RESUMEN

Background: Globally, non-small cell lung cancer (NSCLC) is a leading factor in cancer-related mortality. Additionally, the Geriatric Nutritional Risk Index (GNRI) has been assessed as a predictive and prognostic indicator in various types of carcinomas. Our study aims to assess the prognostic importance of GNRI computed at diagnosis in NSCLC patients receiving immune checkpoint inhibitors (ICIs). Methods: The study evaluated 148 patients who underwent immunotherapy for NSCLC from January 1, 2018, through December 31, 2021, retrospectively. Patients combined with other malignant tumors or severe comorbidities were excluded from the study. The receiver operating characteristic (ROC) curve was employed in regulating the ideal cutoff worth of GNRI. Survival outcomes were evaluated through Kaplan-Meier analysis. Following this, both univariate and multivariate analyses were conducted utilizing Cox regression analysis to identify any potential factors that may influence the survival outcomes. Results: The cutoff point for GNRI was 108.15 [area under the curve (AUC) =0.575, P=0.048]. Further analysis using the Kaplan-Meier method demonstrated that individuals in the high GNRI group had significantly longer progression-free survival (PFS) and overall survival (OS) compared to those in the low GNRI group (P=0.02, P=0.01). The further stratified study showed that GNRI had greater predictive value in tumor node metastasis (TNM) stage II-III and elderly (age ≥65 years) NSCLC patients undergoing ICI therapy. The multivariate Cox regression analysis indicated that GNRI [hazard ratio (HR): 0.536, P=0.03], obesity (HR: 16.283, P<0.001), and surgical history (HR: 0.305, P<0.001) were associated with poorer survival rates. Conclusions: Among patients undergoing ICI therapy for NSCLC, GNRI is an effective independent prognostic indicator, and a high GNRI at diagnosis is substantially related with longer PFS and OS. The incorporation of GNRI in pre-treatment evaluations within clinical settings is beneficial.

RESUMEN

Reactive oxygen species (ROS) are metabolic by-products of cells, and abnormal changes in their levels are often associated with tumor development. Our aim was to determine the role of collagen and calcium binding EGF domain 1 (CCBE1) in oxidative stress and tumorigenesis in non-small cell lung cancer cells (NSCLC). We investigated the tumorigenic potential of CCBE1 in NSCLC using in vitro and in vivo models of CCBE1 overexpression and knockdown. Immunohistochemical staining results showed that the expression of CCBE1 in cancer tissues was significantly higher than that in adjacent tissues. Cell counting Kit 8, clonal formation, wound healing, and transwell experiments showed that CCBE1 gene knockdown significantly inhibited the migration, invasion, and proliferation of NSCLC cell lines. In terms of mechanism, the silencing of CCBE1 can significantly promote the morphological abnormalities of mitochondria, significantly increase the intracellular ROS level, and promote cell apoptosis. This change of oxidative stress can affect cell proliferation, migration, and invasion by regulating the phosphorylation level of ERK/JNK/P38 MAPK. Specifically, the downregulation of CCBE1 inhibits the phosphorylation of ERK/P38 and promotes the phosphorylation of JNK in NSCLC, and this regulation can be reversed by the antioxidant NAC. In vivo experiments confirmed that downregulating CCBE1 gene could inhibit the growth of NSCLC in BALB/c nude mice. Taken together, our results confirm the tumorigenic role of CCBE1 in promoting tumor invasion and migration in NSCLC, and reveal the molecular mechanism by which CCBE1 regulates oxidative stress and the ERK/JNK/P38 MAPK pathway.

