Advances in biological functions and applications of apoptotic vesicles.

BACKGROUND: Apoptotic vesicles are extracellular vesicles generated by apoptotic cells that were previously regarded as containing waste or harmful substances but are now thought to play an important role in signal transduction and homeostasis regulation. METHODS: In the present review, we reviewed many articles published over the past decades on the subtypes and formation of apoptotic vesicles and the existing applications of these vesicles. RESULTS: Apoptotic bodies were once regarded as vesicles released by apoptotic cells, however, apoptotic vesicles are now regarded to include apoptotic bodies, apoptotic microvesicles and apoptotic exosomes, which exhibit variation in terms of biogenesis, sizes and properties. Applications of apoptotic vesicles were first reported long ago, but such reports have been rarer than those of other extracellular vesicles. At present, apoptotic vesicles have been utilized mainly in four aspects, including in direct therapeutic applications, in their engineering as carriers, in their construction as vaccines and in their utilization in diagnosis. CONCLUSION: Building on a deeper understanding of their composition and characteristics, some studies have utilized apoptotic vesicles to treat diseases in more novel ways. However, their limitations for clinical translation, such as heterogeneity, have also emerged. In general, apoptotic vesicles have great application potential, but there are still many barriers to overcome in their investigation. Video Abstract.

Can precancerous stem cells be risk markers for malignant transformation in the oral mucosa?

Accurate assessment of the carcinogenic potential of oral mucosal diseases can significantly reduce the prevalence of oral cancer. We speculate that precancerous stem cells (pCSCs) arise during the evolution of carcinomas based on long-term experimental findings, published literature, and the cancer stem cell (CSC) theory, wherein pCSCs exist in precancerous lesions and have characteristics of both CSCs and normal stem cells. This apparently contradictory feature may be the foundation of the reversible transformation of precancerous lesions. Predicting malignant transformation in potentially malignant oral illnesses would allow for focused treatment, prognosis, and secondary prevention. Currently available clinical assays for chromosomal instability and DNA aneuploidy have several deficiencies. We hope that our study will increase attention to pCSC research and lead to the development of novel strategies for the prevention and treatment of oral cancer by identifying pCSC markers.

microRNA-17 is a tumor suppressor in oral squamous cell carcinoma and is repressed by LSD1.

OBJECTIVE: The effects of epigenetic modifiers have been uncovered on cellular reprogramming and, specifically, on sustaining characteristics of cancer stem cells. We here aim to investigate whether lysine-specific demethylase 1 (LSD1) affects the development of oral squamous cell carcinoma (OSCC) by sustaining the cancer stem cells from OSCC (OSCSCs). METHODS: RT-qPCR detection was firstly conducted to screen out research gene by determining differential expression of histone demethylases and methylases in identified OSCSCs. Then, microarray analysis was carried out in cells with poor expression of LSD1. RESULTS: OSCSCs expressed high levels of LSD1, and LSD1 inhibition reduced cell viability, migration, invasion, and sphere formation of OSCSCs. Later mechanistic studies suggested that LSD1 inhibited microRNA (miR)-17 expression through histone demethylation. miR-17 bound to KPNA2, and LSD1 downstream genes were mainly enriched in the PI3K/AKT pathway. Importantly, miR-17 inhibitor reversed the inhibitory effect of si-LSD1 on cell activity, while si-KPNA2 abolished the promotive effect of miR-17 inhibitor on cell activity both in vitro and in vivo. CONCLUSION: Overall, LSD1 functions as a cancer stem cell supporter in OSCC by catalyzing demethylation of miR-17 and activating the downstream KPNA2/PI3K/AKT pathway, which contributes to understanding of the mechanisms associated with epigenetic regulation in OSCC.

Upregulated circ_0002141 facilitates oral squamous cell carcinoma progression via the miR-1231/EGFR axis.

