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In preparation for active microwave-based data assimilation into a crop modeling system, the mapping of daily 1-km AquaCrop model (v6.1) biomass and surface soil moisture to backscatter was optimised, using two forward operators, i.e. the Water Cloud Model (WCM) and the Support Vector Regression (SVR). Both forward operators were calibrated (2014–2018) with 1-km Sentinel-1 backscatter (ϒ°) observations in VV and VH polarisation, for three different study domains in Europe. For the validation period (2019–2021), the ϒ° simulations showed reasonable performances around Czech Republic and the Iberian Peninsula, to good performances over Belgium, but with strong variations within each domain. The domain-averaged root mean square difference between the model and Sentinel-1 ϒ° remained below 2 dB for both forward operators and all three study domains, and the mean bias for VV remained close to 0 dB, and close 0.5 dB for the VH polarisation. The WCM and SVR performed better in VV than VH and overall the SVR performed slightly better in mapping the AquaCrop soil moisture and vegetation to backscatter than the WCM. Additionally, the assumed linear relationship in the WCM between soil moisture and soil ϒ° holds better for VV than for VH. The remaining differences between WCM or SVR simulations and Sentinel-1 observations are mainly caused by AquaCrop model errors. ispartof: Remote Sensing Of Environment vol:294 status: published

Introduction: Ligands of adenosine A1Rs are potential candidates for the development of drugs for the treatment of paroxysmal supraventricular tachycardia, angina pectoris, hypertriglyceridemia, type 2 diabetes mellitus, neuropathic pain, and heart failure. At the same time, there is a deficiency of drugs that can regulate the functions of A1 receptors. A number of A1-antagonists are at the various stages of clinical trials; other drugs are not very selective or are characterized by an insufficient breadth of their therapeutic action. Therefore, the search for new medicinal compounds for the prevention and treatment of A1-depended diseases among nitro derivatives of tetrazolo[1,5-a]pyrimidine and 1,2,4-triazolo[1,5-a]pyrimidine is of scientific interest. Materials and methods: The search for active compounds was carried out by in silico and in vitro methods. At the first stage, a computer forecast of A1-antagonistic activity was carried out using the Microcosm BioS software. At the second stage, the prediction results were verified in vitro in a model of isolated mouse atria. Results and discussion: Based on the results of the prediction by the method of maximum similarity to standards, the most active compounds III, VIII, and XVII were selected. After testing the prediction results by the isolated atria method, the compound VIII was characterized by A1-blocking effect in vitro at a concentration of 10 μmol/L. Conclusion: The most promising compound with A1-blocking effect in vitro was identified; it is a derivative of tetrazolo[1,5-a]pyrimidine under the code of VIII. It is of interest for us for further in-depth study of its pharmacological properties.

Animal farms have become one of the most important reservoirs of carbapenem-resistant Klebsiella spp. (CRK) owing to the wide usage of veterinary antibiotics. “One Health”-studies observing animals, the environment, and humans are necessary to understand the dissemination of CRK in animal breeding areas. Based on the concept of “One-Health,” 263 samples of animal feces, wastewater, well water, and human feces from 60 livestock and poultry farms in Shandong province, China were screened for CRK. Five carbapenem-resistant Klebsiella pneumoniae (CRKP) and three carbapenem-resistant Klebsiella quasipneumoniae (CRKQ) strains were isolated from animal feces, human feces, and well water. The eight strains were characterized by antimicrobial susceptibility testing, plasmid conjugation assays, whole-genome sequencing, and bioinformatics analysis. All strains carried the carbapenemase-encoding gene blaNDM-5, which was flanked by the same core genetic structure (IS5-blaNDM-5-bleMBL-trpF-dsbD-IS26-ISKox3) and was located on highly related conjugative IncX3 plasmids. The colistin resistance gene mcr-8.1 was carried by three CRKP and located on self-transmissible IncFII(K)/IncFIA(HI1) and IncFII(pKP91)/IncFIA(HI1) plasmids. The genetic context of mcr-8.1 consisted of IS903-orf-mcr-8.1-copR-baeS-dgkA-orf-IS903 in three strains. Single nucleotide polymorphism (SNP) analysis confirmed the clonal spread of CRKP carrying-blaNDM-5 and mcr-8.1 between two human workers in the same chicken farm. Additionally, the SNP analysis showed clonal expansion of CRKP and CRKQ strains from well water in different farms, and the clonal CRKP was clonally related to isolates from animal farms and a wastewater treatment plant collected in other studies in the same province. These findings suggest that CRKP and CRKQ are capable of disseminating via horizontal gene transfer and clonal expansion and may pose a significant threat to public health unless preventative measures are taken.

The existence of infinitely many nontrivial solutions for a nonlocal elliptic system of $(p_1,\ldots,p_n)$-Kirchhoff type with critical exponent is investigated. The approach is based on variational methods and critical point theory.

Cupuassu (Theobroma grandiflorum Schum.) is a typical Amazonian fruit, whose seed is used as raw material to produce cupulate. The by-product of its seeds, cupuassu seed by-product (CSB), is often discarded by the cosmetic and food industry, but studies showed that it has a high content of phenolic compounds with exploitable antioxidant activity. This study aimed to identify the classes of chemical compounds present in the extract of CSB by HPTLC, to confirm them by RMN 1H spectroscopy and to analyze the extract thermal analytical behavior in different processing stages. After elution of the extract in an isocratic system, TLC plates were developed with selective reagents for several classes of chemical compounds and antioxidant activity by the DPPH· method. Butter, CSB and crude extract presented mass losses characteristic of lipid decomposition reactions (92.63, 14.80, and 15.42%, respectively). Thermal degradation of bioactive and nutritional compounds (mainly polyunsaturated fatty acids) present in both CSB and crude extract has occurred at temperatures above 189 °C. Microencapsulation of the CBS extract by spray drying (MECoC) using maltodextrin as coating agent was shown to effectively protect the phenolic compounds. RMN 1H spectra confirmed HPTLC and FTIR results, which allowed us to conclude that the crude extract of the cupuassu by-product was mainly composed of terpenes, steroids and phenolic compounds, mainly flavonoids. These analytical techniques have proven to be effective tools for assessing the bioactive compounds incorporation into the polymeric matrix expected in the pre-formulation stage.

