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1.
BMC Infect Dis ; 24(1): 811, 2024 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-39129008

RESUMEN

OBJECTIVES: Hepatitis B is a liver disease caused by Hepatitis B virus (HBV) infection and is highly prevalent in China. To better understand the epidemiological characteristics of hepatitis B in China and develop effective disease control strategies, we employed temporal and spatial statistical methods. METHODS: We obtained HBV incidence data from the Public Health Science Data Center of the Chinese Center for Disease Control and Prevention for the years 2006 to 2018. Using Geographic Information System (GIS) and SaTScan scanning technology, we conducted spatial autocorrelation analysis and spatiotemporal scan analysis to create a map and visualize the distribution of hepatitis B incidence. RESULTS: While hepatitis B incidence rebounded in 2011 and 2017, the overall incidence in China decreased.In the trend analysis by item, the incidence varies from high to low. The global spatial autocorrelation analysis revealed a clustered distribution, and the Moran index analysis of spatial autocorrelation within local regions identified five provinces as H-H clusters (hot spots), while one province was an L-L cluster (cold spot). Spatial scan analysis identified 11 significant spatial clusters. CONCLUSIONS: We found significant clustering in the spatial distribution of hepatitis B incidence and positive spatial correlation of hepatitis B incidence in China. We also identified high-risk times and regional clusters of hepatitis B incidence.


Asunto(s)
Hepatitis B , Análisis Espacio-Temporal , Humanos , China/epidemiología , Hepatitis B/epidemiología , Incidencia , Virus de la Hepatitis B , Sistemas de Información Geográfica , Análisis por Conglomerados
2.
Foods ; 13(15)2024 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-39123574

RESUMEN

This study investigated the antibacterial effects of S-nitroso-N-acetylcysteine (SNAC) and sodium nitrite (NaNO2) against Escherichia coli and their application in beef sausages. Both SNAC and NaNO2 demonstrated pH-responsive antibacterial activity, with SNAC showing greater efficacy than NaNO2 (p < 0.05) at the same pH (3, 5, and 7). The reactive oxygen species (ROS) and reactive nitrogen species (RNS) induced in E. coli by SNAC were significantly higher than those induced by NaNO2 (p < 0.05), and both ROS and RNS values increased as the pH decreased. In addition, a lower pH led to more pores on the E. coli cell surface and increased membrane permeability, resulting in a more pronounced inhibitory effect. When applied to a beef sausage, SNAC-treated sausages had significantly lower total colony counts and carbonyl content compared to NaNO2-treated ones (p < 0.05). Consequently, SNAC shows great potential as a replacement for NaNO2 in meat products.

3.
Wideochir Inne Tech Maloinwazyjne ; 19(1): 1-10, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38974765

RESUMEN

Introduction: The Pfannenstiel incision is often used in gynecological Cesarean section; however, there is limited research on the use of the Pfannenstiel incision for specimen extraction in laparoscopic surgery for the treatment of colorectal cancer. Aim: To evaluate the safety of using the Pfannenstiel incision for specimen extraction in laparoscopic surgery for colorectal cancer patients. Material and methods: PubMed, Embase, Web of Science, Cochrane Library, CNKI, VIP and WanFangData were searched for studies published up to March 10, 2023; a random-effects model (RCT) and a fixed-effect model were used to evaluate the safety. Operative time, length of extraction skin incision, overall complications, superficial wound infection, organ/space surgical site infection and incisional hernia were evaluated. Results: A total of 5 studies were included in this research. There were no significant advantages in operation time, length of the incision, overall complications, superficial wound infection and organ/space surgical site in the Pfannenstiel group compared to the no Pfannenstiel group. However, the Pfannenstiel incision has a tendency to increase the length of the incision (SMD = 0.05; 95% CI = -0.22 to 0.33; p = 0.71) and the results of the remaining five (operative time,overall complications,incisional hernia, incisional infection and organ/space surgical site infection) are slightly skewed toward the Pfannenstiel incision. It is worth mentioning that incisional hernia (IH) may have an advantage in the Pfannenstiel group compared to the no Pfannenstiel group. Four studies were not at clear risk of bias and two studies were at risk of bias. Conclusions: Our study concludes that the Pfannenstiel incision has a good safety record and it is a good option for extracting specimens during laparoscopic surgery for colon cancer. The Pfannenstiel incision used for laparoscopic surgical specimen extraction has a significantly lower incidence of incisional hernia over no Pfannenstiel.