OBJECTIVES: The dysregulation of circular RNAs (circRNAs) is implicated in the progression of various cancers. This study was aimed at expounding the role and mechanism of hsa_circ_0002141 in the OSCC progression. MATERIALS AND METHODS: Circ_0002141 expression was examined in 52 pairs of OSCC tissues and matched adjacent tissue samples by quantitative real-time polymerase chain reaction (qRT-PCR) assay. After circ_0002141 was overexpressed or knocked down in OSCC cell lines, cell counting kit-8 (CCK-8) assay, Transwell assay, flow cytometry, and Western blotting were conducted to detect the changes in the growth, migration, invasion and apoptosis of OSCC cells. Western blot assay, qRT-PCR and dual-luciferase reporter assay were performed to clarify the interplay among circ_0002141, miR-1231, and epidermal growth factor receptor (EGFR). RESULTS: Circ_0002141 expression was significantly upregulated in OSCC tissues and cell lines. Circ_0002141 overexpression markedly promoted the proliferation, migration, and invasion of OSCC cells whereas reduced the apoptotic of OSCC cells. Also, circ_0002141 knockdown suppressed the malignant characteristics of OSCC cells. EGFR was validated as the target of miR-1231. Besides, circ_0002141 could sponge miR-1231 and upregulate EGFR expression in OSCC cells. CONCLUSION: Circ_0002141/miR-1231/EGFR axis is involved in the progression of OSCC.

Bioleaching performance of vanadium-bearing smelting ash by Acidithiobacillus ferrooxidans for vanadium recovery.

The bioleaching process is widely used in the treatment of ores or solid wastes, but little is known about its application in the treatment of vanadium-bearing smelting ash. This study investigated bioleaching of smelting ash with Acidithiobacillus ferrooxidans. The vanadium-bearing smelting ash was first treated with 0.1 M acetate buffer and then leached in the culture of Acidithiobacillus ferrooxidans. Comparison between one-step and two-step leaching process indicated that microbial metabolites could contribute to the bioleaching. The Acidithiobacillus ferrooxidans demonstrated a high vanadium leaching potential, solubilizing 41.9% of vanadium from the smelting ash. The optimal leaching condition was determined, which was 1% pulp density, 10% inoculum volume, an initial pH of 1.8, and 3 Fe2+g/L. The compositional analysis showed that the fraction of reducible, oxidizable, and acid-soluble was transferred into the leaching liquor. Therefore, as the alternative to the chemical/physical process, an efficient bioleaching process was proposed to enhance the recovery of vanadium from the vanadium-bearing smelting ash.

mTORC1 promotes mineralization via p53 pathway.

The objectives of our study were to investigate the roles of mTORC1 in odontoblast proliferation and mineralization and to determine the mechanism by which mTORC1 regulates odontoblast mineralization. In vitro, MDPC23 cells were treated with rapamycin (10 nmol/L) and transfected with a lentivirus for short hairpin (shRNA)-mediated silencing of the tuberous sclerosis complex (shTSC1) to inhibit and activate mTORC1, respectively. CCK8 assays, flow cytometry, Alizarin red S staining, ALP staining, qRT-PCR, and western blot analysis were performed. TSC1-conditional knockout (DMP1-Cre+ ; TSC1f/f , hereafter CKO) mice and littermate control (DMP1-Cre- ; TSC1f/f , hereafter WT) mice were generated. H&E staining, immunofluorescence, and micro-CT analysis were performed. Transcriptome sequencing analysis was used to screen the mechanism of this process. mTORC1 inactivation decreased the cell proliferation. The qRT-PCR and western blot results showed that mineralization-related genes and proteins were downregulated in mTORC1-inactivated cells. Moreover, mTORC1 overactivation promoted cell proliferation and mineralization-related gene and protein expression. In vivo, the micro-CT results showed that DV/TV and dentin thickness were higher in CKO mice than in controls and H&E staining showed the same results. Mineralization-related proteins expression was upregulated. Transcriptome sequencing analysis revealed that p53 pathway-associated genes were differentially expressed in TSC1-deficient cells. By inhibiting p53 alone or both mTORC1 and p53 with rapamycin and a p53 inhibitor, we elucidated that p53 acts downstream of mTORC1 and that mTORC1 thereby promotes odontoblast mineralization. Taken together, our findings demonstrate that the role of mTORC1 in odontoblast proliferation and mineralization, and confirm that mTORC1 upregulates odontoblast mineralization via the p53 pathway.

