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1.
Plant Sci ; : 112171, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38969140

RESUMEN

The escalating salinity levels in cultivable soil pose a significant threat to agricultural productivity and, consequently, human sustenance. This problem is being exacerbated by natural processes and human activities, coinciding with a period of rapid population growth. Developing halophytic crops is needed to ensure food security is not impaired and land resources can be used sustainably. Evolution has created many close halophyte relatives of our major glycophytic crops, such as Puccinellia tenuiflora (relative of barley and wheat), Oryza coarctata (relative of rice) and Glycine soja (relative of soybean). There are also some halophytes have been subjected to semi-domestication and are considered as minor crops, such as Chenopodium quinoa. In this paper, we examine the prevailing comprehension of robust salinity resilience in halophytes. We summarize the existing strategies and technologies that equip researchers with the means to enhance the salt tolerance capabilities of primary crops and investigate the genetic makeup of halophytes.

2.
Foods ; 13(11)2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38890838

RESUMEN

Chlorphenamine maleate is a prohibited additive found in herbal teas and health foods. Excessive intake of this substance can result in adverse health effects. In this study, two novel haptens, PEM and bepotastine (PB1), mimicking chlorphenamine maleate structure were designed and synthesized based on molecular simulation for developing two corresponding polyclonal antibodies (PEM-Ab and PB1-Ab), respectively. Afterward, an indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) was developed to quickly and accurately detect chlorphenamine maleate in herbal teas using PB1-Ab, which has a high sensitivity and specificity. For chlorphenamine maleate, the half-maximal inhibitory concentration (IC50) and limit of detection (LOD) of PB1-Ab under ideal circumstances were found to be 1.18 µg/L and 0.07 µg/L, respectively. Besides, an environmentally friendly sample pre-treatment strategy was employed that allowed easy and effective elimination of complex matrices. The ic-ELISA method observed the average recovery rate from 87.7% to 94.0% with the variance coefficient (CV) ranging from 2.2% to 9.4%. Additionally, the identification of 25 commercially available herbal teas using liquid chromatography-tandem mass spectrometry (LC-MS/MS) further confirmed the validity of our detection. The results of the two methods are consistent. Overall, the proposed ic-ELISA could be an ultrasensitive and reliable method for chlorphenamine maleate adulterated in foods or exposure to the environment.

3.
Anal Methods ; 16(25): 4060-4065, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38873980

RESUMEN

Methyl parathion, a highly toxic, efficient, and persistent organophosphorus pesticide, is widely used in China. Sibutramine, a non-amphetamine central nervous system depressant, helps lose weight by disrupting hormone regulation, stimulating sympathetic nerves, and suppressing appetite. However, some unethical businesses fail to properly handle raw materials in foods like apple cider vinegar, leading to residual methyl parathion in apples or illegal excessive addition of sibutramine. Therefore, it is imperative to develop an immunoassay for the rapid detection of methyl parathion and sibutramine. The corresponding two haptens were prepared and coupled with the carrier proteins according to methyl parathion-sulfur-bovine serum protein (BSA)/chicken ovalbumin (OVA)-sibutramine (20 : 1 : excess, 15 : 1 : excess, 10 : 1 : excess, and 5 : 1 : excess), and sibutramine-BSA/OVA-methyl parathion (20 : 1 : excess, 10 : 1 : excess: 5 : 1 : excess, and 0 : 1 : excess). The result shows that the inhibition rate of the antibody obtained by methyl parathion-BSA/OVA-sibutramine (20 : 1 : excess) was higher than that of sibutramine-BSA/OVA-methyl parathion, which was 67.93%, and the concentration of methyl parathion was 8.65 ng mL-1 at this inhibition rate. Thus, methyl parathion-BSA/OVA-sibutramine (8.65 : 1 : excess) and the corresponding antibodies were selected for subsequent method establishment. By changing the concentration of the coating and antibody, the inhibition rate was found when the coating was 0.125 ng mL-1 and the antibody was diluted 4000 times. The antibody was used to develop a standard curve for the detection of sibutramine at the half-maximum inhibitory concentration (IC50) is 4.59 ng mL-1, the limit of detection (IC10) is 2.21 ng mL-1, the detection range is 2.89 to 7.28 ng mL-1, methyl p-phosphorus at the half-maximum inhibitory concentration (IC50) is 15.34 ng mL-1, the limit of detection (IC10) is 0.42 ng mL-1, the detection range is ng mL-1. Under these conditions, the recovery rate was between 88% and 102%, within reasonable limits, indicating the successful establishment of a rapid enzyme-linked ELISA assay.


