Soil organic carbon data comparison after 85 years and new 13 C/12 C compositions: The case study of the Ferrara province (Northeastern Italy).

The main causes of soil organic matter (SOM) loss are land use (e.g., conventional agriculture) and land-use change (e.g., conversion of wetlands into croplands). Before World War II and until 1960s, the Ferrara province in the Emilia-Romagna region (Northeast Italy) enlarged its agricultural production area through drainage of wetlands. After that, the newly drained area was put into intensive agricultural production with practices that proved to be unsustainable, and whose negative effects (depletion of soil organic carbon [SOC] and emissions of greenhouse gases [GHGs], e.g., CO2 ) have never been quantified. In this work, we estimated the changes in SOC 85 years after the drainage of the palustrine environment, by comparing 1937 SOC measurements with those made in 2022. Comparison of SOC maps from 1937 and 2022 indicates that most of the area suffered a significant SOC loss (∆OC85 years from 0.05 to 18.57 wt%), except for northern areas in which the peat nature of the soil has been preserved. We also measured the 13 C/12 C on the 2022 soil samples and generated a present-day map of the SOC isotopic ratios, which could be used in future as a benchmark to evaluate changes in soil carbon stocks and fluxes.

The trace element distribution in peat soils affected by natural burning events: A proxy of the original composition and metals mobility assessment.

This work evaluates for the first time the effects on the trace element composition of peat soils affected by natural burning events, a recurrent phenomenon in the reclaimed wetland of the Mezzano Lowland (Padanian plain, NE Italy). The trace element distribution of two neighboring soil profiles, one pristine and one deeply affected by burning events, were compared to identify the original geochemical fingerprint of saltmarsh peat environment. The pre-combustion composition of the fired profile was reconstructed to infer the physico-chemical changes occurred as a consequence of the burning event, with a special attention to the mobility of elements of environmental concern, such as potentially toxic trace metals. The increase in concentration of potentially toxic elements (PTE) was particularly evident in two layers of the fired profile. V, Cr, Cu, Zn, Pb, and As contents progressively increase toward intermediate depths (30-75 cm) together with Th, Sr, Ba, U. On the contrary, Tl, Bi and Cd show a concentration peak in a thin, shallower (14-17 cm depth) horizon. The trace element composition of the unfired profile allowed the identification of specific ratios between immobile elements that can be used as geochemical fingerprint of the soils horizons with different soil organic matter (SOM) content. On the basis of Sr/Rb, Th/U and Ba/Sr it was possible to classify three types of sedimentary deposits characterizing both the unfired and fired profile, as well as to delineate the fire severity trends occurred in the different soil horizons of the fired profile. The distribution of immobile trace element, representative of the organic (U) and mineral (silicate, Th, Ba, REE and non-silicate, Sr) soil fractions with organic matter and bulk density in the non-fired profile, allowed the reconstruction of the original physico-chemical composition of the fired/burned profile and the accurate determination of the relative CO2 lost during the burning event. Moreover, the distribution of PTE with respect to immobile trace elements, used to estimate the element redistribution and mobility after burning in the fired profile, suggested that elements such as Cr, Ni, Zn, V were mainly immobile, whereas Pb, Mo and in particular Tl and Bi suffered a significant redistribution along the burned profile. Nonetheless, results of the gain/loss calculation for the whole soil profile suggested that no significant entry or leak of these elements occurred, limiting their redistribution inside the investigated soil system.

High temperature behaviour of Ag-exchanged Y zeolites used for PFAS sequestration from water.

Per- and polyfluorinated alkyl substances (PFAS) are anthropogenic compounds which have recently drawn great attention due to their high biological, chemical and physical stability and lipid/water repelling properties. The present work aims to provide for the first time insights on the thermal behaviour of Ag-exchanged Y zeolite loaded with perfluorooctanoic acid (PFOA, C8HF15O2) and perfluorooctane sulfonate (PFOS, C8HF17O3S) emphasizing the close link between crystal structure and desorption/dehydration processes. Elemental and isotopic abundance of carbon analysis, thermal analysis, and in situ high-temperature synchrotron X-ray powder diffraction were used to evaluate critically if the thermal regeneration affects the initial zeolites structural features. Rietveld refinements revealed that PFAS sites are emptied in the 550-650 °C temperature range, when the thermal degradation of PFOA and PFOS are reached. The crystallinity of the samples is not affected by the adsorption/desorption processes. Upon heating, the removal of both PFAS and coadsorbed water molecules induced a cation migration of the silver ions and changes of initial geometry of the framework. The dimensions of the channels remain comparable to those of the pristine materials thus suggesting the potential re-use of the samples in other adsorption PFAS cycles. Additionally, once regenerated and reloaded Ag-exchanged Y can re-adsorb PFAS in amounts comparable to that adsorbed in the first cycle with clear benefits on the costs of the whole water treatment process.