LncRNA MAFG-AS1 regulates human periodontal ligament stem cell proliferation and Toll-like receptor 4 expression.

LncRNA MAFG-AS1 is predicted to interact with miR-146a, which can target Toll-like receptor 4 (TLR4), a key player in periodontitis. This study aimed to investigate the roles of MAFG-AS1 in periodontitis. It was observed that MAFG-AS1 was downregulated in the human periodontal ligament stem cells (PDLSCs) derived from periodontitis-affected teeth. Dual-luciferase assay revealed that co-transfection of MAFG-AS1 expression vector and miR-146a mimic showed significantly lower relative luciferase activity comparing to co-transfection of MAFG-AS1 expression vector and negative control (NC) miRNA. However, MAFG-AS1 and miR-146a failed to affect each other. Interestingly, MAFG-AS1 overexpression led to the upregulated TLR4. In addition, MAFG-AS1 overexpression also led to the inhibited proliferation of PDLSCs. Therefore, MAFG-AS1 may regulate the proliferation of PDLSCs and the expression of TLR4 to participate in periodontitis.

Effect of Fe(II) on reactivity of heterotrophic denitrifiers in the remediation of nitrate- and Fe(II)-contaminated groundwater.

Heterotrophic denitrifiers, capable of simultaneous nitrate reduction and Fe(II) oxidation, can be applied for the remediation of nitrate and Fe(II) combined contamination in groundwater. Under strictly anaerobic condition, denitrifying microbial communities were enriched with the coexistence of soluble nitrate, Fe(II) and associated nutrient elements to monitor the denitrification process. Low abundance of Fe(II) (e.g., 10 mg L-1 in this study) tended to stimulate the activity of denitrifying microbial communities. However, elevated Fe(II) concentration (50 and 100 mg L-1 in this study), acted as a stress, strongly inhibited the activity and reproduction of denitrifiers. Besides, through thermodynamics calculations, methanol rather than Fe(II) was proved to be the preferable electron donors for both energy metabolism and anabolism. Betaproteobacteria was found to be the most predominant (sub)phylum in all enriched microbial assemblages. Methylovesartilis was the most predominant group mainly catalyzed for methanol based denitrification, and others denitrifiers included Methylophilaceae, Dechloromonas and Denitratisoma. Excessive Fe(II) in the solution greatly reduced the proportions of these denitrifying groups, while the influence seemed to be less apparent on functional genes composition. As such, a conceptional metabolism pathway of the most dominant genus (i.e., Methylovesartilis) for nitrate reducing as well as methanol and Fe(II) oxidation confirmed that biotic nitrate reducing and Fe(II) oxidizing were potentially proceeded in cytoplasm by enzymes such as NarGHI. The Fe(II) oxidation rate depended on the rate of Fe(II) entering into the cell. These findings provide a clear mechanistic understanding of heterotrophic denitrification coupling with Fe(II) oxidation, and environmental implication for the bioremediation of nitrate and Fe(II) contaminated groundwater.

[Microbial diversity of salt lakes in Badain Jaran desert].

OBJECTIVE: We characterized procaryotic biodiversity, community structure and the relationship between the community structure and environmental factors of salt lakes in Badain Jaran desert, Inner Mongolia, China. METHODS: We constructed 16S rRNA gene clone libraries by molecular biology techniques to analyze the procaryotic phylogenetic relationships, and used R language to compare the community structure of haloalkalophiles in the salt lakes. RESULTS: Water in this region has a high salinity ranging from 165 to 397 g/L. The water is strongly alkaline with pH value above 10. The microbial diversity and community structure of the salt lakes are obviously different. The diversity of bacteria is more abundant than that of archaea. The main categories of bacteria in the samples are Gammaproteobacteria, Bacteroidetes, Alphaproteobacteria, Firmicute and Verrucomicrobia, whereas all archaea only belong to Halobacteriaceae of Euryarchaeota. CONCLUSION: Salinity is the most important environmental factor influencing the bacterial community structure, whereas the archaea community structure was influenced comprehensively by multiple environmental factors.

