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Insulin deficiency in patients with type 2 diabetes mellitus (T2D) is associated with beta-cell dysfunction, a condition increasingly recognized to involve processes such as dedifferentiation and apoptosis. Moreover, emerging research points to a potential role for ferroptosis in the pathogenesis of T2D. In this study, we aimed to investigate the potential involvement of ferroptosis in the dedifferentiation of beta cells in T2D. We performed single-cell RNA sequencing analysis of six public datasets. Differential expression and gene set enrichment analyses were carried out to investigate the role of ferroptosis. Gene set variation and pseudo-time trajectory analyses were subsequently used to verify ferroptosis-related beta clusters. After cells were categorized according to their ferroptosis and dedifferentiation scores, we constructed transcriptional and competitive endogenous RNA networks, and validated the hub genes via machine learning and immunohistochemistry. We found that ferroptosis was enriched in T2D beta cells and that there was a positive correlation between ferroptosis and the process of dedifferentiation. Upon further analysis, we identified two beta clusters that presented pronounced features associated with ferroptosis and dedifferentiation. Several key transcription factors and 2 long noncoding RNAs (MALAT1 and MEG3) were identified. Finally, we confirmed that ferroptosis occurred in the pancreas of high-fat diet-fed mice and identified 4 proteins (NFE2L2, CHMP5, PTEN, and STAT3) that may participate in the effect of ferroptosis on dedifferentiation. This study helps to elucidate the interplay between ferroptosis and beta-cell health and opens new avenues for developing therapeutic strategies to treat diabetes.

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PURPOSE: Despite the involvement of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase3 (PFKFB3) in the proliferation and metastasis of diverse tumor types, its biological functions and related molecular mechanisms in anaplastic thyroid carcinoma (ATC) remain largely unclear. METHODS: Datasets from the Gene Expression Omnibus, the Cancer Genome Atlas and immunohistochemistry (IHC) analyses were employed to measure the expression level of PFKFB3 in ATC. A series of assays were performed to analyze the role of PFKFB3 and its inhibitor KAN0438757 in ATC cell proliferation and migration. Furthermore, Western blotting (WB), IHC and luciferase reporter assay were conducted to investigate the potential mechanisms underlying the involvement of PFKFB3 and KAN0438757 in ATC. Additionally, we established a subcutaneous xenograft tumor model in nude mice to evaluate the in vivo tumor growth. RESULTS: PFKFB3 exhibited a significant increase in its expression level in ATC tissues. The overexpression of PFKFB3 resulted in the stimulation of ATC cell proliferation and migration. Furthermore, this overexpression was associated with the elevated expression levels of p-AKT (ser473), p-GSK3α/ß (ser21/9), nuclear ß-catenin, fibronectin1 (FN1), matrix metallopeptidase 9 (MMP-9) and cyclin D1. It also promoted the nuclear translocation of ß-catenin and the transcription of downstream molecules. Conversely, contrasting results were observed with the downregulation or KAN0438757-mediated inhibition of PFKFB3 in ATC cells. The selective AKT inhibitor MK2206 was noted to reverse the increased expression of p-AKT (ser473) and p-GSK3α/ß (ser21/9) induced by PFKFB3 overexpression. The level of lactate was increased in PFKFB3-overexpressing ATC cells, while the presence of KAN0438757 inhibited lactate production. Moreover, the simultaneous use of PFKFB3 downregulation and KAN0438757 was found to suppress subcutaneous tumor growth in vivo. CONCLUSION: PFKFB3 can enhance ATC cell proliferation and migration via the WNT/ß-catenin signaling pathway and plays a crucial role in the regulation of aerobic glycolysis in ATC cells.

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IMPORTANCE: In this study, we revealed that the variation in rhizosphere and root endosphere microbial assemblage between host plant ecotypes contribute to their differential abilities to withstand cadmium (Cd) stressors. Furthermore, our study found that phenolic compounds, such as benzenoids and flavonoids, could function as both essential carbon sources and semiochemicals, thereby contributing to the assemblage of rhizosphere microbiome to resist Cd stress. Our findings provide new insights into the mechanisms that drive the differential assemblage of rhizosphere and root endosphere microbiomes to enhance plant growth under abiotic stress.

