Up-regulation of RNA m6A methyltransferase like-3 expression contributes to arsenic and benzo[a]pyrene co-exposure-induced cancer stem cell-like property and tumorigenesis.

While arsenic or BaP alone exposure can cause lung cancer, studies showed that arsenic plus BaP co-exposure displays a significantly stronger lung tumorigenic effect. However, the underlying mechanism has not been well understood. Studies showed that RNA molecules are chemically modified. The most frequently occurring RNA modification in eukaryotic messenger RNAs is the N6-methyladenosine (m6A) methylation. This study aimed to determine whether arsenic plus BaP exposure alters RNA m6A methylation and its role in lung tumorigenic effect of arsenic plus BaP exposure. Human bronchial epithelial cells transformed by exposure to arsenic or BaP alone, and arsenic plus BaP and mouse xenograft tumorigenesis models were used in this study. It was found that arsenic plus BaP exposure-transformed cells have significantly higher levels of RNA m6A methylation than arsenic or BaP alone exposure-transformed human bronchial epithelial cells. Western blot analysis showed that arsenic plus BaP exposure greatly up-regulates the m6A writer methyltransferase like-3 (METTL3) expression levels in cultured cells and mouse lung tissues. METTL3 knockdown in cells transformed by arsenic plus BaP exposure drastically reduced their RNA m6A methylation levels. Functional studies revealed that METTL3 knockdown in cells transformed by arsenic plus BaP exposure greatly reduces their anchorage-dependent and -independent growth, cancer stem cell characters and tumorigenesis. The findings from this study suggest that arsenic plus BaP co-exposure causes epitranscriptomic dysregulation, which may contribute significantly to arsenic plus BaP co-exposure-caused synergistic lung tumorigenic effect.

Endophytic bacterial community diversity in genetically related hybrid rice seeds.

The Food and Agriculture Organization of the United Nations (FAO) has identified hybrid rice as ideal for addressing food scarcity in poor nations. A comprehensive investigation of the endophytic bacteria in hybrid rice seeds is essential from a microecological perspective to illuminate the mechanisms underlying its high yield, high quality, and multi-resistance. The endophytic bacterial diversity and community structures of 11 genetically correlated hybrid rice seeds with different rice blast resistance levels were studied using high-throughput sequencing (HTS) on the Illumina MiSeq platform to reveal their "core microbiota" and explore the effect of genotypes, genetic relationships, and resistance. Proteobacteria (78.15-99.15%) represented the most abundant group in the 11 hybrid rice cultivars, while Pantoea, Pseudomonas, and Microbacterium comprised the "core microbiota." Hybrid rice seeds with different genotypes, genetic correlations, and rice blast resistance displayed endophytic bacterial community structure and diversity variation. In addition, the network relationships between the rice seed endophytic bacteria of "the same female parent but different male parents" were more complex than those from "the same male parent but different female parents." Matrilineal inheritance may be the primary method of passing on endophytic bacteria in rice from generation to generation. The endophytic bacterial interaction network in rice blast-resistant hybrid rice seed varieties was more complicated than in susceptible varieties. In summary, this study demonstrated that the genotype, genetic relationship, and rice blast resistance were important factors affecting the community structures and diversity of endophytic bacteria in hybrid rice seeds, which was vital for revealing the interaction between endophytic bacteria and the host. KEY POINTS: • Pantoea, Pseudomonas, and Microbacterium represent the main endophytic bacteria in hybrid rice seeds. • Genotype is the primary factor affecting endophytic bacterial diversity in hybrid rice seeds. • The diversity of the endophytic bacterial community in hybrid rice seeds is related to their genotypes, genetic relationships, and rice blast resistance.

Analysis of Endophytic Bacterial Diversity in Rice Seeds with Regional Characteristics in Yunnan Province, China, Based on High-Throughput Sequencing Technology.

Examining the endophytic bacteria in rice seeds from Yunnan Province displaying regional characteristics is vital for exploring strain resources, improving rice production, and conducting subsequent research. This study investigated nine characteristic rice varieties from Yunnan Province using high-throughput sequencing technology based on the Illumina Novaseq platform to reveal their dominant bacterial communities and discussed their endophytic bacterial community differences. A total of 829 shared OTUs, and 233 unique OTUs were identified in the nine samples, while the bacteria included Proteobacteria, Actinobacteriota, and Firmicutes, of which Proteobacteria was the most dominant. Pantoea and Methylorubrum were the most abundant at the genus level, with Curtobacterium, Brevundimonas, and Luteibacter representing the specific genera in the rice seed samples. This study revealed the endophytic structure and diversity in the seeds of nine rice varieties displaying regional characteristics and provided a foundation for further research into rice containing endophytic bacteria.

