@article{huang_winans_wyman_oaks_faludi_choudhary_lai_lewis_beckford_duarte_et al._2024, title={Rab4A-directed endosome traffic shapes pro-inflammatory mitochondrial metabolism in T cells via mitophagy, CD98 expression, and kynurenine-sensitive mTOR activation}, url={http://dx.doi.org/10.1038/s41467-024-46441-2}, DOI={10.1038/s41467-024-46441-2}, abstractNote={Abstract Activation of the mechanistic target of rapamycin (mTOR) is a key metabolic checkpoint of pro-inflammatory T-cell development that contributes to the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus (SLE), however, the underlying mechanisms remain poorly understood. Here, we identify a functional role for Rab4A-directed endosome traffic in CD98 receptor recycling, mTOR activation, and accumulation of mitochondria that connect metabolic pathways with immune cell lineage development and lupus pathogenesis. Based on integrated analyses of gene expression, receptor traffic, and stable isotope tracing of metabolic pathways, constitutively active Rab4A Q72L exerts cell type-specific control over metabolic networks, dominantly impacting CD98-dependent kynurenine production, mTOR activation, mitochondrial electron transport and flux through the tricarboxylic acid cycle and thus expands CD4 + and CD3 + CD4 − CD8 − double-negative T cells over CD8 + T cells, enhancing B cell activation, plasma cell development, antinuclear and antiphospholipid autoantibody production, and glomerulonephritis in lupus-prone mice. Rab4A deletion in T cells and pharmacological mTOR blockade restrain CD98 expression, mitochondrial metabolism and lineage skewing and attenuate glomerulonephritis. This study identifies Rab4A-directed endosome traffic as a multilevel regulator of T cell lineage specification during lupus pathogenesis.}, journal={Nature Communications}, author={Huang, Nick and Winans, Thomas and Wyman, Brandon and Oaks, Zachary and Faludi, Tamás and Choudhary, Gourav and Lai, Zhi-Wei and Lewis, Joshua and Beckford, Miguel and Duarte, Manuel and et al.}, year={2024}, month={Mar} }
 @article{oaks_patel_huang_choudhary_winans_faludi_krakko_duarte_lewis_beckford_et al._2023, title={Cytosolic aldose metabolism contributes to progression from cirrhosis to hepatocarcinogenesis}, url={https://doi.org/10.1038/s42255-022-00711-9}, DOI={10.1038/s42255-022-00711-9}, abstractNote={Oxidative stress modulates carcinogenesis in the liver; however, direct evidence for metabolic control of oxidative stress during pathogenesis, particularly, of progression from cirrhosis to hepatocellular carcinoma (HCC), has been lacking. Deficiency of transaldolase (TAL), a rate-limiting enzyme of the non-oxidative branch of the pentose phosphate pathway (PPP), restricts growth and predisposes to cirrhosis and HCC in mice and humans. Here, we show that mitochondrial oxidative stress and progression from cirrhosis to HCC and acetaminophen-induced liver necrosis are critically dependent on NADPH depletion and polyol buildup by aldose reductase (AR), while this enzyme protects from carbon trapping in the PPP and growth restriction in TAL deficiency. Both TAL and AR are confined to the cytosol; however, their inactivation distorts mitochondrial redox homeostasis in opposite directions. The results suggest that AR acts as a rheostat of carbon recycling and NADPH output of the PPP with broad implications for disease progression from cirrhosis to HCC.}, journal={Nature Metabolism}, author={Oaks, Z. and Patel, A. and Huang, N. and Choudhary, G. and Winans, T. and Faludi, T. and Krakko, D. and Duarte, M. and Lewis, J. and Beckford, M. and et al.}, year={2023}, month={Jan} }
 @article{oaks_patel_huang_choudhary_winans_faludi_krakko_duarte_lewis_beckford_et al._2023, title={Publisher Correction: Cytosolic aldose metabolism contributes to progression from cirrhosis to hepatocarcinogenesis}, url={https://doi.org/10.1038/s42255-023-00752-8}, DOI={10.1038/s42255-023-00752-8}, journal={Nature Metabolism}, author={Oaks, Z. and Patel, A. and Huang, N. and Choudhary, G. and Winans, T. and Faludi, T. and Krakko, D. and Duarte, M. and Lewis, J. and Beckford, M. and et al.}, year={2023}, month={Feb} }