In hemophilic patients methods are needed to better diagnose joint damage early, so that treatments can be adjusted to slow the progression of hemophilic arthropathy. The aim of this study is to investigate the relationship between the Hemophilia Joint Health Score version 2.1 (HJHS 2.1) and hemophilia early arthropathy detection with ultrasound (HEAD-US) scales, as well as each of their individual items, to better understand the value each provides on the joint condition of patients with hemophilia. The study included data from patients with hemophilia older than 16 years of age, who attended a routine check-up. HJHS 2.1 and HEAD-US assessments were performed on the elbows, knees and ankles. We studied the correlations and agreements between the two scales and analyzed the relationship between the various items of the HJHS 2.1 (inflammation, duration, atrophy, crepitation, flexion deficit, extension deficit, pain, strength, gait) and HEAD-US (synovitis, cartilage and bone). The study included 203 joints from 66 patients with hemophilia (mean age, 34 years). We found a good correlation between the two scales (r = 0.717). However, HJHS 2.1 revealed only 54% of the cases with synovitis and 75% of the cases with osteochondral damage. HEAD-US detected several relevant physical and functional aspects in less than 53% of the cases. HJHS 2.1 and HEAD-US provide complementary data on joint disease in adults with hemophilia; both assessments should therefore, be made available. HEAD-US presented the added value of detecting early joint changes (synovitis and osteochondral damage), while HJHS 2.1 showed the added value of detecting relevant physical and functional changes.

A series of novel σ1 receptor ligands with a 4-(2-aminoethyl)piperidine scaffold was prepared and biologically evaluated. The underlying concept of our project was the improvement of the lipophilic ligand efficiency of previously synthesized potent σ1 ligands. The key steps of the synthesis comprise the conjugate addition of phenylboronic acid at dihydropyridin-4(1H)-ones 7, homologation of the ketones 8 and introduction of diverse amino moieties and piperidine N-substituents. 1-Methylpiperidines showed particular high σ1 receptor affinity and selectivity over the σ2 subtype, whilst piperidines with a proton, a tosyl moiety or an ethyl moiety exhibited considerably lower σ1 affinity. Molecular dynamics simulations with per-residue binding free energy deconvolution demonstrated that different interactions of the basic piperidine-N-atom and its substituents (or the cyclohexane ring) with the lipophilic binding pocket consisting of Leu105, Thr181, Leu182, Ala185, Leu186, Thr202 and Tyr206 are responsible for the different σ1 receptor affinities. Recorded logD7.4 and calculated clogP values of 4a and 18a indicate low lipophilicity and thus high lipophilic ligand efficiency. Piperidine 4a inhibited the growth of human non-small cell lung cancer cells A427 to a similar extent as the σ1 antagonist haloperidol. 1-Methylpiperidines 20a, 21a and 22a showed stronger antiproliferative effects on androgen negative human prostate cancer cells DU145 than the σ1 ligands NE100 and S1RA.

Extracellular DNA (exDNA) widely occurs in the environment due to release by either cell lysis or active secretion. The role of exDNA in plant-soil interactions has been investigated and inhibitory effects on the growth of conspecific individuals by their self-DNA have been reported. Transcriptome analysis in the model plant Arabidopsis thaliana showed a clear recognition by the plant roots of self- and nonself-exDNA, with inhibition occurring only after exposure to the former. In this study, an untargeted metabolomics approach was used to assess at molecular level the plant reactions to exDNA exposure. Thus, the effects on the metabolites profile of A. thaliana after exposure to self- and nonself-exDNA from plants and fish, were studied by NMR, LC-MS, chemometrics and molecular networking analyses. Results show that self-DNA significantly induces the accumulation of RNA constituents (nucleobases, ribonucleosides, dinucleotide and trinucleotide oligomers). Interestingly, AMP and GMP are found along with their cyclic analogues cAMP and cGMP, and in form of cyclic dimers (c-di-AMP and c-di-GMP). Also methylated adenosine monophosphate (m6AMP) and the dimeric dinucleotide N-methyladenylyl-(3'→5') cytidine (m6ApC) increased only in the self-DNA treatment. Such striking evidence of self-DNA effects highlights a major role of exDNA in plant sensing of its environment.

Plasma membrane intrinsic protein (PIP) is one of the largest subfamilies of Aquaporins (AQPs) and plays an important role in plant growth and development, and resistance to abiotic stress. In this study, the full length of the EuPIP1;1 cDNA was cloned from Eucommia ulmoides using the rapid amplification of cDNA ends (RACE) method. The EuPIP1;1 gene was induced by drought treatment and expressed in all tested tissues, with the highest expression level in fruit. The subcellular localization showed that EuPIP1;1 was located in the plasma membrane. Constitutive overexpression of EuPIP1;1 in Arabidopsisthaliana could promote leaf growth and development, and accelerate bolting and flowering. Six genes related to growth and flowering (AtPIF4, AtTCP14, AtCRY1, AtCRY2, AtFCA and AtFT) were significantly up-regulated in transgenic lines. Further, EuPIP1;1 gene improved resistance to drought and salt stress in transgenic Arabidopsis. Under drought and salt stress treatment, the transgenic lines had a higher germination rate and accumulation of osmotic substances, lower membrane damage, and could maintain ion homeostasis. Our results suggest that EuPIP1;1 plays an essential role in plant growth and development and in the response to drought and salt stress.

Objective: Screening variants underlying the single-gene disorder in the general population can help reduce the incidences of birth defects. To determine the most prevalent pathogenic variants causing autosomal recessive diseases, we investigated the frequencies of these variants in six major geographic ancestry groups from Exome Aggregation Consortium (ExAC) database and 26 populations from the 1,000 Genome Project, including three Chinese ethnic groups. Methods: We selected 64 autosomal recessive diseases and collected corresponding causal genes and variants from ClinVar for the analysis. The RS (reference single-nucleotide polymorphism) IDs of these variants were used to search the corresponding VCF file from the 1,000 Genomes Project and ExAC databases. We calculated the frequencies of heterozygotes of each disease variants in the 1,000 Genomes Project and ExAC samples and compared the distribution of disease alleles among different populations. Results: Our analysis revealed that 1,151/212 variants were carried by 60,706/2,504 individuals sequenced in the ExAC/1,000 Genomes Project. The average number of autosomal recessive disease alleles carried by samples from ExAC and 1,000 Genomes Project were 0.53 and 0.68, respectively. These disease alleles showed differential distribution among populations, and some disease alleles were significantly enriched in certain ethnic groups. In addition, 1–2 main pathogenic variants were identified in each disease. Meanwhile, several ClinVar variants with relatively high frequency (>1%) in the samples were found to be benign instead of “conflicting evaluations of pathogenicity.” Conclusions: Our observations revealed that main pathogenic variants existed in certain autosomal recessive disease, suggesting that screening of disease hypermutations in different populations is valuable in reducing the occurrence of birth defects.

