Browsing by Subject "ACIDS"

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  • McVey, Alyssa; Bartlett, Sean; Kajbaf, Mahmoud; Pellacani, Annalisa; Gatta, Viviana; Tammela, Päivi; Spring, David R.; Welch, Martin (2020)
    Pseudomonas aeruginosa is an opportunistic pathogen responsible for many hospital-acquired infections. P. aeruginosa can thrive in diverse infection scenarios by rewiring its central metabolism. An example of this is the production of biomass from C-2 nutrient sources such as acetate via the glyoxylate shunt when glucose is not available. The glyoxylate shunt is comprised of two enzymes, isocitrate lyase (ICL) and malate synthase G (MS), and flux through the shunt is essential for the survival of the organism in mammalian systems. In this study, we characterized the mode of action and cytotoxicity of structural analogs of 2-aminopyridines, which have been identified by earlier work as being inhibitory to both shunt enzymes. Two of these analogs were able to inhibit ICL and MS in vitro and prevented growth of P. aeruginosa on acetate (indicating cell permeability). Moreover, the compounds exerted negligible cytotoxicity against three human cell lines and showed promising in vitro drug metabolism and safety profiles. Isothermal titration calorimetry was used to confirm binding of one of the analogs to ICL and MS, and the mode of enzyme inhibition was determined. Our data suggest that these 2-aminopyridine analogs have potential as anti-pseudomonal agents.
  • Similä, Minna E.; Auranen, Mari; Piirilä, Päivi Liisa (2020)
    Background: A deficiency of muscle phosphofructokinase (PFKM) causes a rare metabolic muscle disease, the Tarui disease (Glycogen storage disease type VII, GSD VII) characterized by exercise intolerance with myalgia due to an inability to use glucose as an energy resource. No medical treatment for GSD VII currently exists. The aim of this study was to determine whether a dietary intervention with excessive fat intake would benefit GSD VII.Patient and Methods: A ketogenic diet (KD) intervention implemented as a modified Atkins diet was established for one patient with PFKM deficiency, with a low late lactate response and very high ammonia levels associated with exercise. We recorded the KD intervention for a total of 5 years with clinical and physiotherapeutic evaluations and regular laboratory parameters. Cardiopulmonary exercise testing, including breath gas analysis and venous lactate and ammonia measurements, was performed before KD and at 3, 8 months and 5 years after initiation of KD.Results: During the 5 years on KD, the patient's muscle symptoms had alleviated and exercise tolerance had improved. In exercise testing, venous ammonia had normalized, the lactate profile remained similar, but oxygen uptake and mechanical efficiency had increased and parameters showing ventilation had improved.Conclusions: This study is the first to show a long-term effect of KD in GSD VII with an alleviation of muscle symptoms, beneficial effects on breathing, and improvement in exercise performance and oxygen uptake. Based on these findings, KD can be recommended under medical and nutritional supervision for selected patients with GSD VII, although further research of this rare disease is warranted.
  • Saarinen, Tuure; Pietiläinen, Kirsi H.; Loimaala, Antti; Ihalainen, Toni; Sammalkorpi, Henna; Penttilä, Anne; Juuti, Anne (2020)
    INTRODUCTION: Data on postoperative bile reflux after one anastomosis gastric bypass (OAGB) is lacking. Bile reflux scintigraphy (BRS) has been shown to be a reliable non-invasive tool to assess bile reflux after OAGB. We set out to study bile reflux after OAGB with BRS and endoscopy in a prospective series (RYSA Trial). METHODS: Forty patients (29 women) underwent OAGB between November 2016 and December 2018. Symptoms were reported and upper gastrointestinal endoscopy (UGE) was done preoperatively. Six months after OAGB, bile reflux was assessed in UGE findings and as tracer activity found in gastric tube and esophagus in BRS (follow-up rate 95%). RESULTS: Twenty-six patients (68.4%) had no bile reflux in BRS. Twelve patients (31.6%) had bile reflux in the gastric pouch in BRS and one of them (2.6%) had bile reflux also in the esophagus 6 months postoperatively. Mean bile reflux activity in the gastric pouch was 5.2% (1-21%) of total activity. De novo findings suggestive of bile reflux (esophagitis, stomal ulcer, foveolar inflammation of gastric pouch) were found for 15 patients (39.5%) in postoperative UGE. BRS and UGE findings were significantly associated (P = 0.022). Eight patients experienced de novo reflux symptoms at 6 months, that were significantly associated with BRS and de novo UGE findings postoperatively (P = 0.033 and 0.0005, respectively). CONCLUSION: Postoperative bile reflux in the gastric pouch after OAGB is a common finding in scintigraphy and endoscopy. The long-term effects of bile exposure will be analyzed in future reports after a longer follow-up. TRIAL REGISTRATION: Clinical Trials Identifier NCT02882685.
