INTRODUCTION: The Covid-19 pandemic affected food systems in many countries and emphasized a lot of already existing social, economic and environmental agri-food problems. Alternative food networks (AFNs), praised for their ability to improve the food systems, were under stress, however, at the same time, the changed conditions may have opened new possibilities. In this paper we address the importance of AFNs during the pandemic and investigate how households have changed their participation in AFNs. Our research is novel by simultaneously focusing on both market and non-market AFNs which are often studied separately. METHODS: A representative questionnaire study of Czech households was carried out in Autumn 2021 to provide a case study of food and consumption behavior of the European country after several waves of Covid-19. RESULTS AND DISCUSSION: Based on the responses of 515 participants, the results show that 68% of Czech households participate in some form of AFNs, be it shopping or food self-provisioning, i.e., non-market food procurement in the form of gardening. Focusing on the market AFNs, farmers' markets and farm gate sales are the most popular. Covid-19 and 2021 emerging economic pressures led to a decrease of consumption of organic food (22% of respondents) as well as fresh fruit and vegetables in general (10% of respondents) and a noticeable occurrence of food insecurity (18% of households). Based on these findings, the paper discusses the ability of AFNs to support food and nutritional resilience. Problems which may endanger market-oriented AFNs are discussed as well. CONCLUSION: By addressing both market and non-market AFNs, the paper brings new knowledge into the food environment and agri-food policies research.
- Klíčová slova
- Agri-food value chains, COVID-19, alternative food networks, food behavior, food self-provisioning, resilience,
- Publikační typ
- časopisecké články MeSH
Bromination of high-pressure, high-temperature (HPHT) nanodiamond (ND) surfaces has not been explored and can open new avenues for increased chemical reactivity and diamond lattice covalent bond formation. The large bond dissociation energy of the diamond lattice-oxygen bond is a challenge that prevents new bonds from forming, and most researchers simply use oxygen-terminated NDs (alcohols and acids) as reactive species. In this work, we transformed a tertiary-alcohol-rich ND surface to an amine surface with ∼50% surface coverage and was limited by the initial rate of bromination. We observed that alkyl bromide moieties are highly labile on HPHT NDs and are metastable as previously found using density functional theory. The strong leaving group properties of the alkyl bromide intermediate were found to form diamond-nitrogen bonds at room temperature and without catalysts. This robust pathway to activate a chemically inert ND surface broadens the modalities for surface termination, and the unique surface properties of brominated and aminated NDs are impactful to researchers for chemically tuning diamond for quantum sensing or biolabeling applications.
- Publikační typ
- časopisecké články MeSH
Mebendazole (MBZ) was developed as a broad-spectrum anthelmintic but has recently shown efficacy as an anticancer agent. The use of MBZ for cancer, however, is challenging due to its poor solubility leading to poor bioavailability. Herein, we developed a prodrug approach with various N-linked promoieties including acyloxymethyl, aminoacyloxymethyl, and substituted phosphonooxymethyl in attempt to improve these characteristics. Compound 12, containing an (((((isopropoxycarbonyl)oxy)methoxy)phosphoryl)oxy)methyl promoiety, showed a >10 000-fold improvement in aqueous solubility. When evaluated in mice, 12 displayed a 2.2-fold higher plasma AUC0- t and a 1.7-fold improvement in brain AUC0- t with a calculated oral bioavailability of 52%, as compared to 24% for MBZ-polymorph C (MBZ-C), the most bioavailable polymorph. In dogs, 12 showed a 3.8-fold higher plasma AUC0- t with oral bioavailability of 41% compared to 11% for MBZ-C. In summary, we have identified a prodrug of MBZ with better physicochemical properties and enhanced bioavailability in both mice and dog.