Asunto(s)
Ciclobutanos , Ensayo de Inmunoadsorción Enzimática , Malus , Metil Paratión , Ciclobutanos/química , Ensayo de Inmunoadsorción Enzimática/métodos , Malus/química , Metil Paratión/análisis , Ácido Acético/química , Depresores del Apetito/análisis , Depresores del Apetito/química , Contaminación de Alimentos/análisis , Animales , Límite de Detección
4.
Lung Cancer ; 192: 107817, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38735177

RESUMEN

OBJECTIVE: The aim of this study is to scrutinize the prognostic significance of inflammatory biomarkers concerning the effectiveness and safety of combining PD-1 inhibition with chemotherapy in the management of advanced NSCLC. METHODS: We conducted a retrospective analysis involving 206 NSCLC patients who received treatment at Qingdao Municipal Hospital. The study encompassed the acquisition of baseline clinical attributes and hematological parameters of these patients. The optimal threshold values for PLT and NLR were ascertained based on pre-treatment evaluations, with a particular focus on their association with PFS. Variables linked to PFS were subject to scrutiny through Kaplan-Meier analysis and logistic regression. The Receiver Operating Characteristic (ROC) curve served as the means to determine the ideal cut-off values for categorizing levels of inflammatory markers into high and low classifications. We employed Chi-square tests to evaluate the relationship between elevated and reduced baseline levels of inflammatory markers and irAE. RESULTS: Kaplan-Meier analysis disclosed that patients in the low baseline PLT group and the low NLR group exhibited a substantially more favorable prognosis in contrast to their counterparts in the high baseline PLT and high NLR groups. Multivariate analysis indicated that diminished baseline PLT and NLR levels before treatment independently foretell extended PFS. Chi-square analysis underscored a substantial correlation between baseline WBC, NEUT, LYMPH, MONO, and NLR levels and irAE. CONCLUSION: Subdued baseline PLT and NLR levels may serve as indicators of a more auspicious prognosis in patients contending with advanced NSCLC undergoing the combination of PD-1 inhibition and chemotherapy. Elevated baseline levels of inflammatory markers antedating PD-1 therapy in advanced NSCLC may be intimately interrelated with the occurrence of irAE.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Inmunoterapia , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Femenino , Masculino , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Persona de Mediana Edad , Estudios Retrospectivos , Pronóstico , Anciano , Inmunoterapia/métodos , Biomarcadores de Tumor , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Adulto , Inflamación , Anciano de 80 o más Años
5.
J Pharmacol Sci ; 155(3): 101-112, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38797534

RESUMEN

Pulmonary inflammation may lead to neuroinflammation resulting in neurological dysfunction, and it is associated with a variety of acute and chronic lung diseases. Paeonol is a herbal phenolic compound with anti-inflammatory and anti-oxidative properties. The aim of this study is to understand the beneficial effects of paeonol on cognitive impairment, pulmonary inflammation and its underlying mechanisms. Pulmonary inflammation-associated cognitive deficit was observed in TNFα-stimulated mice, and paeonol mitigated the cognitive impairment by reducing the expressions of interleukin (IL)-1ß, IL-6, and NOD-like receptor family pyrin domain-containing 3 (NLRP3) in hippocampus. Moreover, elevated plasma miR-34c-5p in lung-inflamed mice was also reduced by paeonol. Pulmonary inflammation induced by intratracheal instillation of TNFα in mice resulted in immune cells infiltration in bronchoalveolar lavage fluid, pulmonary edema, and acute fibrosis, and these inflammatory responses were alleviated by paeonol orally. In MH-S alveolar macrophages, tumor necrosis factor (TNF) α- and phorbol myristate acetate (PMA)-induced inflammasome activation was ameliorated by paeonol. In addition, the expressions of antioxidants were elevated by paeonol, and reactive oxygen species production was reduced. In this study, paeonol demonstrates protective effects against cognitive deficits and pulmonary inflammation by exerting anti-inflammatory and anti-oxidative properties, suggesting a powerful benefit as a potential therapeutic agent.