4.
Sci Rep ; 14(1): 15142, 2024 07 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956267

RESUMEN

Multiple myeloma (MM) is an incurable hematological malignancy with poor survival. Accumulating evidence reveals that lactylation modification plays a vital role in tumorigenesis. However, research on lactylation-related genes (LRGs) in predicting the prognosis of MM remains limited. Differentially expressed LRGs (DELRGs) between MM and normal samples were investigated from the Gene Expression Omnibus database. Univariate Cox regression and LASSO Cox regression analysis were applied to construct gene signature associated with overall survival. The signature was validated in two external datasets. A nomogram was further constructed and evaluated. Additionally, Enrichment analysis, immune analysis, and drug chemosensitivity analysis between the two groups were investigated. qPCR and immunofluorescence staining were performed to validate the expression and localization of PFN1. CCK-8 and flow cytometry were performed to validate biological function. A total of 9 LRGs (TRIM28, PPIA, SOD1, RRP1B, IARS2, RB1, PFN1, PRCC, and FABP5) were selected to establish the prognostic signature. Kaplan-Meier survival curves showed that high-risk group patients had a remarkably worse prognosis in the training and validation cohorts. A nomogram was constructed based on LRGs signature and clinical characteristics, and showed excellent predictive power by calibration curve and C-index. Moreover, biological pathways, immunologic status, as well as sensitivity to chemotherapy drugs were different between high- and low-risk groups. Additionally, the hub gene PFN1 is highly expressed in MM, knocking down PFN1 induces cell cycle arrest, suppresses cell proliferation and promotes cell apoptosis. In conclusion, our study revealed that LRGs signature is a promising biomarker for MM that can effectively early distinguish high-risk patients and predict prognosis.


Asunto(s)
Biomarcadores de Tumor , Regulación Neoplásica de la Expresión Génica , Mieloma Múltiple , Profilinas , Humanos , Mieloma Múltiple/genética , Mieloma Múltiple/mortalidad , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/patología , Pronóstico , Profilinas/genética , Profilinas/metabolismo , Biomarcadores de Tumor/genética , Masculino , Femenino , Nomogramas , Proliferación Celular/genética , Perfilación de la Expresión Génica , Estimación de Kaplan-Meier , Línea Celular Tumoral , Transcriptoma , Apoptosis/genética , Persona de Mediana Edad
5.
J Agric Food Chem ; 72(28): 15653-15661, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38959424

RESUMEN

Phenamacril (PHA) is a highly selective fungicide for controlling fusarium head blight (FHB) mainly caused by F. graminearum and F. asiaticum. However, the C423A mutation in myosin I of F. graminearum (FgMyoI) leads to natural resistance to PHA. Here, based on the computational approaches and biochemical validation, we elucidate the atomic-level mechanism behind the natural resistance of F. graminearum to the fungicide PHA due to the C423A mutation in FgMyoI. The mutation leads to a rearrangement of pocket residues, resulting in increased size and flexibility of the binding pocket, which impairs the stable binding of PHA. MST experiments confirm that the mutant protein FgMyoIC423A exhibits significantly reduced affinity for PHA compared to wild-type FgMyoI and the nonresistant C423K mutant. This decreased binding affinity likely underlies the development of PHA resistance in F. graminearum. Conversely, the nonresistant C423K mutant retains sensitivity to PHA due to the introduction of a strong hydrogen bond donor, which facilitates stable binding of PHA in the pocket. These findings shed light on the molecular basis of PHA resistance and provide new directions for the creation of new myosin inhibitors.