  • Luukkonen, Panu K.; Dufour, Sylvie; Lyu, Kun; Zhang, Xian-Man; Hakkarainen, Antti; Lehtimäki, Tiina E.; Cline, Gary W.; Petersen, Kitt Falk; Shulman, Gerald I.; Yki-Järvinen, Hannele (2020)
    Weight loss by ketogenic diet (KD) has gained popularity in management of nonalcoholic fatty liver disease (NAFLD). KD rapidly reverses NAFLD and insulin resistance despite increasing circulating nonesterified fatty acids (NEFA), the main substrate for synthesis of intrahepatic triglycerides (IHTG). To explore the underlying mechanism, we quantified hepatic mitochondrial fluxes and their regulators in humans by using positional isotopomer NMR tracer analysis. Ten overweight/obese subjects received stable isotope infusions of: [D-7]glucose, [C-13(4)]beta-hydroxybutyrate and [3-C-13]lactate before and after a 6-d KD. IHTG was determined by proton magnetic resonance spectroscopy (H-1-MRS). The KD diet decreased IHTG by 31% in the face of a 3% decrease in body weight and decreased hepatic insulin resistance (-58%) despite an increase in NEFA concentrations (+35%). These changes were attributed to increased net hydrolysis of IHTG and partitioning of the resulting fatty acids toward keto-genesis (+232%) due to reductions in serum insulin concentrations (-53%) and hepatic citrate synthase flux (-38%), respectively. The former was attributed to decreased hepatic insulin resistance and the latter to increased hepatic mitochondrial redox state (+167%) and decreased plasma leptin (-45%) and triiodothyronine (-21%) concentrations. These data demonstrate heretofore unde-scribed adaptations underlying the reversal of NAFLD by KD: That is, markedly altered hepatic mitochondrial fluxes and redox state to promote ketogenesis rather than synthesis of IHTG.
  • Varnai, Aniko; Costa, Thales H. F.; Faulds, Craig B.; Milagres, Adriane M. F.; Siika-aho, Matti; Ferraz, Andre (2014)
    Background: Sugar cane internodes can be divided diagonally into four fractions, of which the two innermost ones are the least recalcitrant pith and the moderately accessible pith-rind interface. These fractions differ in enzymatic hydrolyzability due to structural differences. In general, cellulose hydrolysis in plants is hindered by its physical interaction with hemicellulose and lignin. Lignin is believed to be linked covalently to hemicellulose through hydroxycinnamic acids, forming a compact matrix around the polysaccharides. Acetyl xylan esterase and three feruloyl esterases were evaluated for their potential to fragment the lignocellulosic network in sugar cane and to indirectly increase the accessibility of cellulose. Results: The hydrolyzability of the pith and pith-rind interface fractions of a low-lignin-containing sugar cane clone (H58) was compared to that of a reference cultivar (RC). Acetyl xylan esterase enhanced the rate and overall yield of cellulose and xylan hydrolysis in all four substrates. Of the three feruloyl esterases tested, only TsFaeC was capable of releasing p-coumaric acid, while AnFaeA and NcFaeD released ferulic acid from both the pith and interface fractions. Ferulic acid release was higher from the less recalcitrant clone (H58)/fraction (pith), whereas more p-coumaric acid was released from the clone (RC)/fraction (interface) with a higher lignin content. In addition, a compositional analysis of the four fractions revealed that p-coumaroyl content correlated with lignin, while feruloyl content correlated with arabinose content, suggesting different esterification patterns of these two hydroxycinnamic acids. Despite the extensive release of phenolic acids, feruloyl esterases only moderately promoted enzyme access to cellulose or xylan. Conclusions: Acetyl xylan esterase TrAXE was more efficient in enhancing the overall saccharification of sugar cane, compared to the feruloyl esterases AnFaeA, TsFaeC, and NcFaeD. The hydroxycinnamic acid composition of sugar cane fractions and the hydrolysis data together suggest that feruloyl groups are more likely to decorate xylan, while p-coumaroyl groups are rather linked to lignin. The three different feruloyl esterases had distinct product profiles on non-pretreated sugar cane substrate, indicating that sugar cane pith could function as a possible natural substrate for feruloyl esterase activity measurements. Hydrolysis data suggest that TsFaeC was able to release p-coumaroyl groups esterifying lignin.