P2Y1 receptors play an essential role in inhibitory neuromuscular transmission in the gastrointestinal tract. The signalling pathway involves the opening of small conductance calcium activated potassium-channels (Kca2 family) that results in smooth muscle hyperpolarization and relaxation. Inorganic polyphosphates and dinucleotidic polyphosphates are putative neurotransmitters that potentially act on P2Y1 receptors. A pharmacological approach using both orthosteric (MRS2500) and allosteric (BPTU) blockers of the P2Y1 receptor and openers (CyPPA) and blockers (apamin) of Kca2 channels was used to pharmacologically characterise the effect of these neurotransmitters. Organ bath and microelectrodes were used to evaluate the effect of P1,P4-Di (adenosine-5′) tetraphosphate ammonium salt (Ap4A), inorganic polyphosphates (PolyP) and CyPPA on spontaneous contractions and membrane potential of mouse colonic smooth muscle cells. PolyP neither modified contractions nor membrane potential. In contrast, Ap4A caused a concentration-dependent inhibition of spontaneous contractions reaching a maximum effect at 100 μM Ap4A response was antagonised by MRS2500 (1 μM), BPTU (3 μM) and apamin (1 μM). CyPPA (10 μM) inhibited spontaneous contractions and this response was antagonised by apamin but it was not affected by MRS2500 or BPTU. Both CyPPA and Ap4A caused smooth muscle hyperpolarization that was blocked by apamin and MRS2500 respectively. We conclude that Ap4A but not PolyP activates P2Y1 receptors causing smooth muscle hyperpolarization and relaxation. Ap4A signalling causes activation of Kca2 channels through activation of P2Y1 receptors. In contrast, CyPPA acts directly on Kca2 channels. Further studies are needed to evaluate if dinucleotidic polyphosphates are released from inhibitory motor neurons.

Attaining and maintaining good glycemic control is a cornerstone of diabetes care. The monitoring of glycemic control is currently based on the self-monitoring of blood glucose (SMBG) and laboratory testing for hemoglobin A1c (HbA1c), which is a surrogate biochemical marker of the average glycemia level over the previous 2-3 mo period. Although hyperglycemia is a key biochemical feature of diabetes, both the level of and exposure to high glucose, as well as glycemic variability, contribute to the pathogenesis of diabetic complications and follow different patterns in type 1 and type 2 diabetes. HbA1c provides a valuable, standardized and evidence-based parameter that is relevant for clinical decision making, but several biological and analytical confounders limit its accuracy in reflecting true glycemia. It has become apparent in recent years that other glycated proteins such as fructosamine, glycated albumin, and the nutritional monosaccharide 1, 5-anhydroglucitol, as well as integrated measures from direct glucose testing by an SMBG/continuous glucose monitoring system, may provide valuable complementary data, particularly in circumstances when HbA1c results may be unreliable or are insufficient to assess the risk of adverse outcomes. Long- term associations of these alternative biomarkers of glycemia with the risk of complications need to be investigated in order to provide clinically relevant cut-off values and to validate their utility in diverse populations of diabetes patients.

Introduction: COVID-19 has several overlapping phases. Treatment has focused on the late stage of the disease in hospital. Yet, the continuation of the pandemic is by propagation of the disease in outpatients. The current public health strategy relies solely on vaccines to prevent disease. Areas Covered: We searched the major national registries, pubmed.org, and the preprint servers for all ongoing, completed and published trial results with subject numbers of 100 or more on, and used a targeted search to find announcements of unpublished trial results. As of 2/15/2021, we found 111 publications reporting findings in human studies on 14 classes of agents, and on 9 vaccines. There were 62 randomized controlled studies, the rest retrospective observational analyses. Only 21 publications dealt with outpatient care, the rest all in hospitalized patients. Remdesivir and convalescent plasma have emergency use authorization for hospitalized patients in the U.S.A. There is also support for glucocorticoid treatment of the COVID-19 respiratory distress syndrome. Monoclonal antibodies are authorized for outpatients, but the supply is inadequate to treat all at time of diagnosis. Favipiravir, ivermectin, and interferons are approved in certain countries Expert Opinion: Worldwide vaccination is now underway. Vaccines and antibodies are highly antigen specific and new variants are appearing. There is a need for treatment of outpatients who contract the disease, in addition to mass immunization. We call on public health authorities to authorize treatments with known low risk and potential benefit for use in parallel with mass immunization.

In this work, triangular C 1 interpolation based on Argyris element (AE) is used to develop the ARgyris element based searching (ARES) algorithm, an efficient tool for the accurate identification of stationary points (SPs), e.g. X-point, magnetic axis, snowflake point, etc and separatrix in magnetic confinement fusion application. AE-based interpolation allows the formulation of the nonlinear problem of SP identification on the triangle as a vectorial root-finding problem, addressed via different Newton-like algorithms. The proposed method is able to detect both first-order SP (e.g. X-points and magnetic axis, where the norm of the gradient vanishes) and second-order SP (e.g. snowflake points, where both the norm of the gradient and of the second derivatives vanishes). The separatrix is detected inside the triangles via the novel zero line searching algorithm, and is described by means of quintic spline interpolant of its components. Thanks to its modularity and efficiency, ARES is suitable to run on structured and unstructured triangular meshes, and can be readily integrated with any kind of Grad–Shafranov solver based on 2D triangular finite element method, or used for real-time SP and separatrix identification for control oriented purposes.

Interactions, organization and dynamics within phase-separated ternary blends of hydrophobically modified starch (HMS), sucrose and water are investigated using solid-state NMR and positron annihilation lifetime spectroscopy (PALS). Antiplasticization of HMS by sucrose is demonstrated by PALS and 1H NMR T1 measurements. Selective solid-state 13C NMR experiments show that a large fraction of sucrose is in molecular contact with HMS even at high sucrose contents, indicating that the HMS-sucrose phase separation is only partial. Sucrose is observed to migrate away from the HMS-rich domains at temperatures that are above the lower Tg, but still below the upper Tg. 1H spin diffusion experiments indicate that phase separation occurs on a nanometric scale, in line with recent theory (Van der Sman, Food Hydrocolloids 87, 360–370 (2019)). We infer that the nanoscale structure of the HMS-rich phase allows for intimate molecular contact between the HMS-rich and the sucrose-rich phases and explains the unusual dynamic behavior.

