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1.
J Transl Med ; 22(1): 100, 2024 01 24.
Artículo en Inglés | MEDLINE | ID: mdl-38268004

RESUMEN

BACKGROUND: Asthma is a chronic respiratory disease affecting millions of people worldwide, but early detection can be challenging due to the time-consuming nature of the traditional technique. Machine learning has shown great potential in the prompt prediction of asthma. However, because of the inherent complexity of asthma-related patterns, current models often fail to capture the correlation between data samples, limiting their accuracy. Our objective was to use our novel model to address the above problem via an Affinity Graph Enhanced Classifier (AGEC) to improve predictive accuracy. METHODS: The clinical dataset used in this study consisted of 152 samples, where 24 routine blood markers were extracted as features to participate in the classification due to their ease of sourcing and relevance to asthma. Specifically, our model begins by constructing a projection matrix to reduce the dimensionality of the feature space while preserving the most discriminative features. Simultaneously, an affinity graph is learned through the resulting subspace to capture the internal relationship between samples better. Leveraging domain knowledge from the affinity graph, a new classifier (AGEC) is introduced for asthma prediction. AGEC's performance was compared with five state-of-the-art predictive models. RESULTS: Experimental findings reveal the superior predictive capabilities of AGEC in asthma prediction. AGEC achieved an accuracy of 72.50%, surpassing FWAdaBoost (61.02%), MLFE (60.98%), SVR (64.01%), SVM (69.80%) and ERM (68.40%). These results provide evidence that capturing the correlation between samples can enhance the accuracy of asthma prediction. Moreover, the obtained [Formula: see text] values also suggest that the differences between our model and other models are statistically significant, and the effect of our model does not exist by chance. CONCLUSION: As observed from the experimental results, advanced statistical machine learning approaches such as AGEC can enable accurate diagnosis of asthma. This finding holds promising implications for improving asthma management.


Asunto(s)
Asma , Humanos , Asma/diagnóstico , Biomarcadores , Conocimiento , Aprendizaje Automático
2.
Plant Physiol ; 193(1): 721-735, 2023 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-37103588

RESUMEN

Root-knot nematodes (Meloidogyne spp., RKN) are responsible for extensive crop losses worldwide. During infection, they penetrate plant roots, migrate between plant cells, and establish feeding sites, known as giant cells, near the root vasculature. Previously, we found that nematode perception and early responses in plants were similar to those of microbial pathogens and required the BRI1-ASSOCIATED KINASE1/SOMATIC EMBRYOGENESIS RECEPTOR KINASE3 (BAK1/SERK3) coreceptor in Arabidopsis (Arabidopsis thaliana) and tomato (Solanum lycopersicum). Here, we implemented a reverse genetic screen for resistance or sensitivity to RKN using Arabidopsis T-DNA alleles of genes encoding transmembrane receptor-like kinases to identify additional receptors involved in this process. This screen identified a pair of allelic mutations with enhanced resistance to RKN in a gene we named ENHANCED RESISTANCE TO NEMATODES1 (ERN1). ERN1 encodes a G-type lectin receptor kinase (G-LecRK) with a single-pass transmembrane domain. Further characterization showed that ern1 mutants displayed stronger activation of MAP kinases, elevated levels of the defense marker MYB51, and enhanced H2O2 accumulation in roots upon RKN elicitor treatments. Elevated MYB51 expression and ROS bursts were also observed in leaves of ern1 mutants upon flg22 treatment. Complementation of ern1.1 with 35S- or native promoter-driven ERN1 rescued the RKN infection and enhanced defense phenotypes. Our results indicate that ERN1 is an important negative regulator of immunity.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Solanum lycopersicum , Tylenchoidea , Animales , Arabidopsis/fisiología , Proteínas Quinasas Dependientes de GMP Cíclico/metabolismo , Lectinas/metabolismo , Peróxido de Hidrógeno/metabolismo , Tylenchoidea/fisiología , Solanum lycopersicum/genética , Receptores Mitogénicos/metabolismo , Raíces de Plantas/genética , Raíces de Plantas/metabolismo , Enfermedades de las Plantas/genética , Factores de Transcripción/metabolismo , Proteínas de Arabidopsis/metabolismo
3.
BMC Cancer ; 24(1): 364, 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38515073