  • Boren, Jan; Adiels, Martin; Bjornson, Elias; Matikainen, Niina; Söderlund, Sanni; Rämö, Joel; Ståhlman, Marcus; Ripatti, Pietari; Ripatti, Samuli; Palotie, Aarno; Mancina, Rosellina M.; Hakkarainen, Antti; Romeo, Stefano; Packard, Chris J.; Taskinen, Marja-Riitta (2020)
    Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation. The transmembrane 6 superfamily member 2 (TM6SF2) E167K genetic variant associates with NAFLD and with reduced plasma triglyceride levels in humans. However, the molecular mechanisms underlying these associations remain unclear. We hypothesized that TM65F2 E167K affects hepatic very low-density lipoprotein (VLDL) secretion and studied the kinetics of apolipoprotein 13100 (apoB100) and triglyceride metabolism in VLDL in homozygous subjects. In 10 homozygote TM6SF2 E167K carriers and 10 matched controls, we employed stable-isotope tracer and compartmental modeling techniques to determine apoB100 and triglyceride kinetics in the 2 major VIOL subtractions: large triglyceride-rich VLDL, and smaller, less triglyceride-rich VLDL2. VLDL1-apoB100 production was markedly reduced in homozygote TM6SF2 E167K carriers compared with controls. Likewise. VLDL,-triglyceride production was 35% lower in the TMSSF2 E167K carriers. In contrast, the direct production rates for VLDL2 apo13100 and triglyceride were not different between carriers and controls. In conclusion, the TM6SF2 E167K genetic variant was linked to a specific reduction in hepatic secretion of large triglyceride-rich VLDL1. The impaired secretion of VLDL1 explains the reduced plasma triglyceride concentration and provides a basis for understanding the lower risk of cardiovascular disease associated with the TM6SF2 E167K genetic variant.
  • Mynttinen, Elsi; Wester, Niklas; Lilius, Tuomas; Kalso, Eija; Mikladal, Bjorn; Varjos, Ilkka; Sainio, Sami; Jiang, Hua; Kauppinen, Esko I.; Koskinen, Jari; Laurila, Tomi (2020)
    Oxycodone is a strong opioid frequently used as an analgesic. Although proven efficacious in the management of moderate to severe acute pain and cancer pain, use of oxycodone imposes a risk of adverse effects such as addiction, overdose, and death. Fast and accurate determination of oxycodone blood concentration would enable personalized dosing and monitoring of the analgesic as well as quick diagnostics of possible overdose in emergency care. However, in addition to the parent drug, several metabolites are always present in the blood after a dose of oxycodone, and to date, there is no electrochemical data available on any of these metabolites. In this paper, a single-walled carbon nanotube (SWCNT) electrode and a Nafion-coated SWCNT electrode were used, for the first time, to study the electrochemical behavior of oxycodone and its two main metabolites, noroxycodone and oxymorphone. Both electrode types could selectively detect oxycodone in the presence of noroxycodone and oxymorphone. However, we have previously shown that addition of a Nafion coating on top of the SWCNT electrode is essential for direct measurements in complex biological matrices. Thus, the Nafion/SWCNT electrode was further characterized and used for measuring clinically relevant concentrations of oxycodone in buffer solution. The limit of detection for oxycodone with the Nafion/SWCNT sensor was 85 nM, and the linear range was 0.5-10 mu M in buffer solution. This study shows that the fabricated Nafion/SWCNT sensor has potential to be applied in clinical concentration measurements.
