Energy efficiency assessment of China wastewater treatment plants by unit energy consumption per kg COD removed.

Unit energy consumption per kg pollutant removed (kWh/kgCODremoved) is used for the first time in assessing and ranking the sustainability of main treatment technologies of 1215 wastewater treatment plants (WWTPs) in China. The metric better measures the sustainability of main treatment technologies in WWTPs than unit energy consumption per cubic meter treated (kWh/m3). The energy consumption data of these WWTPs were selected from the database of 1399 WWTPs to evaluate the energy efficiency of different treatment technologies. 80.3% of the WWTPs applied anaerobic-oxic plus anaerobic-anoxic-oxic, oxidation ditch, and sequencing batch reactor as main technologies. Statistical analysis shows that the unit energy consumption of WWTPs decreases with increasing design flow rate, operation loading rate, and influent COD concentration. For example, the average unit energy consumption of SBR decreases from 2.76 kWh/kgCODremoved to 0.83 kWh/kgCODremoved when the design flow rate increases from less than 10,000 m3/d to 100,000-200,000 m3/d. The mean unit energy consumption of SBR decreases from 1.71 kWh/kgCODremoved to 1.32 kWh/ kgCODremoved and 2.85 kWh/ kgCODremoved to 0.63 kWh/kgCODremoved as the operation loading rate and COD removal increase from 40% to 100% and from less than 150 mg/L to over 450 mg/L, respectively. SBR has the lowest unit energy consumption among all the technologies. Therefore, SBR might be the most appropriate technology in small and medium-scale WWTPs in China. Regression equations were developed to predict the unit energy consumption for sustainable design treatment trains by input variables such as design flow rate, operation loading rate, and influent COD concentration.

UV Disinfection sensitivity index of spores or protozoa: A model to predict the required fluence of spores or protozoa.

During UV disinfection, the required UV dose in terms of fluence depends upon the species of bacteria spore and protozoa. To rank their UV disinfection sensitivity, spore sensitivity index (SPSI) and protozoan sensitivity index (PSI) are defined. For spores, shoulder effect exists, therefore, SPSI is defined as the ratio between the ki of any spores for the linear portion of the dose response curve to the kir of Bacillus subtilis as the reference spore. After statistical analysis, the fluence of any spore can be predicted by SPSI through equation, H = (0.8358 ± 0.126)*LogI*SPSI + H0. PSI is defined as the ratio between the inactivation rate constants of a protozoa in reference to that of Cryptosporidium parvum. The equation predicting the fluence of any protozoa in reference to Cryptosporidium parvum is: H = 107.45*(3.86 ± 2.68)*LogI/PSI. Two regression equations suggest that protozoa require significantly higher UV dose than bacteria spores.

Improving CH4/O2 energy ratio of meat processing wastewater treatment systems through micro-sieving.

Micro-sieving is an effective way to prevent organic pollutants enter the main biological process and reduce aeration intensity and sludge production. However, few researchers quantified the effect of micro-sieving on meat processing wastewater treatment. The current study developed Excel-based models to compare the energy consumption and production of historical, conventional and innovative systems. Historical and conventional systems employ activated sludge (AS), nitrification, and denitrification as the main biological processes. Innovative systems are designed by using up-flow anaerobic sludge blanket (UASB) and partial nitrification/Anammox (PN/A) as the main treatment processes. Results show that the CH4/O2 energy ratios of the innovative treatment system are as high as 10 times of the historical and conventional systems. Therefore, innovative system can achieve electrical self-sufficiency. Micro-sieving reduces 5% of aeration demand. Furthermore, the impact of micro-sieving on the innovative treatment systemis assessed by cost-benefit analysis. System with micro-sieving has the shortest payback time of 2.1 years and reduces cost of the innovative treatment system. An excel-based model was developed to quantify the impact of micro-sieving on energy and cost of innovative treatment system, thereby providing a valuable reference for future sustainable engineering design of meat processing wastewater treatment.

Small cell lung cancer: Subtypes and therapeutic implications.