Asunto(s)
Acetofenonas , Disfunción Cognitiva , Enfermedades Pulmonares , Enfermedades Pulmonares/complicaciones , Acetofenonas/farmacología , Acetofenonas/uso terapéutico , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/etiología , Macrófagos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratones Endogámicos C57BL , Masculino , Animales , Ratones , Factor de Necrosis Tumoral alfa , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , MicroARNs/sangre , MicroARNs/genética , Especies Reactivas de Oxígeno/metabolismo
7.
Plant Cell Rep ; 43(5): 131, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38656568

RESUMEN

KEY MESSAGE: The sugar supply in the medium affects the apical hook development of Arabidopsis etiolated seedlings. In addition, we provided the mechanism insights of this process. Dicotyledonous plants form an apical hook structure to shield their young cotyledons from mechanical damage as they emerge from the rough soil. Our findings indicate that sugar molecules, such as sucrose and glucose, are crucial for apical hook development. The presence of sucrose and glucose allows the apical hooks to be maintained for a longer period compared to those grown in sugar-free conditions, and this effect is dose-dependent. Key roles in apical hook development are played by several sugar metabolism pathways, including oxidative phosphorylation and glycolysis. RNA-seq data revealed an up-regulation of genes involved in starch and sucrose metabolism in plants grown in sugar-free conditions, while genes associated with phenylpropanoid metabolism were down-regulated. This study underscores the significant role of sugar metabolism in the apical hook development of etiolated Arabidopsis seedlings.


Asunto(s)
Arabidopsis , Regulación de la Expresión Génica de las Plantas , Plantones , Arabidopsis/crecimiento & desarrollo , Arabidopsis/genética , Arabidopsis/metabolismo , Plantones/crecimiento & desarrollo , Plantones/metabolismo , Plantones/genética , Azúcares/metabolismo , Sacarosa/metabolismo , Glucosa/metabolismo , Etiolado , Metabolismo de los Hidratos de Carbono , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Cotiledón/metabolismo , Cotiledón/crecimiento & desarrollo , Cotiledón/genética
8.
Chem Biol Interact ; 395: 111004, 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38636790

RESUMEN

Head and neck squamous cell carcinoma (HNSCC) faces low response rates to anti-PD-1 immunotherapies, highlighting the need for enhanced treatment strategies. Auranofin, which inhibits thioredoxin reductase (TrxR) through its gold-based composition, has shown potential in cancer treatment. It targets the TrxR system, essential for safeguarding cells from oxidative stress. The overproduction of TrxR in cancerous cells supports their proliferation. However, auranofin's interference with this system can upset the cellular redox equilibrium, boost levels of reactive oxygen species, and trigger the death of cancer cells. This study is the first to highlight TXNRD1 as a crucial factor contributing to resistance to anti-PD-1 treatment in HNSCC. In this study, we identified targetable regulators of resistance to immunotherapy-induced ferroptosis in HNSCC. We observed a link of thioredoxin reductase 1 (TXNRD1) with tumoral PD-L1 expression and ferroptosis suppression in HNSCC. Moreover, HNSCC tumors with aberrant TXNRD1 expression exhibited a lack of PD-1 response, NRF2 overexpression, and PD-L1 upregulation. TXNRD1 inhibition promoted ferroptosis in HNSCC cells with NRF2 activation and in organoid tumors derived from patients lacking a PD-1 response. Mechanistically, TXNRD1 regulated PD-L1 transcription and maintained the redox balance by binding to ribonucleotide reductase regulatory subunit M2 (RRM2). TXNRD1 expression disruption sensitized HNSCC cells to anti-PD-1-mediated Jurkat T-cell activation, promoting tumor killing through ferroptosis. Moreover, TXNRD1 inhibition through auranofin cotreatment synergized with anti-PD-1 therapy to potentiate immunotherapy-mediated ferroptosis by mediating CD8+ T-cell infiltration and downregulating PD-L1 expression. Our findings indicate that targeting TXNRD1 is a promising therapeutic strategy for improving immunotherapy outcomes in patients with HNSCC.


