Multiple Arbuscular Mycorrhizal Fungal Consortia Enhance Yield and Fatty Acids of Medicago sativa: A Two-Year Field Study on Agronomic Traits and Tracing of Fungal Persistence

Arbuscular mycorrhizal fungi are promoted as biofertilizers due to potential benefits in crop productivity, and macro- and microelement uptake. However, crop response to arbuscular mycorrhizal fungi (AMF) inoculation is context-dependent, and AMF diversity and field establishment and persistence of inoculants can greatly contribute to variation in outcomes. This study was designed to test the hypotheses that multiple and local AMF inoculants could enhance alfalfa yield and fatty acids (FA) compared to exotic isolates either single or in the mixture. We aimed also to verify the persistence of inoculated AMF, and which component of the AMF communities was the major driver of plant traits. Therefore, a field experiment of AMF inoculation of alfalfa (Medicago sativa L.) with three single foreign isolates, a mixture of the foreign isolates (FMix), and a highly diverse mixture of local AMF (LMix) was set up. We showed that AMF improved alfalfa yield (+ 68%), nutrient (+ 147% N content and + 182% P content in forage), and FA content (+ 105%). These positive effects persisted for at least 2 years post-inoculation and were associated with enhanced AMF abundance in roots. Consortia of AMF strains acted in synergy, and the mixture of foreign AMF isolates provided greater benefits compared to local consortia (+ 20% forage yield, + 36% forage N content, + 18% forage P content, + 20% total FA in forage). Foreign strains of Funneliformis mosseae and Rhizophagus irregularis persisted in the roots of alfalfa 2 years following inoculation, either as single inoculum or as a component of the mixture. Among inoculants, F. mosseae BEG12 and AZ225C and the FMix exerted a higher impact on the local AMF community compared with LMix and R. irregularis BEG141. Finally, the stimulation of the proliferation of a single-taxa (R. irregularis cluster1) induced by all inoculants was the main determinant of the host benefits. Crop productivity and quality as well as field persistence of inoculated AMF support the use of mixtures of foreign AMF. On the other hand, local mixtures showed a lower impact on native AMF. These results pave the way for extending the study on the effect of AMF mixtures for the production of high-quality forage for the animal diet

The Solid Wastes of Coffee Production and of Olive Oil Extraction: Management Perspectives in Rural Areas

There are two problematic solid residues from agriculture and agro‐industry, produced in vast amounts in rural areas: those from coffee bean production and processing and those deriving from the extraction process of olive oil. Notwithstanding these residues originating in different geographical areas, they have striking similarities. They both derive from traditional, conventional and organic agriculture; they have a high content in lignins, celluloses and (poly)phenols; they are produced in million tonnes annually; they pose relevant environmental problems for disposal; they contain bioactive compounds; and the approach for their re‐use is often similar, sometimes overlapping. The most promising re‐uses in rural areas are for agriculture, as animal feed and for energy production. There are also minor uses, suitable for the production of added‐value commodities. The re‐use will be dependent on a variety of factors according to the diversity of (a) pedoclimatic areas that include altitude and latitude, soil texture and organic matter content, water regime and availability, (b) level of expertise of the small farmers, (c) social environment that includes training opportunities and availability to create associative forms among producers, (d) access to trade and communication networks and (e) easy access to community‐level processing installations. The perspectives of agronomic management and valorization are compatible with the objectives of a regenerative, sustainable agriculture

The impact of new surgical techniques on geographical unwarranted variation: The case of benign hysterectomy

Since the 1980s, the international literature has reported variations for healthcare services,especially for elective ones. Variations are positive if they reflect patient preferences, while ifthey do not, they are unwarranted, and thus avoidable. Benign hysterectomy is among the mostfrequent elective surgical procedures in developed countries, and, in recent years, it has beenincreasingly delivered through minimally invasive surgical techniques, namely laparoscopic orrobotic. The question therefore arises over what the impact of these new surgical techniques onavoidable variation is. In this study we analyze the extent of unwarranted geographical variation oftreatment rates and of the adoption of minimally invasive procedures for benign hysterectomy in anItalian regional healthcare system. We assess the impact of the surgical approach on the provision ofbenign hysterectomy, in terms of efficiency (by measuring the average length of stay) and efficacy (bymeasuring the post-operative complications). Geographical variation was observed among regionalhealth districts for treatment rates and waiting times. At a provider level, we found differences forthe minimally invasive approach. We found a positive and significant association between rates andthe percentage of minimally invasive procedures. Providers that frequently adopt minimally invasiveprocedures have shorter average length of stay, and when they also perform open hysterectomies,fewer complications