Tonoplast aquaporins (intrinsic proteins, TIPs) have been indicated to play important roles in plant tolerance to water deficit and salinity. However, the functions of wheat TIPs in response to the stresses are largely unknown. In this study, we observed that transgenic plants overexpressing wheat TaTIP4;1 in Arabidopsis and rice displayed clearly enhanced seed germination and seedling growth under drought, salt and osmotic stress. Compared with wild type plants, Arabidopsis and rice overexpression lines had heightened water contents, reduced leaf water loss, lowered levels of Na+, Na+/K+, H2O2 and malondialdehyde, and improved activities of catalase and/or superoxide dismutase, and increased accumulation of proline under drought, salinity and/or osmotic stresses. Moreover, the expression levels of multiple drought responsive genes clearly elevated upon water dehydration, and the transcription of some salt responsive genes was markedly induced by NaCl treatment in the overexpression lines. Also, the yeast cells containing TaTIP4;1 showed increased tolerance to NaCl and mannitol, and mutation in one of three serines of TaTIP4;1 caused decreased tolerance to the two stresses. These results suggest that TaTIP4;1 serves as an essential positive regulator of seed germination and seedling growth under drought, salt and/or osmotic stress through impacting water relations, ROS balance, the accumulation of Na+ and proline, and stimulating the expression of dozens of stress responsive genes in Arabidopsis and rice. Phosphorylation may modulate the activity of TaTIP4;1.

Fine particulate matter (PM) is object of particular attention due to its health effects. It is currently regulated by adopting PM2.5 as an indicator to control anthropogenic combustion emissions. Therefore, it is crucial to collect aerosol samples representative of such sources, without including PM from natural sources. Thus, a clean separation between coarse and fine mode aerosol should be set. With this purpose, aerosol size mass distribution was taken in the aerodynamic diameter range from 0.5 to 10 µm. In comparison with a base scenario, characterized by local pollution sources, three case studies were considered, involving desert dust advection, sea salt advection and forest fire aerosol from a remote area. In the base scenario, PM2.5 represented a suitable fine-mode indicator, whereas it was considerably affected by coarse PM in case of desert dust and sea salt aerosol advection. Such interference was considerably reduced by setting the fine/coarse separation at 1.0 µm. Such separation underrepresented fine PM from forest fire long-range transport, nonetheless in the case studies considered, PM1 represented the best indicator of fine aerosol since less affected by coarse natural sources. The data presented clearly support the results from other studies associating the health effects of PM2.5 to PM1, rather than to PM1–2.5. Overall, there is a need to reconsider PM2.5 as an indicator of fine atmospheric aerosol.

Aim: Targeting 5-HT1A receptor (5-HT1AR) as a strategy for CNS disorders and pain control. Methodology: A series of 1,3-dioxolane-based 2-heteroaryl-phenoxyethylamines was synthesized by a convergent approach and evaluated at α1-adrenoceptors and 5-HT1AR by binding and functional experiments. Absorption, distribution, metabolism, excretion and toxicity prediction studies were performed to explore the drug-likeness of the compounds. Results & conclusion: The most promising compound, the pyridin-4-yl derivative, emerged as a potent and selective 5-HT1AR agonist (pKi = 9.2; pD2 = 8.83; 5-HT1A/α1 = 135). In vitro it was able to permeate by passive diffusion MDCKII-MDR1 monolayer mimicking the blood–brain barrier and showed promising neuroprotective activity.

Summary The brain’s endocannabinoid system is a powerful controller of neurotransmitter release, shaping synaptic communication under physiological and pathological conditions. However, our understanding of endocannabinoid signaling in vivo is limited by the inability to measure their changes at timescales commensurate with the high lability of lipid signals, leaving fundamental questions of whether, how, and which endocannabinoids fluctuate with neural activity unresolved. Using novel imaging approaches in awake behaving mice, we now demonstrate that the endocannabinoid 2-arachidonoylglycerol, not anandamide, is dynamically coupled to hippocampal neural activity with high spatiotemporal specificity. Furthermore, we show that seizures amplify the physiological endocannabinoid increase by orders of magnitude and drive the downstream synthesis of vasoactive prostaglandins that culminate in a prolonged stroke-like event. These results shed new light on normal and pathological endocannabinoid signaling in vivo.

β-Cyclodextrin polymer, namely nanosponges (NSs), were synthesized using two cross-linkers: 1,1′-carbonyldiimidazole (CDI) and pyromellitic dianhydride (PMDA). The synthesized NSs were complexed with N,N-diethyl-meta-toluamide (DEET) and, after complex characterization, the NSs cross-linked with CDI were found more effective than those cross-linked with PMDA in terms of encapsulation efficiency and loading capacity. The CDI-NSs were dispersed in a polyacrylic resin, which was thermally polymerized on a polyester fabric surface. The fabric functionalization was evaluated through quantification of DEET extracted from the polyester fabrics, before and after three washing cycles. The results showed that encapsulation into NSs prolongs the persistence of DEET on polyester fabrics.

Посредством гистологических методов изучена морфология и иммуногистохимия структур селезенки после курсового введения 1,2-диметилгидразина. Установлено, что через 1 мес после введения канцерогена в селезенке крыс регистрируется увеличение количества S100+-клеток в герминативных центрах лимфоидных узелков на фоне сокращения площади узелков и центров размножения, ширины маргинальных зон и периартериальных лимфоидных муфт. Кроме того, увеличивается общее количество вторичных лимфоидных узелков на фоне уменьшения их соотношения к первичным лимфоидным узелкам. Через 4 мес после курса инъекций канцерогена отмечается недостоверное уменьшение количества дендритных клеток в герминативных центрах по сравнению с интактными животными того же возрастного периода. Изменения морфологического фенотипа селезенки на этом сроке носят достоверный характер и заключаются в более выраженном сокращении площади лимфоидных узелков с их герминативными центрами, шириной периартериальных лимфоидных муфт и маргинальных зон, а также в увеличении количества вторичных лимфоидных узелков., By means of histological methods the morphology and an immunohistochemistry of structures of a lien after course introduction 1,2-dimethylhydrazines is studied. It is established that in 1 month after administration of carcinogen in a lien of rats the augmentation of quantity of S100+-cells in the germinative the centers of lymphoid nodules against the background of reduction of both the area of nodules, and the centers of reproduction, width of marginal zones and periarterial lymphoid couplings is registered. Besides, the total of secondary lymphoid nodules against the background of decrease of their ratio to primary lymphoid nodules is enlarged. In 4 months after the termination of a course of injections of carcinogen doubtful decrease of quantity of dendritic cells in the germinative the centers in comparison with intact animals of the same age period becomes perceptible. Changes of a morphological phenotype of a lien on this term have reliable character and width of periarterial lymphoid couplings and marginal zones, and also augmentation of quantity of secondary lymphoid nodules consist in more expressed reduction of the areas of lymphoid nodules with their germinative centers.