Asunto(s)
Farmacorresistencia Fúngica , Fungicidas Industriales , Fusarium , Mutación , Fusarium/efectos de los fármacos , Fusarium/genética , Fusarium/metabolismo , Fungicidas Industriales/farmacología , Fungicidas Industriales/química , Farmacorresistencia Fúngica/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/química , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/genética
6.
Pediatr Res ; 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39014239

RESUMEN

BACKGROUND: With the increase in the number of low birth weight infants, oxygen therapy is more widely used. However, chronic high-concentration oxygen environments lead to hyperoxic lung injury in children, which in turn leads to bronchopulmonary dysplasia (BPD). PGE1 is widely used in the clinic for its ability to inhibit inflammation and improve circulation. Therefore, we further investigated whether PGE-1 has a therapeutic effect on hyperoxic lung injury. METHODS: Hyperoxic lung injury model was adopted for investigating the interventional effects and underlying mechanisms of intraperitoneal injection of prostaglandin E1 (PGE-1) on hyperoxic lung injury in newborn rats via relevant experimental techniques, such as Diff-Quick staining, lung wet dry specific gravity measurements, HE staining, TUNEL staining, ELISA, and the Western blot method. RESULTS: Inflammatory and apoptotic cells in the PGE1-treated group were significantly lower than those in the hyperoxic lung injury group (p < 0.05); and the contents of IL-1ß, IL-6 and TNF-α in the treated group were significantly lower than those in the model group (p < 0.05). Caspase-3, CHOP, GRP78 and Bcl-2/Bax protein expression in the treatment group was significantly lower than that in the model group (p < 0.05). CONCLUSION: PGE-1 has a therapeutic effect on hyperoxic lung injury in neonatal rats. IMPACT: PGE1 treatment reduces levels of inflammatory cells and pro-inflammatory cytokines and decreases apoptosis. PGE1 has a therapeutic effect on BPD through the endoplasmic reticulum stress pathway. This study offers the possibility of PGE1 for the treatment of BPD.

7.
ACS Cent Sci ; 10(7): 1383-1395, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39071056

RESUMEN

Spiro-OMeTAD doped with lithium-bis(trifluoromethylsulfonyl)-imide (Li-TFSI) and tertbutyl-pyridine (t-BP) is widely used as a hole transport layer (HTL) in n-i-p perovskite solar cells (PSCs). Spiro-OMeTAD based PSCs typically show poor stability owing to the agglomeration of Li-TFSI, the migration of lithium ions (Li+), and the existence of potential mobile defects originating from the perovskite layer. Thus, it is necessary to search for a strategy that suppresses the degradation of PSCs and overcomes the Shockley Queisser efficiency limit via harvesting excess energy from hot charge carrier. Herein, two covalent organic frameworks (COFs) including BPTA-TAPD-COF and a well-defined donor-acceptor COF (BPTA-TAPD-COF@TCNQ) were developed and incorporated into Spiro-OMeTAD HTL. BPTA-TAPD-COF and BPTA-TAPD-COF@TCNQ could act as multifunctional additives of Spiro-OMeTAD HTL, which improve the photovoltaic performance and stability of the PSC device by accelerating charge-carrier extraction, suppressing the Li+ migration and Li-TFSI agglomeration, and capturing mobile defects. Benefiting from the increased conductivity, the addition of BPTA-TAPD-COF@TCNQ in the device led to the highest power conversion efficiency of 24.68% with long-term stability in harsh conditions. This work provides an example of using COFs as additives of HTL to enable improvements of both efficiency and stability for PSCs.

9.
J Agric Food Chem ; 72(27): 15176-15189, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38943677

RESUMEN

Fusarium head blight caused by Fusarium graminearum is a devastating disease in wheat that seriously endangers food security and human health. Previous studies have found that the secondary metabolite phenazine-1-carboxamide produced by biocontrol bacteria inhibited F. graminearum by binding to and inhibiting the activity of histone acetyltransferase Gcn5 (FgGcn5). However, the detailed mechanism of this inhibition remains unknown. Our structural and biochemical studies revealed that phenazine-1-carboxamide (PCN) binds to the histone acetyltransferase (HAT) domain of FgGcn5 at its cosubstrate acetyl-CoA binding site, thus competitively inhibiting the histone acetylation function of the enzyme. Alanine substitution of the residues in the binding site shared by PCN and acetyl-CoA not only decreased the histone acetylation level of the enzyme but also dramatically impacted the development, mycotoxin synthesis, and virulence of the strain. Taken together, our study elucidated a competitive inhibition mechanism of Fusarium fungus by PCN and provided a structural template for designing more potent phenazine-based fungicides.