RESUMEN

BACKGROUND: Recent studies have demonstrated that APOC1 is associated with cancer progression, exerting cancer-promoting and immune infiltration-promoting effects. Nevertheless, there is currently no report on the presence of APOC1 in ovarian cancer (OV). METHOD: In this study, we conducted data analysis using the GEO and TCGA databases. We conducted a thorough bioinformatics analysis to investigate the function of APOC1 in OV, utilizing various platforms including cBioPortal, STRING, GeneMANIA, LinkedOmics, GSCALite, TIMER, and CellMarker. Additionally, we performed immunohistochemical staining on tissue microarrays and conducted in vitro cellular assays to validate our findings. RESULT: Our findings reveal that APOC1 expression is significantly upregulated in OV compared to normal tissues. Importantly, patients with high APOC1 levels show a significantly poorer prognosis. Furthermore, our study demonstrated that APOC1 exerted a crucial function in promoting the capacity of ovarian cancer cells to proliferate, migrate, and invade. Additionally, we have identified that genes co-expressed with APOC1 are primarily associated with adaptive immune responses. Notably, the levels of APOC1 in OV exhibit a correlation with the presence of M2 Tumor-associated Macrophages (TAMs). CONCLUSION: APOC1 emerges as a promising prognostic biomarker for OV and exhibits a significant association with M2 TAMs in OV.


Asunto(s)
Neoplasias Ováricas , Femenino , Humanos , Biomarcadores , Macrófagos , Neoplasias Ováricas/genética , Pronóstico
4.
Pediatr Allergy Immunol ; 35(6): e14182, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38899630

RESUMEN

BACKGROUND: Polymorphisms in susceptibility genes are a major risk factor for the development of asthma. Understanding these genetic variants helps elucidate asthma's pathogenesis, predict its onset, expedite antiasthma medication development, and achieve precise targeted individualized treatment. This study developed a test kit based on susceptibility genes for predicting asthma in Chinese children. METHODS: The present study constructed a VariantPro Targeted Library Preparation System with 72 single nucleotide polymorphism (SNP) loci associated with asthma from the ClinVar, OMIM, and SNPedia databases. These SNP loci were detected in the peripheral blood of 499 children with asthma and 500 healthy children. Significant differences were discovered for seven SNP loci. Simultaneously, whole exome sequencing of 46 children with asthma and 50 healthy children identified eight SNP loci with significant differences. The 15 SNP loci identified from Chinese children with asthma were validated in an independent population of 97 children with asthma and 93 healthy children by conducting multiplex polymerase chain reaction (PCR)-next-generation sequencing genotyping. RESULTS: Four loci (rs12422149, rs7216389, rs4065275, and rs41453444) were identified, and a single-tube multifluorescent qPCR (real-time quantitative PCR) test kit was developed using these four SNP loci. The kit was tested on 269 children with asthma and 724 children with bronchopneumonia. CONCLUSIONS: We identified four loci as susceptibility genes and developed a quantitative PCR test kit for predicting asthma development in Chinese children.


Asunto(s)
Asma , Secuenciación del Exoma , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Asma/genética , Asma/diagnóstico , Estudios de Casos y Controles , China/epidemiología , Bases de Datos Genéticas , Pueblos del Este de Asia/genética , Secuenciación del Exoma/métodos , Genotipo , Secuenciación de Nucleótidos de Alto Rendimiento/métodos
5.
Environ Sci Technol ; 58(17): 7403-7414, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38627988

