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Background: As highlighted by recent pandemic outbreaks, antiviral drugs are crucial resources in the global battle against viral diseases. Unfortunately, most antiviral drugs are characterized by a plethora of side effects and low efficiency/poor bioavailability owing to their insolubility. This also applies to the arylnaphthalide lignin family member, diphyllin (Diph). Diph acts as a vacuolar ATPase inhibitor and has been previously identified as a promising candidate with broad-spectrum antiviral activity. However, its physicochemical properties preclude its efficient administration in vivo, complicating preclinical testing. Methods: We produced human recombinant H- ferritin (HsaFtH) and used it as a delivery vehicle for Diph encapsulation through pH-mediated reversible reassembly of HsaFtH. Diph nanoformulation was subsequently thoroughly characterized and tested for its non-target cytotoxicity and antiviral efficiency using a panel of pathogenic viral strain. Results: We revealed that loading into HsaFtH decreased the undesired cytotoxicity of Diph in mammalian host cells. We also confirmed that encapsulated Diph exhibited slightly lower antiviral activity than free Diph, which may be due to the differential uptake mechanism and kinetics of free Diph and Diph@HsaFtH. Furthermore, we confirmed that the antiviral effect was mediated solely by Diph with no contribution from HsaFtH. Conclusion: It was confirmed that HsaFtH is a suitable vehicle that allows easy loading of Diph and production of highly homogeneous nanoparticles dispersion with promising broad-spectrum antiviral activity., info:eu-repo/semantics/openAccess

Michaela Vojnikova,1,2,* Martina Sukupova,1,3,* Michal Stefanik,1,4 Petra Strakova,3– 5 Jan Haviernik,4 Katerina Kapolkova,1 Eliska Gruberova,1 Klara Raskova,1 Hana Michalkova,1 Pavel Svec,1 Marie Peskova Kudlickova,1 Ivana Huvarova,4 Daniel Ruzek,3– 5 Jiri Salat,3– 5 Vladimir Pekarik,1 Ludek Eyer,3– 5 Zbynek Heger1 1Department of Chemistry and Biochemistry, Mendel University in Brno, Brno, Czech Republic; 2Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic; 3Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic; 4Department of infectious Diseases and Preventive Medicine, Veterinary Research Institute, Brno, Czech Republic; 5Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Ceske Budejovice, Czech Republic*These authors contributed equally to this workCorrespondence: Zbynek Heger, Research Group for Molecular Biology and Nanomedicine, Department of Chemistry and Biochemistry, Mendel University in Brno, Brno, CZ-613 00, Czech Republic, Tel +420-5-4513-3350, Fax +420-5-4521-2044, Email heger@mendelu.czBackground: As highlighted by recent pandemic outbreaks, antiviral drugs are crucial resources in the global battle against viral diseases. Unfortunately, most antiviral drugs are characterized by a plethora of side effects and low efficiency/poor bioavailability owing to their insolubility. This also applies to the arylnaphthalide lignin family member, diphyllin (Diph). Diph acts as a vacuolar ATPase inhibitor and has been previously identified as a promising candidate with broad-spectrum antiviral activity. However, its physicochemical properties preclude its efficient administration in vivo, complicating preclinical testing.Methods: We produced human recombinant H- ferritin (HsaFtH) and used it as a delivery vehicle for Diph encapsulation through pH-mediated reversible reassembly of HsaFtH. Diph nanoformulation was subsequentl