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Cadmium (Cd) contamination of agricultural soils poses a potential public health issue for humans. Phytoremediation-based accumulating plants are an effective and sustainable technology for Cadmium remediation of contaminated agricultural soil. The rhizosphere microbiome can promote the growth and Cadmium accumulation in hyperaccumulators, but its taxonomic and functional traits remain elusive. The present study used two ecotypes of Sedum alfredii, an accumulating ecotype (AE) and a non-accumulating ecotype (NAE), as model plants to investigate the rhizosphere microbiome assemblages and influence on plant growth under high cadmium conditions. Our results showed that distinct root microbiomes assembled in association with both ecotypes of S. alfredii and that the assemblages were based largely on the lifestyles of the two ecotypes. In addition, we demonstrated that the functions of the microbes inhabiting the rhizosphere soils were closely associated with root-microbe interactions in both ecotypes of S. alfredii. Importantly, our results also demonstrated that the rhizosphere microbiome assembled in the AE rhizosphere soils contributed to plant growth and cadmium uptake under high cadmium conditions through functions such as nitrogen fixation, phosphorus solubilization, indole acetic acid (IAA) synthesis, and siderophore metabolism. However, this phenomenon was not clearly observed in the NAE. Our results suggest that the rhizosphere microbiome plays important roles in biogeochemical nutrient and metal cycling that can contribute to host plant fitness.

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Metal(loid) selection contributes to selection pressure on antibiotic resistance, but to our knowledge, evidence of the dissemination of antibiotic resistance genes (ARGs) induced by metal(loid)s in mine soil ecosystems is rare. In the current study, using a high-throughput sequencing (HTS)-based metagenomic approach, 819 ARG subtypes were identified in a mine soil ecosystem, indicating that these environmental habitats are important reservoirs of ARGs. The results showed that metal(loid)-induced coselection has an important role in the distribution of soil ARGs. Furthermore, metal(loid) selection-induced ARGs were mainly associated with resistance-nodulation-division (RND) antibiotic efflux, which is distinct from what is observed in agricultural soil ecosystems. By using independent genome binning, metal(loid)s were shown impose coselection pressure on multiple ARGs residing on mobile genetic elements (MGEs), which promotes the dissemination of the antibiotic resistome. Interestingly, the current results showed that the density of several MGEs conferring ARGs was considerably higher in organisms most closely related to the priority pathogens Pseudomonas aeruginosa and Escherichia coli. Together, the results of this study indicate that mine soil ecosystems are important reservoirs of ARGs and that metal(loid)-induced coselection plays critical roles in the dissemination of ARGs in this type of soil habitat. KEY POINTS: • Mining soil ecosystem is a reservoir of antibiotic resistance genes (ARGs). • ARGs distribute via bacterial resistance-nodulation-division efflux systems. • Metal(loid)s coselected ARGs residing on mobile genetic elements in P. aeruginosa and E. coli.

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Mining activities lead to elevated levels of antimony (Sb) and arsenic (As) in river systems, having adverse effects on the aquatic environment and human health. Microbes inhabiting river sediment can mediate the transformation of Sb and As, thus changing the toxicity and mobility of Sb and As. Compared to river sediments, natural wetlands could introduce distinct geochemical conditions, leading to the formation of different sedimentary microbial compositions between river sediments and wetland sediments. However, whether such changes in microbial composition could influence the microbially mediated geochemical behavior of Sb or As remains poorly understood. In this study, we collected samples from a river contaminated by Sb tailings and a downstream natural wetland to study the influence of microorganisms on the geochemical behavior of Sb and As after the Sb/As-contaminated river entered the natural wetland. We found that the microbial compositions in the natural wetland soil differed from those in the river sediment. The Sb/As contaminant components (Sb(III), As(III), As(V), Asexe) and nutrients (TC) were important determinants of the difference in the compositions of the microbial communities in the two environments. Taxonomic groups were differentially enriched between the river sediment and wetland soil. For example, the taxonomic groups Xanthomonadales, Clostridiales and Desulfuromonadales were important in the wetland and were likely to involve in Sb/As reduction, sulfate reduction and Fe(III) reduction, whereas Burkholderiales, Desulfobacterales, Hydrogenophilales and Rhodocyclales were important taxonomic groups in the river sediments and were reported to involve in Sb/As oxidation and sulfide oxidation. Our results suggest that microorganisms in both river sediments and natural wetlands can affect the geochemical behavior of Sb/As, but the mechanisms of action are different.

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OBJECTIVE: To identify the chemical components of volatile oil from Gerbera piloselloides. METHODS: Volatile oil was extracted from Gerbera piloselloides by steam distillation, and its chemical components were identified by GC-MS. RESULTS: 22 peaks were detected, among which 17 compounds were identified, accounting for 86.18% of total peak area. CONCLUSION: In the total volatile oil from Gerbera piloselloides, Neryl(s)-2-methylbutanoate (35.99%), 4-hydroxy-3-methylacetophenone (8.74%) and n-Hexadecanoic acid (7.48%) are the main components.

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