Asunto(s)
Proteínas Fúngicas , Fungicidas Industriales , Fusarium , Histona Acetiltransferasas , Fenazinas , Enfermedades de las Plantas , Triticum , Fusarium/metabolismo , Fusarium/efectos de los fármacos , Fusarium/genética , Fenazinas/metabolismo , Fenazinas/farmacología , Fenazinas/química , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/química , Fungicidas Industriales/farmacología , Fungicidas Industriales/química , Fungicidas Industriales/metabolismo , Enfermedades de las Plantas/microbiología , Histona Acetiltransferasas/metabolismo , Histona Acetiltransferasas/genética , Histona Acetiltransferasas/química , Histona Acetiltransferasas/antagonistas & inhibidores , Triticum/microbiología , Sitios de Unión , Acetilación
10.
Water Res ; 259: 121855, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38838482

RESUMEN

Plasmid-mediated conjugative transfer facilitates the dissemination of antibiotic resistance, yet the comprehensive regulatory mechanisms governing this process remain elusive. Herein, we established pure bacteria and activated sludge conjugation system to investigate the regulatory mechanisms of conjugative transfer, leveraging metformin as an exogenous agent. Transcriptomic analysis unveiled that substantial upregulation of genes associated with the two-component system (e.g., AcrB/AcrA, EnvZ/Omp, and CpxA/CpxR) upon exposure to metformin. Furthermore, downstream regulators of the two-component system, including reactive oxygen species (ROS), cytoplasmic membrane permeability, and adenosine triphosphate (ATP) production, were enhanced by 1.7, 1.4 and 1.1 times, respectively, compared to the control group under 0.1 mg/L metformin exposure. Moreover, flow sorting and high-throughput sequencing revealed increased microbial community diversity among transconjugants in activated sludge systems. Notably, the antibacterial potential of human pathogenic bacteria (e.g., Bacteroides, Escherichia-Shigella, and Lactobacillus) was augmented, posing a potential threat to human health. Our findings shed light on the spread of antibiotic resistance bacteria and assess the ecological risks associated with plasmid-mediated conjugative transfer in wastewater treatment systems.


Asunto(s)
Plásmidos , Plásmidos/genética , Aguas del Alcantarillado/microbiología , Conjugación Genética , Bacterias/genética , Antibacterianos/farmacología
11.
Arch Dermatol Res ; 316(6): 328, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38824251

RESUMEN

Observational studies have revealed associations between various dietary factors and skin conditions. However, the causal relationship between diet and skin condition is still unknown. Data on 17 dietary factors were obtained from the UK Biobank. Data on four skin conditions were derived from the UK Biobank and another large-scale GWAS study. Genetic predictions suggested that the intake of oily fish was associated with a lower risk of skin aging (OR: 0.962, P = 0.036) and skin pigmentation (OR: 0.973, P = 0.033); Tea intake was associated with a lower risk of skin pigmentation (OR: 0.972, P = 0.024); Salad/raw vegetables intake was associated with a lower risk of keratinocyte skin cancer (OR: 0.952, P = 0.007). Coffee intake was associated with increased risk of skin aging (OR: 1.040, P = 0.028); Pork intake was associated with increased risk of skin aging (OR: 1.134, P = 0.020); Beef intake was associated with increased risk of cutaneous melanoma (OR: 1.013, P = 0.016); Champagne plus white wine intake was associated with increased risk of cutaneous melanoma (OR: 1.033, P = 0.004); Bread intake was associated with increased risk of keratinocyte skin cancer (OR: 1.026, P = 0.013). Our study results indicate causal relationships between genetically predicted intake of oily fish, tea, salad/raw vegetables, coffee, pork, beef, champagne plus white wine, and bread and skin conditions.