Mechanisms of the synergistic lung tumorigenic effect of arsenic and benzo(a)pyrene combined- exposure.

Humans are often exposed to mixtures of environmental pollutants especially environmental chemical carcinogens, representing a significant environmental health issue. However, our understanding on the carcinogenic effects and mechanisms of environmental carcinogen mixture exposures is limited and mostly relies on the findings from studying individual chemical carcinogens. Both arsenic and benzo(a)pyrene (BaP) are among the most common environmental carcinogens causing lung cancer and other types of cancer in humans. Millions of people are exposed to arsenic via consuming arsenic-contaminated drinking water and even more people are exposed to BaP via cigarette smoking and consuming BaP-contaminated food. Thus arsenic and BaP combined-exposure in humans is common. Previous epidemiology studies indicated that arsenic-exposed people who were cigarette smokers had significantly higher lung cancer risk than those who were non-smokers. Since BaP is one of the major carcinogens in cigarette smoke, it has been speculated that arsenic and BaP combined-exposure may play important roles in the increased lung cancer risk observed in arsenic-exposed cigarette smokers. In this review, we summarize important findings and inconsistencies about the co-carcinogenic effects and underlying mechanisms of arsenic and BaP combined-exposure and propose new areas for future studies. A clear understanding on the mechanism of co-carcinogenic effects of arsenic and BaP combined exposure may identify novel targets to more efficiently treat and prevent lung cancer resulting from arsenic and BaP combined-exposure.

Dysregulations of long non-coding RNAs - The emerging "lnc" in environmental carcinogenesis.

Long non-coding RNAs (lncRNAs) refer to a class of RNA molecules that are more than 200 nucleotides in length and usually lack protein-coding capacity. LncRNAs play important roles in regulating gene expression as well as many aspects of normal physiological processes. Dysregulations of lncRNA expressions and functions are considered to be critically involved in the development and progression of many diseases especially cancer. The lncRNA research in the field of cancer biology over the past decade reveals that a large number of lncRNAs are dysregulated in various types of cancer and that dysregulated lncRNAs may play important roles in cancer initiation, metastasis and therapeutic responses. Metal carcinogens and other common environmental carcinogens such as polycyclic aromatic hydrocarbons, fine particular matters, cigarette smoke, ultraviolet and ionizing radiation are important cancer etiology factors. However, the mechanisms of how metal carcinogens and other common environmental carcinogen exposures initiate cancer and promote cancer progression remain largely unknown. Accumulating evidence show that exposure to metal carcinogens and other common environmental carcinogens dysregulate lncRNA expression in various model systems, which may offer novel mechanistic insights for environmental carcinogenesis. This review will first provide a brief introduction about lncRNA biology and the mechanisms of lncRNA functions, followed by summarizing and discussing recent studies about lncRNA dysregulation by metal carcinogen and other common environment carcinogen exposures and the potential roles of dysregulated lncRNAs in environmental carcinogenesis. A perspective for future studies in this emerging and important field is also presented.

Diversity of endophytic bacteria in hybrid maize seeds and Bacillus mojavensis J2416-7 may be capable of vertical transmission.

The diversity of endophytic bacteria in the progeny is related to the parental lines. In this study, the traditional separation method was used to study the dominant endophytic bacteria of the shared paternal line and its pollen, different maternal lines and their F1 progeny. And the results showed that the dominant endophytic bacteria in maize seeds and the pollen were Bacillus and Pantoea. The Bacillus diversity of the progeny JMC121 and JN728 were the same as both the paternal line and the maternal line, including Bacillus subtilis, Bacillus velezensis, Bacillus mojavensis, and Bacillus licheniformis. The Bacillus subtilis and Bacillus velezensis in JN828 were the same as both the paternal line and the maternal line, while Bacillus licheniformis was only the same as the paternal line. Through the RAPD molecular typing, there was the same strain of Bacillus mojavensis existed in the paternal line J2416, the pollen and the progeny JN728; this meant that the paternal line passed its dominant endophytic bacteria to the progeny through pollen in vertical transmission. This study showed that the dominant endophytic bacteria in maize seeds and the pollen were Bacillus, and the diversity of F1 progeny was related to both the paternal line and the maternal line.