  • Luukkonen, Panu K.; Zhou, You; Sädevirta, Sanja; Leivonen, Marja; Arola, Johanna; Oresic, Matej; Hyotylainen, Tuulia; Yki-Jarvinen, Hannele (2016)
    Background & Aims: Recent data in mice have identified de novo ceramide synthesis as the key mediator of hepatic insulin resistance (IR) that in humans characterizes increases in liver fat due to IR ('Metabolic NAFLD' but not that due to the I148M gene variant in PNPLA3 ('PNPLA3 NAFLD'). We determined which bioactive lipids co-segregate with IR in the human liver. Methods: Liver lipidome was profiled in liver biopsies from 125 subjects that were divided into equally sized groups based on median HOMA-IR ('High and Low HOMA-IR', n = 62 and n = 63) or PNPLA3 genotype (PNPIA3(148MM/MI), n = 61 vs. PNPLA3(148II), n = 64). The subjects were also divided into 4 groups who had either IR, the I148M gene variant, both of the risk factors or neither. Results: Steatosis and NASH prevalence were similarly increased in 'High HOMA-IR' and PNPLA3(148MM/MI) groups compared to their respective control groups. The 'High HOMA-IR' but not the PNPLA3(148MM/MI) group had features of IR. The liver in 'High HOMA-IR' vs. low HOMA-IR' was markedly enriched in saturated and monounsaturated triacylglycerols and free fatty acids, dihydroceramides (markers of de novo ceramide synthesis) and ceramides. Markers of other ceramide synthetic pathways were unchanged. In PNPLA3(148MM/MI) vs. PNPLA3(148II), the increase in liver fat was due to polyunsaturated triacylglycerols while other lipids were unchanged. Similar changes were observed when data were analyzed using the 4 subgroups. Conclusions: Similar increases in liver fat and NASH are associated with a metabolically harmful saturated, ceramide-enriched liver lipidome in 'Metabolic NAFLD' but not in 'PNPLA3 NAFLD'. This difference may explain why metabolic but not PNPLA3 NAFLD increases the risk of type 2 diabetes and cardiovascular disease. (C) 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
  • Kuang, Alan; Erlund, Iris; Herder, Christian; Westerhuis, Johan A.; Tuomilehto, Jaakko; Cornelis, Marilyn C. (2018)
    Coffee is widely consumed and contains many bioactive compounds, any of which may impact pathways related to disease development. Our objective was to identify individual lipid changes in response to coffee drinking. We profiled the lipidome of fasting serum samples collected from a previously reported single blinded, three-stage clinical trial. Forty-seven habitual coffee consumers refrained from drinking coffee for 1 month, consumed 4 cups of coffee/day in the second month and 8 cups/day in the third month. Samples collected after each coffee stage were subject to quantitative lipidomic profiling using ion-mobility spectrometry-mass spectrometry. A total of 853 lipid species mapping to 14 lipid classes were included for univariate analysis. Three lysophosphatidylcholine (LPC) species including LPC (20:4), LPC (22:1) and LPC (22:2), significantly decreased after coffee intake (p <0.05 and q <0.05). An additional 72 species mapping to the LPC, free fatty acid, phosphatidylcholine, cholesteryl ester and triacylglycerol classes of lipids were nominally associated with coffee intake (p <0.05 and q > 0.05); 58 of these decreased after coffee intake. In conclusion, coffee intake leads to lower levels of specific LPC species with potential impacts on glycerophospholipid metabolism more generally.
  • Ren, Hao; Qiu, Xing-Ping; Shi, Yan; Yang, Peng; Winnik, Francoise M. (2019)
    A series of azopyridine-terminated poly(N-isopropylacrylamide)s (PNIPAM) (C12-PN-AzPy) (similar to 5000 <M-w <20 000 g mol(-1), polydispersity index 1.25 or less) were prepared by reversible addition fragmentation chain-transfer polymerization of NIPAM in the presence of a chain-transfer agent that contains an AzPy group and an n-dodecyl chain. In cold water, the polymers form nanoparticles (5.9 nm <R-h <10.9 nm) that were characterized by light scattering (LS), H-1 NMR diffusion experiments, and high-resolution transmission electron microscopy. We monitored the pH-dependent photoisomerization of C12-PN-AzPy nanoparticles by steady-state and time-resolved UV-vis absorption spectroscopy. Azopyridine is known to undergo a very fast cis-to-trans thermal relaxation when the azopyridine nitrogen is quaternized or bound to a hydrogen bond donor. The cis-to-trans thermal relaxation of the AzPy chromophore in an acidic nanoparticle suspension is very fast with a half-life tau = 2.3 ms at pH 3.0. It slows down slightly for nanoparticles in neutral water (tau = 0.96 s, pH 7.0), and it is very slow for AzPy-PNIPAM particles in alkaline medium (tau > 3600 s, pH 10). The pH-dependent dynamics of the cis-to-trans dark relaxation, supported by Fourier transform infrared spectroscopy, H-1 NMR spectroscopy, and LS analysis, suggest that in acidic medium, the nanoparticles consist of a core of assembled C12 chains surrounded by a shell of hydrated PNIPAM chains with the AzPy(+) end groups preferentially located near the particle/water interface. In neutral medium, the shell surrounding the core contains AzPy groups H-bonded to the amide hydrogen of the PNIPAM chain repeat units. At pH 10.0, the amide hydrogen binds preferentially to the hydroxide anions. The AzPy groups reside preferentially in the vicinity of the C12 core of the nanoparticles. The morphology of the nanoparticles results from the competition between the segregation of the hydrophobic and hydrophilic components and weak attractive interactions, such as H-bonds between the AzPy groups and the amide hydrogen of the PNIPAM repeat units.