Asunto(s)

Proteínas de Unión al Calcio , Carcinoma de Pulmón de Células no Pequeñas , Movimiento Celular , Proliferación Celular , Neoplasias Pulmonares , Sistema de Señalización de MAP Quinasas , Especies Reactivas de Oxígeno , Animales , Femenino , Humanos , Masculino , Ratones , Apoptosis , Proteínas de Unión al Calcio/metabolismo , Proteínas de Unión al Calcio/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/genética , Línea Celular Tumoral , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Ratones Endogámicos BALB C , Ratones Desnudos , Estrés Oxidativo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Fosforilación , Especies Reactivas de Oxígeno/metabolismo

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Phytohormones play indispensable roles in plant growth and development. However, the molecular mechanisms underlying phytohormone-mediated regulation of fiber secondary cell wall (SCW) formation in cotton (Gossypium hirsutum) remain largely underexplored. Here, we provide mechanistic evidence for functional interplay between the APETALA2/ethylene response factor (AP2/ERF) transcription factor GhERF108 and auxin response factors GhARF7-1 and GhARF7-2 in dictating the ethylene-auxin signaling crosstalk that regulates fiber SCW biosynthesis. Specifically, in vitro cotton ovule culture revealed that ethylene and auxin promote fiber SCW deposition. GhERF108 RNA interference (RNAi) cotton displayed remarkably reduced cell wall thickness compared with controls. GhERF108 interacted with GhARF7-1 and GhARF7-2 to enhance the activation of the MYB transcription factor gene GhMYBL1 (MYB domain-like protein 1) in fibers. GhARF7-1 and GhARF7-2 respond to auxin signals that promote fiber SCW thickening. GhMYBL1 RNAi and GhARF7-1 and GhARF7-2 virus-induced gene silencing (VIGS) cotton displayed similar defects in fiber SCW formation as GhERF108 RNAi cotton. Moreover, the ethylene and auxin responses were reduced in GhMYBL1 RNAi plants. GhMYBL1 directly binds to the promoters of GhCesA4-1, GhCesA4-2, and GhCesA8-1 and activates their expression to promote cellulose biosynthesis, thereby boosting fiber SCW formation. Collectively, our findings demonstrate that the collaboration between GhERF108 and GhARF7-1 or GhARF7-2 establishes ethylene-auxin signaling crosstalk to activate GhMYBL1, ultimately leading to the activation of fiber SCW biosynthesis.

Asunto(s)

Fibra de Algodón , Factores de Transcripción , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Ácidos Indolacéticos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Gossypium/genética , Gossypium/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Etilenos/metabolismo , Pared Celular/metabolismo

RESUMEN

Microorganisms are an important part of atmospheric particulate matter and are closely related to human health. In this paper, the variations in the characteristics of the chemical components and bacterial communities in PM10 and PM2.5 grouped according to season, pollution degree, particle size, and winter heating stage were studied. The influence of environmental factors on community structure was also analyzed. The results showed that seasonal variations were significant. NO3- contributed the most to the formation of particulate matter in spring and winter, while SO42- contributed the most in summer and autumn. The community structures in summer and autumn were similar, while the community structure in spring was significantly different. The dominant phyla were similar among seasons, but their proportions were different. The dominant genera were no-rank_c_Cyanobacteria, Acidovorax, Escherichia-Shigella and Sphingomonas in spring; Massilia, Bacillus, Acinetobacter, Rhodococcus, and Brevibacillus in summer and autumn; and Rhodococcus in winter. The atmospheric microorganisms in Beijing mainly came from soil, water, and plants. The few pathogens detected were mainly affected by the microbial source on the sampling day, regardless of pollution level. RDA (redundancy analysis) showed that the bacterial community was positively correlated with the concentration of particulate matter and that the wind speed in spring was positively correlated with NO3- levels, NH4+ levels, temperature, and relative humidity in summer and autumn, but there was no clear consistency among winter samples. This study comprehensively analyzed the variations in the characteristics of the airborne bacterial community in Beijing over one year and provided a reference for understanding the source, mechanism, and assessment of the health effects of different air qualities.