RESUMEN

Photochemically generated reactive oxygen species (ROS) are widespread on the earth's surface under sunlight irradiation. However, the nonphotochemical ROS generation in surface water (e.g., paddy overlying water) has been largely neglected. This work elucidated the drivers of nonphotochemical ROS generation and its spatial distribution in undisturbed paddy overlying water, by combining ROS imaging technology with in situ ROS monitoring. It was found that H2O2 concentrations formed in three paddy overlying waters could reach 0.03-16.9 µM, and the ROS profiles exhibited spatial heterogeneity. The O2 planar-optode indicated that redox interfaces were not always generated at the soil-water interface but also possibly in the water layer, depending on the soil properties. The formed redox interface facilitated a rapid turnover of reducing and oxidizing substances, creating an ideal environment for the generation of ROS. Additionally, the electron-donating capacities of water at soil-water interfaces increased by 4.5-8.4 times compared to that of the top water layers. Importantly, field investigation results confirmed that sustainable •OH generation through nonphotochemical pathways constituted of a significant proportion of total daily production (>50%), suggesting a comparable or even greater role than photochemical ROS generation. In summary, the nonphotochemical ROS generation process reported in this study greatly enhances the understanding of natural ROS production processes in paddy soils.


Asunto(s)
Especies Reactivas de Oxígeno , Suelo , Agua , Especies Reactivas de Oxígeno/metabolismo , Suelo/química , Oxidación-Reducción , Peróxido de Hidrógeno
6.
Environ Sci Technol ; 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39023504

RESUMEN

Hydroxyl radicals (•OH) play a significant role in contaminant transformation and element cycling during redox fluctuations in paddy soil. However, these important processes might be affected by widely used agricultural amendments, such as urea, pig manure, and biochar, which have rarely been explored, especially regarding their impact on soil aggregates and associated biogeochemical processes. Herein, based on five years of fertilization experiments in the field, we found that agricultural amendments, especially coapplication of fertilizers and biochar, significantly increased soil organic carbon contents and the abundances of iron (Fe)-reducing bacteria. They also substantially altered the fraction of soil aggregates, which consequently enhanced the electron-donating capacity and the formation of active Fe(II) species (i.e., 0.5 M HCl-Fe(II)) in soil aggregates (0-2 mm), especially in small aggregates (0-3 µm). The highest contents of active Fe(II) species in small aggregates were mainly responsible for the highest •OH production (increased by 1.7-2.4-fold) and naphthalene attenuation in paddy soil with coapplication of fertilizers and biochar. Overall, this study offers new insights into the effects of agricultural amendments on regulating •OH formation in paddy soil and proposes feasible strategies for soil remediation in agricultural fields, especially in soils with frequent occurrences of redox fluctuations.

7.
Environ Sci Technol ; 58(18): 7880-7890, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38670926

RESUMEN

Flooding of paddy fields during the rice growing season enhances arsenic (As) mobilization and greenhouse gas (e.g., methane) emissions. In this study, an adsorbent for dissolved organic matter (DOM), namely, activated carbon (AC), was applied to an arsenic-contaminated paddy soil. The capacity for simultaneously alleviating soil carbon emissions and As accumulation in rice grains was explored. Soil microcosm incubations and 2-year pot experimental results indicated that AC amendment significantly decreased porewater DOM, Fe(III) reduction/Fe2+ release, and As release. More importantly, soil carbon dioxide and methane emissions were mitigated in anoxic microcosm incubations. Porewater DOM of pot experiments mainly consisted of humic-like fluorophores with a molecular structure of lignins and tannins, which could mediate microbial reduction of Fe(III) (oxyhydr)oxides. Soil microcosm incubation experiments cospiking with a carbon source and AC further consolidated that DOM electron shuttling and microbial carbon source functions were crucial for soil Fe(III) reduction, thus driving paddy soil As release and carbon emission. Additionally, the application of AC alleviated rice grain dimethylarsenate accumulation over 2 years. Our results highlight the importance of microbial extracellular electron transfer in driving paddy soil anaerobic respiration and decreasing porewater DOM in simultaneously remediating As contamination and mitigating methane emission in paddy fields.