The Epitranscriptomic Mechanism of Metal Toxicity and Carcinogenesis.

Metals are common toxic environmental pollutants. Acute or chronic exposure to metal pollutants causes severe adverse health effects in animals and humans, such as developmental retardation, abnormal metabolism, and disorders of cardiovascular, neurologic, respiratory, reproductive, and urologic systems. Moreover, several metals (arsenic, cadmium, chromium, and nickel) are classified as potent Group I carcinogens and cause various types of cancer in humans. Although the toxicity and carcinogenicity of metal pollutants are well recognized, the underlying mechanisms have not been clearly defined. The epitranscriptome includes all kinds of chemical modifications of all forms of RNA molecules inside a cell. Recent progresses in demonstrating the reversible pattern of RNA modifications and their roles in physiology and pathogenesis represent a breakthrough in the field of RNA biology and function study. The epitranscriptomic study is now an exciting emerging field in toxicology research. While few studies have been conducted so far to determine the epitranscriptomic effects of metal pollutants, they offer novel insights for understanding the mechanisms of metal toxicity and carcinogenesis. The goal of this review is to discuss recent studies on the epitranscriptomic effects of metals and propose some thoughts for future studies in the field.

The m6A RNA methylation regulates oncogenic signaling pathways driving cell malignant transformation and carcinogenesis.

The m6A RNA methylation is the most prevalent internal modification in mammalian mRNAs which plays critical biological roles by regulating vital cellular processes. Dysregulations of the m6A modification due to aberrant expression of its regulatory proteins are frequently observed in many pathological conditions, particularly in cancer. Normal cells undergo malignant transformation via activation or modulation of different oncogenic signaling pathways through complex mechanisms. Accumulating evidence showing regulation of oncogenic signaling pathways at the epitranscriptomic level has added an extra layer of the complexity. In particular, recent studies demonstrated that, in many types of cancers various oncogenic signaling pathways are modulated by the m6A modification in the target mRNAs as well as noncoding RNA transcripts. m6A modifications in these RNA molecules control their fate and metabolism by regulating their stability, translation or subcellular localizations. In this review we discussed recent exciting studies on oncogenic signaling pathways that are modulated by the m6A RNA modification and/or their regulators in cancer and provided perspectives for further studies. The regulation of oncogenic signaling pathways by the m6A modification and its regulators also render them as potential druggable targets for the treatment of cancer.

Diversity and community structure of endophytic Bacillus with antagonistic and antioxidant activity in the fruits of Xisha Wild Noni (Morinda citrifolia L.).

Noni (Morinda citrifolia L.) is a tropical crop with strong antibacterial, antioxidant and other abilities, and its fruit has a strong potential for adjuvant treatment of diseases. This study aimed to explore the dynamic change of endophytic bacteria in Noni fruit at different stages and the correlation between the antagonistic and antioxidant activity of the Bacillus which was screened and the change of the host's growth stage. In this study, though the high-throughput sequencing technology (HTS), 106 endophytic bacteria species were found in A, B, C, D, E and F stages of Noni fruit, among which the dominant group were Pantoea (0.3%-20.9%), and Candidatus_Uzinura (2.3%-35.2%) etc. The endophytic bacteria were isolated by culture-dependent method. Through their antagonistic experiments on Staphylococcus aureus and Escherichia coli, the results of 16S polyphasic taxonomic identification showed that the 34 antagonistic strains belonged to Bacillus. Five species of these Bacillus were identified by gyrA polyphase taxonomy, including Bacillus subtilis (76% of all Bacillus), Bacillus licheniformis (9%), Bacillus amyloliquefaciens (6%), Bacillus velezensis (6%) and Bacillus mojavensi (3%), and the RAPD showed these Bacillus are no signs of stable passage. In C, D, E and F stages, the average total antioxidant activity of Bacillus endophytic antagonists against Noni was 7.812 U/mL, 8.144 U/mL, 7.817 U/mL and 7.144 U/mL, which was much higher than that of Noni fruit, and antioxidant activity of Noni juice and Bacillus bacterial liquid vary with host's growth period showed the same trend, both rose slowly at first, and reached the highest in period E, then declined slightly in period F, it showed that the antagonistic Bacillus of Noni had synergistic function with Noni fruit. This study clarified the relationship of function between Noni fruit and endophytic bacteria, and laid a foundation for future study on the dynamic change of endophytic flora succession and efficacy.