- MeSH
- anthelmintika metabolismus MeSH
- aplikace orální MeSH
- biologická dostupnost MeSH
- dusík chemie MeSH
- mebendazol metabolismus MeSH
- myši MeSH
- prekurzory léčiv aplikace a dávkování chemie metabolismus farmakokinetika MeSH
- psi MeSH
- rozpustnost MeSH
- stabilita léku MeSH
- tkáňová distribuce MeSH
- voda chemie MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- psi MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- anthelmintika MeSH
- dusík MeSH
- mebendazol MeSH
- prekurzory léčiv MeSH
- voda MeSH
4-Carboxy-α-[3-(hydroxyamino)-3-oxopropyl]-benzenepropanoic acid 1 is a potent hydroxamate-based inhibitor of glutamate carboxypeptidase II. In an attempt to improve its poor oral pharmacokinetics, we synthesized a series of prodrugs by masking its hydrophilic hydroxamate group. Prodrugs were evaluated for oral availability in mice and showed varying degree of plasma exposure to 1. Of these, para-acetoxybenzyl-based, 4-(5-(((4-acetoxybenzyl)oxy)amino)-2-carboxy-5-oxopentyl)benzoic acid, 12, provided 5-fold higher plasma levels of 1 compared to oral administration of 1 itself. Subsequently, para-acetoxybenzyl-based prodrugs with additional ester promoiety(ies) on carboxylate(s) were examined for their ability to deliver 1 to plasma. Isopropyloxycarbonyloxymethyl (POC) ester 30 was the only prodrug that achieved substantial plasma levels of 1. In vitro metabolite identification studies confirmed stability of the ethyl ester of benzoate while the POC group was rapidly hydrolyzed. At oral daily dose-equivalent of 3 mg/kg, 12 exhibited analgesic efficacy comparable to dose of 10 mg/kg of 1 in the rat chronic constrictive injury model of neuropathic pain.
- MeSH
- analgetika chemie farmakokinetika farmakologie terapeutické užití MeSH
- aplikace orální MeSH
- esterifikace MeSH
- glutamátkarboxypeptidasa II antagonisté a inhibitory metabolismus MeSH
- inhibitory enzymů chemie farmakokinetika farmakologie terapeutické užití MeSH
- krysa rodu Rattus MeSH
- kyseliny hydroxamové chemie farmakokinetika farmakologie terapeutické užití MeSH
- lidé MeSH
- myši MeSH
- neuralgie farmakoterapie enzymologie MeSH
- objevování léků MeSH
- potkani Sprague-Dawley MeSH
- prekurzory léčiv chemie farmakokinetika farmakologie terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- analgetika MeSH
- glutamátkarboxypeptidasa II MeSH
- inhibitory enzymů MeSH
- kyseliny hydroxamové MeSH
- prekurzory léčiv MeSH
Fourteen new dipolar cations have been synthesized, containing methoxy or tertiary amino electron donor groups attached to helquat (Hq) acceptors. These Hq derivatives have been characterized as their TfO- salts by using various techniques including NMR and electronic absorption spectroscopies. UV-vis spectra show intense, relatively low energy absorptions with λmax ≈ 400-600 nm, attributable to intramolecular charge-transfer (ICT) excitations. Single-crystal X-ray structures have been solved for two of the chromophores, one as its PF6- salt, revealing centrosymmetric packing arrangements (space groups Pbca and P1̅). Molecular quadratic nonlinear optical (NLO) responses have been determined directly by using hyper-Rayleigh scattering (HRS) with a 800 nm laser, and indirectly via Stark (electroabsorption) spectroscopy for the low energy absorption bands. The obtained static first hyperpolarizabilities β0 range from moderate to large: (9-140) × 10-30 esu from HRS in MeCN and (44-580) × 10-30 esu from the Stark data in PrCN. The magnitude of β0 increases upon either extending the π-conjugation length or replacing a methoxy with a tertiary amino electron donor substituent. Density functional theory (DFT) and time-dependent DFT calculations on selected tertiary amino chromophores confirm that the low energy absorptions have ICT character. Relatively good agreement between the simulated and experimental UV-vis absorption spectra is achieved by using the CAM-B3LYP functional with the 6-311G(d) basis set. The βtot values predicted by using DFT at the same level of theory are large ((472-1443) × 10-30 esu in MeCN). Both the theoretical and experimental results show that para-conjugation between Hq and electron donor fragments is optimal, and enlarging the Hq unit is inconsequential with respect to the molecular quadratic NLO response.