 @article{winans_oaks_choudhary_patel_huang_faludi_krakko_nolan_lewis_blair_et al._2023, title={mTOR-dependent loss of PON1 secretion and antiphospholipid autoantibody production underlie autoimmunity-mediated cirrhosis in transaldolase deficiency}, url={http://dx.doi.org/10.1016/j.jaut.2023.103112}, DOI={10.1016/j.jaut.2023.103112}, abstractNote={Transaldolase deficiency predisposes to chronic liver disease progressing from cirrhosis to hepatocellular carcinoma (HCC). Transition from cirrhosis to hepatocarcinogenesis depends on mitochondrial oxidative stress, as controlled by cytosolic aldose metabolism through the pentose phosphate pathway (PPP). Progression to HCC is critically dependent on NADPH depletion and polyol buildup by aldose reductase (AR), while this enzyme protects from carbon trapping in the PPP and growth restriction in TAL deficiency. Although AR inactivation blocked susceptibility to hepatocarcinogenesis, it enhanced growth restriction, carbon trapping in the non-oxidative branch of the PPP and failed to reverse the depletion of glucose 6-phosphate (G6P) and liver cirrhosis. Here, we show that inactivation of the TAL-AR axis results in metabolic stress characterized by reduced mitophagy, enhanced overall autophagy, activation of the mechanistic target of rapamycin (mTOR), diminished glycosylation and secretion of paraoxonase 1 (PON1), production of antiphospholipid autoantibodies (aPL), loss of CD161+ NK cells, and expansion of CD38+ Ito cells, which are responsive to treatment with rapamycin in vivo. The present study thus identifies glycosylation and secretion of PON1 and aPL production as mTOR-dependent regulatory checkpoints of autoimmunity underlying liver cirrhosis in TAL deficiency.}, journal={Journal of Autoimmunity}, author={Winans, T. and Oaks, Z. and Choudhary, G. and Patel, A. and Huang, N. and Faludi, T. and Krakko, D. and Nolan, J. and Lewis, J. and Blair, Sarah and et al.}, year={2023}, month={Nov} }
 @article{krakkó_heieren_illés_kvamme_dóbé_záray_2022, title={(V)UV degradation of the antibiotic tetracycline: Kinetics, transformation products and pathway}, volume={163}, url={http://dx.doi.org/10.1016/j.psep.2022.05.027}, DOI={10.1016/j.psep.2022.05.027}, abstractNote={Tetracycline (TETR) is an antibiotic drug that is widely used in both human and veterinary medicine. It is frequently detected in activated sludge, wastewater effluent, river and lake water or sediment, usually in the pg/L – µg/L concentration range, but sometimes above the mg/L level. Conventional wastewater treatment plants have low removal efficiency for a large number of small organic molecules including TETR. Their efficiency can be increased by applying e.g., an advanced oxidation method for the post-treatment of the wastewater effluent. One possibility is the use of (V)UV lamps for simultaneous disinfection and micropollutant removal. In this paper, the degradation of TETR by UV (λ = 254 nm) and (V)UV (λ = 185 nm and 254 nm) light was studied, focusing on kinetics, mineralization, transformation products and degradation pathways. The effect of dissolved oxygen during irradiation was also examined. As expected, the degradation rate of TETR drastically increased in (V)UV irradiation compared to the conventional UV light. The degradation rates increased by 9% and 16% in UV and (V)UV experiments in the presence of dissolved oxygen possibly due to the generation of additional oxidative radical species. Total organic carbon removal was generally 15%, high TOC removal could only be achieved with greatly increased photon flux in (V)UV photooxidation. In total, eleven aromatic transformation products (TPs) were identified during the irradiation experiments. Three TPs (TP 418, TP 398 and TP 383) were described for the first time. The main degradation pathways include loss of water, CO, methyl or dimethylamine groups. Based on the kinetic profiles, (V)UV irradiation could effectively degrade all aromatic transformation products.}, journal={Process Safety and Environmental Protection}, publisher={Elsevier BV}, author={Krakkó, Dániel and Heieren, Bjørn Tobiassen and Illés, Ádám and Kvamme, Kristin and Dóbé, Sándor and Záray, Gyula}, year={2022}, month={Jul}, pages={395–404} }