Small cell lung cancer (SCLC) is an extremely aggressive neuroendocrine tumor, accounting for approximated 13% of all lung cancer cases. SCLC is characterized by rapid growth and early metastasis. Despite marked improvements in the number and efficacy of targeted, therapeutic options and overall survival rates in SCLC have remained nearly unchanged for almost three decades. The lack of significant progress can be attributed to our poor understanding of the biology of SCLC. Although immune checkpoint inhibitors were recently approved as front-line therapies for SCLC, we still need to better understand the mechanisms responsible for the selective vulnerability of some SCLCs to these inhibitors. Recent work utilizing sequencing data and single cell analyses identified four distinct subsets of SCLC, based on the expression levels of the transcription factors ASCL1, NEUROD1, POU2F3 and YAP1. Each subset was found to have its own distinct biology and therapeutic vulnerabilities. However, these subsets appear to be phenotypically unstable, representing snapshots in the gradual evolution of a tumor that exhibits significant plasticity. Tumor evolution, a product of this plasticity, results in the emergence of significant intratumoral heterogeneity which plays an important role in multiple aspects of SCLC development and progression, including cell survival and proliferation, metastasis and angiogenesis. The recent paradigm shifting discoveries in the biology of SCLC are now beginning to inform the design of new therapeutic strategies for the management of this intractable disease.

Lung Cancer Stem Cells and Their Clinical Implications.

It is now widely accepted that stem cells exist in various cancers, including lung cancer, which are referred to as cancer stem cells (CSCs). CSCs are defined in this context as the subset of tumor cells with the ability to form tumors in serial transplantation and cloning assays and form tumors at metastatic sites. Mouse models of lung cancer have shown that lung CSCs reside in niches that are essential for the maintenance of stemness, plasticity, enable antitumor immune evasion, and provide metastatic potential. Similar to normal lung stem cells, Notch, Wnt, and the Hedgehog signaling cascades have been recruited by the CSCs to regulate stemness and also provide therapy-driven resistance in lung cancer. Compounds targeting ß-catenin and Sonic hedgehog (Shh) activity have shown promising anti-CSC activity in preclinical murine models of lung cancer. Understanding CSCs and their niches in lung cancer can answer fundamental questions pertaining to tumor maintenance and associated immune regulation and escape that appear important in the quest to develop novel lung cancer therapies and enhance sensitivity to currently approved chemo-, targeted-, and immune therapeutics.

Predicting ROR1/BCL2 combination targeted therapy of small cell carcinoma of the lung.

Small cell lung cancer (SCLC) remains a deadly form of cancer, with a 5-year survival rate of less than 10 percent, necessitating novel therapies. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncofetal protein that is emerging as a therapeutic target and is co-expressed with BCL2 in multiple tumor types due to microRNA coregulation. We hypothesize that ROR1-targeted therapy is effective in small cell lung cancer and synergizes with therapeutic BCL2 inhibition. Tissue microarrays (TMAs) and formalin-fixed paraffin-embedded (FFPE) SCLC patient samples were utilized to determine the prevalence of ROR1 and BCL2 expression in SCLC. Eight SCLC-derived cell lines were used to determine the antitumor activity of a small molecule ROR1 inhibitor (KAN0441571C) alone and in combination with the BCL2 inhibitor venetoclax. The Chou-Talalay method was utilized to determine synergy with the drug combination. ROR1 and BCL2 protein expression was identified in 93% (52/56) and 86% (48/56) of SCLC patient samples, respectively. Similarly, ROR1 and BCL2 were shown by qRT-PCR to have elevated expression in 79% (22/28) and 100% (28/28) of SCLC patient samples, respectively. KAN0441571C displayed efficacy in 8 SCLC cell lines, with an IC50 of 500 nM or less. Synergy as defined by a combination index of <1 via the Chou-Talalay method between KAN0441571C and venetoclax was demonstrated in 8 SCLC cell lines. We have shown that ROR1 inhibition is synergistic with BCL2 inhibition in SCLC models and shows promise as a novel therapeutic target in SCLC.

STK11/LKB1 Loss of Function Is Associated with Global DNA Hypomethylation and S-Adenosyl-Methionine Depletion in Human Lung Adenocarcinoma.

