Groundwater solutes influence the adsorption of short-chain perfluoroalkyl acids (PFAA) to colloidal activated carbon and impact performance for in situ groundwater remediation.

Subsurface injection of colloidal activated carbon (CAC) is an in situ remediation strategy for perfluoroalkyl acids (PFAA), but the influence of groundwater solutes on longevity is uncertain, particularly for short-chain PFAA. We quantify the impact of inorganic anions, dissolved organic matter (DOM), and stabilizing polymer on PFAA adsorption to a commercial CAC. Surface characterization supported PFAA chain-length dependent adsorption results and mechanisms are provided. Inorganic anions decreased adsorption for short-chain PFAA (<7 perfluorinated carbons) due to competitive effects, while long-chain PFAA (≥ 7 perfluorinated carbons) were less impacted. DOM decreased adsorption of all PFAA in a chain-length dependent manner. High DOM concentrations (10 mg/L, ∼5 mg OC/L) decreased PFOA adsorption by a factor of 2, PFPeA by one order of magnitude, and completely hindered PFBA adsorption. High MW DOM has less impact on short-chain PFAA than low MW DOM, possibly due to differences in the ability to access CAC micropores. Low DOM concentrations (1 mg/L, ∼0.5 mg OC/L) did not impact adsorption. CMC (90 kDa average MW) had negligible impact on PFAA adsorption likely due to minimal CAC surface coverage. Longevity modeling demonstrated that groundwater solutes limit the capacity for PFAA in a CAC barrier, particularly for short-chain PFAA.

Polymer Coatings Affect Transport and Remobilization of Colloidal Activated Carbon in Saturated Sand Columns: Implications for In Situ Groundwater Remediation.

Colloidal activated carbon (CAC) is an emerging technology for the in situ remediation of groundwater impacted by per- and polyfluoroalkyl substances (PFAS). In assessing the long-term effectiveness of a CAC barrier, it is crucial to evaluate the potential of emplaced CAC particles to be remobilized and migrate away from the sorptive barrier. We examine the effect of two polymer stabilizers, carboxymethyl cellulose (CMC) and polydiallyldimethylammonium chloride (PolyDM), on CAC deposition and remobilization in saturated sand columns. CMC-modified CAC showed high mobility in a wide ionic strength (IS) range from 0.1 to 100 mM, which is favorable for CAC delivery at a sufficient scale. Interestingly, the mobility of PolyDM-modified CAC was high at low IS (0.1 mM) but greatly reduced at high IS (100 mM). Notably, significant remobilization (release) of deposited CMC-CAC particles occurred upon the introduction of solution with low IS following deposition at high IS. In contrast, PolyDM-CAC did not undergo any remobilization following deposition due to its favorable interactions with the quartz sand. We further elucidated the CAC deposition and remobilization behaviors by analyzing colloid-collector interactions through the application of Derjaguin-Landau-Verwey-Overbeek theory, and the inclusion of a discrete representation of charge heterogeneity on the quartz sand surface. The classical colloid filtration theory was also employed to estimate the travel distance of CAC in saturated columns. Our results underscore the roles of polymer coatings and solution chemistry in CAC transport, providing valuable guidelines for the design of in situ CAC remediation with maximized delivery efficiency and barrier longevity.

Impacts of free nitrous acid on stabilizing food waste and sewage sludge for anaerobic digestion.

This work investigated the effectiveness of free nitrous acid (FNA) in enhancing organic waste solubilization to improve biogas production in anaerobic digestion (AD). The results indicated that FNA pretreatment can enhance soluble organic content and control H2S odor in tested organic wastes, including food waste, sewage sludge, and their combination. However, a significant decrease (>50 %) in FNA concentration was found in the reactors, possibly due to denitrifier-driven NO2- consumption. Biochemical methane potential (BMP) tests showed a 25 ± 8 % enhancement in CH4 production in the reactors fed with mixed substrate pretreated with 2.9 mg FNA-N/L. However, the presence of NO2- (325.6-2368.0 mg N/L) in some BMP reactors, due to carryover from FNA pretreatment, adversely affected CH4 production (>55 %) and prolonged lag time (>4.2 times). These findings are valuable for researchers and practitioners in waste management, offering insights for implementing FNA pretreatment to enhance the biodegradability of organic wastes in AD.