Asunto(s)
Auranofina , Antígeno B7-H1 , Ferroptosis , Neoplasias de Cabeza y Cuello , Tiorredoxina Reductasa 1 , Humanos , Tiorredoxina Reductasa 1/metabolismo , Tiorredoxina Reductasa 1/antagonistas & inhibidores , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/patología , Ferroptosis/efectos de los fármacos , Auranofina/farmacología , Antígeno B7-H1/metabolismo , Línea Celular Tumoral , Animales , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Ratones , Receptor de Muerte Celular Programada 1/metabolismo , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Factor 2 Relacionado con NF-E2/metabolismo , Especies Reactivas de Oxígeno/metabolismo
9.
ACS Appl Mater Interfaces ; 16(11): 13466-13480, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38445450

RESUMEN

Guided bone regeneration (GBR) technology has been widely used for the regeneration of periodontal bone defects. However, the limited mechanical properties and bone regeneration potential of the currently available GBR membranes often limit their repair effectiveness. In this paper, serum-derived growth factor lysophosphatidic acid (LPA) nanoparticles and dopamine-decorative nanohydroxyapatite (pDA/nHA) particles were double-loaded into polylactic-glycolic acid/polycaprolactone (PLGA/PCL) scaffolds as an organic/inorganic biphase delivery system, namely, PP-pDA/nHA-LPA scaffolds. Physicochemical properties and osteogenic ability in vitro and in vivo were performed. Scanning electron microscopy and mechanical tests showed that the PP-pDA/nHA-LPA scaffolds had a 3D bionic scaffold structure with improved mechanical properties. In vitro cell experiments demonstrated that the PP-pDA/nHA-LPA scaffolds could significantly enhance the attachment, proliferation, osteogenic differentiation, and mineralization of MC3T3-E1 cells. In vivo, the PP-pDA/nHA-LPA scaffolds exhibited great cytocompatibility and cell recruitment ability in 2- and 4-week subcutaneous implantation experiments and significantly promoted bone regeneration in the periodontal defect scaffold implantation experiment. Moreover, LPA-loaded scaffolds were confirmed to enhance osteogenic activities by upregulating the expression of ß-catenin and further activating the Wnt/ß-catenin pathway. These results demonstrate that the biphase PP-pDA/nHA-LPA delivery system is a promising material for the GBR.


Asunto(s)
Indoles , Lisofosfolípidos , Osteogénesis , Polímeros , Andamios del Tejido , Andamios del Tejido/química , beta Catenina , Regeneración Ósea , Durapatita/química , Ingeniería de Tejidos/métodos
10.
Food Chem ; 446: 138912, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38452509

RESUMEN

Screening for the hazardous adulterant phenolphthalein (PTH) in slimming foods is necessary. Herein, the linkage of the PTH target epitope with various spacer arms was proposed for hapten design, aiming to produce highly sensitive and specific antibodies targeting PTH. To understand the influence of spacer arms on epitope, comprehensive evaluations were conducted using computer-aided chemistry and animal immunization. The resulting antibody exhibited maximal half-inhibitory concentration (IC50) of 0.25 ng/mL. Then, a lateral flow immunoassay (LFIA) was established with detection capability for screening (CCß) of less than 140, 240, and 25 ng/g for PTH in tea, instant coffee, and oral liquid, respectively. Furthermore, blind sample results agreed well with LFIA and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Therefore, this work not only provides a robust tool for detecting PTH adulteration but also suggests that the careful pairing of spacer arms with hapten epitope is a key factor in advancing rational hapten design.


Asunto(s)
Fenolftaleína , Espectrometría de Masas en Tándem , Animales , Cromatografía Liquida , Epítopos , Espectrometría de Masas en Tándem/métodos , Inmunoensayo/métodos , Anticuerpos , Haptenos/química
11.
Food Funct ; 15(7): 3615-3628, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38470843