Asunto(s)
Arsénico , Carbono , Oryza , Suelo , Arsénico/metabolismo , Suelo/química , Contaminantes del Suelo , Carbón Orgánico/química , Metano
8.
Environ Sci Technol ; 58(16): 6900-6912, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38613493

RESUMEN

Foliar application of beneficial nanoparticles (NPs) exhibits potential in reducing cadmium (Cd) uptake in crops, necessitating a systematic understanding of their leaf-root-microorganism process for sustainable development of efficient nano-enabled agrochemicals. Herein, wheat grown in Cd-contaminated soil (5.23 mg/kg) was sprayed with different rates of four commonly used NPs, including nano selenium (SeNPs)/silica (SiO2NPs)/zinc oxide/manganese dioxide. SeNPs and SiO2NPs most effectively reduced the Cd concentration in wheat grains. Compared to the control, Cd concentration in grains was significantly decreased by 35.0 and 33.3% by applying 0.96 mg/plant SeNPs and 2.4 mg/plant SiO2NPs, and the grain yield was significantly increased by 33.9% with SeNPs application. Down-regulated gene expression of Cd transport proteins (TaNramp5 and TaLCT1) and up-regulated gene expression of vacuolar Cd fixation proteins (TaHMA3 and TaTM20) were observed with foliar SeNPs and SiO2NPs use. SeNPs increased the levels of leaf antioxidant metabolites. Additionally, foliar spray of SeNPs resulted in lower abundances of rhizosphere organic acids and reduced Cd bioavailability in rhizosphere soil, and soil microorganisms related to carbon and nitrogen (Solirubrobacter and Pedomicrobium) were promoted. Our findings underscore the potential of the foliar application of SeNPs and SiO2NPs as a plant and rhizosphere soil metabolism-regulating approach to reduce Cd accumulation in wheat grains.

9.
J Immunol ; 209(2): 401-411, 2022 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-35777852

RESUMEN

Necrotizing enterocolitis (NEC) is a common disorder in premature infants that is characterized by hyperinflammation and severe necrosis in the intestine. The pathogenesis of NEC remains to be elucidated. In this study, we demonstrate that adenosine, a metabolite more abundant in infants than in adults, plays an important role in the prevention of NEC. Administration of adenosine or its analog, adenosine-5'-N-ethyluronamide (NECA), dramatically relieved the severity of NEC in neonatal mice. Meanwhile, adenosine treatment significantly enhanced the immunosuppressive function, antibacterial activity, and migration of myeloid-derived suppressor cells (MDSCs). However, depletion of MDSCs or inhibition of their migration using the CXCR2 inhibitor SB225002 almost completely abrogated the protective effect of adenosine on NEC. Mechanistic studies showed that MDSCs in newborns expressed abundant adenosine receptor A2B (A2BR) that elicits intracellular cAMP signaling and its downstream target NF-κB. Importantly, intestinal tissues from patients with NEC showed significantly lower infiltration of A2BR-positive MDSCs than those from healthy donors. These observations revealed that adenosine-induced MDSCs represent an essential immune axis for intestinal homeostasis in newborns.


Asunto(s)
Enterocolitis Necrotizante , Células Supresoras de Origen Mieloide , Adenosina , Animales , Enterocolitis Necrotizante/tratamiento farmacológico , Enterocolitis Necrotizante/metabolismo , Humanos , Inmunosupresores , Recién Nacido , Ratones , Células Supresoras de Origen Mieloide/metabolismo , FN-kappa B/metabolismo , Transducción de Señal/fisiología
10.
Mar Drugs ; 22(2)2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38393034

RESUMEN

Six benzophenone derivatives, carneusones A-F (1-6), along with seven known compounds (7-13) were isolated from a strain of sponge-derived marine fungus Aspergillus carneus GXIMD00543. Their chemical structures were elucidated by detailed spectroscopic data and quantum chemical calculations. Compounds 5, 6, and 8 exhibited moderate anti-inflammatory activity on NO secretion using lipopolysaccharide (LPS)-induced RAW 264.7 cells with EC50 values of 34.6 ± 0.9, 20.2 ± 1.8, and 26.8 ± 1.7 µM, while 11 showed potent effect with an EC50 value of 2.9 ± 0.1 µM.