A novel disulfidptosis-related prognostic gene signature and experimental validation identify ACTN4 as a novel therapeutic target in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is a prevalent form of malignancy globally. Disulfidptosis is novel programmed cell death pathway based on disulfide proteins, may have a positive impact on the development of LUAD treatment strategies. OBJECTIVE: To investigate the impact of disulfidptosis-related genes (DRGs) on the prognosis of LUAD, developed a risk model to facilitate the diagnosis and prognostication of patients. We also explored ACTN4 (DRGs) as a new therapeutic biomarker for LUAD. METHODS: We investigated the expression patterns of DRGs in both LUAD and noncancerous tissues. To assess the prognostic value of the DRGs, we developed risk models through univariate Cox analysis and lasso regression. The expression and function of ACTN4 was evaluated by qRT-PCR, immunohistochemistry and in vitro experiments. The TIMER examined the association between ACTN4 expression and immune infiltration in LUAD. RESULTS: Ten differentially expressed DRGs were identified. And ACTN4 was identified as potential risk factors through univariate Cox regression analysis (P< 0.05). ACTN4 expression and riskscore were used to construct a risk model to predict overall survival in LUAD, and high-risk demonstrated a significantly higher mortality rate compared to the low-risk cohort. qRT-PCR and immunohistochemistry assays indicated ACTN4 was upregulated in LUAD, and the upregulation was associated with clinicopathologic features. In vitro experiments showed the knockdown of ACTN4 expression inhibited the proliferation in LUAD cells. The TIMER analysis demonstrated a correlation between the expression of ACTN4 and the infiltration of diverse immune cells. Elevated ACTN4 expression was associated with a reduction in memory B cell count. Additionally, the ACTN4 expression was associated with m6A modification genes. CONCLUSIONS: Our study introduced a prognostic model based on DRGs, which could forecast the prognosis of patients with LUAD. The biomarker ACTN4 exhibits promise for the diagnosis and management of LUAD, given its correlation with tumor immune infiltration and m6A modification.

Assessing the performance of polyphosphate accumulating organisms in a full-scale side-stream enhanced biological phosphorous removal.

Phosphorous (P) removal in wastewater treatment is essential to prevent eutrophication in water bodies. Side-stream enhanced biological phosphorous removal (S2EBPR) is utilized to improve biological P removal by recirculating internal streams within a side-stream reactor to generate biodegradable carbon (C) for polyphosphate accumulating organisms (PAOs). In this study, a full-scale S2EBPR system in a water resource recovery facility (WRRF) was evaluated for 5 months. Batch experiments revealed a strong positive correlation (r = 0.91) between temperature and C consumption rate (3.56-8.18 mg-COD/g-VSS/h) in the system, with temperature ranging from 14°C to 18°C. The anaerobic P-release to COD-uptake ratio decreased from 0.93 to 0.25 mg-P/mg-COD as the temperature increased, suggesting competition between PAOs and other C-consumers, such as heterotrophic microorganisms, to uptake bioavailable C. Microbial community analysis did not show a strong relationship between abundance and activity of PAO in the tested WRRF. An assessment of the economic feasibility was performed to compare the costs and benefits of a full scale WRRF with and without implementation of the S2EBPR technology. The results showed the higher capital costs required for S2EBPR were estimated to be compensated after 5 and 11 years of operation, respectively, compared to chemical precipitation and conventional EBPR. The results from this study can assist in the decision-making process for upgrading a conventional EBPR or chemical P removal process to S2EBPR. PRACTITIONER POINTS: Implementation of S2EBPR presents adaptable configurations, exhibiting advantages over conventional setups in addressing prevalent challenges associated with phosphorous removal. A full-scale S2EBPR WRRF was monitored over 5 months, and activity tests were used to measure the kinetic parameters. The seasonal changes impact the kinetic parameters of PAOs in the S2EBPR process, with elevated temperatures raising the carbon demand. PAOs abundance showed no strong correlation with their activity in the full-scale S2EBPR process in the tested WRRF. Feasibility assessment shows that the benefits from S2EBPR operation can offset upgrading costs from conventional BPR or chemical precipitation.

