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.

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.

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.

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

BACKGROUND: Clear cell renal cell carcinoma (CCRCC) is characterized by a highly metastatic potential. The stromal communication between stem cells and cancer cells critically influences metastatic dissemination of cancer cells. METHODS: The effect of exosomes isolated from cancer stem cells (CSCs) of CCRCC patients on the progress of epithelial-mesenchymal transition (EMT) and lung metastasis of CCRCC cells were examined. RESULTS: CSCs exosomes promoted proliferation of CCRCC cells and accelerated the progress of EMT. Bioactive miR-19b-3p transmitted to cancer cells by CSC exosomes induced EMT via repressing the expression of PTEN. CSCs exosomes derived from CCRCC patients with lung metastasis produced the strongest promoting effect on EMT. Notably, CD103+ CSC exosomes were enriched in tumor cells and in lung as well, highlighting the organotropism conferred by CD103. In addition, CD103+ exosomes were increased in blood samples from CCRCC patients with lung metastasis. CONCLUSIONS: CSC exosomes transported miR-19b-3p into CCRCC cells and initiated EMT promoting metastasis. CD103+ acted to guide CSC exosomes to target cancer cells and organs, conferring the higher metastatic capacity of CCRCC to lungs, suggesting CD103+ exosomes as a potential metastatic diagnostic biomarker. ᅟ.

Sparsity-based continuous wave terahertz lens-free on-chip holography with sub-wavelength resolution.

We demonstrate terahertz (THz) lens-free in-line holography on a chip in order to achieve 40 µm spatial resolution corresponding to ~0.7λ with a numerical aperture of ~0.87. We believe that this is the first time that sub-wavelength resolution in THz holography and the 40 µm resolution were both far better than what was already reported. The setup is based on a self-developed high-power continuous wave THz laser at 5.24 THz (λ = 57.25 µm) and a high-resolution microbolometer detector array (640 × 512 pixels) with a pitch of 17 µm. This on-chip in-line holography, however, suffers from the twin-image artifacts which obfuscate the reconstruction. To address this problem, we propose an iterative optimization framework, where the conventional object constraint and the L1 sparsity constraint can be combined to efficiently reconstruct the complex amplitude distribution of the sample. Note that the proposed framework and the sparsity-based algorithm can be applied to holography in other wavebands without limitation of wavelength. We demonstrate the success of this sparsity-based on-chip holography by imaging biological samples (i.e., a dragonfly wing and a bauhinia leaf).

Mechanisms and Control of NO2- Inhibition of Anaerobic Ammonium Oxidation (Anammox).

Nitrite (NO2-), one of the main substrates in the anaerobic ammonium oxidation (anammox) process, has the potential to inhibit anammox bacteria. The sensitivity of anammox cells with different energy status to NO2- was evaluated, and addition of nitrate (NO3-) inhibition on the basis of narK gene with the putative function of facilitating NO3-/NO2- antiporter. The results showed that the resistance of anammox bacteria to NO2- inhibition follows the order: active-cells > starved-cells > resting-cells > starved-/resting-cells. Anammmox resting cells have increasing tolerance to NO2- in the pH range from 7.0 to 7.5. Dissipating the proton gradient by using carbonyl cyanide m-chlorophenyl hydrazine (CCCP) caused severe inhibition at all pH values including pH = 7.5. Addition of NO3- enabled activity recovery of NO2--inhibited anammox bacteria regardless of whether the proton gradient was disrupted or not, supporting the hypothesis of NO3--dependent detoxification via a secondary transport system.

Resolution and quality enhancement in terahertz in-line holography by sub-pixel sampling with double-distance reconstruction.

We demonstrate the enhancement of resolution and image quality in terahertz (THz) lens-free in-line digital holography by sub-pixel sampling with double-distance reconstruction. Multiple sub-pixel shifted low-resolution (LR) holograms recorded by a pyroelectric array detector (100 µm × 100 µm pixel pitch, 124 × 124 pixels) are aligned precisely to synthesize a high-resolution (HR) hologram. By this method, the lateral resolution is no more limited by the pixel pitch, and lateral resolution of 150 µm is obtained, which corresponds to 1.26λ with respect to the illuminating wavelength of 118.8 µm (2.52 THz). Compared with other published works, to date, this is the highest resolution in THz digital holography when considering the illuminating wavelength. In addition, to suppress the twin-image and zero-order artifacts, the complex amplitude distributions of both object and illuminaing background wave fields are reconstructed simultaneously. This is achieved by iterative phase retrieval between the double HR holograms and background images at two recording planes, which does not require any constraints on object plane or a priori knowledge of the sample.

Nitrate Reverses Severe Nitrite Inhibition of Anaerobic Ammonium Oxidation (Anammox) Activity in Continuously-Fed Bioreactors.

