Crosstalk between lncRNAs and Wnt/ß-catenin signaling pathways in lung cancers: From cancer progression to therapeutic response.

Lung cancer (LC) is considered to have the highest mortality rate around the world. Because there are no early diagnostic signs or efficient clinical alternatives, distal metastasis and increasing numbers of recurrences are a challenge in the clinical management of LC. Long non-coding RNAs (lncRNAs) have recently been recognized as a critical regulator involved in the progression and treatment response to LC. The Wnt/ß-catenin pathway has been shown to influence LC occurrence and progress. Therefore, discovering connections between Wnt signaling pathway and lncRNAs may offer new therapeutic targets for improving LC treatment and management. In this review, the purpose of this article is to present possible therapeutic approaches by reviewing particular relationships, key processes, and molecules associated to the beginning and development of LC.

Altered Resting-State Brain Activity and Functional Connectivity in Post-Stroke Apathy: An fMRI Study.

Apathy is a common neuropsychiatric disease after stroke and is linked to a lower quality of life while undergoing rehabilitation. However, it is still unknown what are the underlying neural mechanisms of apathy. This research aimed to explore differences in the cerebral activity and functional connectivity (FC) of subjects with post-stroke apathy and those without it. A total of 59 individuals with acute ischemic stroke and 29 healthy subjects with similar age, sex, and education were recruited. The Apathy Evaluation Scale (AES) was used to evaluate apathy at 3 months after stroke. Patients were split into two groups-PSA (n = 21) and nPSA (n = 38)-based on their diagnosis. The fractional amplitude of low-frequency fluctuation (fALFF) was used to measure cerebral activity, as well as region-of-interest to region-of-interest analysis to examine functional connectivity among apathy-related regions. Pearson correlation analysis between fALFF values and apathy severity was performed in this research. The values of fALFF in the left middle temporal regions, right anterior and middle cingulate regions, middle frontal region, and cuneus region differed significantly among groups. Pearson correlation analysis showed that the fALFF values in the left middle temporal region (p < 0.001, r = 0.66) and right cuneus (p < 0.001, r = 0.48) were positively correlated with AES scores in stroke patients, while fALFF values in the right anterior cingulate (p < 0.001, r = -0.61), right middle frontal gyrus (p < 0.001, r = -0.49), and middle cingulate gyrus (p = 0.04, r = -0.27) were negatively correlated with AES scores in stroke patients. These regions formed an apathy-related subnetwork, and functional connectivity analysis unveiled that altered connectivity was linked to PSA (p < 0.05). This research found that abnormalities in brain activity and FC in the left middle temporal region, right middle frontal region, right cuneate region, and right anterior and middle cingulate regions in stroke patients were associated with PSA, revealing a possible neural mechanism and providing new clues for the diagnosis and treatment of PSA.

Carbonate Minerals and Dissimilatory Iron-Reducing Organisms Trigger Synergistic Abiotic and Biotic Chain Reactions under Elevated CO2 Concentration.

Increasing CO2 emission has resulted in pressing climate and environmental issues. While abiotic and biotic processes mediating the fate of CO2 have been studied separately, their interactions and combined effects have been poorly understood. To explore this knowledge gap, an iron-reducing organism, Orenia metallireducens, was cultured under 18 conditions that systematically varied in headspace CO2 concentrations, ferric oxide loading, and dolomite (CaMg(CO3)2) availability. The results showed that abiotic and biotic processes interactively mediate CO2 acidification and sequestration through "chain reactions", with pH being the dominant variable. Specifically, dolomite alleviated CO2 stress on microbial activity, possibly via pH control that transforms the inhibitory CO2 to the more benign bicarbonate species. The microbial iron reduction further impacted pH via the competition between proton (H+) consumption during iron reduction and H+ generation from oxidization of the organic substrate. Under Fe(III)-rich conditions, microbial iron reduction increased pH, driving dissolved CO2 to form bicarbonate. Spectroscopic and microscopic analyses showed enhanced formation of siderite (FeCO3) under elevated CO2, supporting its incorporation into solids. The results of these CO2-microbe-mineral experiments provide insights into the synergistic abiotic and biotic processes that alleviate CO2 acidification and favor its sequestration, which can be instructive for practical applications (e.g., acidification remediation, CO2 sequestration, and modeling of carbon flux).

Circ-MKLN1/miR-377-3p/CTGF Axis Regulates the TGF-ß2-induced Posterior Capsular Opacification in SRA01/04 Cells.