Impacts of crude glycerol on anaerobic ammonium oxidation (Anammox) process in wastewater treatment.

This work investigated the impact of a waste-derived carbon source, crude glycerol (CG), on Anammox. Batch bioassays were conducted to identify inhibitory component(s) in CG, and the relationship between Anammox activity and the concentration of CG, pure glycerol, and methanol were assessed. The results showed that the half-maximal inhibitory concentration of CG and methanol are 434.5 ± 51.8 and 143.0 ± 19.6 mg chemical oxygen demand (COD) L-1, respectively, while pure glycerol at 0-2283 mg COD L-1 had no significant adverse effect on Anammox. The results suggested methanol is the major inhibitor in CG via a non-competitive inhibition mechanism. COD/total inorganic nitrogen ratio of > 1.3 was observed to cause a significant Anammox inhibition (>20 %), especially at low substrate level. These results are valuable for evaluating the feasibility of using CG for nitrogen removal in water resource recovery facilities, promoting sustainable development.

Multi-omics analyses reveal spatial heterogeneity in primary and metastatic oesophageal squamous cell carcinoma.

BACKGROUND: Biopsies obtained from primary oesophageal squamous cell carcinoma (ESCC) guide diagnosis and treatment. However, spatial intra-tumoral heterogeneity (ITH) influences biopsy-derived information and patient responsiveness to therapy. Here, we aimed to elucidate the spatial ITH of ESCC and matched lymph node metastasis (LNmet ). METHODS: Primary tumour superficial (PTsup ), deep (PTdeep ) and LNmet subregions of patients with locally advanced resectable ESCC were evaluated using whole-exome sequencing (WES), whole-transcriptome sequencing and spatially resolved digital spatial profiling (DSP). To validate the findings, immunohistochemistry was conducted and a single-cell transcriptomic dataset was analysed. RESULTS: WES revealed 15.72%, 5.02% and 32.00% unique mutations in PTsup , PTdeep and LNmet , respectively. Copy number alterations and phylogenetic trees showed spatial ITH among subregions both within and among patients. Driver mutations had a mixed intra-tumoral clonal status among subregions. Transcriptome data showed distinct differentially expressed genes among subregions. LNmet exhibited elevated expression of immunomodulatory genes and enriched immune cells, particularly when compared with PTsup (all P < .05). DSP revealed orthogonal support of bulk transcriptome results, with differences in protein and immune cell abundance between subregions in a spatial context. The integrative analysis of multi-omics data revealed complex heterogeneity in mRNA/protein levels and immune cell abundance within each subregion. CONCLUSIONS: This study comprehensively characterised spatial ITH in ESCC, and the findings highlight the clinical significance of unbiased molecular classification based on multi-omics data and their potential to improve the understanding and management of ESCC. The current practices for tissue sampling are insufficient for guiding precision medicine for ESCC, and routine profiling of PTdeep and/or LNmet should be systematically performed to obtain a more comprehensive understanding of ESCC and better inform treatment decisions.

Clinicopathological features and prognostic nomogram of giant cell carcinoma of the lung: A population-based study.