Down-regulation of lncRNA MEG3 promotes chronic low dose cadmium exposure-induced cell transformation and cancer stem cell-like property.

Cadmium (Cd) is a toxic heavy metal and one of carcinogens that cause lung cancer. However, the exact mechanism of Cd carcinogenesis remains unclear. To investigate the mechanism of Cd carcinogenesis, we exposed human bronchial epithelial cells (BEAS-2B) to a low dose of Cd (2.5 µM, CdCl2) for 9 months, which caused cell malignant transformation and generated cancer stem cell (CSC)-like cells. The goal of this study is to investigate the underlying mechanism. The long non-coding RNA (lncRNA) microarray analysis showed that the expression level of a tumor suppressive lncRNA maternally expressed 3 (MEG3) is significantly down-regulated in Cd-transformed cells, which is confirmed by further q-PCR analysis. Mechanistically, it was found that chronic Cd exposure up-regulates the levels of DNA methyltransferases (DNMTs), which increases the methylation of the differentially methylated region (DMR) 1.5 kb upstream of MEG3 transcription start site to reduce MEG3 expression. Functional studies showed that stably overexpressing MEG3 in Cd-transformed cells significantly reduces their transformed phenotypes. Moreover, stably overexpressing MEG3 in parental non-transformed human bronchial epithelial cells significantly impaired the capability of chronic Cd exposure to induce cell transformation and CSC-like property. Further mechanistic studies revealed that the cell cycle inhibitor p21 level is reduced and retinoblastoma protein (Rb) phosphorylation is increased in Cd-transformed cells to promote cell cycle progression. In addition, Cd-transformed cells also expressed higher levels of Bcl-xL and displayed apoptosis resistance. In contrast, stably overexpressing MEG3 increased p21 levels and reduced Rb phosphorylation and Bcl-xL levels in Cd-exposed cells and reduced their cell cycle progression and apoptosis resistance. Together, these findings suggest that MEG3 down-regulation may play important roles in Cd-induced cell transformation and CSC-like property by promoting cell cycle progression and apoptosis resistance.

Diversity, enzyme production and antibacterial activity of Bacillus strains isolated from sesame-flavored liquor Daqu.

Daqu provides enzymes and precursors for liquor fermentation, and is the core of liquor fermentation. In this study, 11 Bacillus strains were isolated from sesame-flavored liquor Daqu, which can not only produce protease and amylase, but also have antagonistic effects on common pathogens Escherichia coli and Staphylococcus aureus. According to the gyrA gene phylogeny analysis, these 11 Bacillus strains belong to three species, B1, Y14, Y15, and YPDW9 belong to Bacillus mojavensis, W7, W13, YPDW6, and YPDW12 belong to Bacillus subtilis, and W14, Y5, and YPDW1 belong to Bacillus velezensis. According to the results of random amplified polymorphic DNA (RAPD) typing, there are three strains in Bacillus mojavensis, among which Y14 and Y15 are the same ones. All four Bacillus subtilis strains and three Bacillus velezensis strains are different. The specific primers were used to randomly amplify the biological control genes expressing lipopeptide antibiotics (bioA, bmyB, ituC, fenD, srfAA, srfAB, yngG,and yndJ), and the results showed that antagonistic genes other than fenD gene were amplified in four Bacillus mojavensis strains; Bacillus subtilis amplification was significantly different, but srfAA, bmyB and yndJ genes were all present; All genes were amplified in Bacillus velezensis except YPDW1 without ituC. This research provides new ideas for strengthening Daqu and lays a foundation for improving the quality of liquor.

High-throughput sequencing-based analysis of the composition and diversity of endophytic bacterial community in seeds of upland rice.