- Publikační typ
- časopisecké články MeSH
Nanoparticle-cell interactions begin with the cellular uptake of the nanoparticles, a process that eventually determines their cellular fate. In the present work, we show that the morphological features of nanodiamonds (NDs) affect both the anchoring and internalization stages of their endocytosis. While a prickly ND (with sharp edges/corners) has no trouble of anchoring onto the plasma membrane, it suffers from difficult internalization afterwards. In comparison, the internalization of a round ND (obtained by selective etching of the prickly ND) is not limited by its lower anchoring amount and presents a much higher endocytosis amount. Molecular dynamics simulation and continuum modelling results suggest that the observed difference in the anchoring of round and prickly NDs likely results from the reduced contact surface area with the cell membrane of the former, while the energy penalty associated with membrane curvature generation, which is lower for a round ND, may explain its higher probability of the subsequent internalization.
- MeSH
- biologické modely MeSH
- buněčná membrána chemie MeSH
- buňky Hep G2 MeSH
- endocytóza MeSH
- HeLa buňky MeSH
- lidé MeSH
- nanodiamanty chemie MeSH
- simulace molekulární dynamiky MeSH
- viabilita buněk MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- nanodiamanty MeSH
Three new dipolar cations have been synthesised, containing ferrocenyl (Fc) electron donor groups attached to helquat (Hq) acceptors. These organometallic Hq derivatives have been characterised as their TfO- salts by using various techniques including NMR and electronic absorption spectroscopies and electrochemical measurements. UV-vis spectra show multiple intense low energy absorptions attributable to intramolecular charge-transfer (ICT) excitations. Each compound displays a reversible Fc+/0 redox process, together with two reversible one-electron reductions of the Hq fragment. Molecular quadratic nonlinear optical (NLO) responses have been determined by using hyper-Rayleigh scattering at 1064 nm, and Stark (electroabsorption) spectroscopic studies on the visible absorption bands. The obtained first hyperpolarizabilities β are moderate, consistent with the relatively short π-conjugation lengths between the Fc and attached pyridinium group. A single-crystal X-ray structure has been solved for one of the complexes as its PF6- salt, revealing a centrosymmetric packing in the triclinic space group P1[combining macron]. Density functional theory (DFT) and time-dependent DFT calculations indicate that the lowest energy absorption bands have mainly metal-to-ligand charge-transfer character. The donor orbitals involved in the electronic transitions forming the next lowest energy ICT band also have substantial contributions from the Fe atom. Good agreement between the simulated and experimental UV-vis absorption spectra is achieved by using the PBE0 functional with the 6-311++G(d)/LANL2DZ mixed basis set, and the theoretical β values are reasonably large. Oxidation of the Fc unit is predicted to cause the βtot value to decrease by more than 80% in one of the complexes.