Arsenic release from shallow aquifers of the Hetao basin, Inner Mongolia: evidence from bacterial community in aquifer sediments and groundwater.

Indigenous microbes play crucial roles in arsenic mobilization in high arsenic groundwater systems. Databases concerning the presence and the activity of microbial communities are very useful in evaluating the potential of microbe-mediated arsenic mobilization in shallow aquifers hosting high arsenic groundwater. This study characterized microbial communities in groundwaters at different depths with different arsenic concentrations by DGGE and one sediment by 16S rRNA gene clone library, and evaluated arsenic mobilization in microcosm batches with the presence of indigenous bacteria. DGGE fingerprints revealed that the community structure changed substantially with depth at the same location. It indicated that a relatively higher bacterial diversity was present in the groundwater sample with lower arsenic concentration. Sequence analysis of 16S rRNA gene demonstrated that the sediment bacteria mainly belonged to Pseudomonas, Dietzia and Rhodococcus, which have been widely found in aquifer systems. Additionally, NO3(-)-reducing bacteria Pseudomonas sp. was the largest group, followed by Fe(III)-reducing, SO4(2-)-reducing and As(V)-reducing bacteria in the sediment sample. These anaerobic bacteria used the specific oxyanions as electron acceptor and played a significant role in reductive dissolution of Fe oxide minerals, reduction of As(V), and release of arsenic from sediments into groundwater. Microcosm experiments, using intact aquifer sediments, showed that arsenic release and Fe(III) reduction were microbially mediated in the presence of indigenous bacteria. High arsenic concentration was also observed in the batch without amendment of organic carbon, demonstrating that the natural organic matter in sediments was the potential electron donor for microbially mediated arsenic release from these aquifer sediments.

Photosynthetic response of Chlamydomonas reinhardtii and Chlamydomonas sp. 1710 to zinc toxicity.

Zinc (Zn) is an essential trace element but can lead to water contamination and ecological deterioration when present in excessive amounts. Therefore, investigating the photosynthetic response of microalgae to Zn stress is of great significance. In this study, we assessed the photosynthetic responses of neutrophilic Chlamydomonas reinhardtii and acidophilic Chlamydomonas sp. 1710 to Zn exposure for 96 h. The specific growth rate (µ), chlorophyll-a (Chl-a) content, and chlorophyll fluorescence parameters were determined. The results demonstrated that Chlamydomonas sp. 1710 was much more tolerant to Zn than C. reinhardtii, with the half-maximal inhibitory concentration (IC50) values of 225.4 mg/L and 23.4 mg/L, respectively. The µ and Chl-a content of C. reinhardtii decreased in the presence of 15 mg/L Zn, whereas those of Chlamydomonas sp. 1710 were unaffected by as high as 100 mg/L Zn. Chlorophyll fluorescence parameters indicated that the regulation of energy dissipation, including non-photochemical quenching, played a crucial role in Zn stress resistance for both Chlamydomonas strains. However, in the case of C. reinhardtii, non-photochemical quenching was inhibited by 5 mg/L Zn in the first 48 h, whereas for Chlamydomonas sp. 1710, it remained unaffected under 100 mg/L Zn. Chlamydomonas sp. 1710 also exhibited a 20 times stronger capacity for regulating the electron transfer rate than C. reinhardtii under Zn stress. The light energy utilization efficiency (α) of Chlamydomonas sp. 1710 had the most highly non-linear correlation with µ, indicating the energy utilization and regulation process of Chlamydomonas sp. 1710 was well protected under Zn stress. Collectively, our findings demonstrate that the photosystem of Chlamydomonas sp. 1710 is much more resilient and tolerant than that of C. reinhardtii under Zn stress.

Metagenomic insight into the acidophilic functional communities driving elemental geochemical cycles in an acid mine drainage lake.