STK11 (liver kinase B1, LKB1) is the fourth most frequently mutated gene in lung adenocarcinoma, with loss of function observed in up to 30% of all cases. Our previous work identified a 16-gene signature for LKB1 loss of function through mutational and nonmutational mechanisms. In this study, we applied this genetic signature to The Cancer Genome Atlas (TCGA) lung adenocarcinoma samples and discovered a novel association between LKB1 loss and widespread DNA demethylation. LKB1-deficient tumors showed depletion of S-adenosyl-methionine (SAM-e), which is the primary substrate for DNMT1 activity. Lower methylation following LKB1 loss involved repetitive elements (RE) and altered RE transcription, as well as decreased sensitivity to azacytidine. Demethylated CpGs were enriched for FOXA family consensus binding sites, and nuclear expression, localization, and turnover of FOXA was dependent upon LKB1. Overall, these findings demonstrate that a large number of lung adenocarcinomas exhibit global hypomethylation driven by LKB1 loss, which has implications for both epigenetic therapy and immunotherapy in these cancers. SIGNIFICANCE: Lung adenocarcinomas with LKB1 loss demonstrate global genomic hypomethylation associated with depletion of SAM-e, reduced expression of DNMT1, and increased transcription of repetitive elements.

Co-digestive performance of food waste and hydrothermal pretreated corn cob.

Anaerobic co-digestion of lignocellulosic biomass and food waste (FW) has been extensively applied. However, whether hydrothermal pretreatment (HTP) of lignocellulosic biomass can enhance the performance in co-digestion deserves further investigation. In this study, corn cob (CC) was adopted as a typical lignocellulosic biomass for co-digestion with FW at different VS ratios of 1:3 (S1-S4) and 1:6 (S5-S8), attempting to evaluate the effect of HTP of CC at different temperature gradients (125, 150 and 175 °C) on the co-digestion performance. The emphasis was placed on hydrolysis, acidification and methanogenesis for different feedstock conditions. Results illustrated that the HTP had a certain destroying effect on the lignocellulose structure in CC and the crystallinity of cellulose decreased, significantly facilitating its co-digestion with FW. For FW/CC co-digestion at the VS ratio of 1:3, the S3 group (CC was pretreated at 150 °C) reached the maximum cumulative biogas yield (CBY) of 4660 mL and the maximum specific methane yield (SMY) of 316.9 mL/g·VS. Moreover, at 1:6, S7 group (pretreated at 150 °C) exhibited the optimal CBY of 4100 mL while achieving the SMY of 277.6 mL/g·VS among the digesters, indicating that the co-digestion of pretreated CC and FW could achieve higher methane production, and 150 °C refers to the optimal pretreatment temperature. Moreover, the peak values of the accumulated VFAs in digesters S1-S4 (2000-3000 mg/L) is higher than that in digesters S5-S8 (800-1500 mg/L). As suggested from microbial community and diversity date, the HTP expedited the enrichment of system hydrolyzing and acidogenic bacteria. These results are significant and provide certain guidance for optimizing the co-digestion of FW and CC in actual engineering.

Food-processing wastes.

Literature published in 2018 and literature published in 2019 related to food-processing wastes treatment for industrial applications are reviewed. This review is a subsection of the Treatment Systems section of the annual Water Environment Federation literature review and covers the following food-processing industries and applications: general, meat and poultry, fruits and vegetables, dairy and beverage, and miscellaneous treatment of food wastes. PRACTITIONER POINTS: This article summarizes literature reviews published in 2018 and in 2019 related to food processing wastes treatment for industrial applications are reviewed. This review is a subsection of the Treatment Systems section of the annual Water Environment Federation literature review and covers the following food processing industries and applications: general, meat and poultry, fruits and vegetables, dairy and beverage, and miscellaneous treatment of food wastes.

RB constrains lineage fidelity and multiple stages of tumour progression and metastasis.