Synthesis and cycloxygenase inhibitory properties of new naphthalene-methylsulfonamido, naphthalene-methylsulfonyl and tetrahydronaphthalen-methylsulfonamido compounds

We synthesized a series of new naphthalene derivatives: naproxen- and 6-methoxy naphthalene acetic acid-like 1–5. In these compounds the carboxylic function, typical of the classical NSAIDs, was replaced by a methylsulfonamido (1, 2 and 6a–c) or methylsulfonyl (3–5) group present in some selective COX-2 inhibitors. We also synthesized compounds 7 and 8 in which the naphthalene portion was substituted by tetrahydronaphthalene ring. Some of the new compounds were assayed for their enzymatic inhibitory activity towards cycloxygenase enzymes. Compounds 4 and 6b, at a concentration of 10 µM exhibit percentage inhibition values of 65%, 50% and 29%, 87% towards COX-2 and COX-1, respectively. The substitution of carboxylic group with a mehylsulfonamido or a methylsulfonyl groups does not allow to direct the selectivity versus to cycloxygenase enzymes

Effective bioremediation of clarithromycin and diclofenac in wastewater by microbes and Arundo donax L

: Bioremediation of pharmaceuticals has gained large research efforts, but there is still a need to improve the performance of bioremediation systems by selecting effective organisms. In this study, we characterized the capability to remove clarithromycin (CLA) and diclofenac (DCF) by the bacterium Streptomyces rochei, and the fungi Phanerochaete chrysosporium and Trametes versicolor. The macrolide antibiotic CLA and the non-steroid anti-inflammatory DCF were selected because these are two of the most frequently detected drugs in water bodies. Growth and content of the PhCs and a DCF metabolite (MET) by the energy crop Arundo donax L. were also evaluated under hydroponic conditions. The removal rate (RR) by S. rochei increased from 24 to 40% at 10 and 100 µg CLA L-1, respectively, averaged over incubation times. At 144 h, the RR by P. chrysosporium was 84%, while by T. versicolor was 70 and 45% at 10 and 100 CLA µg L-1. The RR by S. rochei did not exceed 30% at 1 mg DCF L-1 and reached 60% at 10 mg DCF L-1, whereas approached 95% and 63% by P. chrysosporium and T. versicolor, respectively, at both doses. Root biomass and length of A. donax were strongly affected at 100 µg CLA L-1. CLA concentration in roots and shoots increased with the increase of the dose and translocation factor (TF) was about 1. DCF severely affected both shoot fresh weight and root length at the highest dose and concentration in roots and shoots increased with the increase of the dose. DCF concentrations were 16-19 times higher in roots than in shoots, and TF was about 0.1. MET was detected only in roots and its proportion over the parent compound decreased with the increase of the DCF dose. This study highlights the potential contribution of A. donax and the tested microbial inoculants for improving the effectiveness of bioremediation systems for CLA and DCF removal

Ionic liquid-promoted green synthesis of biologically relevant diaryl thioethers

This study reports an ionic liquid (IL) promoted green method to obtain diaryl thioethers useful as key intermediates for the synthesis of matrix metalloproteinase (MMP) inhibitors. The synthetic pathway includes a sequential Ullmann reaction and Suzuki cross-coupling. The Ullmann conditions were optimized as regards the catalyst, the ionic liquid, reaction time, and temperature. Under optimal conditions (1-butyl-3-methylimidazolium bromide ([BMIM]Br) as solvent; catalyst, Cu; base, K2CO3; reaction time, 22 h; reaction temperature, 150°C) the aryl iodide conversion was 95%. The Suzuki cross-coupling was conducted in 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM]BF4) at 110°C, using Pd(PPh3)4 as catalyst and Na2CO3 as base. For both reactions, a combination of ILs with microwave (MW) irradiation determined a substantial improvement of reaction time and yields compared to conventional heating. This multi-step process reduces reaction times and removes organic solvents providing a more eco-friendly alternative for the synthesis of important pharmaceutical building blocks