Ketoprofen, lysine and gabapentin co-crystal magnifies synergistic efficacy and tolerability of the constituent drugs: Pre-clinical evidences towards an innovative therapeutic approach for neuroinflammatory pain.

Chronic pain is an enormous public health concern, and its treatment is still an unmet medical need. Starting from data highlighting the promising effects of some nonsteroidal anti-inflammatory drugs in combination with gabapentin in pain treatment, we sought to combine ketoprofen lysine salt (KLS) and gabapentin to obtain an effective multimodal therapeutic approach for chronic pain. Using relevant in vitro models, we first demonstrated that KLS and gabapentin have supra-additive effects in modulating key pathways in neuropathic pain and gastric mucosal damage. To leverage these supra-additive effects, we then chemically combined the two drugs via co-crystallization to yield a new compound, a ternary drug-drug co-crystal of ketoprofen, lysine and gabapentin (KLS-GABA co-crystal). Physicochemical, biodistribution and pharmacokinetic studies showed that within the co-crystal, ketoprofen reaches an increased gastrointestinal solubility and permeability, as well as a higher systemic exposure in vivo compared to KLS alone or in combination with gabapentin, while both the constituent drugs have increased central nervous system permeation. These unique characteristics led to striking, synergistic anti-nociceptive and anti-inflammatory effects of KLS-GABA co-crystal, as well as significantly reduced spinal neuroinflammation, in translational inflammatory and neuropathic pain rat models, suggesting that the synergistic therapeutic effects of the constituent drugs are further boosted by the co-crystallization. Notably, while strengthening the therapeutic effects of ketoprofen, KLS-GABA co-crystal showed remarkable gastrointestinal tolerability in both inflammatory and chronic neuropathic pain rat models. In conclusion, these results allow us to propose KLS-GABA co-crystal as a new drug candidate with high potential clinical benefit-to-risk ratio for chronic pain treatment.

Branched-Chain Amino Acids and Di-Alanine Supplementation in Aged Mice: A Translational Study on Sarcopenia.

In age-related sarcopenia, the gradual loss of skeletal muscle mass, function and strength is underpinned by an imbalanced rate of protein synthesis/breakdown. Hence, an adequate protein intake is considered a valuable strategy to mitigate sarcopenia. Here, we investigated the effects of a 12-week oral supplementation with branched-chain amino acids (BCAAs: leucine, isoleucine, and valine) with recognized anabolic properties, in 17-month-old (AGED) C57BL/6J male mice. BCAAs (2:1:1) were formulated in drinking water, alone or plus two L-Alanine equivalents (2ALA) or dipeptide L-Alanyl-L-Alanine (Di-ALA) to boost BCAAs bioavailability. Outcomes were evaluated on in/ex vivo readouts vs. 6-month-old (ADULT) mice. In vivo hind limb plantar flexor torque was improved in AGED mice treated with BCAAs + Di-ALA or 2ALA (recovery score, R.S., towards ADULT: ≥20%), and all mixtures significantly increased hind limb volume. Ex vivo, myofiber cross-sectional areas were higher in gastrocnemius (GC) and soleus (SOL) muscles from treated mice (R.S. ≥ 69%). Contractile indices of isolated muscles were improved by the mixtures, especially in SOL muscle (R.S. ≥ 20%). The latter displayed higher mTOR protein levels in mice supplemented with 2ALA/Di-ALA-enriched mixtures (R.S. ≥ 65%). Overall, these findings support the usefulness of BCAAs-based supplements in sarcopenia, particularly as innovative formulations potentiating BCAAs bioavailability and effects.

Multi stable isotope ratio analysis for the traceability of northern Italian apples.

Isotope ratio mass spectrometry is a well-known technique used to trace the origin of agri-food products from different countries. Here this method was tested to trace the exact orchard of provenance of Italian apples harvested at sites close to each other. We measured the δ13C, δ15N, and δ34S values of apple subfractions (peel, petiole, pulp, seed) from two orchards in Ferrara and one orchard in Trento. Sulfur represents the best marker for tracing the regions of provenance of samples because it is linked to the presence of sulfate (Ferrara1: +9.0 ‰; Ferrara 2: +7.3 ‰) and sulfide (Trento: -1.3 ‰) minerals in soils. However, the δ13C of apple subfractions combined with the δ34S of seed in a linear discrimination analysis better discriminated the three orchards. The isotopic fingerprint of apples is thus significantly affected by the relative terroir, and it can be used as "isotopic identity card" to certify "protected designations of origin".