 @article{sorption of selected pharmaceuticals on river benthic biofilms formed on artificial substrata_2022, volume={138}, url={http://dx.doi.org/10.1016/j.ecolind.2022.108837}, DOI={10.1016/j.ecolind.2022.108837}, abstractNote={The dissolved organic and inorganic contaminants in rivers, lakes and seas are distributed among the aquatic phase, biota, sediments and biofilms formed on different artificial and natural substrata. Since the biofilms play an important role in the food web of aquatic ecosystems, it is necessary to clarify what kind of contaminants are bounded to these biological surfaces. In this study the concentration of eight pharmaceuticals (carbamazepine, ciprofloxacin, clarithromycin, diclofenac, metoprolol, sitagliptin, sulfamethoxazole and tetracycline) was determined in the Danube water at Budapest (Hungary) and in the biofilms formed on glass and polycarbonate substrata during a six weeks long growing period at the same sampling site. The target compounds were extracted from the dried biofilms by microwave (MW) assisted hot water treatment, however, the recovery of tetracycline was extremely low, indicating damage and loss of this constituent caused by MW treatment. The concentrations of the other seven pharmaceuticals were determined by LC-MS following the solid phase extraction of analytes. Clarithromycin, ciprofloxacin, diclofenac, metoprolol and sitagliptin were detectable in the biofilms due to biological uptake and electrostatic-mediated adsorption on the negatively charged biofilms, however, carbamazepine and sulfamethoxazole with neutral charge were not detected. The bioaccumulation factors of biofilms grown on glass or polycarbonate substrata changed between 175 and 614 and 148–314 L/kg, respectively, and increased in order of diclofenac < sitagliptin < clarithromycin < ciprofloxacin < metoprolol. These values are about 2–3 orders of magnitude lower than the published data for different metal cations which form chemical complexes or chelates with carboxyl and hydroxyl groups of extracellular polymer matrix. Due to the higher amount of adsorbed pharmaceuticals and the higher biodiversity of diatom species in the biofilms formed on glass substrata, compared to polycarbonate, as artificial substrata the glass carrier plates can be recommended for biofilm studies.}, journal={Ecological Indicators}, publisher={Elsevier BV}, year={2022}, month={May}, pages={108837} }
 @article{krakkó_illés_domján_demeter_dóbé_záray_2022, title={UV and (V)UV irradiation of sitagliptin in ultrapure water and WWTP effluent: Kinetics, transformation products and degradation pathway}, volume={288}, url={https://doi.org/10.1016/j.chemosphere.2021.132393}, DOI={10.1016/j.chemosphere.2021.132393}, abstractNote={Sitagliptin (SITA) is an antidiabetic drug consumed worldwide in high quantities. Because of the low removal rate of this compound in conventional wastewater treatment plants (WWTPs), it enters receiving surface waters with the discharged WWTP effluents. SITA can be detected up to μg/L concentration in rivers. In this study, UV (254 nm) and (V)UV (185 nm + 254 nm) irradiation was applied in laboratory scale to degrade SITA. The effect of three parameters was evaluated on the degradation rate, namely i) the efficiency in UV and (V)UV irradiation, ii) the presence or absence of dissolved oxygen, iii) the matrix effect of WWTP effluent. Degradation rate of SITA was largely increased by (V)UV irradiation, and decreased in WWTP effluent as expected. The presence of dissolved oxygen increased the degradation rate only in UV experiments and did not have a considerable effect in (V)UV experiments. In total, 14 transformation products (TPs) were identified (twelve new); their structures were proposed based on high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy analyses. The most characteristic reaction steps of the degradation of SITA involved nucleophilic aromatic photosubstitution whereas hydroxide ions acted as attacking nucleophiles and replaced F atoms of the phenyl moiety by hydroxide groups, in agreement with the increase in photolysis rate with increasing pH. The photochemical degradation pathway of SITA was also interpreted. Kinetic profiles revealed TP 421, TP 208 and TP 192 to be the most recalcitrant TPs.}, journal={Chemosphere}, publisher={Elsevier BV}, author={Krakkó, Dániel and Illés, Ádám and Domján, Attila and Demeter, Attila and Dóbé, Sándor and Záray, Gyula}, year={2022}, month={Feb}, pages={132393} }