Acidophiles play a key role in the generation, evolution and attenuation of acid mine drainage (AMD), which is characterized by strong acidity (pH<3.5) and high metal concentrations. In this study, the seasonal changes of acidophilic communities and their roles in elemental cycling in an AMD lake (pH∼3.0) in China were analyzed through metagenomics. The results showed eukaryotic algae thrived in the lake, and Coccomyxa was dominant in January (38.1%) and May (33.9%), while Chlorella in July (9.5%). The extensive growth of Chlamydomonas in December (22.7%) resulted in an ultrahigh chlorophyll a concentration (587 µg/L), providing abundant organic carbon for the ecosystem. In addition, the iron-oxidizing and nitrogen-fixing bacterium Ferrovum contributed to carbon fixation. Ammonia oxidation likely occurred in the acidic lake, as was revealed by archaea Ca. Nitrosotalea. To gain a competitive advantage in the nutrient-poor environment, some acidophiles exhibited facultative characteristics, e.g. the most abundant bacterium Acidiphilium utilized both organic and inorganic carbon, and obtained energy from organic matter, inorganic sulfur, and sunlight simultaneously. It was suggested that sunlight, rather than chemical energy of reduced iron-sulfur was the major driver of elemental cycling in the AMD lake. The results are beneficial to the development of bioremediation strategies for AMD.

Effects of AIM2 and IFI16 on Infectious Diseases and Inflammation.

Both absent in melanoma 2 (AIM2) and interferon-inducible protein 16 (IFI16) are intracellular innate immune receptors that recognize double-stranded DNA released during pathogenic infection, leading to the assembly of the inflammasome. The assembly of the inflammasome results in the secretion of bioactive interleukin (IL)-1ß and IL-18 and induces cell death through an inflammatory process called pyroptosis. Although the AIM2 inflammasome is generally harmful in the context of some aseptic inflammatory illnesses, it plays a protective role in infectious diseases. During inflammatory processes, there is competition between IFI16 and AIM2. In this review, we explore the impacts of IFI16 and AIM2 in infectious disease and aseptic inflammation, respectively, and how they compete.

Roles of bacterial extracellular vesicles in systemic diseases.

Accumulating evidence suggests that in various systems, not all bidirectional microbiota-host interactions involve direct cell contact. Bacterial extracellular vesicles (BEVs) may be key participants in this interkingdom crosstalk. BEVs mediate microbiota functions by delivering effector molecules that modulate host signaling pathways, thereby facilitating host-microbe interactions. BEV production during infections by both pathogens and probiotics has been observed in various host tissues. Therefore, these vesicles released by microbiota may have the ability to drive or inhibit disease pathogenesis in different systems within the host. Here, we review the current knowledge of BEVs and particularly emphasize their interactions with the host and the pathogenesis of systemic diseases.

Odontoblasts release exosomes to regulate the odontoblastic differentiation of dental pulp stem cells.

BACKGROUND: Dental pulp stem cells (DPSCs) play a crucial role in dentin-pulp complex regeneration. Further understanding of the mechanism by which DPSCs remain in a quiescent state could contribute to improvements in the dentin-pulp complex and dentinogenesis. METHODS: TSC1 conditional knockout (DMP1-Cre+; TSC1f/f, hereafter CKO) mice were generated to increase the activity of mechanistic target of rapamycin complex 1 (mTORC1). H&E staining, immunofluorescence and micro-CT analysis were performed with these CKO mice and littermate controls. In vitro, exosomes were collected from the supernatants of MDPC23 cells with different levels of mTORC1 activity and then characterized by transmission electron microscopy and nanoparticle tracking analysis. DPSCs were cocultured with MDPC23 cells and MDPC23 cell-derived exosomes. Alizarin Red S staining, ALP staining, qRT‒PCR, western blotting analysis and micro-RNA sequencing were performed. RESULTS: Our study showed that mTORC1 activation in odontoblasts resulted in thicker dentin and higher dentin volume/tooth volume of molars, and it increased the expression levels of the exosome markers CD63 and Alix. In vitro, when DPSCs were cocultured with MDPC23 cells, odontoblastic differentiation was inhibited. However, the inhibition of odontoblastic differentiation was reversed when DPSCs were cocultured with MDPC23 cells with mTORC1 overactivation. To further study the effects of mTORC1 on exosome release from odontoblasts, MDPC23 cells were treated with rapamycin or shRNA-TSC1 to inactivate or activate mTORC1, respectively. The results revealed that exosome release from odontoblasts was negatively correlated with mTORC1 activity. Moreover, exosomes derived from MDPC23 cells with active or inactive mTORC1 inhibited the odontoblastic differentiation of DPSCs at the same concentration. miRNA sequencing analysis of exosomes that were derived from shTSC1-transfected MDPC23 cells, rapamycin-treated MDPC23 cells or nontreated MDPC23 cells revealed that the majority of the miRNAs were similar among these groups. In addition, exosomes derived from odontoblasts inhibited the odontoblastic differentiation of DPSCs, and the inhibitory effect was positively correlated with exosome concentration. CONCLUSION: mTORC1 regulates exosome release from odontoblasts to inhibit the odontoblastic differentiation of DPSCs, but it does not alter exosomal contents. These findings might provide a new understanding of dental pulp complex regeneration.