Pristine peatlands are carbon (C) accumulating wetland ecosystems sustained by a high water table (WT) and consequent anoxia that slows down decomposition. Persistent WT drawdown as a response to climate and/or land-use change affects decomposition either directly through environmental factors such as increased oxygenation, or indirectly through changes in plant community composition. This study attempts to disentangle the direct and indirect effects of WT drawdown by measuring the relative importance of environmental parameters (WT depth, temperature, soil chemistry) and litter type and/or litter chemical quality on the 2-year decomposition rates of above- and belowground litter (altogether 39 litter types). Consequences for organic matter accumulation were estimated based on the annual litter production. The study sites were chosen to form a three stage chronosequence from pristine (undrained) to short-term (years) and long-term (decades) WT drawdown conditions at three nutrient regimes. The direct effects of WT drawdown were overruled by the indirect effects via changes in litter type composition and production. Short-term responses to WT drawdown were small. In long-term, dramatically increased litter inputs resulted in large accumulation of organic matter in spite of increased decomposition rates. Further, the quality of the accumulated matter greatly changed from that accumulated in pristine conditions. Our results show that the shift in vegetation composition as a response to climate and/or land-use change is the main factor affecting peatland ecosystem C cycle and thus dynamic vegetation is a necessity in any models applied for estimating responses of C fluxes to changing environment. We provide possible grouping of litter types into plant functional types that the models could utilize. Further, our results clearly show a drop in soil summer temperature as a response to WT drawdown when an initially open peatland converts into a forest ecosystem, which has n

Peatlands are carbon (C) storage ecosystems sustained by a high water level (WL). High WL creates anoxic conditions that suppress the activity of aerobic decomposers and provide conditions for peat accumulation. Peatland function can be dramatically affected by WL drawdown caused by land-use and/or climate change. Aerobic decomposers are directly affected by WL drawdown through environmental factors such as increased oxygenation and nutrient availability. Additionally, they are indirectly affected via changes in plant community composition and litter quality. We studied the relative importance of direct and indirect effects of WL drawdown on aerobic decomposer activity in plant litter. We did this by profiling 11 extracellular enzymes involved in the mineralization of organic C, nitrogen, phosphorus and sulphur. Our study sites represented a three-stage chronosequence from pristine (undrained) to short-term (years) and long-term (decades) WL drawdown conditions under two nutrient regimes. The litter types included reflected the prevalent vegetation, i.e., Sphagnum mosses, graminoids, shrubs and trees. WL drawdown had a direct and positive effect on microbial activity. Enzyme allocation shifted towards C acquisition, which caused an increase in the rate of decomposition. However, litter type overruled the direct effects of WL drawdown and was the main factor shaping microbial activity patterns. Our results imply that changes in plant community composition in response to persistent WL drawdown will strongly affect the C dynamics of peatlands.

Changes in the structure of plant communities may have much more impact on ecosystem carbon (C) cycling than any phenotypic responses to environmental changes. We studied these impacts via the response of plant litter quality, at the level of species and community, to persistent water-level (WL) drawdown in peatlands. We studied three sites with different nutrient regimes, and water-level manipulations at two time scales. The parameters used to characterize litter quality included extractable substances, cellulose, holocellulose, composition of hemicellulose (neutral sugars, uronic acids), Klason lignin, CuO oxidation phenolic products, and concentrations of C and several nutrients. The litters formed four chemically distinct groups: non-graminoid foliar litters, graminoids, mosses and woody litters. Direct effects of WL drawdown on litter quality at the species level were overruled by indirect effects via changes in litter type composition. The pristine conditions were characterized by Sphagnum moss and graminoid litters. Short-term (years) responses of the litter inputs to WL drawdown were small. In longterm (decades), total litter inputs increased, due to increased tree litter inputs. Simultaneously, the litter type composition and its chemical quality at the community level greatly changed. The changes that we documented will strongly affect soil properties and C cycle of peatlands.