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Contaminantes Atmosféricos , Microbiota , Beijing , China , Monitoreo del Ambiente/métodos , Humanos , Material Particulado , Estaciones del Año

RESUMEN

Microbial degraders play crucial roles in wastewater treatment processes, but their use is limited as most microbes are yet unculturable. Stable isotope probing (SIP) is a cultivation-independent technique identifying functional-yet-uncultivable microbes in ambient environment, but is unsatisfactory for substrates with low assimilation rate owing to the low isotope incorporation into DNA. In this study, we used acetonitrile as the target low-assimilation chemical in many wastewater treatment plants and attempted to identify the active acetonitrile degraders in the activated sludge, via DNA-SIP and magnetic-nanoparticle mediated isolation (MMI) which is another cultivation-independent approach without the requirement of substrate labeling. The two approaches identified different active acetonitrile degraders in a 3-day short-term anaerobic ammonium oxidation (ANAMMOX). MMI enriched significantly more acetonitrile-degraders than SIP, showing the advantages in identifying the active degraders for low-assimilation substrates. Sequencing batch reactor (SBR, 30-day degradation) helped in more incorporation of 15N-labeled acetonitrile into the active degraders, thus the same acetonitrile-degraders and acetonitrile-degrading genes were identified by SIP and MMI. Different acetonitrile degraders between ANAMMOX and SBR were attributed to the distinct hydrological conditions. Our study for the first time explored the succession of acetonitrile-degraders in wastewater and identified the active acetonitrile-degraders which could be further enriched for enhancing acetonitrile degradation performance. These findings provide new insights into the acetonitrile metabolic process in wastewater treatment plants and offer suggestive conclusions for selecting appropriate treatment strategy in wastewater management.

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Compuestos de Amonio , Nanopartículas , Acetonitrilos , Anaerobiosis , Biodegradación Ambiental , Isótopos , Fenómenos Magnéticos

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Using reclaimed water as a resource for landscape water replenishment may alleviate the major problems of water resource shortages and water environment pollution. However, the safety of the reclaimed water and the risk of eutrophication caused by the reclaimed water replenishment are unclear to the public and to the research community. This study aimed to reveal the differences between natural water and reclaimed water and to discuss the rationality of reclaimed water replenishment from the perspective of microorganisms. The microbial community structures in natural water, reclaimed water and natural biofilms were analyzed, and the community succession was clarified along the ecological niches, water resources, fluidity and time using 16S rRNA gene amplicon sequencing. Primary biofilms without the original community were added to study the formation of microbial community structures under reclaimed water acclimation. The results showed that the difference caused by ecological niches was more than those caused by the fluidity of water and different water resources. No significant difference caused by the addition of reclaimed water was found in the microbial diversity and community structure. Based on the results of microbial analysis, reclaimed water replenishment is a feasible solution that can be used for supplying river water.

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Microbiota , Aguas Residuales , Microbiología del Agua , ARN Ribosómico 16S , Ríos , Agua

RESUMEN

Complete-nitrifying bacteria (comammox) play important roles in nitrogen-overloading aquatic systems. However, the understanding of the environmental relevance is still limited. Here, we studied the responses of comammox bacteria (Nitrospira inopinata) in a tributary of the Yellow River, with the water and sediment, microbial, seasonal, and chemical variations considered. Illumina sequencing indicated that the predominant phyla in the river sediment were Proterobacteria, Bacteroidetes, Actinobacteria, and Chloroflex. Quantitative PCR revealed that N. inopinata-like comammox were approximately twice as abundant in the water during the wet season and in the sediment during the dry season than that of other conditions. Significant correlations were found between the abundance of N. inopinata-like comammox and pH (r = 0.58), temperature (r = 0.63), and dissolved oxygen (r = - 0.77). The abundance of N. inopinata-like comammox was higher than that of ammonia oxidizing archaea (AOA), and lower than that of ammonia oxidizing bacteria (AOB) and nitrite oxidizing bacteria (NOB). Furthermore, a significant correlation was discovered between N. inopinata-like comammox and NOB (r = 0.60), and so was anammox bacteria (r = 0.358). Interestingly, N. inopinata-like comammox also showed positive relationships with denitrifying microbes (r = 0.559).