Quartz-bearing rhyolitic melts in the Earth's mantle.

The occurrence of rhyolite melts in the mantle has been predicted by high pressure-high temperature experiments but never observed in nature. Here we report natural quartz-bearing rhyolitic melt inclusions and interstitial glass within peridotite xenoliths. The oxygen isotope composition of quartz crystals shows the unequivocal continental crustal derivation of these melts, which approximate the minimum composition in the quartz-albite-orthoclase system. Thermodynamic modelling suggests rhyolite was originated from partial melting of near-anhydrous garnet-bearing metapelites at temperatures ~1000 °C and interacted with peridotite at pressure ~1 GPa. Reaction of rhyolite with olivine converted lherzolite rocks into orthopyroxene-domains and orthopyroxene + plagioclase veins. The recognition of rhyolitic melts in the mantle provides direct evidence for element cycling through earth's reservoirs, accommodated by dehydration and melting of crustal material, brought into the mantle by subduction, chemically modifying the mantle source, and ultimately returning to surface by arc magmatism.

Isotope Geochemistry for Seafood Traceability and Authentication: The Northern Adriatic Manila Clams Case Study.

In Italy, the production of manila clams (Ruditapes philippinarum, Adams and Reeve, 1850) is mainly localized in northern Adriatic lagoons in the Po River delta, where shellfish farming provides important socio-economic revenue. However, in our globalized world, the seafood market is threated by fraudulent activities, in which agri-food products whose provenance is not certified are sold, posing a risk to consumer health. Multi-isotope ratio analysis is commonly used to trace the provenance of goods produced in different countries with different climatic and environmental conditions. Here, we investigated the reliability of this approach in terms of tracing the exact provenance of manila clams harvested in three Adriatic northern lagoons that are close to each other. We also verified the origin of samples bought at a local supermarket with a certificate of provenance. We carried out elemental analyses of carbon (C), nitrogen (N), and sulfur (S) and the respective isotopic ratios (13C/12C; 15N/14N; 34S/32S) on manila clam tissues, plus isotopic analyses of carbon (13C/12C), oxygen (18O/16O), and strontium (87Sr/86Sr) on manila clam shells. Each isotopic parameter can be used to identify the marine and continental contributions of water and/or nutrient supplies occurring in the lagoons. Therefore, the combination of isotopic parameters in a linear discriminant analysis (LDA) allowed for the identification of the lagoons in which the manila clams were produced.

Inflammation-Independent Antinociceptive Effects of DF2755A, a CXCR1/2 Selective Inhibitor: A New Potential Therapeutic Treatment for Peripheral Neuropathy Associated to Non-Ulcerative Interstitial Cystitis/Bladder Pain Syndrome.

Interstitial cystitis (IC)/bladder pain syndrome (BPS) is a chronic bladder disease of unknown etiology characterized by urinary frequency and episodic and chronic pain. Analgesic treatments for IC/BPS are limited, especially for patients with non-Hunner (non-ulcerative) type IC who usually have poor overall outcomes. Here, we demonstrate that oral treatment with DF2755A, a potent and selective inhibitor of chemokine receptors CXCR1/2, can prevent and reverse peripheral neuropathy associated to non-Hunner IC/BPS by directly inhibiting chemokine-induced excitation of sensory neurons. We tested DF2755A antinociceptive effects in a cyclophosphamide (CYP)-induced non-ulcerative IC rat model characterized by severe peripheral neuropathy in the absence of bladder inflammatory infiltrate, urothelial hyperplasia, and hemorrhage. Treatment with DF2755A prevented the onset of peripheral neuropathy and reversed its development in CYP-induced IC rats, showing a strong and long-lasting anti-hyperalgesic effect. Ex vivo and in vitro studies showed that DF2755A treatment strongly inhibited the expression of CXCR2 agonists, CXCL1/KC, and CXCL5 and of transient receptor potential vanilloid 1 (TRPV1) compared to vehicle, suggesting that its effects can be due to the inhibition of the nociceptive signaling passing through the CXCL1/CXCR1-2 axis and TRPV1. In conclusion, our results highlight the key pathophysiological role played by the CXCL1/CXCR1-2 axis and TRPV1 in the onset and development of peripheral neuropathy in non-Hunner IC and propose DF2755A as a potential therapeutic approach for the treatment of not only inflammatory painful conditions but also neuropathic ones and in particular non-Hunner IC/BPS.