Mutations in the retinoblastoma (RB) tumour suppressor pathway are a hallmark of cancer and a prevalent feature of lung adenocarcinoma1-3. Although RB was the first tumour suppressor to be identified, the molecular and cellular basis that underlies selection for persistent RB loss in cancer remains unclear4-6. Methods that reactivate the RB pathway using inhibitors of cyclin-dependent kinases CDK4 and CDK6 are effective in some cancer types and are currently under evaluation for the treatment of lung adenocarcinoma7-9. Whether RB pathway reactivation will have therapeutic effects and whether targeting CDK4 and CDK6 is sufficient to reactivate RB pathway activity in lung cancer remains unknown. Here we model RB loss during lung adenocarcinoma progression and pathway reactivation in established oncogenic KRAS-driven tumours in mice. We show that RB loss enables cancer cells to bypass two distinct barriers during tumour progression. First, RB loss abrogates the requirement for amplification of the MAPK signal during malignant progression. We identify CDK2-dependent phosphorylation of RB as an effector of MAPK signalling and critical mediator of resistance to inhibition of CDK4 and CDK6. Second, RB inactivation deregulates the expression of cell-state-determining factors, facilitates lineage infidelity and accelerates the acquisition of metastatic competency. By contrast, reactivation of RB reprograms advanced tumours towards a less metastatic cell state, but is nevertheless unable to halt cancer cell proliferation and tumour growth due to adaptive rewiring of MAPK pathway signalling, which restores a CDK-dependent suppression of RB. Our study demonstrates the power of reversible gene perturbation approaches to identify molecular mechanisms of tumour progression, causal relationships between genes and the tumour suppressive programs that they control and critical determinants of successful cancer therapy.

Food-Processing Wastes.

Literature published in 2017 and early 2018 related to food processing wastes treatment for industrial applications are reviewed. This review is a subsection of the Treatment Systems section of the annual Water Environment Federation literature review and covers the following food processing industries and applications: general, meat and poultry, fruits and vegetables, dairy and beverage, and miscellaneous treatment of food wastes.

Towards reliable quantification of hydroxyl radicals in the Fenton reaction using chemical probes.

Quantification of hydroxyl radical concentration using two chemical probes was assessed through the Fenton reaction. The probes were 1,2-benzopyrone (coumarin) for fluorescence and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) for electron spin resonance (ESR). The corresponding hydroxylated species, namely 7-hydroxycoumarin (7HC) and 2-hydroxy-5,5-dimethyl-1-pyrroline-N-oxide (DMPO-OH adduct), were monitored by fluorescence and ESR-spin trapping techniques, respectively. The experiments were designed according to the theoretical conditions determined for stable fluorescence and EPR signals. The results demonstrate that: the optimal [chemical probe] : [H2O2] ratio predicted by a simplified quasi-steady-state model was in good agreement with the optimal [chemical probe] : [H2O2] ratio observed experimentally for [H2O2] : [Fe2+] = 10, and the proper adjustment of the [chemical probe] : [H2O2] ratio at a given concentration of the Fenton's reagent improves the detected amount of hydroxyl radicals. Finally, using DMPO required a higher concentration compared to coumarin to yield the same amount of ˙OH detected but resulted in a more reliable probe for detecting ˙OH under the consideration of this study.

Food-Processing Wastes.

Literature published in 2016 and early 2017 related to food processing wastes treatment for industrial applications are reviewed. This review is a subsection of the Treatment Systems section of the annual Water Environment Federation literature review and covers the following food processing industries and applications: general, meat and poultry, fruits and vegetables, dairy and beverage, and miscellaneous treatment of food wastes.

Food-Processing Wastes.

Literature published in 2015 and early 2016 related to food processing wastes treatment for industrial applications are reviewed. This review is a subsection of the Treatment Systems section of the annual Water Environment Federation literature review and covers the following food processing industries and applications: general, meat and poultry, fruits and vegetables, dairy and beverage, and miscellaneous treatment of food wastes.

Soluble guanylate cyclase activation during ischemic injury in mice protects against postischemic inflammation at the mitochondrial level.