 @article{krakkó_illés_licul-kucera_dávid_dobosy_pogonyi_demeter_mihucz_dóbé_záray_2021, title={Application of (V)UV/O3 technology for post-treatment of biologically treated wastewater: A pilot-scale study}, volume={275}, url={https://doi.org/10.1016/j.chemosphere.2021.130080}, DOI={10.1016/j.chemosphere.2021.130080}, abstractNote={For the first time, high energy VUV photons and generation of O3 by (V)UV lamps were applied together for removal of active pharmaceutical ingredients (APIs) from biologically treated wastewater (BTWW) in pilot-scale. The core of the pilot container unit was a photoreactor assembly consisting of six photoreactors, each containing a low-pressure Hg lamp (UV dose of 1.2 J/cm2 and 6.6 J/cm2 at 185 nm and 254 nm, respectively). BTWW was irradiated (4.75 min residence time) by (V)UV light in presence of in situ photochemically generated O3 from coolant air of the lamps. Experiments were conducted at the site of two wastewater treatment plants. Out of seven target APIs (namely carbamazepine, ciprofloxacin, clarithromycin, diclofenac, metoprolol, sitagliptin, and sulfamethoxazole), 80–100% removal was accomplished for five and 40–80% for two compounds. Two degradation products of carbamazepine were detected. Degradation products of other target compounds were not found. The applied O3 dose was 30–45 μg O3/mg dissolved organic carbon. Inactivation of up to log-4.8, log-4.5 and log-3.8 could be achieved for total coliform, Escherichia coli and Enterococcus faecalis, respectively. SOS Chromotest indicated no genotoxicity nor acute toxicity. Generation of neither NH4+, NO2− nor NO3− was observed during post-treatment. Electric energy per order values were calculated for the first time for (V)UV/O3 treatment in BTWW with a median value of 1.5 kWh/m3. This technology can be proposed for post-treatment of BTWWs of small settlements or livestock farms to degrade micropollutants before water discharge or for production of irrigation water. Further studies are essential in pilot-scale for other applications.}, journal={Chemosphere}, publisher={Elsevier BV}, author={Krakkó, Dániel and Illés, Ádám and Licul-Kucera, Viktória and Dávid, Bence and Dobosy, Péter and Pogonyi, Andrea and Demeter, Attila and Mihucz, Victor G. and Dóbé, Sándor and Záray, Gyula}, year={2021}, month={Jul}, pages={130080} }
 @article{laponite immobilized tio<inf>2</inf> catalysts for photocatalytic degradation of phenols_2020, volume={387}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85073416419&partnerID=MN8TOARS}, DOI={10.1016/j.jphotochem.2019.112045}, abstractNote={Laponite immobilized titania catalysts were prepared by a pillaring process and by hydrothermal synthesis (HT) applying different titania sources such as TiCl4 and TiOSO4. Textural investigations (XRD, TEM, N2 physisorption) evidenced that by the pillaring procedure a high specific surface area (∼450 m2 g−1) mesoporous composite with 5–6 nm sized anatase nanoparticles were formed retaining the morphology of parent laponite structure. In contrast, by hydrothermal treatment with titanium oxysulfate the initial laponite structure was destroyed and a more opened nanoporous silica/titania material was formed with bigger, about 14 nm anatase particles. FT-IR spectroscopic investigations revealed the different acidic character of titania/Laponite composite samples showing stronger Lewis and weak Brönsted acid sites on both catalysts. However, acidic centers in titania pillared laponite stem from Ti–O–Si bonds, whereas in HT sample from the separated, ionic, surface sulfate species on titania. Catalytic activity of titania/Laponite composites were tested in photo-oxidation of model 10–5 M phenol and 2,4,6-trichlorophenol (TCP) water solutions. Catalytic tests were carried out in a home constructed batch-type photo-reactor with oxygen bubbling, and applying commercial low pressure Hg lamps emitting UV-light at 254 nm and 361 nm. Catalytic results showed that utilization of titania/Laponite catalysts enhanced the photo-oxidation activity. Hydrothermally prepared sample showed much better catalytic performance than titanium chloride pillared one, probably due to the bigger titania particles and the more opened mesoporous structure of titania/Laponite HT, and moreover to the peculiar surface acidic properties of sulfated titania species. Separation of catalysts from reaction media even in tap water was much easier than that of commercial titania, i.e. by self-settling.}, journal={Journal of Photochemistry and Photobiology A: Chemistry}, year={2020} }