BACKGROUND: Due to its rarity, the features and prognosis of giant cell carcinoma of the lung (GCCL) are not well defined. The present study aimed to describe the clinicopathological features and prognostic analysis of this rare disease, compare it with lung adenocarcinoma (LAC), further determine the prognostic factors and establish a nomogram. METHODS: Patients diagnosed with GCCL and LAC were identified from the SEER database between 2004 and 2016. The features and survival between GCCL and LAC were compared in the unmatched and matched cohorts after propensity score matching (PSM) analysis. Univariate and multivariate Cox analyses were used to identify the prognostic factors, and a nomogram was constructed. Area under the curve (AUC), C-index, calibration curve and decision curve analysis (DCA) were used to confirm the established nomogram. RESULTS: A total of 295 patient diagnosed with GCCL and 149 082 patients with LAC were identified. Compared with LAC, patients with GCCL tend to be younger, male, black and have pathological Grade III/IV GCCL, more proportion of AJCC-TNM-IV, T3/T4 and distant metastases. The 1-, 2- and 5-year OS rates of the patients with GCCL were 21.7%, 13.4% and 7.9%, respectively. The median OS and CSS were 3 and 4 months, respectively. Patients with GCCL had significantly shorter OS and CSS than those with LAC in the unmatched and matched cohorts after PSM. Multivariate Cox analysis demonstrated that T, N and M stages and use of chemotherapy and surgery were independent of survival. Furthermore, we constructed a prognostic nomogram for OS and CSS by using independent prognostic factors. The C-index of OS-specific nomogram is 0.78 (0.74-0.81), and the C-index of CSS-specific nomogram is 0.77 (0.73-0.80). The calibration curve and ROC analysis showed good predictive capability of these nomograms. DCA showed that the nomogram had greater clinical practical value in predicting the OS and CSS of GCCL than TNM staging. CONCLUSION: GCCL have distinct clinicopathological characteristics and significantly worse clinical outcomes. Prognostic nomograms for overall survival (OS) and CSS were constructed.

Pyroptosis-Related Subtypes Predict the Response of Clear Cell Renal Cell Carcinoma to Targeted Therapy.

BACKGROUND: Pyroptosis plays a crucial role in anti-tumor immunity and in formation of the immune microenvironment. However, whether pyroptosis is involved in the progression of clear cell renal cell carcinoma (ccRCC) is still unclear. Personalized treatment of ccRCC requires detailed molecular classification to inform a specific therapy. METHODS: Molecular subtyping of ccRCC was performed based on consensus clustering of pyroptosis-related genes. The characteristics of these molecular subtypes were explored at the genome, transcriptome and protein levels. Single-cell RNA sequencing and CIBERSORT analysis were used to analyse the immune microenvironment of ccRCC, while Lasso regression was used to develop a prediction model based on hub genes. Expression of the pyroptosis-related gene GSDMB was also investigated at the tissue and cellular levels. RESULTS: Two molecular subtypes were identified based on the clustering of pyroptosis-related genes. Cluster 1 was associated with activation of classical oncogenic pathways, especially the angiogenesis pathway. Cluster 2 was associated with activation of immune-related pathways and high levels of immunosuppressive cells, exhausted CD8+ T cells, and tumor-associated fibroblast infiltration. Clusters 1 and 2 were thus defined as the angiogenic and inflamed subtypes, respectively. The two subtypes were predictive of the response of ccRCC to anti-angiogenic therapy and immunotherapy, with Cluster 1 patients benefiting from anti-angiogenic therapy and Cluster 2 patients showing better response to anti-PD1 inhibitor therapy. Furthermore, a 9-gene expression signature (HJURP, NUF2, KIF15, MELK, TPX2, PLK1, CDCA3, CTLA4, FOXP3) was identified that could predict outcome and response to immune checkpoint blockade therapy in test cohorts. Finally, GSDMB was found to be involved in the development of renal clear cell carcinoma. CONCLUSIONS: These results on pyroptosis-related genes in ccRCC provide a theoretical basis for understanding molecular heterogeneity and for the development of individualized treatment strategies.

PTEN loss promotes Warburg effect and prostate cancer cell growth by inducing FBP1 degradation.