Asunto(s)
Antiinflamatorios , Aspergillus , Animales , Ratones , Estructura Molecular , Aspergillus/química , Antiinflamatorios/farmacología , Células RAW 264.7
11.
J Asian Nat Prod Res ; : 1-8, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38753589

RESUMEN

A pair of atropisomers secofumitremorgins C (1a) and D (1b), together with fifteen known alkaloids (2-16), were isolated from a saltern-derived fungus Aspergillus fumigatus GXIMD00544. The structures of atropisomers 1a and 1b were elucidated by the detailed spectroscopic data, chemical reaction and quantum chemical calculations. Compounds 1 and 8 displayed antifungal spore germination effects against plant pathogenic fungus associated with sugarcane Fusarium sp. with inhibitory rates of 53% and 77% at the concentration of 100 µM, repectively. Atropisomers 1 also exhibited antifouling potential against Balanus amphitrite larval settlement with an inhibitory rate of 96% at the concentration of 100 µM.

12.
Bull Environ Contam Toxicol ; 113(1): 9, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38981934

RESUMEN

Cadmium (Cd) contamination of farmland soils leads to Cd accumulation in crops and reduced micronutrient uptake, posing grave risks to food safety. Herein, we investigated the enrichment and transportation patterns of Cd and trace elements in different parts of six wheat genotypes grown in weakly alkaline Cd-contaminated soils via pot experiments. The results revealed that the wheat grain variety with high Cd accumulation (Ningmai13) demonstrated a 1.94-fold increase compared to the variety with low accumulation (Yanong0428). The transfer factor of Cd from wheat straw to grain ranged from 0.319 to 0.761, while the transfer factor of Cd from root to straw ranged from 0.167 to 0.461. Furthermore, the concentrations of other metals in wheat grains followed the order of Zn > Mn > Fe > Cu. There was a significant positive correlation between Cd and Mn in grains, indicating a potential synergistic effect. Overall, this study provides valuable insights into the regulation of micronutrient intake to modulate Cd uptake in wheat.


Asunto(s)
Cadmio , Genotipo , Contaminantes del Suelo , Oligoelementos , Triticum , Triticum/metabolismo , Cadmio/metabolismo , Cadmio/análisis , Contaminantes del Suelo/metabolismo , Contaminantes del Suelo/análisis , Oligoelementos/metabolismo , Oligoelementos/análisis , Suelo/química
13.
Angew Chem Int Ed Engl ; 63(15): e202400428, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38291811

RESUMEN

Tandem nitrate electroreduction reaction (NO3 -RR) is a promising method for green ammonia (NH3) synthesis. However, the mismatched kinetics processes between NO3 --to-NO2 - and NO2 --to-NH3 results in poor selectivity for NH3 and excess NO2 - evolution in electrolyte solution. Herein, a Ni2+ substitution strategy for developing oxide heterostructure in Co/Fe layered double oxides (LDOs) was designed and employed as tandem electrocataltysts for NO3 -RR. (Co0.83Ni0.16)2Fe exhibited a high NH3 yield rate of 50.4 mg ⋅ cm-2 ⋅ h-1 with a Faradaic efficiency of 97.8 % at -0.42 V vs. reversible hydrogen electrode (RHE) in a pulsed electrolysis test. By combining with in situ/operando characterization technologies and theoretical calculations, we observed the strong selectivity of NH3 evolution over (Co0.83Ni0.16)2Fe, with Ni playing a dual role in NO3 -RR by i) modifying the electronic behavior of Co, and ii) serving as complementary site for active hydrogen (*H) supply. Therefore, the adsorption capacity of *NO2 and its subsequent hydrogenation on the Co sites became more thermodynamically feasible. This study shows that Ni substitution promotes the kinetics of the NO3 -RR and provides insights into the design of tandem electrocatalysts for NH3 evolution.