- Publikační typ
- časopisecké články MeSH
Noncovalent molecular interactions between helquats, a new class of dicationic helical extended diquats, and several chiral acidic aromatic drugs and catalysts have been investigated using partial-filling affinity capillary electrophoresis (PF-ACE). Helquats dissolved at 1mM concentration in the aqueous background electrolyte (40mM Tris, 20mM acetic acid, pH 8.1) were introduced as ligand zones of variable length (0-130mm) into the hydroxypropylcellulose coated fused silica capillary whereas 0.1mM solutions of negatively charged chiral drugs or catalysts (warfarin, ibuprofen, mandelic acid, etodolac, binaphthyl phosphate and 11 other acidic aromatic compounds) were applied as a short analyte zone at the injection capillary end. After application of electric field, analyte and ligand migrated against each other and in case of their interactions, migration time of the analyte was increasing with increasing length of the ligand zone. From the tested compounds, only isomers of those exhibiting helical chirality and/or possessing conjugated aromatic systems were enantioselectively separated through their differential interactions with helquats. Some compounds with conjugated aromatic groups interacted with helquats moderately strongly but non-enantiospecifically. Small compounds with single benzene ring exhibited no or very weak non-enantiospecific interactions. PF-ACE method allowed to determine binding constants of the analyte-helquat complexes from the changes of migration times of the analytes. Binding constants of the weakest complexes of the analytes with helquats were less than 50L/mol, whereas binding constants of the strongest complexes were in the range 1 000-1 400L/mol.
- Klíčová slova
- Affinity capillary electrophoresis, Binding constant, Chiral separation, Helquats, Noncovalent interactions, Partial filling,
- MeSH
- algoritmy MeSH
- aromatické uhlovodíky analýza MeSH
- barvicí látky MeSH
- celulosa analogy a deriváty MeSH
- elektroforéza kapilární metody MeSH
- indikátory a reagencie MeSH
- léčivé přípravky analýza MeSH
- ligandy MeSH
- stereoizomerie MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- aromatické uhlovodíky MeSH
- barvicí látky MeSH
- celulosa MeSH
- hydroxypropylcellulose MeSH Prohlížeč
- indikátory a reagencie MeSH
- léčivé přípravky MeSH
- ligandy MeSH
Inhibition of glutamate carboxypeptidase II (GCPII) is effective in preclinical models of neurological disorders associated with excessive activation of glutamatergic systems. Here we report synthesis, structural characterization, and biological activity of new hydroxamic acid-based inhibitors with nanomolar affinity for human GCPII. Crystal structures of GCPII/hydroxamate complexes revealed an unprecedented binding mode in which the putative P1' glutarate occupies the spacious entrance funnel rather than the conserved glutamate-binding S1' pocket. This unique binding mode provides a mechanistic explanation for the structure-activity relationship data, most notably the lack of enantiospecificity and the tolerance for bulky/hydrophobic functions as substituents of a canonical glutarate moiety. The in vivo pharmacokinetics profile of one of the inhibitors will be presented along with analgesic efficacy data from the rat chronic constrictive injury model of neuropathic pain.
- MeSH
- antigeny povrchové metabolismus MeSH
- glutamátkarboxypeptidasa II antagonisté a inhibitory metabolismus MeSH
- inhibitory enzymů chemická syntéza chemie farmakologie MeSH
- kyseliny hydroxamové chemická syntéza chemie farmakologie MeSH
- lidé MeSH
- molekulární modely MeSH
- molekulární struktura MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antigeny povrchové MeSH
- FOLH1 protein, human MeSH Prohlížeč
- glutamátkarboxypeptidasa II MeSH
- inhibitory enzymů MeSH
- kyseliny hydroxamové MeSH
Chirality induction phenomena attract attention because of their relevance to intermolecular interactions encountered in living matter. Usually, such effects are weak. However, enantiomers of a [6]helquat dye were found to induce exceptionally strong chirality in several achiral solvents containing nitrile groups. This effect was observable as an intense Raman optical activity (ROA) induced in acetonitrile, acetonitrile-d3, and liquid hydrogen cyanide solvents. The observation was verified by measurement of both helquat enantiomers which provided mirror image ROA spectra. Theoretical analysis indicated that the 532 nm laser excitation light was in a near resonance with electronic transitions of the dye, which made the effect observable in very dilute solutions (1 : 200 000 helquat to nitrile ratio) and thus the phenomenon can be generally useful in analytical chemistry.
- Publikační typ
- časopisecké články MeSH
