wheat mycobiome, and mycotoxins. The results revealed significant differences in the wheat mycobiome and co-occurrence network between contaminated and uncontaminated wheat samples. Fusarium was identified as the main differential taxon responsible for inducing DON contamination in wheat. Correlation analysis identified key factors affecting mycotoxin contamination. The results indicate that both environmental factors and the wheat mycobiome play significant roles in the production and accumulation of DON. Environmental factors can affect the wheat mycobiome assembly, and wheat mycobiome mediates the interaction between environmental factors and mycotoxin contamination. Furthermore, a random forest (RF) model was developed using key biological indicators and environmental features to predict DON contamination in wheat with accuracies exceeding 90 %. The findings provide data support for the accurate prediction of mycotoxin contamination and lay the foundation for the research on biological control technologies of mycotoxin through the assembly of synthetic microbial communities.


Asunto(s)
Micobioma , Micotoxinas , Triticum , Triticum/microbiología , Micotoxinas/análisis , Micotoxinas/metabolismo , China , Grano Comestible/microbiología , Contaminación de Alimentos/análisis , Tricotecenos/análisis , Tricotecenos/metabolismo , Fusarium , Monitoreo del Ambiente
19.
PLoS One ; 19(4): e0298778, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38568911

RESUMEN

BACKGROUND: Previous observational studies have reported an association between Sjögren's syndrome (SS) and an increased risk of Parkinson's Disease (PD). However, the causal relationship between these conditions remains unclear. The objective of this study was to investigate the causal impact of SS on the risk of developing PD, utilizing the Mendelian randomization (MR) approach. METHODS: We conducted a bidirectional MR analysis using publicly available genome-wide association studies (GWAS) data. The primary analysis utilized the inverse-variance weighted (IVW) method. Complementary methods, such as MR-Egger regression, weighted mode, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO), were utilized to identify and correct for the presence of horizontal pleiotropy. RESULTS: The IVW MR analysis revealed no significant association between SS and PD (IVW: OR = 1.00, 95% CI = 0.94-1.07, P = 0.95). Likewise, the reverse MR analysis did not identify any significant causal relationship between PD and SS (IVW: OR = 0.98, 95% CI = 0.85-1.12, P = 0.73). The results from MR-Egger regression, weighted median, and weighted mode approaches were consistent with the IVW method. Sensitivity analyses suggested that horizontal pleiotropy is unlikely to introduce bias to the causal estimates. CONCLUSION: This study does not provide evidence to support the assertion that SS has a conclusive impact on the risk of PD, which contradicts numerous existing observational reports. Further investigation is necessary to determine the possible mechanisms behind the associations observed in these observational studies.


Asunto(s)
Enfermedad de Parkinson , Síndrome de Sjögren , Humanos , Síndrome de Sjögren/genética , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Enfermedad de Parkinson/genética
20.
Int J Biol Macromol ; 268(Pt 1): 131559, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38631576

RESUMEN

Expansins are important plant cell wall proteins. They can loosen and soften the cell walls and lead to wall extension and cell expansion. To investigate their role in wood formation and fiber elongation, the PagEXPA1 that highly expressed in cell differentiation and expansion tissues was cloned from 84K poplar (Populus alba × P. glandulosa). The subcellular localization showed that PagEXPA1 located in the cell wall and it was highly expressed in primary stems and young leaves. Compared with non-transgenic 84K poplar, overexpression of PagEXPA1 can promote plant-growth, lignification, and fiber cell elongation, while PagEXPA1 Cas9-editing mutant lines exhibited the opposite phenotype. Transcriptome analysis revealed that DEGs were mainly enriched in some important processes, which are associated with cell wall formation and cellulose synthesis. The protein interaction prediction and expression analysis showed that PagCDKB2:1 and PagEXPA1 might have an interaction relationship. The luciferase complementary assay and bimolecular fluorescence complementary assay validated that PagEXPA1 can combined with PagCDKB2;1. So they promoted the expansion of xylem vascular tissues and the development of poplar though participating in the regulation of cell division and differentiation by programming the cell-cycle. It provides good foundation for molecular breeding of fast-growing and high-quality poplar varieties.


Asunto(s)
Pared Celular , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas , Populus , Populus/genética , Populus/crecimiento & desarrollo , Populus/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Pared Celular/metabolismo , Pared Celular/genética , Plantas Modificadas Genéticamente , Perfilación de la Expresión Génica , Xilema/metabolismo , Xilema/genética , Desarrollo de la Planta/genética , Madera/genética , Madera/crecimiento & desarrollo
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