14.
Mol Plant Microbe Interact ; 36(5): 283-293, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37022145

RESUMEN

The oomycete Pythium myriotylum is a necrotrophic pathogen that infects many crop species worldwide, including ginger, soybean, tomato, and tobacco. Here, we identified a P. myriotylum small cysteine-rich protein, PmSCR1, that induces cell death in Nicotiana benthamiana by screening small, secreted proteins that were induced during infection of ginger and did not have a predicted function at the time of selection. Orthologs of PmSCR1 were found in other Pythium species, but these did not have cell death-inducing activity in N. benthamiana. PmSCR1 encodes a protein containing an auxiliary activity 17 family domain and triggers multiple immune responses in host plants. The elicitor function of PmSCR1 appears to be independent of enzymatic activity, because the heat inactivation of PmSCR1 protein did not affect PmSCR1-induced cell death or other defense responses. The elicitor function of PmSCR1 was also independent of BAK1 and SOBIR1. Furthermore, a small region of the protein, PmSCR186-211, is sufficient for inducing cell death. A pretreatment using the full-length PmSCR1 protein promoted the resistance of soybean and N. benthamiana to Phytophthora sojae and Phytophthora capsici infection, respectively. These results reveal that PmSCR1 is a novel elicitor from P. myriotylum, which exhibits plant immunity-inducing activity in multiple host plants. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


Asunto(s)
Phytophthora , Pythium , Cisteína , Proteínas/metabolismo , Phytophthora/metabolismo , Inmunidad de la Planta , Nicotiana , Enfermedades de las Plantas
15.
Appl Environ Microbiol ; 89(2): e0203622, 2023 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-36744963

RESUMEN

The oomycete Pythium oligandrum is a soil-inhabiting parasite and predator of both fungi and oomycetes, and uses hydrolytic enzymes extensively to penetrate and hydrolyze its host or prey. Other mechanisms have been studied less, and we investigated the contribution of P. oligandrum-produced volatile organic compounds (VOCs) to parasitism. The growth-inhibiting activity of P. oligandrum VOCs was tested on Pythium myriotylum-a host or prey of P. oligandrum-coupled with electron microscopy, and biochemical and transcriptomic analyses. The P. oligandrum-produced VOCs reduced P. myriotylum growth by 80% and zoospore levels by 60%. Gas chromatography-mass spectrometry (GC-MS) identified 23 VOCs, and methyl heptenone, d-limonene, 2-undecanone, and 1-octanal were potent inhibitors of P. myriotylum growth and led to increased production of reactive oxygen species at a concentration that did not inhibit P. oligandrum growth. Exposure to the P. oligandrum VOCs led to shrinkage of P. myriotylum hyphae and lysis of the cellular membranes and organelles. Transcriptomics of P. myriotylum exposed to the P. oligandrum VOCs at increasing levels of growth inhibition initially showed a strong upregulation of putative detoxification-related genes that was not maintained later. The inhibition of P. myriotylum growth continued immediately after the exposure to the VOCs was discontinued and led to the reduced infection of its plant hosts. The VOCs produced by P. oligandrum could be another factor alongside hydrolytic enzymes contributing to its ecological role as a microbial parasite in particular ecological niches such as in soil, and may also contribute to the biocontrol of diseases using P. oligandrum commercial preparations. IMPORTANCE Microbe-microbe interactions in nature are multifaceted, with multiple mechanisms of action, and are crucial to how plants interact with microbes. Volatile organic compounds (VOCs) have diverse functions, including contributing to parasitism in ecological interactions and potential applications in biocontrol. The microbial parasite P. oligandrum is well known for using hydrolytic enzymes as part of its parasitism. We found that P. oligandrum VOCs reduced the growth of, and caused major damage to, the hyphae of P. myriotylum (a host or prey of P. oligandrum). Transcriptomic analyses of P. myriotylum exposed to the VOCs revealed the upregulation of genes potentially involved in an attempt to detoxify the VOCs. The inhibitory effects of the VOCs had a knock-on effect by reducing the virulence of P. myriotylum toward its plant hosts. The P. oligandrum VOCs could contribute to its ecological role as a microbial parasite. The VOCs analyzed here may also contribute to the biocontrol of diseases using P. oligandrum commercial preparations.