Depending on the substitution pattern and stereochemistry, 1,3-dioxanes 1 with an aminoethyl moiety in 4-position represent potent σ1 receptor antagonists. In order to increase the stability, a cyclohexane ring first replaced the acetalic 1, 3-dioxane ring of 1. A large set of aminoethyl substituted cyclohexane derivatives was prepared in a six-step synthesis. All enantiomers and diastereomers were separated by chiral HPLC at the stage of the primary alcohol 7, and their absolute configuration was determined by CD spectroscopy. Neither the relative nor the absolute configuration had a large impact on the σ1 affinity. The highest σ1 affinity was found for cis-configured benzylamines (1R,3S)-11 (Ki = 0.61 nM) and (1S,3R)-11 (Ki = 1.3 nM). Molecular dynamics simulations showed that binding of (1R,3S)-11 at the σ1 receptor is stabilized by the typical polar interaction of the protonated amino moiety with the carboxy group of E172 which is optimally oriented by an H-bond interaction with Y103. The lipophilic interaction of I124 with the N-substituent also contributes to the high σ1 affinity of the benzylamines. The antagonistic activity was determined in a Ca2+ influx assay in retinal ganglion cells. The enantiomeric cis-configured benzylamines (1R,3S)-11 and (1S,3R)-11 were able to inhibit the growth of DU145 cells, a highly aggressive human prostate tumor cell line. Moreover, cis-11 could also inhibit the growth of further human tumor cells expressing σ1 receptors. The experimentally determined logD7.4 value of 3.13 for (1R,3S)-11 is in a promising range regarding membrane penetration. After incubation with mouse liver microsomes and NADPH for 90 min, 43% of the parent (1R,3S)-11 remained unchanged, indicating intermediate metabolic stability. Altogether, nine metabolites including one glutathione adduct were detected by means of LC-MS analysis.

In this work, we report halogen bonded cocrystals of four o-hydroxy imines with two halogen bond donors, 1, 2- diiodotetrafluorobenzene and 1, 4- diiodotetrafluorobenzene, prepared by both mechanochemical synthesis (liquid-assisted grinding) and conventional solution-based method. We have used, as halogen bond acceptors, imines derived from o-vanillin and four selected aromatic amines: 2- aminonaphthalene, 3-aminoacetophenone, 4- aminoacetophenone, and 4-aminobenzonitrile. The selected imines have both a hydroxy and a methoxy group on the aldehyde moiety, and three of the imines have an additional functional group on the amine moiety, a carbonyl or a nitrile group. Crystal structure determination of cocrystals revealed that the molecules are connected via halogen bonds of I···O or I···N type as well as the existence of halogen bond acceptor competition (hydroxy, methoxy, carbonyl, and nitrile groups). To the best of our knowledge, we report the first known halogen bonded cocrystals of o-hydroxy imines as well as cocrystals with a novel robust I(···O)2 halogen bond motif, containing a bifurcated halogen bond donor with hydroxy and methoxy groups. In the crystal structures of cocrystals with the imine derived from 4- aminobenzonitrile, only the I···N(nitrile) halogen bond was found, demonstrating a competition between hydroxy/methoxy and nitrile groups as acceptors in favor of I···N(nitrile) halogen bond.

The new coordination polymers (CPs) [Zn(tr2ad)Cl2]n, {[Cu(tr2ad)Cl]Cl∙4H2O}n, [Cd2(tr2ad)Cl4]n, {[Cu(tr2ad)(NO3)](NO3)}n and {[Cd(tr2ad)(NO3)](NO3)∙H2O}n were obtained in the form of air- and moisture-stable microcrystalline powders by the solvothermal reactions of zinc(II), copper(II) and cadmium(II) chlorides or nitrates with the ligand 1,3-bis(1,2,4-triazol-4-yl)adamantane (tr2ad). Investigation of the thermal behaviour assessed the thermal stability of these CPs, with [Cd2(tr2ad)Cl4]n starting to decompose only around 365 &deg, C. As retrieved by powder X-ray diffraction, while [Zn(tr2ad)Cl2]n features 1-D chains along which the metal centre shows a tetrahedral geometry and the spacer is exo-bidentate, the other CPs contain 2-D double-layers in which the metal ions possess an octahedral stereochemistry and the linker is exo-tetradentate. A comparative structural analysis involving known coordination compounds containing the tr2ad ligand enabled us to disclose (i) the versatility of the ligand, as far as the coordination modes are concerned, (ii) the variability in crystal structure dimensionality, ranging from 1-D to 3-D, (iii) the fact that, to the best of our knowledge, [Zn(tr2ad)Cl2]n is the first ZnII-based CP containing the tr2ad spacer.

Anaplastic thyroid cancer (ATC) is a rare neoplasia with a poor prognosis. Proliferation and apoptosis assays were performed on ATC cell lines (8305C, 8505C) exposed to vinorelbine, lenvatinib, as well as to concomitant combinations. ABCB1, ABCG2 and CSF-1 mRNA expression was evaluated by real time PCR. The relative levels of pospho Akt were investigated as part of a human phospho-kinase array analysis, and CSF-1 and VEGFR-2 protein levels were measured by ELISA. The intracellular concentration of lenvatinib in ATC cells was measured by combined reversed-phase liquid chromatography-tandem mass spectrometry. An ATC subcutaneous xenograft tumor model in nude mice was treated with vinorelbine, lenvatinib, or vinorelbine plus lenvatinib. After treatment with vinorelbine, lenvatinib, a significant antiproliferative effect in ATC cell lines was observed. The concomitant treatment of vinorelbine and lenvatinib revealed synergism for all the fractions of affected cells. A decrease in ABCB1 expression was reported in both ATC cell lines treated with the lenvatinib plus vinorelbine combination, as was an increase in the intracellular concentration of lenvatinib. The combination caused a decrease in Akt, GSK3α/β, PRAS40 and Src phosphorylation, and in both CSF-1 mRNA and protein levels. In the subcutaneous tumor model, the combination reduced the tumor volume during the treatment period. Our results establish the synergistic ATC antitumor activity of a vinorelbine and lenvatinib combination.