 @article{enhanced photolytic and photooxidative treatments for removal of selected pharmaceutical ingredients and their degradation products in water matrices_2019, volume={150}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85082295339&partnerID=MN8TOARS}, DOI={10.1016/j.microc.2019.104136}, abstractNote={Photolytic and photooxidative degradations of diclofenac (DICL), naproxen (NAPR) and carbamazepine (CARB) were compared by a conventional low-pressure mercury-vapor lamp with λmax = 254 nm and a vacuum UV (VUV) one, emitting also at 185 nm (in 11%) in ultra-pure water (UPW) and municipal wastewater (WW) spiked with 5 × 10−6 M for each drug. Almost complete photolytic and photooxidative degradations were observed by VUV irradiation for all three compounds in 2 min. About 75% decrease in the total organic carbon content was determined in UPW irradiated samples spiked at the 2–5 × 10−5 M levels in 15 min. Effective degradations of DICL, NAPR and CARB were achieved in spiked WW by photolysis and photooxidation (PhO) at 185 nm (11%) within 1, 2 and 10 min, respectively. Several aromatic degradation products of DICL, NAPR and CARB were identified by quadrupole time-of-flight mass spectrometer hyphenated to an ultra-high performance liquid chromatograph after preconcentration with off-line solid phase extraction upon irradiation of the UPW matrix spiked with the selected drugs at 254 nm. For several degradation products, chemical structures differing from those previously reported have been proposed. Moreover, acridine has not yet been reported as photodegradation product for DICL. Degradation pathways have been also proposed. Almost complete degradation of DICL, NAPR and CARB as well as their degradation products by VUV + PhO in WW took place in 5, 10 and 30 min, respectively. However, the total organic content decreased by only 25% in the WW sample.}, journal={Microchemical Journal}, year={2019} }
 @article{krakkó_licul-kucera_záray_mihucz_2019, title={Single-run ultra-high performance liquid chromatography for quantitative determination of ultra-traces of ten popular active pharmaceutical ingredients by quadrupole time-of-flight mass spectrometry after offline preconcentration by solid phase extraction from drinking and river waters as well as treated wastewater}, volume={148}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85065191155&partnerID=MN8TOARS}, DOI={10.1016/j.microc.2019.04.047}, abstractNote={A fit-to-purpose ultra-high performance liquid chromatographic high resolution mass spectrometric method was developed for the ultra-trace analysis of 10 active pharmaceutical ingredients in one chromatographic run as follows: atorvastatin, carbamazepine (CARB), ciprofloxacin (CIPR), clarithromycin (CLAR), diclofenac (DICL), metoprolol (METO), naproxen (NAPR), sitagliptin (SITA), sulfamethoxazole (SULF) and tetracycline. By applying Oasis HLB solid phase extraction cartridges, a 1250-fold enrichment was achieved. For quantitative determination, internal standard calibration was applied. Lower limits of quantification for the analytes were ≤0.025 μg/L. Good linearity was found between 0.01 and 5 μg/L in most cases. Generally, overall recovery for drinking, river and treated wastewater samples spiked with the target analytes at one concentration level comparable with the blank values and another one by one order of magnitude higher was between 80 and 120%. The relative standard deviation values were ≤16%. The proposed method has been applied for the aforementioned water matrices sampled monthly between January and March 2019. Concentration of CARB in drinking water per se was about 0.025 μg/L, confirming the low removal rates during river bank filtration applied for drinking water production. Seven compounds were present in the river water in ≤50 ng/L. Eight compounds were detected at least once from the treated wastewater samples including CARB, DICL, NAPR and SITA in >1 μg/L. Concentration of CARB, DICL, METO, SITA used for chronic affections was almost constant during the monitored time period. To the contrary, concentration of CIPR, CLAR, SULF used for acute infections registered peak values in the same samples taken in winter.}, journal={Microchemical Journal}, author={Krakkó, D. and Licul-Kucera, V. and Záray, G. and Mihucz, V.G.}, year={2019}, pages={108–119} }