Asunto(s)
Pythium , Compuestos Orgánicos Volátiles , Pythium/genética , Compuestos Orgánicos Volátiles/farmacología , Hongos , Interacciones Microbianas , Suelo
16.
Rheumatology (Oxford) ; 62(3): 1216-1226, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-35961045

RESUMEN

OBJECTIVES: Anti-melanoma differentiation-associated gene 5 positive (anti-MDA5+) DM has a close relationship with rapidly progressive interstitial lung disease (RPILD) and is associated with high mortality. However, data regarding the time-dependent risk of RPILD and deaths during disease progression are limited. We conducted this study to investigate whether the risk of RPILD and death were time-dependent or not in anti-MDA5+ DM. METHODS: We assessed a cohort of 272 patients with anti-MDA5+ DM. The clinical characteristics of patients with anti-MDA5+ were collected, and COX regression was used to analyse independent risk factors for RPILD and death. We also described changes in risk of RPILD and death over time and their potential clinical implications. RESULTS: There were 272 anti-MDA5+ DM patients enrolled in this study. According to the multivariate cox regression analysis, short disease course, high CRP level, anti-Ro52 positive and anti-MDA5 titre (++∼+++) were independent risk factors of RPILD. High creatine kinase level, high CRP level and RPILD were independent risk factors for death, and >90% RPILD and 84% mortality occurred in the first 6 months after disease onset. Notably, the first 3 months is a particularly high-risk period, with 50% of RPILD and 46% of deaths occurring. Hazards regarding RPILD and mortality diminished over time during a median follow-up of 12 months. CONCLUSION: These results suggest significant, time-dependent changes in RPILD and mortality risk in anti-MDA5+ DM patients, providing a cut-off time window to estimate disease progression and poor prognosis.


Asunto(s)
Dermatomiositis , Enfermedades Pulmonares Intersticiales , Humanos , Estudios de Cohortes , Helicasa Inducida por Interferón IFIH1 , Dermatomiositis/complicaciones , Autoanticuerpos , Enfermedades Pulmonares Intersticiales/etiología , Progresión de la Enfermedad , China , Estudios Retrospectivos , Pronóstico
17.
BMC Cancer ; 23(1): 429, 2023 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-37170184

RESUMEN

OBJECTIVE: To study the effect of inhibitor of differentiation 3 (ID3) on radiotherapy in patients with rectal cancer and to explore its primary mechanism. METHODS: Cell proliferation and clonogenic assays were used to study the relationship between ID3 and radiosensitivity. Co-immunoprecipitation and immunofluorescence were performed to analyze the possible mechanism of ID3 in the radiosensitivity of colorectal cancer. At the same time, a xenograft tumor model of HCT116 cells in nude mice was established to study the effect of irradiation on the tumorigenesis of ID3 knockdown colorectal cancer cells in vivo. Immunohistochemistry was performed to analyze the relationship between ID3 expression and the efficacy of radiotherapy in 46 patients with rectal cancer. RESULTS: Proliferation and clonogenic assays revealed that the radiosensitivity of colorectal cancer cells decreased with ID3 depletion through p53-independent pathway. With the decrease in ID3 expression, MDC1 was downregulated. Furthermore, the expression of ID3, MDC1, and γH2AX increased and formed foci after irradiation. ID3 interacted with PPARγ and form a positive feedback loop to enhance the effect of ID3 on the radiosensitivity of colorectal cancer. Irradiation tests in nude mice also confirmed that HCT116 cells with ID3 knockdown were more affected by irradiation. Immunohistochemical study showed that rectal cancer patients with low expression of ID3 had better radiotherapy efficacy. CONCLUSIONS: ID3 and PPARγ influence the radiosensitivity of colorectal cancer cells by interacting with MDC1 to form a positive feedback loop that promotes DNA damage repair. Patients with low expression of ID3 who received neoadjuvant chemoradiotherapy can obtain a better curative effect.


Asunto(s)
Reparación del ADN , PPAR gamma , Neoplasias del Recto , Animales , Humanos , Ratones , Línea Celular Tumoral , Daño del ADN , Reparación del ADN/genética , Retroalimentación , Proteínas Inhibidoras de la Diferenciación/genética , Ratones Desnudos , Proteínas de Neoplasias/genética , PPAR gamma/genética , Tolerancia a Radiación/genética , Neoplasias del Recto/genética , Neoplasias del Recto/radioterapia
18.
Environ Sci Technol ; 57(43): 16340-16347, 2023 10 31.
Artículo en Inglés | MEDLINE | ID: mdl-37856081