The aim was to determine whether treatment with BAY 60-2770, a selective activator of oxidized soluble guanylate cyclase (sGC), near the end of an ischemic event would prevent postischemic inflammation and mitochondrial dysfunction in wild-type (WT) and heme oxygenase-1 KO (HO-1(-/-)) mice. This protocol prevented increases in leukocyte rolling (LR) and adhesion (LA) to intestinal venules along with elevated TNFα and circulating neutrophil levels that accompany ischemia-reperfusion (I/R) in both animal models. We further hypothesized that a component of BAY 60-2770 treatment involves maintenance of mitochondrial membrane integrity during I/R. Measurements on isolated enterocytes of calcein fluorescence (mitochondrial permeability) and JC-1 fluorescence ratio (mitochondrial membrane potential) were reduced by I/R, indicating formation of mitochondrial permeability transition pores (mPTP). These effects were abrogated by BAY 60-2770 as well as cyclosporin A and SB-216763, which prevented mPTP opening and inhibited glycogen synthase kinase-3ß (GSK-3ß), respectively. Western blots of WT and HO-1(-/-) enterocytes indicated that GSK-3ß phosphorylation on Ser(9) (inhibitory site) was reduced by half following I/R alone (increased GSK-3ß activity) and increased by one-third (reduced GSK-3ß activity) following BAY 60-2770. Other investigators have associated phosphorylation of the GSK-3ß substrate cyclophilin D (pCyPD) with mPTP formation. We observed a 60% increase in pCyPD after I/R, whereas BAY 60-2770 treatment of sham and I/R groups reduced pCyPD by about 20%. In conclusion, selective activation of oxidized sGC of WT and HO-1(-/-) during ischemia protects against I/R-induced inflammation and preserves mucosal integrity in part by reducing pCyPD production and mPTP formation.

Food-Processing Wastes.

Literature published in 2014 and early 2015 related to food processing wastes treatment for industrial applications are reviewed. This review is a subsection of the Treatment Systems section of the annual Water Environment Federation literature review and covers the following food processing industries and applications: general, meat and poultry, fruits and vegetables, dairy and beverage, and miscellaneous treatment of food wastes.

Virus Sensitivity Index of UV disinfection.

A new concept of Virus Sensitivity Index (VSI) is defined as the ratio between the first-order inactivation rate constant of a virus, ki, and that of MS2-phage during UV disinfection, kr. MS2-phage is chosen as the reference virus because it is recommended as a virus indicator during UV reactor design and validation by the US Environmental Protection Agency. VSI has wide applications in research, design, and validation of UV disinfection systems. For example, it can be used to rank the UV disinfection sensitivity of viruses in reference to MS2-phage. There are four major steps in deriving the equation between Hi/Hr and 1/VSI. First, the first-order inactivation rate constants are determined by regression analysis between Log I and fluence required. Second, the inactivation rate constants of MS2-phage are statistically analysed at 3, 4, 5, and 6 Log I levels. Third, different VSI values are obtained from the ki of different viruses dividing by the kr of MS2-phage. Fourth, correlation between Hi/Hr and 1/VSI is analysed by using linear, quadratic, and cubic models. As expected from the theoretical analysis, a linear relationship adequately correlates Hi/Hr and 1/VSI without an intercept. VSI is used to quantitatively predict the UV fluence required for any virus at any log inactivation (Log I). Four equations were developed at 3, 4, 5, and 6 Log I. These equations have been validated using external data which are not used for the virus development. At Log I less than 3, the equation tends to under-predict the required fluence at both low Log I such as 1 and 2 Log I. At Log I greater than 3 Log I, the equation tends to over-predict the fluence required. The reasons for these may very likely be due to the shoulder at the beginning and the tailing at the end of the collimated beam test experiments. At 3 Log I, the error percentage is less than 6%. The VSI is also used to predict inactivation rate constants under two different UV disinfection scenarios such as under sunlight and different virus aggregates. The correlation analysis shows that viruses will be about 40% more sensitive to sunlight than to UV254. On the other hand, virus size of 500 nm will reduce their VSI by 10%. This is the first attempt to use VSI to predict the required fluence at any given Log I. The equation can be used to quantitatively evaluate other parameters influencing UV disinfection. These factors include environmental species, antibiotic-resistant bacteria or genes, photo and dark repair, water quality such as suspended solids, and UV transmittance.

Reverse osmosis and nanofiltration of biologically treated leachate.