[Characteristics of the eukaryotic community structure in acid mine drainage lake in Anhui Province, China].

OBJECTIVE: We characterized eukaryotic community structure and the relationship between the community structure and environmental factors in acidic mine drainage (AMD) lake of a sulfide mine in Anhui Province, China. METHODS: The 18S rRNA gene clone libraries were constructed by using molecular biology techniques to analyze the eukaryotic phylogenetic relationships, and the canonical correspondence analysis (CCA) was used to analyze the relationship between the community structure and environmental factors. RESULTS: The phylogenetic analysis shows that Ascomycota is widespread in the four samples and dominated in the AMD-1 and AMD-3 clone libraries, whereas Chlorophyta and Basidiomycota are the predominant in AMD-2 and AMD-4 samples, respectively. Moreover, many sequences in libraries were closely related to those of acid-resisting and metal-resisting eukaryotic microbes, such as Sarcinomyces petricola, Penicillium janthinellum, Coniochaeta velutina, Trichoderma viride, Chlorella protothecoides var. acidicola, Ochromonas sp., and there are high content of known human pathogens, such as Lecythophora hoffmannii, Cryptococcus neoformans. CCA analysis revealed that the critical factors influencing the eukaryotic community structure include TN, SO4(2-), Fe2+ and Eh. CONCLUSION: Difference of eukaryotic community structure in time and spare may be related with physico-chemical properties of acidic mine drainage. High content of human pathogens was detected in the acidic ecosystem. The ecological study of eukaryotes under the acidic conditions can help to find efficient methods to process acid mine drainage.

Revealing the nexus between tourism development and CO2 emissions in Asia: does asymmetry matter?

Asia is one of the fastest-growing regions in international tourism, economic growth, and CO2 emissions around the globe. However, the relationships between tourism and CO2 emissions are little and unclearly identified. The purpose of the study is to explore the asymmetric nexus between tourism and CO2 emissions in a panel of five high emitters Asian countries covering the period of 1995-2019 by using panel-NARDL-AMG. The empirical results reveal that a positive shock in tourism arrivals increases CO2 emissions, while a negative shock also increases CO2 emissions in the long run. Moreover, a negative shock has a greater effect on CO2 emissions than a positive shock in Asia in the long run. Tourism receipts are expected to maintain the robustness of CO2 emissions in the long run in Asian economies. The authorities should develop and design green international tourism activities in the Asian economies.

Both pH and salinity shape the microbial communities of the lakes in Badain Jaran Desert, NW China.

Badain Jaran Desert (BJD), characterized by extremely arid climate and tallest sand dunes in the world, is the second largest desert in China. Surprisingly, there are a large number of permanent lakes in this desert. At present, little is known about the composition and distribution of microbial communities in these desert lakes, which are an important bioresource and play a fundamental role in the elemental cycles of the lakes. In this study, the physicochemical characteristics and microbial communities of water samples from 15 lakes in BJD were comparatively investigated. The results showed that the lakes were rich in Na+, Cl-, CO32- and HCO3- while Ca2+ and Mg2+ were scarce, with pH 8.52-10.27 and salinity 1.05-478.70 g/L. Bacteria dominated exclusively in low saline lakes (salinity < 50 g/L) while archaea were predominant in hypersaline lakes (salinity > 250 g/L), which abundance increased along salinity gradient linearly. Genera Flavobacterium, Synechocystis and Roseobacter from phyla Bacteroidetes, Cyanobacteria, Alphaproteobacteria were the major members in low saline lakes whereas Halomonas, Aliidiomarina and Halopelagius from Gammaproteobacteria and Euryarchaeota were abundant in moderately saline lakes (salinity 50-250 g/L). The hypersaline lakes were predominated by extreme halophiles such as Halorubrum, Halohasta and Natronomonas from Euryarchaeota. The correlation among the microbes in the lakes was mainly positive, suggesting they can survive in the harsh environments through synergistic interactions. Statistical analyses indicated that physicochemical characteristics rather than spatial factors shaped the microbial communities in the desert lakes. The pH was the most important environmental factor controlling alpha diversity, while salinity was the major driver determining microbial community structure in BJD lakes. In contrast, geographic factors had no significant impact on the microbial community compositions.