Pristine peatlands are carbon (C) accumulating wetland ecosystems sustained by a high water level (WL) and consequent anoxia that slows down decomposition. Persistent WL drawdown as a response to climate and/or land-use change directly affects decomposition: increased oxygenation stimulates decomposition of the old C (peat) sequestered under prior anoxic conditions. Responses of the new C (plant litter) in terms of quality, production and decomposability, and the consequences for the whole C cycle of peatlands are not fully understood. WL drawdown induces changes in plant community resulting in shift in dominance from Sphagnum and graminoids to shrubs and trees. There is increasing evidence that the indirect effects of WL drawdown via the changes in plant communities will have more impact on the ecosystem C cycling than any direct effects. The aim of this study is to disentangle the direct and indirect effects of WL drawdown on the new C by measuring the relative importance of 1) environmental parameters (WL depth, temperature, soil chemistry) and 2) plant community composition on litter production, microbial activity, litter decomposition rates and, consequently, on the C accumulation. This information is crucial for modelling C cycle under changing climate and/or land-use. The effects of WL drawdown were tested in a large-scale experiment with manipulated WL at two time scales and three nutrient regimes. Furthermore, the effect of climate on litter decomposability was tested along a north-south gradient. Additionally, a novel method for estimating litter chemical quality and decomposability was explored by combining Near infrared spectroscopy with multivariate modelling. WL drawdown had direct effects on litter quality, microbial community composition and activity and litter decomposition rates. However, the direct effects of WL drawdown were overruled by the indirect effects via changes in litter type composition and production. Short-term (years) responses to WL, Luonnontilaiset suot ovat hiiltä sitovia ekosysteemejä. Niissä maaperän märkyydestä johtuva hapen niukkuus hidastaa orgaanisen aineen hajotusta. Ilmaston tai maankäytön muutos voi aiheuttaa suon pitkäkestoisen kuivumisen. Se vaikuttaa sekä suorasti että epäsuorasti hajotukseen ja sitä kautta hiilen kiertoon ja hiilitaseeseen. Merkittävin suora vaikutus on maaperän hapekkuuden lisääntyminen, mikä nopeuttaa hajotusta. Epäsuorasti kuivuminen vaikuttaa muuttamalla suon kasviyhteisöä: tyypillisten suokasvien, kuten rahkasammalten ja sarojen, biomassa, tuotos ja karikesyöte vähenevät, kun taas varpujen ja puiden lisääntyvät. Kasviyhteisössä ja sen karikesyötteessä tapahtuvilla muutoksilla voi olla suurempi vaikutus hiilen kiertoon kuin vedenpinnan alenemisella sinänsä. Näiden muutosten suuntaa ja merkitystä koko ekosysteemin hiilitaseelle ei kuitenkaan vielä tunneta riittävästi. Tässä työssä tarkasteltiin vedenpinnan tason vaikutusta suohon tulevan karikkeen määrään, kemiallisiin ominaisuuksiin, mikrobiaktiivisuuteen ja hajoamisnopeuteen, ja näiden lopputulemana tapahtuvaan uuden orgaanisen aineen kertymään. Kuivumisen suorien ja epäsuorien vaikutusten merkitystä arvioitiin vertailemalla ympäristötekijöiden (vedenpinnan taso sekä maan lämpötila ja kemialliset ominaisuudet) ja kasvillisuuden koostumuksen selitysvoimaa. Tätä tietoa tarvitaan, kun mallinnetaan soiden hiilen kiertoa muuttuvissa olosuhteissa. Lyhyt- (muutamia vuosia) ja pitkäkestoisen (muutamia vuosikymmeniä) kuivumisen vaikutuksia tutkittiin kolmella eri ravinteisuustasolla. Ilmaston vaikutusta arvioitiin lisäksi vertailemalla Pohjois- ja Etelä-Suomessa sekä Virossa sijaitsevia koealoja. Karikkeen kemiallisen koostumuksen ja hajotettavuuden arviointiin kokeiltiin perinteisten uuttomenetelmien ja regressiomallien lisäksi nopeaa ja edullista infrapunaspektroskopiaa ja monimuuttuja-analyysiä. Vedenpinnan aleneminen vaikutti kasvilajitasolla karikkeen laatuun, kariketta hajottavaan mikrobiyhteisöön ja karikkeen h