Upland rice is an ecotype crop resulting from the long-term domestication and evolution of rice in dry land without a water layer. Generally, the stems and leaves are thick and luxuriant, while the leaves also typically broad and light. The root system is developed with abundant root hair, and the osmotic pressure of the root and cell juice concentration in the leaves is high, while this plant is drought-resistant, heat-resistant, and water absorbent. This study aims to reveal the "core flora" of the endophytes in upland rice seeds by examining their diversity and community structures. It further intends to reveal the impact of the soil environment on the formation of endophyte community structures in upland rice seeds by comparing the environmental soil microorganisms in upland rice habitats. In this study, high-throughput sequencing technology based on the Illumina Hiseq 2500 platform was used to investigate the structure and diversity of endophytic bacterial communities using upland rice varieties collected from different locations and soil samples from unified planting sites as materials. Here, 42 endophytic OTUs were found to coexist in the 14 samples. At the phylum level, the first dominant phyla in all the samples were Proteobacteria (93.81-99.99%). At the genus level, Pantoea (8.77-87.77%), Pseudomonas (1.15-61.58%), Methylobacterium (0.40-4.64%), Sphingomonas (0.26-3.85%), Microbacterium (0.01-4.67%) and Aurantimonas (0.04-4.34%), which represent the core microflora in upland rice seeds, served as the dominant genera that coexisted in all the upland rice seeds tested. This study significant for the isolation, screening, functional evaluation, and re-action of various functional microorganisms in upland rice to improve its agronomic traits. It also provides a specific reference for the interaction between microorganisms and plants.

MicroRNA Regulation of Breast Cancer Stemness.

Recent advances in our understanding of breast cancer have demonstrated that cancer stem-like cells (CSCs, also known as tumor-initiating cell (TICs)) are central for progression and recurrence. CSCs are a small subpopulation of cells present in breast tumors that contribute to growth, metastasis, therapy resistance, and recurrence, leading to poor clinical outcome. Data have shown that cancer cells can gain characteristics of CSCs, or stemness, through alterations in key signaling pathways. The dysregulation of miRNA expression and signaling have been well-documented in cancer, and recent studies have shown that miRNAs are associated with breast cancer initiation, progression, and recurrence through regulating CSC characteristics. More specifically, miRNAs directly target central signaling nodes within pathways that can drive the formation, maintenance, and even inhibition of the CSC population. This review aims to summarize these research findings specifically in the context of breast cancer. This review also discusses miRNAs as biomarkers and promising clinical therapeutics, and presents a comprehensive summary of currently validated targets involved in CSC-specific signaling pathways in breast cancer.

Metal carcinogen exposure induces cancer stem cell-like property through epigenetic reprograming: A novel mechanism of metal carcinogenesis.

Arsenic, cadmium, nickel and hexavalent chromium are among the most common environmental pollutants and potent carcinogens. Chronic exposure to these metals causes various types of cancer in humans, representing a significant environmental health issue. Although under active investigation, the mechanisms of metal carcinogenesis have not been clearly defined. One common feature of these metal carcinogens is that they are all able to cause various epigenetic dysregulations, which are believed to play important roles in their carcinogenicity. However, how metal carcinogen-caused epigenetic dysregulation contributes to metal carcinogenesis remains largely unknown. The evolution of cancer stem cell (CSC) theory has opened exciting new avenues for studying the mechanism of metal carcinogenesis. Increasing evidence indicates that chronic metal carcinogen exposure produces CSC-like cells through dysregulated epigenetic mechanisms. This review will first provide some brief introductions about CSC, epigenetics and epigenetic regulation of CSCs; then summarize progresses in recent studies on metal carcinogen-induced CSC-like property through epigenetic reprograming as a novel mechanism of metal carcinogenesis. Some perspectives for future studies in this field are also presented.

Low dose lead exposure at the onset of puberty disrupts spermatogenesis-related gene expression and causes abnormal spermatogenesis in mouse.

Implications of lead (Pb) exposure in dysregulated spermatogenesis in sexually active individuals during adulthood is well established; however, the effect of Pb exposure on spermatogenesis in the early stages of puberty is not clear yet. Moreover, the mechanism of Pb mediated dysregulation of spermatogenesis in adults is also poorly understood. Exposure to environmental toxicants during puberty may cause serious consequences in adulthood causing developmental retardations, especially in the reproductive system. Here we investigated the effects of lead exposure on spermatogenesis at the onset of puberty and the underlying mechanisms of these effects. Male ICR mice were exposed to low (50 mg/L) and high (200 mg/L) doses of Pb through the drinking water for 90 days. At the end of this period, the blood Pb level of the low-dose and high-dose exposure groups were found 6.14 ± 0.34 µg/dL and 11.92 ± 2.92 µg/dL respectively which were in agreement with the US CDC-recommended (5 µg/dL) and Chinese CDC-recommended (10 µg/dL) reference blood Pb level for the children. Although no visible toxicity was observed in either group, Pb exposure caused considerable histopathological changes in testis and epididymis; increased sperm DNA fragmentation indices as well as disrupted sperm heads and head-neck conjunctions. Moreover, both low and high-dose Pb exposures caused aberrant expressions of several important spermatogenesis-related genes in epididymis and testis. These results suggest that although the blood Pb levels are close to the recommended-reference values, low dose Pb exposure at the onset of puberty can disrupt spermatogenesis-related gene expression and cause abnormal mouse spermatogenesis.