RNA-binding protein IGF2BP2 enhances circ_0000745 abundancy and promotes aggressiveness and stemness of ovarian cancer cells via the microRNA-3187-3p/ERBB4/PI3K/AKT axis.

BACKGROUND: Circular RNAs (circRNAs) are increasingly recognized as important regulators in cancer including ovarian cancer (OC). This work focuses on the effects of circ_0000745 on the OC development of and molecules involved. METHODS: Expression of circ_0000745 in collected OC tissues and the acquired OC cell lines was examined by RT-qPCR. The stability of circ_0000745 in cells was examined by RNase R treatment. The target transcripts interacted with circ_0000745 were predicted using bioinformatic systems. Gain- and loss-of-function studies of circ_0000745, microRNA (miR)-3187-3p and erb-b2 receptor tyrosine kinase 4 (ERBB4) were conducted to determine their functions on proliferation, migration, invasion and stem cell property of OC cells. RESULTS: Circ_0000745 and ERBB4 were abundantly expressed while miR-3187-3p was poorly expressed in OC tissues and cells. Circ_0000745 sequestered miR-3187-3p and blocked its repressive effect on ERBB4. Downregulation of circ_0000745 reduced proliferation, aggressiveness, epithelial-mesenchymal transition, and stemness of SK-OV-3 cells, but this reduction was blocked upon miR-3187-3p inhibition or ERBB4 upregulation. By contrast, artificial induction of circ_0000745 upregulation, miR-3187-3p upregulation and ERBB4 downregulation led to inverse trends in ES-2 cells. ERBB4 promoted the phosphorylation of the PI3K/AKT signaling pathway. An RNA binding protein IGF2BP2 was found to circ_0000745 bind to and promote its expression and stability. CONCLUSION: This study demonstrated that circ_0000745 upregulated by IGF2BP2 promotes aggressiveness and stemness of OC cells through a miR-3187-3p/ERBB4/PI3K/AKT axis. Circ_0000745 may serve as a promising target for OC treatment.

Succession of Microbial Communities in Waste Soils of an Iron Mine in Eastern China.

The reclamation of mine dump is largely centered on the role played by microorganisms. However, the succession of microbial community structure and function in ecological restoration of the mine soils is still poorly understood. In this study, soil samples with different stacking time were collected from the dump of an iron mine in China and the physicochemical characteristics and microbial communities of these samples were comparatively investigated. The results showed that the fresh bare samples had the lowest pH, highest ion concentration, and were the most deficient in nutrients while the acidity and ion concentration of old bare samples decreased significantly, and the nutritional conditions improved remarkably. Vegetated samples had the weakest acidity, lowest ion concentration, and the highest nutrient concentration. In the fresh mine soils, the iron/sulfur-oxidizers such as Acidiferrobacter and Sulfobacillus were dominant, resulting in the strongest acidity. Bacteria from genera Acidibacter, Metallibacterium, and phyla Cyanobacteria, WPS-2 were abundant in the old bare samples, which contributed to the pH increase and TOC accumulation respectively. Acidobacteriota predominated in the vegetated samples and promoted nutrient enrichment and plant growth significantly. The microbial diversity and evenness of the three types of soils increased gradually, with more complex microbial networks, suggesting that the microbial community became more mature with time and microorganisms co-evolved with the mine soils.