OBJECTIVE: Posterior capsular opacification (PCO) is a common postoperative ocular complication after cataract surgery. Little research focused on the regulation of circular RNAs (circRNAs) in PCO. This study was designed to investigate the function of circRNA-muskelin (circ-MKLN1) in PCO. METHODS: SRA01/04 cells were treated with transforming growth factor (TGF)-ß2. Cell viability was analyzed by Cell Counting Kit-8 (CCK-8) assay. Transwell assay was used for cell migration and invasion detection. Cell migration was also measured by wound healing assay. Epithelial-mesenchymal transition (EMT)-related proteins and connective tissue growth factor (CTGF) were quantified using western blot. RESULTS: Cell viability, migration, invasion and EMT process in SRA01/04 cells were facilitated by TGF-ß2. Circ-MKLN1 expression was enhanced in 17 PCO lens samples relative to 19 normal lens samples and TGF-ß2-treated SRA01/04 cells contrasted to control cells. Downregulation of circ-MKLN1 inhibited the effects of TGF-ß2 on SRA01/04 cells. Circ-MKLN1 targeted miR-377-3p and the regulation of si-circ-MKLN1 for the TGF-ß2-induced influences was related to the upregulation of miR-377-3p. CTGF was the target gene for miR-377-3p. CTGF knockdown also abolished the TGF-ß2-mediated cell growth, migration and invasion of SRA01/04 cells. The function of miR-377-3p was achieved by reducing the CTGF level. TGF-ß2-induced CTGF expression promotion was alleviated by si-circ-MKLN1 through upregulating the expression of miR-377-3p. CONCLUSION: These results showed that circ-MKLN1 contributed to the progression of PCO in vitro by increasing the CTGF expression via sponging miR-377-3p. Circ-MKLN1 might be important for improving the molecular target therapy in PCO.

EphA2 inhibits SRA01/04 cells apoptosis by suppressing autophagy via activating PI3K/Akt/mTOR pathway.

This study attempted to determine the effect of EphA2 on H2O2-treated lens epithelial cells (SRA01/04) and the underlying mechanisms. MTT assay and flow cytometry were performed to assess cell viability and cell apoptosis. Western blot was carried out to examine the levels of proteins associated with apoptosis and autophagy. Our results revealed that EphA2 significantly elevated the reduced cell viability, and inhibited the increased cell apoptosis in H2O2-treated SRA01/04 cells, along with the significant up-regulated Bcl-2 and down-regulated Cleaved-caspase-3 and Bax protein levels, but which were all abolished by Rapa (autophagy activator). We also found that EphA2 significantly suppressed cell autophagy in H2O2-treated SRA01/04 cells. Additionally, EphA2 significantly up-regulated the protein levels of p-Akt and p-mTOR in H2O2-treated SRA01/04 cells, and the inhibition of Akt by MK-2206 and inhibition of mTOR by Rapa both obviously reversed EphA2-mediated the inhibition of autophagy in H2O2-treated SRA01/04 cells. In summary, these data demonstrated that EphA2 inhibited the apoptosis of SRA01/04 cells by inhibiting autophagy via activating PI3K/Akt/mTOR pathway.

Lymph Node Metastatic Patterns and Survival Predictors Based on Tumor Size in Pancreatic Ductal Adenocarcinoma.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. Larger tumor size is widely acknowledged to be associated with increased lymph node (LN) metastatic potential. However, the quantitative relationships between tumor size and LN metastasis or survival remain unclear. This study aims to quantify the objective relationship between tumor size and the prevalence of LN metastases across a spectrum primary tumor size. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify 9958 patients with resected PDAC without distant metastasis. The prevalence of LN metastases, LN ratio (LNR), and N2/N1 ratio were assessed amongst different tumor sizes, and the relationships were displayed by matched curves. RESULTS: In the enrolled cohort, age, tumor site, grade, American Joint Committee on Cancer (AJCC) 8th node staging, tumor size, chemotherapy, and radiotherapy were identified as significant independent predictors for overall survival (OS) and cancer-specific survival (CSS). For tumors within 1-40 mm in size, the prevalence of node-positive disease is closely modelled using a logarithmic formula [0.249 × ln (size) + 0.452] × 100%. The prevalence plateaued between 70% and 80% beyond 40 mm. The mean LNR increased in a stepwise manner as tumor size increased from 1-5 mm (LNR = 0.024) to 41-45 mm (LNR = 0.177); then, beyond 45 mm, it plateaued near 0.170. N2/N1 ratio gradually increased along with tumor size from 1-5 mm (N2/N1 = 0.286) to 41-45 mm (N2/N1 = 1.016), and when tumor size reached to 41-45 mm or more, the ratio stabilized around 1.000. In addition, significant survival prediction by AJCC N staging was observed when tumors ranging between 16 and 45 mm in size. CONCLUSION: Regional LN involvement demonstrated a logarithmic growth with increasing tumor sizes in patients with resected PDAC . The probability of metastasis in each regional LN for resected PDAC with tumors greater than 40 mm in size was near 17.0% and their overall prevalence of LN metastasis was 70-80%. Among which, 50% of patients had an N2 stage. Such prediction may be a potential and promising tool for guiding lymphadenectomy in PDAC surgery.