In some environments, a number of crops, notably maize and nuts can be contaminated by aflatoxin B1 and related compounds resulting from the growth of aflatoxin-producing Aspergilli. Fungal peroxidases have been shown to degrade a number of mycotoxins, including aflatoxin B1 (AFB1). Therefore, the purpose of this study was to investigate the in vitro enzymatic degradation AFB1 by a recombinant type B dye decolorizing peroxidase (Rh_DypB). Analysis of the reaction products by HPLC-MS analysis showed that under optimized conditions AFB1 was efficiently transformed by Rh_DypB, reaching a maximum of 96% conversion after 4 days of reaction at 25 °C. Based on high resolution mass spectrometry analysis, AFB1 was demonstrated to be quantitatively converted to AFQ1, a compound with a significantly lower toxicity. A number of low molecular mass compounds were also present in the final reaction mixture in small quantities. The results presented in this study are promising for a possible application of the enzyme Rh_DypB for aflatoxin reduction in feed.

Adenosine receptors (ARs), like many otherGprotein-coupledreceptors (GPCRs), are targets of primary interest indrug design. However, one of the main limits for the development of drugs for this class of GPCRs is the complex selectivity profile usually displayed by ligands. Numerous efforts have been madefor clarifying the selectivity of ARs, leading to the development of many ligand-based models. The structure of the AR subtype A1 (A1AR) has been recently solved,providing important structural insights. In the present work, we rationalized the selectivity profile of two selective A1AR and A2AAR antagonists, investigating their recognition trajectories obtained by Supervised Molecular Dynamics from an unbound state and monitoring the role of the water molecules in the binding site.

Mammalian target of rapamycin (mTOR) is a phosphoinositide 3-kinase-related protein kinase which controls cell growth and is frequently deregulated in many cancers. Therefore, mTOR inhibitors are used as antineoplastic agents for cancer treatment. In this study, 1,2,4-triazine derivatives containing different arylidene-hydrazinyl moieties were designed and synthesized. Cytotoxicity of the compounds was evaluated on HL-60 and MCF-7 cell lines by MTT assay. S1, S2 and S3 exhibited good cytotoxic activity on both cell lines with an IC50 range of 6.42 - 20.20 μM. In general, substitution of a five-membered heterocyclic ring containing NO2, such as 5-nitrofuran-2-yl, resulted in the best potency. Molecular docking analysis was performed to study the possible interactions and binding modes of all the triazine derivatives with mTOR receptor. The most promising compound, S1, was well accommodated within the active site and had the least estimated free energy of binding (even less than the inherent ligand of the protein, PDB ID: 4JT6). It is concluded from both MTT assay and docking studies that the arylidene moiety linked to the hydrazinyl part of the structure had a prominent role in cytotoxicity and mTOR inhibitory activity.

Bakrom katalizirana Huisgenova 1, 3-dipolarna cikloadicija azida i terminalnih alkina kojom regioselektivno nastaju 1, 4-disupstituirani 1, 2, 3-triazoli često je primjenjivana metoda sintetske organske kemije. Zahvaljujući jednostavnim reakcijskim uvjetima, zauzela je značajno mjesto i u području nukleozidne kemije jer omogućuje dobivanje velikog broja potencijalno biološki aktivnih spojeva s nizom zanimljivih dodatnih svojstava induciranih uvođenjem 1, 2, 3-triazolnog strukturnog motiva u molekulu.

Melatonin (MLT) is a neurohormone implicated in several physiological processes such as sleep. Contrasting results have been produced on whether or not it may act as a hypnotic agent, and the neurobiological mechanism through which it controls the vigilance states has not yet been elucidated. In this study we investigated the effect of MLT (40 mg/kg), a non-selective MT1/MT2 receptor agonist (UCM793, 40 mg/kg), and a selective MT2 partial agonist (UCM924, 40 mg/kg) on the 24-h vigilance states. EEG and EMG sleep-wake patterns were registered across the 24-h light-dark cycle in adult Sprague-Dawley male rats. MLT decreased (-37%) the latency to the first episode of non rapid eye movement sleep (NREMS), enhanced the power of NREMS delta band (+33%), but did not alter the duration of any of the three vigilance states. Differently, UCM793 increased the number of episodes (+52%) and decreased the length of the episodes (-38%) of wakefulness but did not alter the 24-h duration of wakefulness, NREMS and REMS. UCM924 instead reduced the latency (-56%) and increased (+31%) the duration of NREMS. Moreover, it raised the number of REMS episodes (+57%) but did not affect REMS duration. Taken together, these findings show that MLT and non-selective MT1/MT2 receptor agonists do not increase the quantity of sleep but differently influence the three vigilance states. In addition, they support the evidence that selective MT2 receptor agonists increase NREMS duration compared to MLT and non-selective MT1/MT2 agonists.

Mitochondria produce the bulk of cellular energy and work as decisional "hubs" for cellular responses by integrating different input signals. The determinant in the physiopathology of mammals, they attract major attention, nowadays, for their contribution to brain degeneration. How they can withstand or succumb to insults leading to neuronal death is an object of great attention increasing the need for a better understanding of the interplay between inner and outer mitochondrial pathways residing in the cytosol. Of the latter, those dictating protein metabolism and therefore influencing the quality function and control of the organelle are of our most immediate interest and here we describe the Transglutaminase type 2 (TG2) contribution to mitochondrial function, dysfunction and neurodegeneration. Besides reviewing the latest evidences we share also the novel ones on the IF1 pathway depicting a molecular conduit governing mitochondrial turnover and homeostasis relevant to envisaging preventive and therapeutic strategies to respectively predict and counteract deficiencies associated with deregulated mitochondrial function in neuropathology. (C) 2014 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

International audience; Isothermal vapor-liquid equilibrium data are reported for ethylene + 1,1,2,3,3,3-hexafluoro-1-propene mixtures at six temperatures in the 258.35-307.38 K range, and pressures up to 4.56 MPa. The experimental data were measured using an apparatus based on the "static-analytic" method equipped with a movable ROLSI™ capillary sampler for repeatable and reliable equilibrium phase sampling and handling. The isothermal P-x-y data are well correlated with a model comprised of the Peng-Robinson equation of state containing the Mathias-Copeman alpha function, Wong-Sandler mixing rule, and NRTL local composition model. The combined model is termed "PR-MC-WS-NRTL". The studied system does not exhibit azeotropic behavior nor liquid-liquid immiscibility over the range of investigated temperatures. Mixture critical points are calculated from the experimental vapor-liquid equilibrium data via the extended scaling laws and the PR-MC-WS-NRTL model, and are found to be in good agreement with the experimental isothermal phase envelopes.