RESUMEN

Aflatoxin B1 (AFB1) causes serious immunotoxicity and has attracted considerable attention owing to its high sensitivity and common chemical-viral interactions in living organisms. However, the sensitivity of different species to AFB1 widely varies, which cannot be explained by the different metabolism in species. The gut microbiota plays a crucial role in the immune system, but the interaction of the microbiota with AFB1-induced immunotoxicity still needs to be determined. Our results indicated that AFB1 exposure disrupted the structure of the gut microbiota and damaged the gut barrier, which caused translocation of microbiota metabolites, lipopolysaccharides, to the spleen. Subsequently, pyroptosis of the spleen was activated. Interestingly, AFB1 exposure had little effect on the splenic pyroptosis of pseudo-germfree mice (antibiotic mixtures eliminated their gut microbiota, ABX). Then, fecal microbiota transplant (FMT) and sterile fecal filtrate (SFF) were employed to validate the function of the gut microbiota and its metabolites in AFB1-induced splenic pyroptosis. The AFB1-disrupted microbiota and its metabolites significantly promoted splenic pyroptosis, which was worse than that in control mice. Overall, AFB1-induced splenic pyroptosis is associated with the gut microbiota and its metabolites, which was further demonstrated by FMT and SFF. The mechanism of AFB1-induced splenic pyroptosis was explored for the first time, which paves a new way for preventing and treating the immunotoxicity from mycotoxins by regulating the gut microbiota.


Asunto(s)
Microbioma Gastrointestinal , Piroptosis , Animales , Ratones , Aflatoxina B1/toxicidad , Bazo , Heces
12.
Life (Basel) ; 14(2)2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38398727

RESUMEN

Mycoplasma ovipneumoniae (M. ovipneumoniae) causes a fatal infection in goats, leading to significant economic losses in the small-ruminant industry worldwide. The present study aimed to characterize the strains of M. ovipneumoniae infecting goats with pneumonia in Anhui Province, China. From November 2021 to January 2023, among 20 flocks, a total of 1320 samples (600 samples of unvaccinated blood, 400 nasal swabs, 200 samples of pleural fluid, and 120 samples of lung tissue) were obtained from goats with typical signs of pneumonia, such as a low growth rate, appetite suppression, increased temperature, discharge from the nose, and a cough. Necropsied goats showed increased pleural fluid, fibrinous pleuropneumonia, and attached localized pleural adhesions. M. ovipneumoniae isolated from the samples were subjected to an indirect hemagglutination test (IHA), PCR amplicon sequencing, phylogenetic analysis, and biochemical identification tests. The overall positivity rate of M. ovipneumoniae was 27.50%. Mycoplasmas were obtained from 80 (20.0%) nasal swabs, 21 (10.5%) pleural fluid samples, and 15 (12.5%) lung samples. PCR amplicon (288 bp) sequencing identified eight strains of M. ovipneumoniae. In a phylogenetic tree, the isolated strains were homologous to the standard strain M. ovipneumoniae Y-98 and most similar to M. ovipneumoniae FJ-SM. Local strains of M. ovipneumoniae were isolated from goats in Anhui province. The identified genomic features and population structure will promote further study of M. ovipneumoniae pathogenesis and could form the basis for vaccine and therapy development.

13.
J Transl Med ; 22(1): 219, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38424541

RESUMEN

BACKGROUND: The rapid emergence and global dissemination of the Omicron variant of SARS-CoV-2 have posed formidable challenges in public health. This scenario underscores the urgent need for an enhanced understanding of Omicron's pathophysiological mechanisms to guide clinical management and shape public health strategies. Our study is aimed at deciphering the intricate molecular mechanisms underlying Omicron infections, particularly focusing on the identification of specific biomarkers. METHODS: This investigation employed a robust and systematic approach, initially encompassing 15 Omicron-infected patients and an equal number of healthy controls, followed by a validation cohort of 20 individuals per group. The study's methodological framework included a comprehensive multi-omics analysis that integrated proteomics and metabolomics, augmented by extensive bioinformatics. Proteomic exploration was conducted via an advanced Ultra-High-Performance Liquid Chromatography (UHPLC) system linked with mass spectrometry. Concurrently, metabolomic profiling was executed using an Ultra-Performance Liquid Chromatography (UPLC) system. The bioinformatics component, fundamental to this research, entailed an exhaustive analysis of protein-protein interactions, pathway enrichment, and metabolic network dynamics, utilizing state-of-the-art tools such as the STRING database and Cytoscape software, ensuring a holistic interpretation of the data. RESULTS: Our proteomic inquiry identified eight notably dysregulated proteins (THBS1, ACTN1, ACTC1, POTEF, ACTB, TPM4, VCL, ICAM1) in individuals infected with the Omicron variant. These proteins play critical roles in essential physiological processes, especially within the coagulation cascade and hemostatic mechanisms, suggesting their significant involvement in the pathogenesis of Omicron infection. Complementing these proteomic insights, metabolomic analysis discerned 146 differentially expressed metabolites, intricately associated with pivotal metabolic pathways such as tryptophan metabolism, retinol metabolism, and steroid hormone biosynthesis. This comprehensive metabolic profiling sheds light on the systemic implications of Omicron infection, underscoring profound alterations in metabolic equilibrium. CONCLUSIONS: This study substantially enriches our comprehension of the physiological ramifications induced by the Omicron variant, with a particular emphasis on the pivotal roles of coagulation and platelet pathways in disease pathogenesis. The discovery of these specific biomarkers illuminates their potential as critical targets for diagnostic and therapeutic strategies, providing invaluable insights for the development of tailored treatments and enhancing patient care in the dynamic context of the ongoing pandemic.