LncRNA KCNQ1OT1 knockdown inhibits viability, migration and epithelial-mesenchymal transition in human lens epithelial cells via miR-26a-5p/ITGAV/TGF-beta/Smad3 axis.

BACKGROUND: Long noncoding RNA potassium voltage-gated channel subfamily Q member 1 opposite strand/antisense transcript 1 (KCNQ1OT1) takes part in diabetic cataract progression. This research aims to analyze the function and mechanism of KCNQ1OT1 on viability, migration and epithelial-mesenchymal transition (EMT) in lens epithelial cells. METHODS: 20 diabetic cataract posterior lens capsule tissues and normal samples were collected. Lens epithelial cells (SRA01/04) were stimulated via high glucose (HG). The levels of KCNQ1OT1, miR-26a-5p, integrin αV (ITGAV), TGF-ß, Smad3 and phosphorylated (p)-Smad3 were measured via quantitative real-time polymerase chain reaction or Western blot. Cell viability, migration and EMT were analyzed via MTT, wound healing, transwell and Western blot assays. The target relationship between miR-26a-5p and KCNQ1OT1 or ITGAV was determined via luciferase reporter assay. RESULTS: KCNQ1OT1 was up-regulated and miR-26a-5p level was reduced in diabetic cataract tissues and HG-treated SRA01/04 cells. Silence of KCNQ1OT1 or miR-26a-5p up-regulation repressed cell viability, migration and EMT in SRA01/04 cells stimulated via HG. KCNQ1OT1 could target miR-26a-5p and controlled cell viability, migration and EMT via regulating miR-26a-5p. ITGAV was targeted via miR-26a-5p and positively regulated via KCNQ1OT1. ITGAV overexpression promoted cell viability, migration and EMT in HG-treated SRA01/04 cells, which were mitigated by KCNQ1OT1 silence. KCNQ1OT1 knockdown mitigated HG-induced the activation of TGF-ß/Smad3 signaling by regulating miR-26a-5p. CONCLUSION: KCNQ1OT1 knockdown represses cell viability, migration and EMT through miR-26a-5p/ITGAV/TGF-ß/Smad3 axis in SRA01/04 cells under HG condition, providing a new target for the treatment of diabetic cataract.

Degradation of 2, 2', 4, 4'-Tetrabrominated diphenyl ether (BDE-47) via the Fenton reaction driven by the dissimilatory metal-reducing bacterium Shewanella oneidensis MR-1.

A microbially facilitated approach was developed to degrade 2, 2', 4, 4'-tetrabrominated diphenyl ether (BDE-47). This approach consisted of biological production of Fe(II) and H2O2 by the dissimilatory metal-reducing bacterium Shewanella oneidensis MR-1 during the repetitive anoxic/oxic cycles and abiotic production of hydroxyl radical (HO●) with the biologically produced Fe(II) and H2O2 via Fenton reaction. Under the condition tested, BDE-47 did not inhibit the growth of S. oneidensis MR-1. Water soluble Fe(III)-citrate and the solid minerals ferrihydrite [Fe(III)2O3•0.5H2O] and goethite [Fe(III)OOH] were tested in this study. Under anoxic condition, the amounts of Fe(II) produced by S. oneidensis MR-1 varied among the Fe(III)s tested, which decreased in the order of Fe(III)-citrate > ferrihydrite > goethite. Under subsequent oxic condition, H2O2 was produced via O2 reduction by S. oneidensis MR-1. The amounts of H2O2 detected also varied, which decreased in the order of the reactions with Fe(III)-citrate > goethite > ferrihydrite. S. oneidensis MR-1 maintained its ability to produce Fe(II) and H2O2 for up to seven anoxic/oxic cycles. At each end of anoxic/oxic cycle, HO● was detected. The amount of HO● produced decreased in the order of the reactions with ferrihydrite > goethite > Fe(III)-citrate, which was opposite to that of H2O2 detected. Compared to the controls without HO●, the amounts of BDE-47 in the reactions with HO● decreased. The more HO● in the reaction, the less amount of BDE-47 detected. Furthermore, no BDE-47 degradation was observed when HO● was scavenged or ferrihydrite was either omitted or replaced by nitrate. Finally, identification of degradation products, such as hydroxylated BDE-47 and trisBDE, dibromophenol and monobromophenol, suggested that OH-addition and Br-substitution by HO● were the main mechanisms for degrading BDE-47. Collectively, all these results demonstrated for the first time that the Fenton reaction driven by S. oneidensis MR-1 degraded BDE-47 effectively.