Rationale: Fructose-1,6-bisphosphatase (FBP1) is a tumor suppressor and a key enzyme negatively regulating Warburg effect in cancer. However, regulation of FBP1 protein expression and its exact role in prostate cancer (PCa) is largely unclear. Phosphatase and tensin homolog (PTEN) is one of the most frequently deleted tumor suppressor genes in human PCa. However, the role of PTEN loss in aberrant Warburg effect in cancer remains poorly understood. Methods: Expression of PTEN and FBP1 was analyzed in several PCa cell lines and prostate tumor tissues in mice. Western blot (WB) and RT-PCR approaches were used to examine how PTEN regulates FBP1 expression. Co-immunoprecipitation (co-IP) and in vivo ubiquitination assays were used to define the regulatory mechanisms. A PCa xenograft model was employed to determine the impact of PTEN regulation of FBP1 on PCa growth in vivo. Result: We demonstrated that in a manner dependent of PI3K/AKT signal pathway PTEN regulated FBP1 expression in various PCa cell lines and tumors in mice. We confirmed that this regulation took place at the protein level and was mediated by SKP2 E3 ubiquitin ligase. Mechanistically, we showed that serine 271 phosphorylation of FBP1 by cyclin-dependent kinases (CDKs) was essential for SKP2-mediated degradation of FBP1 protein induced by PTEN loss. Most importantly, we further showed that loss of PTEN expression enhanced Warburg effect and PCa growth in mice in a manner dependent, at least partially on FBP1 protein degradation. Conclusions: Our results reveal a novel tumor-suppressive feature of PTEN in restraining FBP1 degradation and the Warburg effect. These results also suggest that prohibiting FBP1 protein degradation could be a viable therapeutic strategy for PTEN-deficient PCa.

Vitamin D3 deficiency induced intestinal inflammatory response of turbot through nuclear factor-κB/inflammasome pathway, accompanied by the mutually exclusive apoptosis and autophagy.

Vitamin D3 (VD3) participated widely in the nuclear factor-κB (NF-κB)-mediated inflammation, apoptosis, and autophagy through the vitamin D receptor (VDR). However, the molecular mechanisms remain not understood in teleost. The present study investigated the functions of VD3/VDR on intestinal inflammation, autophagy, and apoptosis of turbot in vivo and in vitro. Triple replicates of 30 fish were fed with each of three diets with graded levels of 32.0 (D0), 1012.6 (D1), and 3978.2 (D2) IU/kg VD3. Obvious intestinal enteritis was observed in the D0 group and followed with dysfunction of intestinal mucosal barriers. The intestinal inflammatory response induced by VD3 deficiency was regulated by the NF-κB/inflammasome signalling. The promotion of intestinal apoptosis and suppression of intestinal autophagy were also observed in the D0 group. Similarly, VD3 deficiency in vitro induced more intense inflammation regulated by NF-κB/inflammasome signalling. The mutually exclusive apoptosis and autophagy were also observed in the group without 1,25(OH)2D3 in vitro, accompanied by similar changes in apoptosis and autophagy increased apoptosis. The gene expression of VDRs was significantly increased with the increasing VD3 supplementation both in vivo and in vitro. Moreover, VDR knockdown in turbot resulted in intestinal inflammation, and this process relied on the activation of inflammasome mediated by NF-κB signalling. Simultaneously, intestinal apoptosis was promoted, whereas intestinal autophagy was inhibited. In conclusion, VD3 deficiency could induce intestinal inflammation via activation of the NF-κB/inflammasome pathway, intestinal apoptosis, and autophagy formed a mutually exclusive relation in teleost. And VDR is the critical molecule in those processes.

Transformable ECM Deprivation System Effectively Suppresses Renal Cell Carcinoma by Reversing Anoikis Resistance and Increasing Chemotherapy Sensitivity.

Extracellular matrix (ECM) is crucial in various biological functions during tumor progression, including induction of anoikis resistance and cell adhesion-mediated drug resistance (CAM-DR). Fibronectin (FN) is a vital ECM component with direct regulatory effects on ECM-mediated anoikis resistance and CAM-DR, making it an attractive and innovative therapeutic target for depriving ECM in tumor tissue. Herein, an ECM deprivation system (EDS) is developed based on FN targeting self-assembly peptide for constructing nanofibers in the ECM of renal cell carcinoma (RCC), which contributes to: i) targeting and recognizing FN to form nanofibers for long-term retention in ECM, ii) reversing anoikis resistance via arresting the FN signaling pathway, and iii) serving as a drug-loading platform for sensitizing chemotherapy by ameliorating CAM-DR. The results reveal that EDS significantly reverses anoikis resistance of RCC cells by inhibiting the phosphorylation of FAK, a positive regulator of the FN signaling pathway. Meanwhile, EDS serves as a chemotherapy-sensitizer of cancer, exerting significant synergistic effects with doxorubicin (DOX). In vivo validation experiments show that EDS effectively suppresses metastasis and tumor growth with chemotherapy resistance. Collectively, the innovative EDS notably inhibits the tumor-promoting effect of ECM and may provide a novel approach for suppressing ECM and enhancing chemo-drug sensitivity.