  • Koskela, Harri; Andjelkovic, Boban; Pettersson, Annette; Rapinoja, Marja-Leena; Kuitunen, Marja-Leena; Vanninen, Paula (2018)
    The NMR-observable nuclei of the acidic and basic compounds experience pH dependence in chemical shift. This phenomenon can be exploited in NMR titrations to deter- mine pK a values of compounds, or in pH measurement of solutions using dedicated pH reference compounds. On the other hand, this sensitivity can also cause problems in, for example, metabolomics, where slight changes in pH result in significant difficulties for peak alignment between spectra of set of samples for comparative analysis. In worst case, the pH sensitivity of chemical shifts can prevent unambiguous identification of compounds. Here, we propose an alternative approach for NMR identification of pH-sensitive analytes. The H-1 and X (C-13, N-15, P-31, ...) chemical shifts in close proximity to the acidic or basic functional group should, when presented as ordered pairs, express piecewise linear correlation with distinct slope, intercept, and range. We have studied the pH dependence of H-1 and P-31 chemical shifts of the CH3-P moiety in urinary metabolites of nerve agents sarin, soman and VX using 2D H-1-P-31 fast-HMQC spectroscopy. The H-1 and P-31 chemical shifts of these chemicals appear in very narrow range, and due to subtle changes in sample pH the identification on either H-1 or P-31 chemical shift alone is uncertain. However, if the observed H-1 and P-31 chemical shifts of the CH3-P moiety of individual compounds are presented as ordered pairs, they fall into distinct linear spaces, thus, facilitating identification with high confidence.
  • Gerritsen, Jacoline; Umanets, Alexander; Staneva, Ivelina; Hornung, Bastian; Ritari, Jarmo; Paulin, Lars; Rijkers, Ger T.; de Vos, Willem M.; Smidt, Hauke (2018)
    A Gram-stain-positive, motile, rod-shaped, obligately anaerobic bacterium, designated FRIFIT, was isolated from human ileostoma effluent and characterized. On the basis of 16S rRNA gene sequence similarity, strain FRIFIT was most closely related to the species Romboutsia ilealis CRIBT (97.7 %), Romboutsia lituseburensis DSM 797(T) (97.6 %) and Romboutsia sedimentorum LAM201(T) (96.6 %). The level of DNA-DNA relatedness between strain FRIFIT and R. ilealis CRIBT was 13.9 +/- 3.3% based on DNA-DNA hybridization. Whole genome sequence-based average nucleotide identity between strain FRIFIT and closely related Romboutsia strains ranged from 78.4-79.1 %. The genomic DNA G+C content of strain FRIFIT was 27.8 mol%. The major cellular fatty acids of strain FRIFI T were saturated and unsaturated straight-chain C12-C19 fatty acids as well as cyclopropane fatty acids, with C-16:0 being the predominant fatty acid. The polar lipid profile comprised five phospholipids and six glycolipids. These results, together with differences in phenotypic features, support the proposal that strain FRIFIT represents a novel species within the genus Romboutsia, for which the name Romboutsia hominis sp. nov. is proposed. The type strain is FRIFIT (=DSM 28814(T) = KCTC 15553(T)).