Nitrite (NO2-) substrate under certain conditions can cause failure of N-removal processes relying on anaerobic ammonium oxidizing (anammox) bacteria. Detoxification of NO2- can potentially be achieved by using exogenous nitrate (NO3-). In this work, continuous experiments in bioreactors with anammox bacteria closely related to "Candidatus Brocadia caroliniensis" were conducted to evaluate the effectiveness of short NO3- additions to reverse NO2- toxicity. The results show that a timely NO3- addition immediately after a NO2- stress event completely reversed the NO2- inhibition. This reversal occurs without NO3- being metabolized as evidence by lack of any 30N2 formation from 15N-NO3-. The maximum recovery rate was observed with 5 mM NO3- added for 3 days; however, slower but significant recovery was also observed with 5 mM NO3- for 1 day or 2 mM NO3- for 3 days. Without NO3- addition, long-term NO2- inhibition of anammox biomass resulted in irreversible damage of the cells. These results suggest that a short duration dose of NO3- to an anammox bioreactor can rapidly restore the activity of NO2--stressed anammox cells. On the basis of the results, a hypothesis about the detoxification mechanism related to narK genes in anammox bacteria is proposed and discussed.

Circulating CD14(+)HLA-DR(-/low) myeloid-derived suppressor cell is an indicator of poor prognosis in patients with ESCC.

Accumulating evidences demonstrate that a population of suppressive cells known as myeloid-derived suppressor cells (MDSCs) is key immune modulators which suppress antitumor immunity. In this study, we found that the level of circulating CD14(+)HLA-DR(-/low) cells in patients was significantly higher than that of healthy donors and was correlated with tumor burden, lymph node metastasis, and tumor, node, and metastasis (TNM) clinical stage. More importantly, we for the first time find the level of CD14(+)HLA-DR(-/low) is a biological indicator of poor prognosis through the analysis of 3-year overall survival. Furthermore, we evidenced that the proportion of CD14(+)HLA-DR(-/low) cells in the tumor metastatic tumor-draining lymph nodes (TDLNs) was notably higher compared to tumor-free TDLNs. Additionally, CD14(+)HLA-DR(-/low) cells from esophageal squamous cell carcinoma (ESCC) patients expressed dramatically increased programmed death ligand 1 (PD-L1) comparing to that from healthy control. Subsequently, blocking PD-L1 pathway by antibody could effectively reverse the suppressive effect on autologous T cell proliferation mediated by CD14(+)HLA-DR(-/low) cells in vitro. In conclusion, our data revealed CD14(+)HLA-DR(-/low) MDSCs which increase in ESCC patients is a novel poor prognostic indicator and may exert immunosuppressive properties through PD-L1/PD-1 pathway.

The role of pH on the resistance of resting- and active anammox bacteria to NO2- inhibition.

The anaerobic oxidation of ammonium (anammox) uses nitrite as terminal electron acceptor. The nitrite can cause inhibition to the bacteria that catalyze the anammox reaction. The literature shows a great divergence on the levels of NO2 (-) causing inhibition. Moreover, the conditions influencing the resistance of anammox bacteria to NO2 (-) inhibitory effect are not well understood. This work investigated the effect of the pH and the concentration of nitrite on the activity and metabolism of anammox granular sludge under different physiological conditions. Batch activity tests in a range of pH values were carried out in which either actively metabolizing cells or resting cells were exposed to nitrite in the presence or absence of the electron donating substrate ammonium, respectively. The response of the bacteria was evaluated by analyzing the specific anammox activity, the accumulation of nitric oxide, and the evolution of the ATP content in the biomass. Additionally, the effect of the pH on the tolerance of the biomass to single substrate feeding interruptions was evaluated in continuous anammox bioreactors. The results show that the influence of the pH on the NO2 (-) inhibition of anammox bacteria is greater under non-metabolizing conditions than during active metabolism. The exposure of resting cells to NO2 (-) (100 mg N L(-1) ) at pH values below 7.2 caused complete inhibition of the anammox activity. The inhibition was accompanied by accumulation of the intermediate, nitric oxide, in the gas phase. In contrast, just mild inhibition was observed for resting cells exposed to the same NO2 (-) concentration at pH values higher than 7.5 or any of the pH values tested in assays with actively metabolizing cells. ATP initially increased and subsequently decreased in time after resting cells were exposed to NO2 (-) suggesting an active response of the cells to nitrite stress. Furthermore, bioreactors operated at pH lower than 6.8 had greater sensitivity to NO2 (-) during an ammonium feed interruption than a bioreactor operated at pH 7.1. The results suggest that the ability of resting cells to tolerate NO2 (-) inhibition is seriously impeded at mildly acidic pH values; whereas actively metabolizing biomass is resistant to NO2 (-) toxicity over a wide range of pH values.

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.

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.

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.

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.

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.

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.