Prognostic Signature for Lung Adenocarcinoma Patients Based on Cell-Cycle-Related Genes.

OBJECTIVE: To screen lung adenocarcinoma (LUAC)-specific cell-cycle-related genes (CCRGs) and develop a prognostic signature for patients with LUAC. METHODS: The GSE68465, GSE42127, and GSE30219 data sets were downloaded from the GEO database. Single-sample gene set enrichment analysis was used to calculate the cell cycle enrichment of each sample in GSE68465 to identify CCRGs in LUAC. The differential CCRGs compared with LUAC data from The Cancer Genome Atlas were determined. The genetic data from GSE68465 were divided into an internal training group and a test group at a ratio of 1:1, and GSE42127 and GSE30219 were defined as external test groups. In addition, we combined LASSO (least absolute shrinkage and selection operator) and Cox regression analysis with the clinical information of the internal training group to construct a CCRG risk scoring model. Samples were divided into high- and low-risk groups according to the resulting risk values, and internal and external test sets were used to prove the validity of the signature. A nomogram evaluation model was used to predict prognosis. The CPTAC and HPA databases were chosen to verify the protein expression of CCRGs. RESULTS: We identified 10 LUAC-specific CCRGs (PKMYT1, ETF1, ECT2, BUB1B, RECQL4, TFRC, COCH, TUBB2B, PITX1, and CDC6) and constructed a model using the internal training group. Based on this model, LUAC patients were divided into high- and low-risk groups for further validation. Time-dependent receiver operating characteristic and Cox regression analyses suggested that the signature could precisely predict the prognosis of LUAC patients. Results obtained with CPTAC, HPA, and IHC supported significant dysregulation of these CCRGs in LUAC tissues. CONCLUSION: This prognostic prediction signature based on CCRGs could help to evaluate the prognosis of LUAC patients. The 10 LUAC-specific CCRGs could be used as prognostic markers of LUAC.

Neoadjuvant treatment of pembrolizumab plus platinum-doublet chemotherapy in stage IIIA squamous cell carcinoma of the lung: a case report.

With the popularity of neoadjuvant therapy as first-line treatment, especially for advanced squamous cell carcinoma (SCC), the focus has become accurate individualized treatment. Specifically, toxic side effects of traditional platinum-doublet chemotherapy are high, so treatment with pembrolizumab plus platinum-doublet chemotherapy is safer and more effective. Pembrolizumab is a humanized monoclonal IgG4 kappa anti-PD1 antibody. It is devoid of any cytotoxic activity among the drug effect. Pembrolizumab has been tested clinically in a series of KEYNOTE studies and 12 categories of malignancies have been tested to determine their clinical effects. A 64-year-old man with IIIA SCC of the lung without any surgical contraindications in the preoperative period successfully underwent radical resection and had a great prognosis after neoadjuvant treatment. Chest computed tomography (CT) showed that the left upper lung lesion, hilar and mediastinal lymph nodes were obviously smaller than before, meanwhile, obstructive pneumonia was significantly absorbed. No sign of metastasis was detected by head-abdominopelvic CT and bone scan. Although radiation pneumonitis was an adverse event after postoperative adjuvant therapy, symptoms were relieved with low-dose glucocorticoids. In conclusion, traditional chemotherapy with single agents alone has been gradually replaced by pembrolizumab plus platinum-doublet chemotherapy as a first-line therapy now.

MRPL42 is activated by YY1 to promote lung adenocarcinoma progression.