Asunto(s)
Multiómica , Proteómica , Humanos , Metabolómica , Metabolismo de los Lípidos , Biomarcadores
14.
Neural Netw ; 172: 106112, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38218025

RESUMEN

Recent advances in unsupervised domain adaptation have shown that mitigating the domain divergence by extracting the domain-invariant features could significantly improve the generalization of a model with respect to a new data domain. However, current methodologies often neglect to retain domain private information, which is the unique information inherent to the unlabeled new domain, compromising generalization. This paper presents a novel method that utilizes mutual information to protect this domain-specific information, ensuring that the latent features of the unlabeled data not only remain domain-invariant but also reflect the unique statistics of the unlabeled domain. We show that simultaneous maximization of mutual information and reduction of domain divergence can effectively preserve domain-private information. We further illustrate that a neural estimator can aptly estimate the mutual information between the unlabeled input space and its latent feature space. Both theoretical analysis and empirical results validate the significance of preserving such unique information of the unlabeled domain for cross-domain generalization. Comparative evaluations reveal our method's superiority over existing state-of-the-art techniques across multiple benchmark datasets.


Asunto(s)
Benchmarking , Generalización Psicológica
15.
Toxicol Appl Pharmacol ; 483: 116818, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38215994

RESUMEN

The recurrence and metastasis in breast cancer within 3 years after the chemotherapies or surgery leads to poor prognosis with approximately 1-year overall survival. Large-scale scanning research studies have shown that taking lipid-lowering drugs may assist to reduce the risk of death from many cancers, since cholesterol in lipid rafts are essential for maintain integral membrane structure and functional signaling regulation. In this study, we examined five lipid-lowering drugs: swertiamarin, gemfibrozil, clofibrate, bezafibrate, and fenofibrate in triple-negative breast cancer, which is the most migration-prone subtype. Using human and murine triple-negative breast cancer cell lines (Hs 578 t and 4 T1), we found that fenofibrate displays the highest potential in inhibiting the colony formation, wound healing, and transwell migration. We further discovered that fenofibrate reduces the activity of pro-metastatic enzymes, matrix metalloproteinases (MMP)-9 and MMP-2. In addition, epithelial markers including E-cadherin and Zonula occludens-1 are increased, whereas mesenchymal markers including Snail, Twist and α-smooth muscle actin are attenuated. Furthermore, we found that fenofibrate downregulates ubiquitin-dependent GDF-15 degradation, which leads to enhanced GDF-15 expression that inhibits cell migration. Besides, nuclear translocation of FOXO1 is also upregulated by fenofibrate, which may responsible for GDF-15 expression. In summary, fenofibrate with anti-cancer ability hinders TNBC from migration and invasion, and may be beneficial to repurposing use of fenofibrate.


Asunto(s)
Fenofibrato , Neoplasias de la Mama Triple Negativas , Animales , Humanos , Ratones , Neoplasias de la Mama Triple Negativas/metabolismo , Fenofibrato/farmacología , Fenofibrato/uso terapéutico , Factor 15 de Diferenciación de Crecimiento/farmacología , Factor 15 de Diferenciación de Crecimiento/uso terapéutico , Línea Celular Tumoral , Movimiento Celular , Hipolipemiantes/farmacología , Hipolipemiantes/uso terapéutico , Transición Epitelial-Mesenquimal , Lípidos , Proliferación Celular
16.
Endocr Relat Cancer ; 31(3)2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38224097