Controls on Iron Reduction and Biomineralization over Broad Environmental Conditions as Suggested by the Firmicutes Orenia metallireducens Strain Z6.

Microbial iron reduction is a ubiquitous biogeochemical process driven by diverse microorganisms in a variety of environments. However, it is often difficult to separate the biological from the geochemical controls on bioreduction of Fe(III) oxides. Here, we investigated the primary driving factor(s) that mediate secondary iron mineral formation over a broad range of environmental conditions using a single dissimilatory iron reducer, Orenia metallireducens strain Z6. A total of 17 distinct geochemical conditions were tested with differing pH (6.5-8.5), temperature (22-50 °C), salinity (2-20% NaCl), anions (phosphate and sulfate), electron shuttle (anthraquinone-2,6-disulfonate), and Fe(III) oxide mineralogy (ferrihydrite, lepidocrocite, goethite, hematite, and magnetite). The observed rates and extent of iron reduction differed significantly with kint between 0.186 and 1.702 mmol L-1 day-1 and Fe(II) production ranging from 6.3% to 83.7% of the initial Fe(III). Using X-ray absorption and scattering techniques (EXAFS and XRD), we identified and assessed the relationship between secondary minerals and the specific environmental conditions. It was inferred that the observed bifurcation of the mineralization pathways may be mediated by differing extents of Fe(II) sorption on the remaining Fe(III) minerals. These results expand our understanding of the controls on biomineralization during microbial iron reduction and aid the development of practical applications.

Critical role of OX40 in the expansion and survival of CD4 T-cell-derived double-negative T cells.

CD4+ T-cell-converted CD4-CD8- double negative (cDNT) have strong suppressive activity in the maintenance of immune tolerance, whereas IL-2 promotes cDNT proliferation and enhances cDNT resistance to apoptosis. However, the intrinsic mechanisms that regulate the survival of cDNT are still unknown. Here we demonstrate that the OX40 molecule was highly expressed on cDNT. The expression of OX40 was necessary to promote proliferation and inhibit apoptosis of cDNT in vivo and in vitro. OX40 promoted the survival of cDNT by regulating the expression of Bcl-2, Bcl-xL, Survivin, and BCL2L11. Canonical NF-κB cell signaling played an important role in the transmission of essential division and survival signals through OX40 in cDNT. IL-2 promoted the survival of cDNT in part via elevating the expression of the OX40 molecule. IL-2 promoted OX40 expression via downregulating the PPARα expression. In conclusion, we elucidated that OX40 is a key molecule that regulates cDNT proliferation and survival. IL-2 promoted OX40 expression by downregulating the PPARα binding to the OX40 promoter, leading to the elevated expression of Bcl-2, Bcl-xL, and Survivin in cDNT, which finally resulted in the promoted proliferation and decreased apoptosis of cDNT.

A Combination of Stable Isotope Probing, Illumina Sequencing, and Co-occurrence Network to Investigate Thermophilic Acetate- and Lactate-Utilizing Bacteria.

Anaerobic digestion is a complicated microbiological process that involves a wide diversity of microorganisms. Acetate is one of the most important intermediates, and interactions between acetate-oxidizing bacteria and archaea could play an important role in the formation of methane in anoxic environments. Anaerobic digestion at thermophilic temperatures is known to increase methane production, but the effects on the microbial community are largely unknown. In the current study, stable isotope probing was used to characterize acetate- and lactate-oxidizing bacteria in thermophilic anaerobic digestion. In microcosms fed 13C-acetate, bacteria related to members of Clostridium, Hydrogenophaga, Fervidobacterium, Spirochaeta, Limnohabitans, and Rhodococcus demonstrated elevated abundances of 13C-DNA fractions, suggesting their activities in acetate oxidation. In the treatments fed 13C-lactate, Anaeromyxobacter, Desulfobulbus, Syntrophus, Cystobacterineae, and Azospira were found to be the potential thermophilic lactate utilizers. PICRUSt predicted that enzymes related to nitrate and nitrite reduction would be enriched in 13C-DNA fractions, suggesting that the acetate and lactate oxidation may be coupled with nitrate and/or nitrite reduction. Co-occurrence network analysis indicated bacterial taxa not enriched in 13C-DNA fractions that may also play a critical role in thermophilic anaerobic digestion.