Integrin α9 depletion promotes ß-catenin degradation to suppress triple-negative breast cancer tumor growth and metastasis.

Although integrin α9 (ITGA9) is known to be involved in cell adhesion and motility, its expression in cancer and its role in tumor growth and metastasis remain largely unknown. Our study was designed to investigate the role of ITGA9 in triple-negative breast cancer (TNBC). ITGA9 expression in TNBC cells was knocked out (KO) using CRISPR/Cas9 technology. Four orthotopic mouse mammary xenograft tumor models coupled with cell culture studies were performed to determine the effect of ITGA9 depletion on TNBC tumor growth and metastasis and the underlying mechanism. Bioinformatics analysis showed that ITGA9 level is significantly higher in TNBC than other breast cancer subtypes, and higher ITGA9 level is associated with significantly worse distant metastasis-free survival and recurrence-free survival in TNBC patients. Experimentally, ITGA9 KO significantly reduced TNBC cell cancer stem cell (CSC)-like property, tumor angiogenesis, tumor growth and metastasis by promoting ß-catenin degradation. Further mechanistic studies revealed that ITGA9 KO causes integrin-linked kinase (ILK) relocation from the membrane region to the cytoplasm, where it interacts with protein kinase A (PKA) and inhibits PKA activity leading to increased activity of glycogen synthase kinase 3 (GSK3) and subsequent ß-catenin degradation. Overexpressing ß-catenin in ITGA9 KO cells reversed the inhibitory effect of ITGA9 KO on tumor growth and metastasis. Furthermore, ITGA9 downregulation in TNBC tumors by nanoparticle-mediated delivery of ITGA9 siRNA drastically decreased tumor angiogenesis, tumor growth and metastasis. These findings indicate that ITGA9 depletion suppresses TNBC tumor growth and metastasis by promoting ß-catenin degradation through the ILK/PKA/GSK3 pathway.

RNA-binding protein trinucleotide repeat-containing 6A regulates the formation of circular RNA circ0006916, with important functions in lung cancer cells.

Circular RNAs (circRNAs) are widespread and diverse endogenous RNAs distinct from traditional linear RNAs, which may regulate gene expression in eukaryotes. However, the function of human circRNAs, including their potential role in lung cancer, remains largely unknown. We screened the circRNA circ0006916, which was evidently down-regulated in 16HBE-T cells (anti-benzopyrene-trans-7, 8-dihydrodiol-9, 10-epoxide-transformed human bronchial epithelial cells), and in A549 and H460 cell lines. Silencing of circ0006916, but not its parental gene homer scaffolding protein 1 (HOMER1), promoted cell proliferation via speeding up the cell cycle process rather than by inhibiting apoptosis; conversely, overexpression of circ0006916 had the opposite effect. Luciferase-screening assay indicated that circ0006916 bound to miR-522-3p and inhibited pleckstrin homology domain and leucine rich repeat protein phosphatase 1 (PHLPP1) activity. We also explored the effect of the RNA-binding protein trinucleotide repeat-containing 6A (TNRC6A) on circ0006916 production. Circ0006916 expression was decreased after silencing TNRC6A. TNRC6A bound to the intron regions around the circRNA-forming exons of circ0006916, as shown by RNA immunoprecipitation assay combined with sequencing analysis. The association of circ0006916 with TNRC6A was further verified by RNA pull-down assays. We then constructed a carrier and confirmed that TNRC6A binding to the flanked intron region of circ0006916 was necessary for generation of circ0006916. These results demonstrate that TNRC6A regulates the biogenesis of the circRNA circ0006916, which has a regulatory role in cell growth.