Asunto(s)
Dieta , Análisis de la Aleatorización Mendeliana , Neoplasias Cutáneas , Humanos , Dieta/efectos adversos , Dieta/estadística & datos numéricos , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/etiología , Envejecimiento de la Piel/genética , Pigmentación de la Piel/genética , Café/efectos adversos , Estudio de Asociación del Genoma Completo , Reino Unido/epidemiología , Té/efectos adversos , Factores de Riesgo
12.
J Hazard Mater ; 475: 134828, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38876015

RESUMEN

The prediction of ecological toxicity plays an increasingly important role in modern society. However, the existing models often suffer from poor performance and limited predictive capabilities. In this study, we propose a novel approach for ecological toxicity assessment based on pre-trained models. By leveraging pre-training techniques and graph neural network models, we establish a highperformance predictive model. Furthermore, we incorporate a variational autoencoder to optimize the model, enabling simultaneous discrimination of toxicity to bees and molecular degradability. Additionally, despite the low similarity between the endogenous hormones in bees and the compounds in our dataset, our model confidently predicts that these hormones are non-toxic to bees, which further strengthens the credibility and accuracy of our model. We also discovered the negative correlation between the degradation and bee toxicity of compounds. In summary, this study presents an ecological toxicity assessment model with outstanding performance. The proposed model accurately predicts the toxicity of chemicals to bees and their degradability capabilities, offering valuable technical support to relevant fields.


Asunto(s)
Redes Neurales de la Computación , Abejas/efectos de los fármacos , Animales , Ecotoxicología , Pruebas de Toxicidad
13.
Curr Med Imaging ; 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38803184

RESUMEN

OBJECTIVE: This study aimed to develop an ultrasomics model for predicting lymph node metastasis preoperative in patients with gastric cancer (GC). METHODS: This study enrolled GC patients who underwent preoperative ultrasound examination. Manual segmentation of the region of interest (ROI) was performed by an experienced radiologist to extract radiomics features using the Pyradiomics software. The Z-score algorithm was used for feature normalization, followed by the Wilcoxon test to identify the most informative features. Linear prediction models were constructed using the least absolute shrinkage and selection operator (LASSO). The performance of the ultrasomics model was evaluated using the area under curve (AUC), sensitivity, specificity, and the corresponding 95% confidence intervals (CIs). RESULTS: A total of 464 GC patients (mean age: 60.4 years ±11.3 [SD]; 328 men [70.7%]) were analyzed, of whom 291 had lymph node metastasis. The patients were randomly assigned to either the training (n=324) or test (n=140) sets, using a 7:3 ratio. An ultrasomics model that consisted of 19 radiomics features was developed using Wilcoxon and LASSO algorithms in the training set. Our ultrasomics model showed moderate performance for lymph node metastasis prediction in both the training (AUC: 0.802, 95%CI: 0.752-0.851, P<0.001) and test sets (AUC: 0.802, 95%CI: 0.724-0.879, P<0.001). The calibration curve analysis indicated good agreement between the predicted probabilities of ultrasomics and actual lymph node metastasis status. CONCLUSION: Our study highlights the potential of a machine learning-based ultrasomics model in predicting lymph node metastasis in GC patients, offering implications for personalized therapy approaches.

14.
Methods ; 227: 78-85, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38754711

RESUMEN

Pathogenic bacteria represent a formidable threat to human health, necessitating substantial resources for prevention and treatment. With the escalating concern regarding antibiotic resistance, there is a pressing need for innovative approaches to combat these pathogens. Repurposing existing drugs offers a promising solution. Our present work hypothesizes that proteins harboring ligand-binding pockets with similar chemical environments may be able to bind the same drug. To facilitate this drug-repurposing strategy against pathogenic bacteria, we introduce an online server, PharmaRedefine. Leveraging a combination of sequence and structure alignment and protein pocket similarity analysis, this platform enables the prediction of potential targets in representative bacteria for specific FDA-approved drugs. This novel approach holds tremendous potential for drug repositioning that effectively combat infections caused by pathogenic bacteria. PharmaRedefine is freely available at http://guolab.mpu.edu.mo/pharmredefine.