Beyond Glycemic Control in Diabetes Mellitus: Effects of Incretin-Based Therapies on Bone Metabolism

Diabetes mellitus (DM) and osteoporosis (OP) are common disorders with a significant health burden, and an increase in fracture risk has been described both in type 1 (T1DM) and in type 2 (T2DM) diabetes. The pathogenic mechanisms of impaired skeletal strength in diabetes remain to be clarified in details and they are only in part reflected by a variation in bone mineral density. In T2DM, the occurrence of low bone turnover together with a decreased osteoblast activity and compromised bone quality has been shown. Of note, some antidiabetic drugs (e.g., thiazolidinediones, insulin) may deeply affect bone metabolism. In addition, the recently introduced class of incretin-based drugs (i.e., GLP-1 receptor agonists and DPP-4 inhibitors) is expected to exert potentially beneficial effects on bone health, possibly due to a bone anabolic activity of GLP-1, that can be either direct or indirect through the involvement of thyroid C cells. Here we will review the established as well as the putative effects of incretin hormones and of incretin-based drugs on bone metabolism, both in preclinical models and in man, taking into account that such therapeutic strategy may be effective not only to achieve a good glycemic control, but also to improve bone health in diabetic patients

N-(aroyl)-N-(arylmethyloxy)-α-alanines: selective inhibitors of aldose reductase

Aldose reductase (ALR2), a NADPH-dependent reductase, is the first and rate-limiting enzyme of the polyol pathway of glucose metabolism and is implicated in the pathogenesis of secondary diabetic complications. In the last decades, this enzyme has been targeted for inhibition but despite the numerous efforts made to identify potent and safe ALR2 inhibitors, many clinical candidates have been a failure. For this reason the research of new ALR2 inhibitors highly effective, selective and with suitable pharmacokinetic properties is still of great interest. In this paper some new N-(aroyl)-N-(arylmethyloxy)alanines have been synthesized and tested for their ability to inhibit ALR2. Some of the synthesized compounds exhibit IC50 in the low micromolar range and all have proved to be highly selective towards ALR2. The N-(aroyl)-N-(arylmethyloxy)-α-alanines are a promising starting point for the development of new ALR2 selective drugs with the aim of delaying the onset of diabetic complications

Synthesis, experimental evaluation and molecular modelling of hydroxamate derivatives as zinc metalloproteinase inhibitors

Manuscript. Published version available in European Journal of Medicinal Chemistry, Vol. 108, 27 January 2016, pp 141–153Enzymes of the M4 family of zinc-metalloproteinases are virulence factors secreted from gram-positive or gram-negative bacteria, and putative drug targets in the treatment of bacterial infections. In order to have a therapeutic value such inhibitors should not interfere with endogenous zinc-metalloproteinases. In the present study we have synthesised a series of hydroxamate derivatives and validated the compounds as inhibitors of the M4 enzymes thermolysin and pseudolysin, and the endogenous metalloproteinases ADAM-17, MMP-2 and MMP-9 using experimental binding studies and molecular modelling. In general, the compounds are stronger inhibitors of the MMPs than of the M4 enzymes, however, an interesting exception is LM2. The compounds bound stronger to pseudolysin than to thermolysin, and the molecular modelling studies showed that occupation of the S2’ subpocket by an aromatic group is favourable for strong interactions with pseudolysin

Discovery of Dimeric Arylsulfonamides as Potent ADAM8 Inhibitors

The metalloproteinase ADAM8 is upregulated in several cancers but has a dispensable function under physiological conditions. In tumor cells, ADAM8 is involved in invasion, migration and angiogenesis. The use of bivalent inhibitors could impair migration and invasion, through the double binding to a homodimeric form of ADAM8 located on the cell surface of tumor cells. Herein we report the rational design and synthesis of the first dimeric ADAM8 inhibitors selective over ADAM10 and MMPs. Bivalent derivatives have been obtained by dimerizing the structure of a previously described ADAM17 inhibitor, JG26. In particular, derivative 2 showed to inhibit ADAM8 proteolytic activity in vitro and in cell-based assays, at nanomolar concentration. Moreover, it was more effective than the parent monomeric compound in blocking invasiveness in breast cancer MDA-MB-231 cell line, thus supporting our hypothesis about the importance of inhibiting the active homodimer of ADAM8