Many studies have shown that the presence of 1,25-dihydroxyvitamin D3 in the eye is able to modulate inflammatory responses. In fact, it has been demonstrated that topical administration of vitamin D3 inhibits Langerhans cells migration from the central cornea, corneal neovascularization, and production of cytokines (i.e., interleukin-1-6-8) in experimental animals. Moreover, both in vitro and in vivo studies have demonstrated that vitamin D is a potent inhibitor of retinal neovascularization. It has been shown that calcitriol, the biologically active form of vitamin D, inhibits angiogenesis both in cultured endothelial cells and in retinas from guinea pigs with retinoblastoma or oxygen-induced ischemic retinopathy. In addition, it seems that this compound is able to prevent the progression from early to neovascular age-related macular degeneration (AMD) and, at the same time, to down-regulate the characteristic inflammatory cascade at the retinal pigment epithelium-choroid interface due to its anti-inflammatory and immunomodulatory capabilities. Furthermore, 1,25-dihydroxyvitamin D3 and its analogue, 2-methylene-19-nor-1,25-dihydroxyvitamin D3, are able to modulate intraocular pressure (IOP) through gene expression. Several studies have suggested a role in glaucoma and diabetic retinopathy therapies for vitamin D3. In conclusion, this review summarizes our current knowledge on the potential use of vitamin D3 in the protection and treatment of ocular diseases in ophthalmology.

This study is aimed to monitor by 1H NMR spectroscopy the effect of a 12-month storage period on the 1,2-diglycerides over 1,3-diglycerides ratio for five mono-cultivar ‘extra virgin olive oils’ (EVOO) (Arbequina, Arbosana, Cerasuola, Nocellara and FS17) and one blend of two different cultivars (Nocellara + Biancolilla) preserved in the dark and at room temperature. These quantifications, at 500 MHz, are readily extracted through a specific and original integration difference method. Albeit it was known that the isomerisation rate is affected by the free acidity, we here demonstrate that it also depends on the presence of specific macromolecules (lipases), indeed, different EVOO cultivars with similar free acidity, show different isomerisation rate. Our results are consistent with similar diglyceride monitoring performed on Greek and Spanish EVOOs by 31P NMR.

Autoradiography of radiolabeled GTPγS ([(35)S]GTPγS) binding is a relevant method to study the function of G protein-coupled receptors (GPCRs), in tissue sections. Here, we describe the protocol for such a binding autoradiography, suitable to investigate the functionality of CB1 receptor in tissue slices from rodent brain.

This paper presents the investigation of sorption and mechanical properties of single flax fibers (fiber bundle) cross-linked with polycarboxylic acids (PCA; citric acid [CA] and 1, 2, 3, 4-butanetetracarboxylic acid [BTCA]). The improvement of the chemical modification performance was carried out by pre-treating of the fibers with sodium hydroxide and ultrasound (US). Thus, the purpose of the investigations was to determine whether the sorption and mechanical properties of the cross-linked fibers would be enhanced by a preswelling and US treatment before the application of PCA. The effect of cross-linking PCA with cellulose molecules on flax fiber properties was determined by measuring and comparing the properties (fineness, tenacity, and elongation at break; breaking twist; moisture absorption; and water-retention value) of untreated and modified flax fibers. The test results indicate that treatment with PCA undoubtedly changes the tested properties: water retention values decrease while the resistance to tenacity increases. The observed changes are the result of structural alterations in fibers. Fourier-transform infrared (FT-IR) spectra confirmed that cross-linking between the carboxyl groups of acids and the hydroxyl groups of cellulose occurs due to the esterification reaction. Preswelling and US treatments have increased the accessibility of cellulose in flax fibers, and cross-linking was achieved with less fiber damage, whereby US proved to be a more successful pre-treatment.

In a preliminary article, we reported the potent allosteric enhancer activity at the A(1) adenosine receptor of a small series of 2-amino-3-(4-chlorobenzoyl)-4-[4-(aryl)piperazin-1-yl)methyl]thiophene derivatives bearing electron-withdrawing or electron-releasing groups at the para-position of the phenylpiperazine moiety. In the present study, we report the development of the compounds previously studied by modifying both the number and position of substituents on the phenylpiperazine moiety, aimed at establishing a structure-activity relationship identifying additional compounds with improved activity. The nature and the position of substituents on the phenyl ring tethered to the piperazine seemed to exert a fundamental influence on the allosteric enhancer activity, with the 3,4-difluoro 4i, 3-chloro-4-fluoro 4o, and 4-trifluoromethoxy 4ak derivatives being the most active compounds in binding (saturation and competition experiments) and functional cAMP studies. This study shows that it is also possible to obtain a good separation between allosteric enhancement and antagonistic activity at the A(1) adenosine receptor.

There is a need for a tool to assess dietary intake related to the habitual dietary glycaemic index (GI) and fibre in groups with large numbers of individuals. Novel metabolite-profiling techniques may be a useful approach when applied to human urine. In a long-term, controlled dietary intervention study, metabolomics were applied to assess dietary patterns. A targeted approach was used to evaluate the effects on urinary C-peptide excretion caused by the dietary treatments. Seventy-seven overweight subjects followed an 8-week low-calorie diet (LCD) and were then randomly assigned to a high-GI or low-GI diet for 6 month during which they completed 24-h urine collections at baseline (prior to the 8-week LCD) and after randomisation to the dietary intervention, at month 1, 3 and 6, respectively. Metabolite profiling in 24-h urine was performed by (1)H NMR and chemometrics. Partial least squares (PLS) analysis indicated that urinary formate could discriminate between high-GI and low-GI diets (correlation coefficient r = 0.82), and this finding was confirmed statistically (P = 0.01). PLS analysis also indicated that urinary hippurate could be associated with fibre intake, but this finding was not confirmed statistically. No associations between GI and urinary C-peptide were found. Our results emphasise that application of metabolomics is useful in the assessment of dietary exposure related to dietary GI and fibre seen at group level in a nutritional metabolomic study of human urine. As our design allowed for large variations in individually selected food items, biomarkers identified at group level may be interpreted as more general and robust markers, largely not confounded with markers from single dietary factors.