Asunto(s)
Antibacterianos , Reposicionamiento de Medicamentos , Reposicionamiento de Medicamentos/métodos , Antibacterianos/farmacología , Antibacterianos/química , Humanos , Bacterias/efectos de los fármacos , Programas Informáticos , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Sitios de Unión
15.
J Thorac Dis ; 16(4): 2528-2538, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38738248

RESUMEN

Background: The mortality rate of coronary artery disease ranks first in developed countries, and coronary revascularization therapy is an important cornerstone of its treatment. The postoperative pulmonary complications (PPCs) in patients receiving one-stop hybrid coronary revascularization (HCR) aggravate the dysfunction of multiple organs such as the heart and lungs, therefore increasing mortality. However, the risk factors are still unclear. The objective of this study was to explore the risk factors of PPCs after HCR surgery. Methods: In this study, the perioperative data of 311 patients undergoing HCR surgery were reviewed. All patients were divided into two groups according to whether the PPCs occurred. The baseline information and surgery-related indicators in preoperative laboratory examination, intraoperative fluid management, and anesthesia management were compared between the two groups. Results: Advanced age [odds ratio (OR): 1.065, 95% confidence interval (CI): 1.030-1.101, P<0.001], high body mass index (BMI; OR: 1.113, 95% CI: 1.011-1.225, P=0.02), history of percutaneous coronary intervention (PCI) surgery (OR: 2.831, 95% CI: 1.388-5.775, P=0.004), one-lung volume ventilation (OR: 3.804, 95% CI: 1.923-7.526, P<0.001), inhalation of high concentration oxygen (OR: 3.666, 95% CI: 1.719-7.815, P=0.001), the application of positive end-expiratory pressure (PEEP; OR: 2.567, 95% CI: 1.338-4.926, P=0.005), and long one-lung ventilation time (OR: 1.015, 95% CI: 1.006-1.023, P=0.001) may be risk factors for postoperative PPCs in patients undergoing one-stop coronary revascularization surgery. Using the above seven factors to jointly predict the risk of PPCs in patients undergoing one-stop coronary revascularization surgery, the receiver operating characteristic (ROC) curve showed an area under the curve (AUC) =0.873, 95% CI: 0.835-0.911, sensitivity: 84.81%, and specificity: 75.82%; the predictive model was shown to be effective. Conclusions: Patients undergoing HCR surgery with advanced age, high BMI, a history of PCI surgery, one-lung volume ventilation, inhalation of high concentration oxygen, use of PEEP, and prolonged single lung ventilation are more prone to PPCs.

16.
ACS Nano ; 18(19): 12386-12400, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38699808

RESUMEN

Current cancer vaccines face challenges due to an immunosuppressive tumor microenvironment and their limited ability to produce an effective immune response. To address the above limitations, we develop a 3-(2-spiroadamantyl)-4-methoxy-4-(3-phosphoryloxy)-phenyl-1,2-dioxetane (alkaline phosphatase substrate) and XMD8-92 (extracellular signal-regulated kinase 5 inhibitor)-codelivered copper-tetrahydroxybenzoquinone (Cu-THBQ/AX) nanosized metal-organic framework to in situ-generate therapeutic vaccination. Once inside the early endosome, the alkaline phosphatase overexpressed in the tumor cells' membrane activates the in situ type I photodynamic effect of Cu-THBQ/AX for generating •O2-, and the Cu-THBQ/AX catalyzes O2 and H2O2 to •O2- and •OH via semiquinone radical catalysis and Fenton-like reactions. This surge of ROS in early endosomes triggers caspase-3-mediated proinflammatory pyroptosis via activating phospholipase C. Meanwhile, Cu-THBQ/AX can also induce the oligomerization of dihydrolipoamide S-acetyltransferase to trigger tumor cell cuproptosis. The production of •OH could also trigger the release of XMD8-92 for effectively inhibiting the efferocytosis of macrophages to convert immunosuppressive apoptosis of cancer cells into proinflammatory secondary necrosis. The simultaneous induction of pyroptosis, cuproptosis, and secondary necrosis effectively converts the tumor microenvironment from "cold" to "hot" conditions, making it an effective antigen pool. This transformation successfully activates the antitumor immune response, inhibiting tumor growth and metastasis.