Upregulation of histone-lysine methyltransferases plays a causal role in hexavalent chromium-induced cancer stem cell-like property and cell transformation.

While hexavalent chromium [Cr(VI)] is generally considered as a genotoxic environmental carcinogen, studies showed that Cr(VI) exposure also causes epigenetic changes. However, whether Cr(VI)-caused epigenetic dysregulations plays an important role in Cr(VI) carcinogenicity remain largely unknown. The aim of this study was to determine if chronic low dose Cr(VI) exposure causes epigenetic changes, the underlying mechanism and whether chronic low dose Cr(VI) exposure-caused epigenetic dysregulation contributes causally to Cr(VI)-induced cancer stem cell (CSC)-like property and cell transformation. Two immortalized human bronchial epithelial cell lines (BEAS-2B and 16HBE) were exposed to 0.25 µM of K2Cr2O7 for 20 and 40 weeks to induce cell transformation, respectively. Cr(VI)-induced epigenetic changes were examined in Cr(VI)-transformed cells and Cr(VI) exposure-caused human lung cancer tissues. Pharmacological inhibitors and gene knockdown experiments were used to determine the role of epigenetic dysregulation in Cr(VI) carcinogenicity. We found that chronic Cr(VI) exposure causes epigenetic dysregulation as evidenced by the increased levels of histone H3 repressive methylation marks (H3K9me2 and H3K27me3) and the related histone-lysing methyltransferases (HMTases). Pharmacological inhibition or knockdown of HMTases reduces H3 repressive methylation marks and malignant phenotypes of Cr(VI)-transformed cells. Moreover, knockdown of HMTases in parental cells significantly reduces chronic Cr(VI) exposure-induced CSC-like property and cell transformation. Further mechanistic study revealed that knockdown of HMTases decreases Cr(VI) exposure-caused DNA damage. Our findings indicate that chronic Cr(VI) exposure increases H3 repressive methylation marks by increasing the related HMTases expression; and that increased expression of HMTases plays a causal role in Cr(VI)-induced CSC-like property and cell transformation.

Application of the Mahalanobis distance on evaluating the overall performance of moving-grate incineration of municipal solid waste.

In this study, there were 54 municipal solid waste (MSW) moving-grate incineration power plants investigated in China. The flue gas emission data of CO, NOx, SO2, HCl, and particles were collected as monthly means directly from the plants for 12 consecutive months from 2011 to 2012, as well as the annual cumulative consumption data of activated carbon, CaO/Ca(OH)2, and #0 diesel. Eventually, 37 out of the 54 plants were evaluated on the overall performance using the Mahalanobis distance. As a result, there were 31 total outliers (potential errors or risks in the operation) detected from the flue gas emission data in 9 out of 37 plants. The results revealed that the Mahalanobis distance was an effective method to evaluate the overall performance of MSW moving-gate incineration from the massive normal-looking flue gas emission data. It was also illustrated that reducing the frequency of the load changes was more important than reducing the magnitude of the load changes, especially in the range between - 10 and 10% of the load changes. Furthermore, the average consumption of activated carbon, CaO/Ca(OH)2, and #0 diesel in the MSW moving-grate incineration power plants was 0.32 ± 0.13 kg, 7.75 ± 3.06 kg, and 0.15 ± 0.12 kg per ton of MSW, respectively.

A novel regulatory network among LncRpa, CircRar1, MiR-671 and apoptotic genes promotes lead-induced neuronal cell apoptosis.

Lead is a metal that has toxic effects on the developing nervous system. However, the mechanisms underlying lead-induced neurotoxicity are not well understood. Non-coding RNAs (ncRNAs) play an important role in epigenetic regulation, but few studies have examined the function of ncRNAs in lead-induced neurotoxicity. We addressed this in the present study by evaluating the functions of a long non-coding RNA (named lncRpa) and a circular RNA (named circRar1) in a mouse model of lead-induced neurotoxicity. High-throughput RNA sequencing showed that both lncRpa and circRar1 promoted neuronal apoptosis. We also found that lncRpa and circRar1 induced the upregulation of apoptosis-associated factors caspase8 and p38 at the mRNA and protein levels via modulation of their common target microRNA miR-671. This is the first report of a regulatory interaction among a lncRNA, circRNA, and miRNA mediating neuronal apoptosis in response to lead toxicity.