Discovery of Novel TRPM8 Blockers Suitable for the Treatment of Somatic and Ocular Painful Conditions: A Journey through pKa and LogD Modulation.

Transient receptor potential melastatin 8 (TRPM8) is crucially involved in pain modulation and perception, and TRPM8 antagonists have been proposed as potential therapeutic approaches for pain treatment. Previously, we developed two TRPM8 antagonists and proposed them as drug candidates for topical and systemic pain treatment. Here, we describe the design and synthesis of these two TRPM8 antagonists (27 and 45) and the rational approach of modulation/replacement of bioisosteric chemical groups, which allowed us to identify a combination of narrow ranges of pKa and LogD values that were crucial to ultimately optimize their potency and metabolic stability. Following the same approach, we then pursued the development of new TRPM8 antagonists suitable for the topical treatment of ocular painful conditions and identified two new compounds (51 and 59), N-alkoxy amide derivatives, that can permeate across ocular tissue and reduce the behavioral responses induced by the topical ocular menthol challenge in vivo.

Design, synthesis and biological evaluation of new thiazole scaffolds as potential TRPM8 antagonists.

The preliminary results on the development of a viable methodology for the further functionalization of 4-hydroxythiazole derivatives to afford target TRPM8 antagonists are reported. The combined Sonogashira coupling/annulation reactions of the ethyl 2-(3-fluorophenyl)-4-tifluoromethylsulfonyloxy-1,3-thiazole-5-carboxylate have been applied to the synthesis of analogues of the selective blocker of TRPM8 DFL23448. Among all the synthetised derivatives, the most promising compound resulted to be active as TRPM8 blocker (IC50 = 4.06 µM), showing an excellent metabolic stability and no cytotoxic effects. Finally, in silico characterisation of the derivatives showed no violation of the drug-likeness rules.

Peat Soil Burning in the Mezzano Lowland (Po Plain, Italy): Triggering Mechanisms and Environmental Consequences.

The effects of peat burning on organic-rich agricultural soils of the Mezzano Lowland (NE Italy) were evaluated on soil profiles variously affected by smoldering. Profiles were investigated for pH, electrical conductivity, bulk density, elemental and isotopic composition of distinct carbon (and nitrogen) fractions. The results suggest that the horizons affected by carbon loss lie at depths 10-70 cm, where the highest temperatures are developed. We suggest that the exothermal oxidation of methane (mediated by biological activity) plays a significant role in the triggering mechanism. In the interested soils we estimated a potential loss of Soil Organic Carbon of approximately 110 kg m -2 within the first meter, corresponding to 580 kg CO2 m -3. The released greenhouse gas is coupled with a loss of soil structure and nutrients. Moreover, the process plausibly triggers mobility of metals bound in organometallic complexes. All these consequences negatively affect the environment, the agricultural activities and possibly also health of the local people.

BCAAs and Di-Alanine supplementation in the prevention of skeletal muscle atrophy: preclinical evaluation in a murine model of hind limb unloading.

Skeletal muscle atrophy occurs in response to various pathophysiological stimuli, including disuse, aging, and neuromuscular disorders, mainly due to an imbalance of anabolic/catabolic signaling. Branched Chain Amino Acids (BCAAs: leucine, isoleucine, valine) supplements can be beneficial for counteracting muscle atrophy, in virtue of their reported anabolic properties. Here, we carried out a proof-of-concept study to assess the in vivo/ex vivo effects of a 4-week treatment with BCAAs on disuse-induced atrophy, in a murine model of hind limb unloading (HU). BCAAs were formulated in drinking water, alone, or plus two equivalents of L-Alanine (2 ALA) or the dipeptide L-Alanyl-L-Alanine (Di-ALA), to boost BCAAs bioavailability. HU mice were characterized by reduction of body mass, decrease of soleus - SOL - muscle mass and total protein, alteration of postural muscles architecture and fiber size, dysregulation of atrophy-related genes (Atrogin-1, MuRF-1, mTOR, Mstn). In parallel, we provided new robust readouts in the HU murine model, such as impaired in vivo isometric torque and ex vivo SOL muscle contractility and elasticity, as well as altered immune response. An acute pharmacokinetic study confirmed that L-ALA, also as dipeptide, enhanced plasma exposure of BCAAs. Globally, the most sensitive parameters to BCAAs action were muscle atrophy and myofiber cross-sectional area, muscle force and compliance to stress, protein synthesis via mTOR and innate immunity, with the new BCAAs + Di-ALA formulation being the most effective treatment. Our results support the working hypothesis and highlight the importance of developing innovative formulations to optimize BCAAs biodistribution.