Asunto(s)
Vacunas contra el Cáncer , Cobre , Macrófagos , Estructuras Metalorgánicas , Piroptosis , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Animales , Ratones , Piroptosis/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Humanos , Cobre/química , Cobre/farmacología , Vacunas contra el Cáncer/química , Microambiente Tumoral/efectos de los fármacos , Nanopartículas/química , Fagocitosis/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/química , Línea Celular Tumoral , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/metabolismo , Ratones Endogámicos BALB C , Eferocitosis , Nanovacunas
17.
Talanta ; 276: 126207, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38718650

RESUMEN

Metal-Organic Framework (MOF) based nanozymes with clear structure are beneficial for exploration of structural-performance and exhibit broad prospects in improving activity. In this study, the prepared bimetallic Fe3Ni-MOF nanozyme was superior to single metal MOF in the peroxidase-like activity. Subsequently, a derivative nanozyme (Fe3Ni-MOF-Ar) was prepared by pyrolysis using Fe3Ni-MOF as the precursor in argon atomoshere with controlled temperature. The investigated of Fe3Ni-MOF-Ar revealed that the irregular macroporous state and the presence of heterovalent FeIII/FeII sites of Fe3Ni-MOF-Ar enable the retention, exposure, and electronic structure regulation of active sites, promoting the dual mechanism (the generation of •OH and electron transfer mechanism) and significantly increasing the peroxidase-like activity. Fe3Ni-MOF-Ar exhibited a strong affinity for substrate H2O2, which is higher than horseradish peroxidase. Ascorbic acid and cysteine are typical substances of antioxidants. Fe3Ni-MOF-Ar was used for sensitive colorimetric detection of ascorbic acid and cysteine, and the detection limit was as low as 150 and 60 nM. In addition, the smartphone devices was used to detection of antioxidant equivalent ascorbic acid, with a detection range of 0.5-120 µM. Fe3Ni-MOF-Ar nanozyme is feasible for sensitive detection of saliva total antioxidant capacity.


Asunto(s)
Antioxidantes , Ácido Ascórbico , Estructuras Metalorgánicas , Saliva , Teléfono Inteligente , Saliva/química , Estructuras Metalorgánicas/química , Humanos , Antioxidantes/análisis , Antioxidantes/química , Ácido Ascórbico/análisis , Ácido Ascórbico/química , Dominio Catalítico , Peróxido de Hidrógeno/química , Peróxido de Hidrógeno/análisis , Peroxidasa/química , Peroxidasa/metabolismo , Cisteína/análisis , Cisteína/química , Colorimetría/métodos , Níquel/química , Límite de Detección
18.
Microb Genom ; 10(5)2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38700925

RESUMEN

Paramyxoviruses are a group of single-stranded, negative-sense RNA viruses, some of which are responsible for acute human disease, including parainfluenza virus, measles virus, Nipah virus and Hendra virus. In recent years, a large number of novel paramyxoviruses, particularly members of the genus Jeilongvirus, have been discovered in wild mammals, suggesting that the diversity of paramyxoviruses may be underestimated. Here we used hemi-nested reverse transcription PCR to obtain 190 paramyxovirus sequences from 969 small mammals in Hubei Province, Central China. These newly identified paramyxoviruses were classified into four clades: genera Jeilongvirus, Morbillivirus, Henipavirus and Narmovirus, with most of them belonging to the genus Jeilongvirus. Using Illumina sequencing and Sanger sequencing, we successfully recovered six near-full-length genomes with different genomic organizations, revealing the more complex genome content of paramyxoviruses. Co-divergence analysis of jeilongviruses and their known hosts indicates that host-switching occurred more frequently in the evolutionary histories of the genus Jeilongvirus. Together, our findings demonstrate the high prevalence of paramyxoviruses in small mammals, especially jeilongviruses, and highlight the diversity of paramyxoviruses and their genome content, as well as the evolution of jeilongviruses.