Hematite Reduction Buffers Acid Generation and Enhances Nutrient Uptake by a Fermentative Iron Reducing Bacterium, Orenia metallireducens Strain Z6.

Fermentative iron-reducing organisms have been identified in a variety of environments. Instead of coupling iron reduction to respiration, they have been consistently observed to use ferric iron minerals as an electron sink for fermentation. In the present study, a fermentative iron reducer, Orenia metallireducens strain Z6, was shown to use iron reduction to enhance fermentation not only by consuming electron equivalents, but also by generating alkalinity that effectively buffers the pH. Fermentation of glucose by this organism in the presence of a ferric oxide mineral, hematite (Fe2O3), resulted in enhanced glucose decomposition compared with fermentation in the absence of an iron source. Parallel evidence (i.e., genomic reconstruction, metabolomics, thermodynamic analyses, and calculation of electron transfer) suggested hematite reduction as a proton-consuming reaction effectively consumed acid produced by fermentation. The buffering effect of hematite was further supported by a greater extent of glucose utilization by strain Z6 in media with increasing buffer capacity. Such maintenance of a stable pH through hematite reduction for enhanced glucose fermentation complements the thermodynamic interpretation of interactions between microbial iron reduction and other biogeochemical processes. This newly discovered feature of iron reducer metabolism also has significant implications for groundwater management and contaminant remediation by providing microbially mediated buffering systems for the associated microbial and/or chemical reactions.

Tepidibacillus decaturensis sp. nov., a microaerophilic, moderately thermophilic iron-reducing bacterium isolated from 1.7 km depth groundwater.

A Gram-stain-negative, microaerophilic rod-shaped organism designated as strain Z9T was isolated from groundwater of 1.7 km depth from the Mt. Simon Sandstone of the Illinois Basin, Illinois, USA. Cells of strain Z9T were rod shaped with dimensions of 0.3×(1-10) µm and stained Gram-negative. Strain Z9T grew within the temperature range 20-60 °C (optimum at 30-40 °C), between pH 5 and 8 (optimum 5.2-5.8) and under salt concentrations of 1-5 % (w/v) NaCl (optimum 2.5 % NaCl). In addition to growth by fermentation and nitrate reduction, this strain was able to reduce Fe(III), Mn(IV), Co(III) and Cr(VI) when H2 or organic carbon was available as the electron donor, but did not actively reduce oxidized sulfur compounds (e.g. sulfate, thiosulfate or S0). The G+C content of the DNA from strain Z9T was 36.1 mol%. Phylogenetic analysis of the 16S rRNA gene from strain Z9T showed that it belongs to the class Bacilli and shares 97 % sequence similarity with the only currently characterized member of the genus Tepidibacillus, T.fermentans. Based on the physiological distinctness and phylogenetic information, strain Z9T represents a novel species within the genus Tepidibacillus, for which the name Tepidibacillus decaturensis sp. nov. is proposed. The type strain is Z9T (=ATCC BAA-2644T=DSM 103037T).

Microbial communities inhabiting oil-contaminated soils from two major oilfields in Northern China: Implications for active petroleum-degrading capacity.

Although oilfields harbor a wide diversity of microorganisms with various metabolic potentials, our current knowledge about oil-degrading bacteria is limited because the vast majority of oil-degrading bacteria remain uncultured. In the present study, microbial communities in nine oil-contaminated soils collected from Daqing and Changqing, two of the largest oil fields in China, were characterized through highthroughput sequencing of 16S rRNA genes. Bacteria related to the phyla Proteobacteria and Actinobacteria were dominant in four and three samples, respectively. At the genus level, Alkanindiges, Arthrobacter, Pseudomonas, Mycobacterium, and Rhodococcus were frequently detected in nine soil samples. Many of the dominant genera were phylogenetically related to the known oil-degrading species. The correlation between physiochemical parameters within the microbial communities was also investigated. Canonical correspondence analysis revealed that soil moisture, nitrate, TOC, and pH had an important impact in shaping the microbial communities of the hydrocarbon-contaminated soil. This study provided an in-depth analysis of microbial communities in oilcontaminated soil and useful information for future bioremediation of oil contamination.