Unexpected Salt/Cocrystal Polymorphism of the Ketoprofen-Lysine System: Discovery of a New Ketoprofen-l-Lysine Salt Polymorph with Different Physicochemical and Pharmacokinetic Properties.

Ketoprofen-l-lysine salt (KLS) is a widely used nonsteroidal anti-inflammatory drug. Here, we studied deeply the solid-state characteristics of KLS to possibly identify new polymorphic drugs. Conducting a polymorph screening study and combining conventional techniques with solid-state nuclear magnetic resonance, we identified, for the first time, a salt/cocrystal polymorphism of the ketoprofen (KET)-lysine (LYS) system, with the cocrystal, KET-LYS polymorph 1 (P1), being representative of commercial KLS, and the salt, KET-LYS polymorph 2 (P2), being a new polymorphic form of KLS. Interestingly, in vivo pharmacokinetics showed that the salt polymorph has significantly higher absorption and, thus, different pharmacokinetics compared to commercial KLS (cocrystal), laying the basis for the development of faster-release/acting KLS formulations. Moreover, intrinsic dissolution rate (IDR) and electronic tongue analyses showed that the salt has a higher IDR, a more bitter taste, and a different sensorial kinetics compared to the cocrystal, suggesting that different coating/flavoring processes should be envisioned for the new compound. Thus, the new KLS polymorphic form with its different physicochemical and pharmacokinetic characteristics can open the way to the development of a new KET-LYS polymorph drug that can emphasize the properties of commercial KLS for the treatment of acute inflammatory and painful conditions.

Traceability and Authentication of Manila Clams from North-Western Adriatic Lagoons Using C and N Stable Isotope Analysis.

In the Adriatic lagoons of northern Italy, manila clam (Ruditapes philippinarum) farming provides important socio-economic returns and local clams should be registered with the Protected Designations of Origin scheme. Therefore, there is a need for the development of rapid, cost-effective tests to guarantee the origin of the product and to prevent potential fraud. In this work, an elemental analysis (EA) coupled with isotope ratio mass spectrometry (IRMS) was employed to identify the isotopic fingerprints of clams directly collected onsite in three Adriatic lagoons and bought at a local supermarket, where they exhibited certification. In particular, a multivariate analysis of C/N, δ13C and δ15N in manila clam tissues as well as δ13C in shells and Δ13C (calculated as δ13Cshell-δ13Ctissues) seems a promising approach for tracking the geographical origin of manila clams at the regional scale.

A new synthetic dual agonist of GPR120/GPR40 induces GLP-1 secretion and improves glucose homeostasis in mice.

G-protein coupled receptors 40 and 120 (GPR40 and GPR120) are increasingly emerging as potential therapeutic targets for the treatment of altered glucose homeostasis, and their agonists are under evaluation for their glucagon-like peptide-1 (GLP-1)-mediated therapeutic effects on insulin production and sensitivity. Here, we characterized a new dual GPR40 and GPR120 agonist (DFL23916) and demonstrated that it can induce GLP-1 secretion and improve glucose homeostasis. Resulting from a rational drug design approach aimed at identifying new dual GPR120/40 agonists able to delay receptor internalization, DFL23916 had a good activity and a very high selectivity towards human GPR120 (long and short isoforms) and GPR40, as well as towards their mouse orthologous, by which it induced both Gαq/11-initiated signal transduction pathways with subsequent Ca2+ intracellular spikes and G protein-independent signaling via ß-arrestin with the same activity. Compared to the endogenous ligand alpha-linolenic acid (ALA), a selective GPR120 agonist (TUG-891) and a well-known dual GPR40 and GPR120 agonist (GW9508), DFL23916 was the most effective in inducing GLP-1 secretion in human and murine enteroendocrine cells, and this could be due to the delayed internalization of the receptor (up to 3 h) that we observed after treatment with DFL23916. With a good pharmacokinetic/ADME profile, DFL23916 significantly increased GLP-1 portal vein levels in healthy mice, demonstrating that it can efficiently induce GLP-1 secretion in vivo. Contrary to the selective GPR120 agonist (TUG-891), DFL23916 significantly improved also glucose homeostasis in mice undergoing an oral glucose tolerance test (OGTT).