Enantiomerically pure 1,4-dihydropyridines are pre- pared taking advantage of magnesium nitride as a useful and conve- nient source of 'solid ammonia'. The products possess various substituents at carbons 3, 4 and 5 of the dihydropyridine moiety.

Treatment of 3-alkoxycarbonyl-4-acyl- or 3,4-dialkoxycarbonyl-substituted isoxazolidines with a mild base, such as tetrabutylammonium fluoride, affords β-enaminones and/or 3-methylamino-2(5H)-furanones according to the nature of the substituents at C 4 and C 5 . Two alternative mechanisms (lactonization and retro-aldolization) have been rationalized by DFT quantum chemical methods. Any realistic theoretical modeling requires the explicit inclusion of countercation and solvent effects.

This review is an overview of the last ten years' use of the Mizoroki-Heck coupling applied to 1,2- and 1,3-dienes. Since both these systems form pi-allyl palladium intermediates in Pd(0) coupling, they show particular chemical behavior. Many examples of 1,2-dienes Heck reactions are presented. 1,2-Dienes are important substrates because of their high reactivity that makes them useful building blocks for the synthesis of biologically relevant structures.

The 1,3-dipolar cycloaddition reaction of unsymmetrically N-substituted and N-unsubstituted 1,3-oxazolium-5-olates with selected 3-substituted coumarins has been examined. Various types of pyrrole derivatives are isolated and their formation seems to be a function of the regio- and diastereochemistry of the initial cycloaddition step.

The stereochemical outcome of reaction of 2,5-bis-trifluoromethyl-1,3,4-oxadiazole with 7-oxanorbornenes under various conditions was investigated. For the first time, microwave irradiation in carrying this type of reactions was used, resulting in comparable yields in significantly shorter reaction times. Regardless on substrate, in all reactions mixtures of the two isomeric O 3 -[3]polynorbornanes, bent and linear were obtained, with slight preference for bent structure. In some cases, retro Diels–Alder fragmentation was observed resulting in formation of isobenzofuran species. Reaction mechanism was also studied computationally (RHF/6-31G* method), and the origin of stereoselectivity explained by repulsive lone pair interactions between oxygen bridges in the transition state of the 1,3-dipolar addition.

The vapor pressures above the solid hexachlorobenzene (HCB) and above both the solid and liquid 1,2,3,4,5,6-hexachlorocyclohexane (lindane) were determined in the ranges 332–450 K and 347–429 K, respectively, by measuring the mass loss rates recorded by thermogravimetry under both isothermal and nonisothermal conditions. The results obtained were compared with those taken from literature. From the temperature dependence of vapor pressure derived by the experimental thermogravimetry

Novel classes of CB2 agonists based on 4-oxo-1,4-dihydroquinoline and 4-oxo-1,4-dihydro-1,5-, -1,6- and -1,8-naphthyridine scaffolds have shown high binding affinity toward CB2 receptor and good selectivity over CB1. A computational study of comparative molecular fields analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) was performed, in order to identify the key structural features impacting their binding affinity. The final CoMSIA model resulted to be the more predictive, showing \( r_{ncv}^2 = 0.84 \), \( r_{cv}^2 = ~0.619 \), SEE = 0.369, and \( r_{pred}^2 = 0.75 \). The study provides useful suggestions for the synthesis of new selective analogues with improved affinity.

The chemical composition of the essential oil of Portuguese myrtle was determined at different developmental stages of the plant: pre-flowering, flowering, unripe and ripe berries. The oil was extracted separately by Clevenger distillation from leaves, branches and berries. The yields vary from 0.33% to 0.74% for leaves, 0.02% to 0.19% for branches, and 0.11% to 0.23% for berries. The highest yields were obtained for the leaves in October, and for the berries in September; branches show similar values in the months of June, July and September, and the samples collected in May and October produced very little amount of oil. Altogether, September seems to be the month with the best yields for the three parts of the plant. The essential oils were analyzed by GC and GC/MS, and a total of thirty five components were identified. The major components were limonene+1,8-cineole [25.9% (berries)-39.5% (leaves)], myrtenyl acetate [6.6% (berries)-24.8% (leaves)], alpha-pinene [9.7% (berries)-21.5% (leaves)], and linalool [6.2% (leaves)-36.5% (berries)]. Portuguese myrtle belongs to the group of myrtles which are characterized by the presence of myrtenyl acetate as one of the major components.

Ring opening of2,2-dimethylthiirane by deactivated aromatic amines to afford 2-(arylamino)ethanethiols as 6-substituted 1,4-benzothiazine precursors, was investigated. The reaction takes place under mild conditions using copper(II) triflate or indium(III) triflate as catalysts. The regioselectivity of the addition depends on the catalysts and the substituents of the arylamines.

The solid-state supramolecular architectures of 1-aminoanthraquinone and 1, 5-diaminoanthraquinone were determined by single-crystal X-ray structural analysis. In this paper, revised model − in space group P21/c − is given for the crystal structure of 1-aminanthraquinone. 1-Aminoantaquinone molecules are joined together in infinite chains by N− H· · · O hydrogen bonds which are stacked by face-to-face and edge-to-face π − π interactions thus creating layers and the characteristic herring-bone motif. In the structure of 1, 5-diaminoanthraquinone, the molecules are connected via N− H· · · O hydrogen bonds in the 2D networks of (4, 4) topology. These molecular networks are further stacked by face-to-face π − π and carbonyl− π interactions. The supramolecular organizations of these two compounds are compared with other simple aminoanthraquinones (with at least one non-substituted amino group) thus providing more insights into the basic principles of the solid-state assembling for this class of molecules.

A new and efficient synthetic protocol for the preparation of α-, β- and γ-cyclodextrin (CD) homo- and heterodimers is presented. A microwave-promoted Huisgen 1,3-dipolar cycloaddition will efficiently link together monoazido and monoacetylenic CD derivatives through a 1,2,3-triazole bridge. This well-known click reaction provides a versatile method to yield 'head-to-tail' and 'tail-to-tail' CD dimers in a broad range of combinations. Such an easy access to this kind of molecular architecture may be used to fashion ad hoc tailored CD cavities such as pinching-type structures to be exploited as nanosized reactors or molecular carriers. Preliminary estimates of the relative distances and orientations of the two CD units in each kind of dimer were obtained by molecular dynamics simulations and related calculations.