RESUMEN

Frequent cycles of flooding and drainage in paddy soils lead to the reductive dissolution of iron (Fe) minerals and the reoxidation of Fe(II) species, all while generating a robust and consistent output of reactive oxygen species (ROS). In this study, we present a comprehensive assessment of the temporal and spatial variations in Fe species and ROS during the flooding-drainage process in a representative paddy soil. Our laboratory column experiments showed that a decrease in dissolved O2 concentration led to rapid Fe reduction below the water-soil interface, and aqueous Fe(II) was transformed into solid Fe(II) phases over an extended flooding time. As a result, the •OH production capacity of liquid phases was reduced while that of solid phases improved. The •OH production capacity of solid phases increased from 227-271 µmol kg-1 (within 1-11 cm depth) to 500-577 to 499-902 µmol kg-1 after 50 day, 3 month, and 1 year incubation, respectively. During drainage, dynamic •OH production was triggered by O2 consumption and Fe(II) oxidation. ROS-trapping film and in situ capture revealed that the soil surface was the active zone for intense H2O2 and •OH production, while limited ROS production was observed in the deeper soil layers (>5 cm) due to the limited oxygen penetration. These findings provide more insights into the complex interplay between dynamic Fe cycling and ROS production in the redox transition zones of paddy fields.


Asunto(s)
Oryza , Contaminantes del Suelo , Suelo , Radical Hidroxilo , Especies Reactivas de Oxígeno , Peróxido de Hidrógeno , Oxidación-Reducción , Agua , Compuestos Ferrosos
19.
Environ Sci Technol ; 57(22): 8335-8346, 2023 06 06.
Artículo en Inglés | MEDLINE | ID: mdl-37211672

RESUMEN

Antimicrobial transformation products (ATPs) in the environment have raised extensive concerns in recent years due to their potential health risks. However, only a few ATPs have been investigated, and most of the transformation pathways of antimicrobials have not been completely elucidated. In this study, we developed a nontarget screening strategy based on molecular networks to detect and identify ATPs in pharmaceutical wastewater. We identified 52 antimicrobials and 49 transformation products (TPs) with a confidence level of three or above. Thirty of the TPs had not been previously reported in the environment. We assessed whether TPs could be classified as persistent, mobile, and toxic (PMT) substances based on recent European criteria for industrial substances. Owing to poor experimental data, definitive PMT classifications could not be established for novel ATPs. PMT assessment based on structurally predictive physicochemical properties revealed that 47 TPs were potential PMT substances. These results provide evidence that novel ATPs should be the focus of future research.


Asunto(s)
Antiinfecciosos , Contaminantes Químicos del Agua , Aguas Residuales , Contaminantes Químicos del Agua/análisis
20.
Environ Sci Technol ; 57(48): 19463-19472, 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-37943691

RESUMEN

Prebiotics may stimulate beneficial gut microorganisms. However, it remains unclear whether they can lower the oral bioavailability of early life arsenic (As) exposure via regulating gut microbiota and altering As biotransformation along the gastrointestinal (GI) tract. In this study, weanling mice were exposed to arsenate (iAsV) via diet (7.5 µg As g-1) amended with fructooligosaccharides (FOS), galactooligosaccharides (GOS), and inulin individually at 1% and 5% (w/w). Compared to As exposure control mice, As concentrations in mouse blood, liver, and kidneys and As urinary excretion factor (UEF) were reduced by 43.7%-74.1% when treated with 5% GOS. The decrease corresponded to a significant proliferation of Akkermansia and Psychrobacter, reduced percentage of inorganic arsenite (iAsIII) and iAsV by 47.4% and 65.4%, and increased proportion of DMAV in intestinal contents by 101% in the guts of mice treated with 5% GOS compared to the As control group. In contrast, FOS and inulin either at l% or 5% did not reduce As concentration in mouse blood, liver, and kidneys or As UEF. These results suggest that GOS supplementation may be a gut microbiota-regulating approach to lower early life As exposure via stimulating the growth of Akkermansia and Psychrobacter and enhancing As methylation in the GI tract.


Asunto(s)
Arsénico , Microbioma Gastrointestinal , Ratones , Animales , Inulina/metabolismo , Prebióticos , Hígado/metabolismo
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