Mammalian mitochondrial ribosomal proteins are a group of protein factors encoded by nuclear genes, responsible for the synthesis of proteins in mitochondria. As a member of mitochondrial ribosomal proteins, MRPL42 (mitochondrial ribosomal protein L42) belongs to 28S and 39S subunits. The current literature showed that its role in lung adenocarcinoma (LUAD) was not clear. We found that MRPL42 was highly expressed in early-stage LUAD tissues and cell lines, and remarkably related to the prognosis of patients. Knockdown of MRPL42 could reduce the proliferation and colonization, promote cell cycle arrest in G1/S phase, and weaken the migration and invasion ability of LUAD cells in vitro. Moreover, depletion of MRPL42 also inhibited tumor growth in vivo. Bioinformatics analysis found that YY1 may bind to the promoter region upstream of the MRPL42 gene to promote the transcription of MRPL42, which was verified by the ChIP and Dual luciferase reporter assay. QRT-PCR confirmed that knocking down YY1 could attenuate the expression of MRPL42. In summary, MRPL42 acts as an oncogene in LUAD, and its expression level is regulated by YY1.

The roles and mechanisms of the circular RNA circ_104640 in early-stage lung adenocarcinoma: a potential diagnostic and therapeutic target.

BACKGROUND: In recent years, there have been increasing reports that dysregulated circular RNAs (circRNAs) play a key role in the carcinogenesis of lung adenocarcinoma (LUAC). However, the role of circRNAs in early-stage LUAC is poorly understood. METHODS: The Gene Expression Omnibus (GEO) database and qRT-PCR were used to verify the abnormal expression of circRNAs, miRNAs and genes in early-stage LUAC tissues. shRNA and miRNA inhibitor are designed and synthesized to knock down circ_104640 and microRNA (miR)-145-5p expression. CCK-8 assay, colony formation assay and flow cytometry were used to study the effect of circ_104640 on cell proliferation and apoptosis. Bioinformatics analysis, dual luciferase reporter assays and argonaute 2 (Ago2) RNA immunoprecipitation (RIP) assays were chosen to find out the potential target of circ_104640. RESULTS: Based on the GEO database and tissue sample from our institution, we identified that the circRNA circ_104640, the miR-145-5p, and CCL20 (C-C motif chemokine ligand 20) were abnormally expressed in the tissues of early-stage LUAC. In vitro experiments showed that circ_104640 could exist stably in the cytoplasm, and a short pin RNA that targeted circ_104640 (sh-circ) inhibited cell growth and promoted apoptosis of LUAC cells. Dual luciferase reporter assays and Ago2 (RIP) assays confirmed the Ago2-dependent interaction of circ_104640 and miR-145-5p. In terms of mechanisms, we found that circ_104640 increased the expression of CCL20 by sponging miR-145-5p. CONCLUSIONS: Our research demonstrated that circ_104640 could accelerate the proliferation of LUAC cells, while inhibiting LUAC cell apoptosis. circ_104640 may be a potential novel biomarker and therapeutic target for early-stage LUAC.

Correction to: CD103-positive CSC exosome promotes EMT of clear cell renal cell carcinoma: role of remote MiR-19b-3p.

An amendment to this paper has been published and can be accessed via the original article.

Low levels of AMPK promote epithelial-mesenchymal transition in lung cancer primarily through HDAC4- and HDAC5-mediated metabolic reprogramming.

AMP-activated protein kinase (AMPK) serves as a "supermetabolic regulator" that helps maintain cellular energy homeostasis. However, the role of AMPK in glucose metabolism reprogramming in lung cancer remains unclear. Here, our study shows that low AMPK expression correlates with metastasis and clinicopathologic parameters of non-small-cell lung cancer. Low AMPK significantly enhances the Warburg effect in HBE and A549 cells, which in turn induces the expression of mesenchymal markers and enhances their invasion and migration. At the mechanistic level, low AMPK up-regulates HK2 expression and glycolysis levels through HDAC4 and HDAC5. Collectively, our findings demonstrate that low AMPK-induced metabolism can promote epithelial-mesenchymal transition progression in normal bronchial epithelial cells and lung cancer cells, and increase the risk for tumour metastasis.