RESUMEN

Adrenocortical carcinoma (ACC) is a malignancy with a poor prognosis and high mortality rate. A high tumor mutational burden (TMB) has been found to be associated with poor prognosis in ACC. Thus, exploring ACC biomarkers based on TMB holds significant importance for patient risk stratification. In our research, we utilized weighted gene coexpression network analysis and an assay for transposase-accessible chromatin with high-throughput sequencing to identify genes associated with TMB. Through the comprehensive analysis of various public datasets, Lamin B1 (LMNB1) was identified as a biomarker associated with a high TMB and low chromatin accessibility. Immunohistochemical staining demonstrated high expression of LMNB1 in ACC compared to noncancerous tissues. Functional enrichment analyses revealed that the function of LMNB1 is associated with cell proliferation and division. Furthermore, cell assays suggested that LMNB1 promotes tumor proliferation and invasion. In addition, mutation analysis suggested that the high expression of LMNB1 is associated with TP53 mutations. Additionally, LMNB1 was highly expressed in the vast majority of solid tumors across cancers. In our immune analysis, we discovered that the high expression of LMNB1 might suppress the infiltration of CD8+ T cells in the ACC microenvironment. In summary, LMNB1 is a predictive factor for the poor prognosis of adult and pediatric ACC. Its high expression in ACC is positively associated with high TMB and lower chromatin accessibility, and it promotes ACC cell proliferation and invasion. Therefore, LMNB1 holds promise as a novel biomarker and potential therapeutic target for ACC.


Asunto(s)
Carcinoma Corticosuprarrenal , Lamina Tipo B , Adulto , Niño , Humanos , Carcinoma Corticosuprarrenal/genética , Biomarcadores , Biomarcadores de Tumor/genética , Cromatina , Lamina Tipo B/genética , Lamina Tipo B/metabolismo , Pronóstico , Microambiente Tumoral
17.
BMC Public Health ; 24(1): 58, 2024 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-38166939

RESUMEN

BACKGROUND: While mother-to-child transmission (MTCT) of hepatitis B virus (HBV) remains a significant challenge in China, research investigating the effectiveness of the September 2017 pilot program to eliminate MTCT of HIV, syphilis, and HBV is limited. Baoan district, which has a higher-than-average rate of hepatitis B infection among pregnant women and strong support from the government, was one of six national pilot districts selected for the program. Therefore, this study aims to assess the progress and implementation of the elimination of MTCT of HBV in Baoan district over a period of 5 years. METHODS: Data was collected from the national information system for the prevention of MTCT, registration forms, and follow-up forms of pregnant women and their live births from 2018 to 2022. Joinpoint models were used to analyze changing trends over time, calculating annual percentage change (APC) and the corresponding 95% confidence interval (95%CI). Multivariate logistic regression models were used to analyze risk factors for HBV MTCT. RESULTS: From 2018 to 2022, the coverage of HBV screening during pregnancy increased from 98.29 to 99.55% (APC = 0.30, P = 0.012). The coverage of HBV early screening within 13 gestational weeks increased from 40.76 to 86.42% (APC = 18.88, P = 0.033). The prevalence of maternal HBV infection declined by an APC of - 3.50 (95% CI -6.28 ~ - 0.63). The coverage of antiviral therapy among high-risk pregnant women increased from 63.59 to 90.04% (APC = 11.90, P = 0.031). Coverage for timely administration of hepatitis B immunoglobulin, hepatitis B birth dose vaccine, and three-dose hepatitis B vaccination remained consistently above 97.50%. The coverage of post-vaccination serological testing (PVST) in high-risk infants was 56.15% (1352/2408), and the MTCT rate of HBV was 0.18%. Mothers with high-school education or below (OR = 3.76, 95% CI 1.04 ~ 13.60, P = 0.04) and hepatitis B e antigen (HBeAg) positivity (OR = 18.89, 95% CI 1.98 ~ 18.50, P = 0.01) had increased MTCT risk. CONCLUSIONS: The implementation of comprehensive prevention strategies in Baoan district, including screening, treatment, and immunoprophylaxis, has proven effective in maintaining the MTCT of HBV at an extremely low level. However, it remains crucial to raise public awareness, specifically on the importance of improving the coverage of PVST for infants exposed to HBV.