Asunto(s)

Bacterias/metabolismo , Nitrificación , Ciclo del Nitrógeno , Estaciones del Año , Amoníaco/metabolismo , Bacterias/citología , Betaproteobacteria , Sedimentos Geológicos/microbiología , Nitrógeno/metabolismo , Oxidación-Reducción , Filogenia , Ríos/microbiología

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As the important source of natural fibers in the textile industry, cotton fiber quality and yield are often restricted to drought conditions because most of cotton plants in the world grow in the regions with water shortage. WRKY transcription factors regulate multiple plant physiological processes, including drought stress response. However, little is known of how the WRKY genes respond to drought stress in cotton. Our previous study revealed GhWRKY33 is leaf-specific and induced by drought stress. In this study, our data showed GhWRKY33 protein localizes to the cell nucleus and is able to bind to "W-box" cis-acting elements of the target promoters. Under drought stress, GhWRKY33 overexpressing transgenic Arabidopsis was withered much more quickly than wild type due to faster water loss. Moreover, GhWRKY33 transgenic plants displayed more tolerance to abscisic acid (ABA), relative to wild type. Expression of some drought stress-related genes and ABA-responsive genes were changed in the GhWRKY33 transgenic Arabidopsis with drought or ABA treatment. Collectively, our findings indicate that GhWRKY33 may act as a negative regulator to mediate plant response to drought stress and to participate in the ABA signaling pathway.

Asunto(s)

Proteínas de Arabidopsis/genética , Arabidopsis/genética , Gossypium/genética , Estrés Fisiológico/genética , Factores de Transcripción/genética , Ácido Abscísico/metabolismo , Adaptación Fisiológica/genética , Arabidopsis/crecimiento & desarrollo , Sequías , Regulación de la Expresión Génica de las Plantas , Gossypium/crecimiento & desarrollo , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/crecimiento & desarrollo , Regiones Promotoras Genéticas/genética , Tolerancia a la Sal/genética , Transducción de Señal/genética , Estrés Fisiológico/fisiología

RESUMEN

In this study, particulate matter (PM) with aerodynamic diameters of ≤2.5 and ≤10 µm (PM2.5 and PM10, respectively), which was found at different concentrations in spring, was collected in Beijing. The chemical composition and bacterial community diversity of PM were determined, and the relationship between them was studied by 16S rRNA sequencing and mathematical statistics. Chemical composition analysis revealed greater relative percentages of total organic compounds (TOC) and secondary ions (NO3-, SO42-, and NH4+). The concentrations of Ca2+, Na+, Mg2+, K+ and SO42- increased in high-concentration PM, which was associated with the contribution of soil, dust and soot. Microbiological analysis revealed 1191 operational taxonomic units. Microbial community structure was stable at the phylum level. The most abundant phyla were Proteobacteria, Actinobacteria, Firmicutes, Bacteroidetes and Cyanobacteria. Community clustering analysis at the genus level showed that the difference in bacterial community structure between different PM concentrations (clean air vs. smog) was greater than that between different particle sizes. The dominant genera varied in different concentrations of PM. An unclassified genus of Cyanobacteria and Comamonadaceae were most abundant in low- and high-concentration PM, respectively. The microbial community structure was dynamic at the genus level due to different environmental factors. The dominant bacteria in high-concentration PM were widely distributed in soils, indicating that the soil contributed more to the increase in the PM. The individual microbes that were detected did not increase significantly as the PM concentration increased. The bacterial community structure was strongly correlated with K+, Ca2+, Na+, Mg2+, SO42- and TOC in high-concentration PM and had a good correlation with NO3-, Cl-, NH4+ and TIC in low-concentration PM. Soil and dust contributed to the increase in the concentration of the particles, and the relevant chemical components also produced differences in the bacterial community structure in different concentrations of PM.

Asunto(s)

Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente , Material Particulado/análisis , Atmósfera/química , Beijing , China , Tamaño de la Partícula , ARN Ribosómico 16S , Estaciones del Año