Experiments of nano-filtration (NF) and reverse osmosis (RO) were conducted to remove most pollutants from the biological treated leachate. For example, the purified permeate after reverse osmosis treatment with spiral membranes reached effluent water quality as follows: COD of 57 mg O2/l, BOD7 of 35 mg O2/l, and suspended solid of 1 mg/l which satisfies the discharge standards in Estonia. For both RO and NF, conductivity can be reduced by 91% from 6.06 to 0.371 mS/cm by RO and 99% from 200 to 1 mS/cm by NF. To test the service life of the RO spiral membranes, the process was able to reduce chemical oxygen demand (COD) and biological oxygen demand (BOD) of biologically treated leachate by 97.9% and 93.2% even after 328 and 586 hours, respectively. However, only 39.0% and 21.7% reductions of Ptot and Ntot were achieved. As a result, neither RO (spiral membranes process) nor NF was able to reduce the total nitrogen (TN) to the required discharge limit of 15 mg/l.

Fenton treatment of landfill leachate under different COD loading factors.

The application of Fenton treatment technology for treatment of landfill leachate greatly depends on the optimum Fenton operating conditions for a specific leachate. Determining optimum Fenton conditions requires multiple experiments using variable reaction parameters (pH, temperature, and H2O2 and Fe(2+) doses) and previous researches show a wide range of optimal operating conditions. In this study, the applicability of the dimensionless loading factor (LCOD), which is defined as the initial COD (COD0) of leachate with respect to available O2 for oxidation, was examined to derive optimum Fenton oxidant dose using reduced set of experiments. The Fenton experiments were conducted using leachates with three different COD0 concentrations, 1092, 546, and 273mgL(-1), LCOD in the range of 0.25-1.0, and H2O2/Fe(2+) 1.8 (w/w). The experimental data were analyzed to determine the correlation between the LCOD factor and selected feasibility parameters, amongst which were: (i) the COD removal kinetics, (ii) the total COD removal, (iii) the usability of H2O2 with respect to COD removal, (iv) leachate biodegradability, and (v) treatment cost incurred by chemical usage. The experimental COD removal with respect to the amount of O2 supplied by H2O2 was compared with respect to the optimum COD removal efficiency by the equation: η(FP(optimum)=0.733L(COD)-0.182 as developed by Singh and Tang (2013) and a LCOD of 0.75 was determined to be the optimum L(COD) for leachate treatment.

Preconditioning with soluble guanylate cyclase activation prevents postischemic inflammation and reduces nitrate tolerance in heme oxygenase-1 knockout mice.

Previously we have shown that, unlike wild-type mice (WT), heme oxygenase-1 knockout (HO-1-/-) mice developed nitrate tolerance and were not protected from inflammation caused by ischemia-reperfusion (I/R) when preconditioned with a H2S donor. We hypothesized that stimulation (with BAY 41-2272) or activation (with BAY 60-2770) of soluble guanylate cyclase (sGC) would precondition HO-1-/- mice against an inflammatory effect of I/R and increase arterial nitrate responses. Intravital fluorescence microscopy was used to visualize leukocyte rolling and adhesion to postcapillary venules of the small intestine in anesthetized mice. Relaxation to ACh and BAY compounds was measured on superior mesenteric arteries isolated after I/R protocols. Preconditioning with either BAY compound 10 min (early phase) or 24 h (late phase) before I/R reduced postischemic leukocyte rolling and adhesion to sham control levels and increased superior mesenteric artery responses to ACh, sodium nitroprusside, and BAY 41-2272 in WT and HO-1-/- mice. Late-phase preconditioning with BAY 60-2770 was maintained in HO-1-/- and endothelial nitric oxide synthase knockout mice pretreated with an inhibitor (dl-propargylglycine) of enzymatically produced H2S. Pretreatment with BAY compounds also prevented the I/R increase in small intestinal TNF-α. We speculate that increasing sGC activity and related PKG acts downstream to H2S and disrupts signaling processes triggered by I/R in part by maintaining low cellular Ca²âº. In addition, BAY preconditioning did not increase sGC levels, yet increased the response to agents that act on reduced heme-containing sGC. Collectively these actions would contribute to increased nitrate sensitivity and vascular function.