Asunto(s)
Hepatitis B , Complicaciones Infecciosas del Embarazo , Lactante , Femenino , Embarazo , Humanos , Virus de la Hepatitis B , Antígenos de Superficie de la Hepatitis B , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Hepatitis B/diagnóstico , Hepatitis B/epidemiología , Hepatitis B/prevención & control , Antígenos e de la Hepatitis B , Vacunas contra Hepatitis B/uso terapéutico , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/prevención & control , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , China/epidemiología
18.
Small ; 20(6): e2303352, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37794624

RESUMEN

Antimicrobial resistance has become a serious threat to the global public health. Accurate and rapid antimicrobial susceptibility testing (AST) allows evidence-based prescribing of antibiotics to improve patient care and clinical outcomes. Current culture-based AST assays are inherently limited by the doubling time of bacterial reproduction, which require at least 24 h to have a decisive result. Herein, a label-free electrical impedance-based microfluidic platform designed to expedite and streamline AST procedure for clinical practice is presented. Following a 30-min exposure of bacterial samples to antibiotics, the presented high-throughput, single-bacterium level impedance characterization platform enables a rapid 2-min AST assay. The platform facilitates accurate analysis of individual bacterial viability, as indicated by changes in electrical characteristics, thereby enabling the determination of antimicrobial resistance. Moreover, the potential clinical applicability of this platform is demonstrated by testing different E. coli strains against five antibiotics, yielding 100% categorical agreements compared to standard culture methods.


Asunto(s)
Escherichia coli , Microfluídica , Humanos , Impedancia Eléctrica , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Bacterias
19.
Int Wound J ; 21(4): e14603, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38155392

RESUMEN

Surgical site infections (SSIs) pose significant risks to patients undergoing colorectal cancer (CRC) surgery. With increasing evidence on the benefits of oral probiotics in various clinical contexts, there is a need to assess their efficacy and safety in reducing SSIs following CRC surgery. A systematic review and meta-analysis were conducted in line with PRISMA guidelines using the PICO framework. On 19 September 2023, four major databases (PubMed, Embase, Web of Science and Cochrane Library) were searched without any temporal or language restrictions. Rigorous inclusion and exclusion criteria were employed. Data extraction was independently undertaken by two assessors, and any discrepancies were discussed. The Cochrane Collaboration's risk of bias instrument was utilized to assess study quality. The meta-analysis incorporated a fixed-effects model or random-effects model based on the I2 statistic to assess heterogeneity. The initial search yielded 1282 articles, of which 10 met the inclusion criteria and were analysed. Probiotic administration not only significantly reduced the incidence of SSIs but also curtailed the duration of hospital stays. Moreover, the subgroup analysis indicated that interventions employing multiple strains of probiotics were more effective in reducing postoperative infections than those utilizing a single strain. Probiotics effectively prevent postoperative infections and shorten hospital stays. Multi-strain probiotics outperform single strain in efficacy. Future studies should focus on their safety and optimal clinical use.


Asunto(s)
Neoplasias Colorrectales , Probióticos , Humanos , Infección de la Herida Quirúrgica/prevención & control , Infección de la Herida Quirúrgica/tratamiento farmacológico , Antibacterianos/uso terapéutico , Probióticos/uso terapéutico , Incidencia , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/inducido químicamente , Neoplasias Colorrectales/tratamiento farmacológico
20.
Clin Lab ; 69(12)2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38084683

RESUMEN

BACKGROUND: Urachal remnants (URs) represent uncommon and underdiagnosed entities that are usually detected incidentally at imaging or present clinically different manifestations. METHODS: Here we presented a boy with UR infection. Ultrasonography and bacterial culture and identification were performed. He received antibiotic treatment and underwent surgical excision of the cyst. RESULTS: The patient presented with both a urachal cyst and umbilical-urachal sinus. UR infection was caused by Actinomyces turicensis. He recovered well from the operation without complications. CONCLUSIONS: The present case reminds clinicians to be familiar with imaging features of different types of URs and their potential complications and indicates the necessity of pathogenic microorganism analysis to tailor antibiotic treatment and post-operative follow-up to prevent complications.


Asunto(s)
Laparoscopía , Quiste del Uraco , Uraco , Masculino , Humanos , Laparoscopía/métodos , Uraco/cirugía , Quiste del Uraco/diagnóstico , Quiste del Uraco/cirugía , Antibacterianos/uso terapéutico
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