Asunto(s)
Infecciones por Paramyxoviridae , Paramyxovirinae , Paramyxovirinae/genética , Infecciones por Paramyxoviridae/epidemiología , Infecciones por Paramyxoviridae/veterinaria , Mamíferos , China , Filogenia , Genoma Viral , Especificidad del Huésped
19.
Nat Neurosci ; 27(8): 1534-1544, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38802591

RESUMEN

Oligodendrocyte-lineage cells, including NG2 glia, undergo prominent changes in various neurodegenerative disorders. Here, we identify a neuroprotective role for NG2 glia against prion toxicity. NG2 glia were activated after prion infection in cerebellar organotypic cultured slices (COCS) and in brains of prion-inoculated mice. In both model systems, depletion of NG2 glia exacerbated prion-induced neurodegeneration and accelerated prion pathology. Loss of NG2 glia enhanced the biosynthesis of prostaglandin E2 (PGE2) by microglia, which augmented prion neurotoxicity through binding to the EP4 receptor. Pharmacological or genetic inhibition of PGE2 biosynthesis attenuated prion-induced neurodegeneration in COCS and mice, reduced the enhanced neurodegeneration in NG2-glia-depleted COCS after prion infection, and dampened the acceleration of prion disease in NG2-glia-depleted mice. These data unveil a non-cell-autonomous interaction between NG2 glia and microglia in prion disease and suggest that PGE2 signaling may represent an actionable target against prion diseases.


Asunto(s)
Dinoprostona , Microglía , Neuroglía , Neuronas , Enfermedades por Prión , Transducción de Señal , Animales , Microglía/metabolismo , Dinoprostona/metabolismo , Ratones , Transducción de Señal/fisiología , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Neuronas/patología , Neuroglía/metabolismo , Enfermedades por Prión/metabolismo , Enfermedades por Prión/patología , Ratones Endogámicos C57BL , Antígenos/metabolismo , Proteoglicanos/metabolismo , Subtipo EP4 de Receptores de Prostaglandina E/metabolismo , Priones/metabolismo , Priones/toxicidad , Cerebelo/metabolismo , Cerebelo/patología
20.
J Ultrasound Med ; 43(9): 1661-1672, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38822195

RESUMEN

PURPOSE: To develop a deep neural network system for the automatic segmentation and risk stratification prediction of gastrointestinal stromal tumors (GISTs). METHODS: A total of 980 ultrasound (US) images from 245 GIST patients were retrospectively collected. These images were randomly divided (6:2:2) into a training set, a validation set, and an internal test set. Additionally, 188 US images from 47 prospective GIST patients were collected to evaluate the segmentation and diagnostic performance of the model. Five deep learning-based segmentation networks, namely, UNet, FCN, DeepLabV3+, Swin Transformer, and SegNeXt, were employed, along with the ResNet 18 classification network, to select the most suitable network combination. The performance of the segmentation models was evaluated using metrics such as the intersection over union (IoU), Dice similarity coefficient (DSC), recall, and precision. The classification performance was assessed based on accuracy and the area under the receiver operating characteristic curve (AUROC). RESULTS: Among the compared models, SegNeXt-ResNet18 exhibited the best segmentation and classification performance. On the internal test set, the proposed model achieved IoU, DSC, precision, and recall values of 82.1, 90.2, 91.7, and 88.8%, respectively. The accuracy and AUC for GIST risk prediction were 87.4 and 92.0%, respectively. On the external test set, the segmentation models exhibited IoU, DSC, precision, and recall values of 81.0, 89.5, 92.8, and 86.4%, respectively. The accuracy and AUC for GIST risk prediction were 86.7 and 92.5%, respectively. CONCLUSION: This two-stage SegNeXt-ResNet18 model achieves automatic segmentation and risk stratification prediction for GISTs and demonstrates excellent segmentation and classification performance.


Asunto(s)
Aprendizaje Profundo , Tumores del Estroma Gastrointestinal , Ultrasonografía , Tumores del Estroma Gastrointestinal/diagnóstico por imagen , Humanos , Femenino , Masculino , Medición de Riesgo/métodos , Persona de Mediana Edad , Estudios Retrospectivos , Ultrasonografía/métodos , Anciano , Adulto , Neoplasias Gastrointestinales/diagnóstico por imagen , Reproducibilidad de los Resultados , Estudios Prospectivos , Abdomen/diagnóstico por imagen , Anciano de 80 o más Años , Adulto Joven
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