  • Qadri, Sami; Lallukka-Brück, Susanna; Luukkonen, Panu K.; Zhou, You; Gastaldelli, Amalia; Orho-Melander, Marju; Sammalkorpi, Henna; Juuti, Anne; Penttilä, Anne K.; Perttilä, Julia; Hakkarainen, Antti; Lehtimäki, Tiina E.; Oresic, Matej; Hyötyläinen, Tuulia; Hodson, Leanne; Olkkonen, Vesa M.; Yki-Järvinen, Hannele (2020)
    Background & Aims The I148M variant in PNPLA3 is the major genetic risk factor for non-alcoholic fatty liver disease (NAFLD). The liver is enriched with polyunsaturated triglycerides (PUFA-TGs) in PNPLA3-I148M carriers. Gene expression data indicate that PNPLA3 is liver-specific in humans, but whether it functions in adipose tissue (AT) is unknown. We investigated whether PNPLA3-I148M modifies AT metabolism in human NAFLD. Methods Profiling of the AT lipidome and fasting serum non-esterified fatty acid (NEFA) composition was conducted in 125 volunteers (PNPLA3(148MM/MI), n = 63; PNPLA3(148II), n = 62). AT fatty acid composition was determined in 50 volunteers homozygous for the variant (PNPLA3(148MM), n = 25) or lacking the variant (PNPLA3(148II), n = 25). Whole-body insulin sensitivity of lipolysis was determined using [H-2(5)]glycerol, and PNPLA3 mRNA and protein levels were measured in subcutaneous AT and liver biopsies in a subset of the volunteers. Results PUFA-TGs were significantly increased in AT in carriers versus non-carriers of PNPLA3-I148M. The variant did not alter the rate of lipolysis or the composition of fasting serum NEFAs. PNPLA3 mRNA was 33-fold higher in the liver than in AT (P <.0001). In contrast, PNPLA3 protein levels per tissue protein were three-fold higher in AT than the liver (P <.0001) and nine-fold higher when related to whole-body AT and liver tissue masses (P <.0001). Conclusions Contrary to previous assumptions, PNPLA3 is highly abundant in AT. PNPLA3-I148M locally remodels AT TGs to become polyunsaturated as it does in the liver, without affecting lipolysis or composition of serum NEFAs. Changes in AT metabolism do not contribute to NAFLD in PNPLA3-I148M carriers.
  • Nie, Wei; Hong, Juan; Häme (o.s. Häkkinen), Silja A. K.; Ding, Aijun; Li, Yugen; Yan, Chao; Hao, Liqing; Mikkilä, Jyri; Zheng, Longfei; Xie, Yuning; Zhu, Caijun; Xu, Zheng; Chi, Xuguang; Huang, Xin; Zhou, Yang; Lin, Peng; Virtanen, Annele; Worsnop, Douglas R.; Kulmala, Markku; Ehn, Mikael; Yu, Jianzhen; Kerminen, Veli-Matti; Petäjä, Tuukka (2017)
    The volatility of organic aerosols remains poorly understood due to the complexity of speciation and multiphase processes. In this study, we extracted humic-like substances (HULIS) from four atmospheric aerosol samples collected at the SORPES station in Nanjing, eastern China, and investigated the volatility behavior of particles at different sizes using a Volatility Tandem Differential Mobility Analyzer (VTDMA). In spite of the large differences in particle mass concentrations, the extracted HULIS from the four samples all revealed very high-oxidation states (O : C > 0.95), indicating secondary formation as the major source of HULIS in Yangtze River Delta (YRD). An overall low volatility was identified for the extracted HULIS, with the volume fraction remaining (VFR) higher than 55% for all the regenerated HULIS particles at the temperature of 280 degrees C. A kinetic mass transfer model was applied to the thermodenuder (TD) data to interpret the observed evaporation pattern of HULIS, and to derive the mass fractions of semi-volatile (SVOC), low-volatility (LVOC) and extremely low-volatility components (ELVOC). The results showed that LVOC and ELVOC dominated (more than 80 %) the total volume of HULIS. Atomizing processes led to a size-dependent evaporation of regenerated HULIS particles, and resulted in more ELVOC in smaller particles. In order to understand the role of interaction between inorganic salts and atmospheric organic mixtures in the volatility of an organic aerosol, the evaporation of mixed samples of ammonium sulfate (AS) and HULIS was measured. The results showed a significant but nonlinear influence of ammonium sulfate on the volatility of HULIS. The estimated fraction of ELVOC in the organic part of the largest particles (145 nm) increased from 26 %, in pure HULIS samples, to 93% in 1 : 3 (mass ratio of HULIS : AS) mixed samples, to 45% in 2 : 2 mixed samples, and to 70% in 3 : 1 mixed samples, suggesting that the interaction with ammonium sulfate tends to decrease the volatility of atmospheric organic compounds. Our results demonstrate that HULIS are important low-volatility, or even extremely low-volatility, compounds in the organic-aerosol phase. As important formation pathways of atmospheric HULIS, multiphase processes, including oxidation, oligomerization, polymerization and interaction with inorganic salts, are indicated to be important sources of low-volatility and extremely low-volatility species of organic aerosols.