Petrographic and mineral-glass chemical dataset of igneous rock clasts from Early Oligocene Aveto-Petrignacola Formation (Northern Italy).

This dataset article contains petrographic and mineral-glass chemical data of igneous rock clasts from Early Oligocene Aveto-Petrignacola Formation (APF; Northern Italy). Methods for obtaining the dataset include optical microscopy, scanning electron microscopy and electron probe microanalysis. The APF volcanic rocks are basalts, basaltic andesites, andesites, dacites and rhyolites. Rare gabbroic cumulate nodules complete the dataset. Basalts are porphyritic, with calcic plagioclase (An72-92Ab7-27Or0-1), ferroan enstatite (En59-68Fs29-37Wo3-4) and augite (En38-39Fs18-20Wo41-44) phenocrysts, in a hypocrystalline groundmass made up of bytownite (An71-85Ab14-28Or1), augite (En37-38Fs19Wo43-44), ferroan enstatite (En62-68Fs30-35Wo1-4) and rare pigeonite (En46-50Fs37-42Wo7-17). The basaltic andesites are porphyritic to glomeroporphyritic with phenocrysts of zoned plagioclase (An44-67Ab32-55Or1), orthopyroxene, Mg-rich augite (En38-42Fs15-17Wo43-45), rare pargasite to edenite amphibole (Mg# 69-59) and very rare biotite in a hypocrystalline to holohyaline groundmass. Andesites are highly porphyritic with phenocrysts of plagioclase (An47-79Ab20-52Or0-1), pargasite to magnesio-hornblende (Mg# 72-67), Mg-rich augite (En43-46Fs12-17Wo41-43), subordinate ferroan enstatite (En68-74Fs23-29Wo3-4), biotite (Mg# 53) and Ti-magnetite (Usp29-41). Dacites (massive lavas and ignimbrites) are porphyritic, with phenocrysts and phenoclasts of plagioclase (An33-79Ab20-62Or0-4), calcic amphibole (Ti-pargasite, Mg-hornblende and edenite; Mg# 81-46), biotite (Mg# 67-56), very rare Mg-rich augite (En41-42Fs16-18Wo40-43) and resorbed quartz in hypohyaline to holohyaline groundmass with a dense mat of anhedral quartz, labradorite-andesine (An36-66Ab33-61Or1-4) and rare anorthoclase (An22Ab66Or12). Rhyolitic compositions have been found both as volcanic clasts (massive lava and ignimbrites) with andesine to oligoclase phenoclasts (An25-38Ab61-71Or1-4), quartz, biotite (Mg# 55-53) and Ti-magnetite (Usp18-77), and as interstitial glasses (residual melt drops) in other APF volcanic rocks. The cumulate nodules are olivine-gabbro and amphibole-gabbro/gabbronorite with a mineral paragenesis dominated by plagioclase (An41-73Ab26-57Or1-3), olivine (Fo68-72), Mg-rich augite to ferroan diopside (En41-45Fs12-15Wo42-45; Mg# 79-74), ferroan enstatite (En65-74Fs24-33Wo2-3; Mg# 76-68), magnetite (Usp15-28) and titanian pargasite (Mg# 67-65). The main cumulus phases are plagioclase, olivine and pyroxene, while intercumulus/postcumulus phases are titanian pargasite and magnetite. The dataset can be used to compare petrographic features and chemical compositions of calc-alkaline rocks emplaced in other subduction-related settings. Above all, it can represent a useful contribution in solving the problem linked to the identification of a hidden Early-Oligocene source of the thick volcaniclastic APF succession in the Alpine-Apennine belt geodynamic evolution.

Ergogenic Effect of BCAAs and L-Alanine Supplementation: Proof-of-Concept Study in a Murine Model of Physiological Exercise.

BACKGROUND: Branched-chain amino acids (BCAAs: leucine, isoleucine, valine) account for 35% of skeletal muscle essential amino acids (AAs). As such, they must be provided in the diet to support peptide synthesis and inhibit protein breakdown. Although substantial evidence has been collected about the potential usefulness of BCAAs in supporting muscle function and structure, dietary supplements containing BCAAs alone may not be effective in controlling muscle protein turnover, due to the rate-limiting bioavailability of other AAs involved in BCAAs metabolism. METHODS: We aimed to evaluate the in vivo/ex vivo effects of a 4-week treatment with an oral formulation containing BCAAs alone (2:1:1) on muscle function, structure, and metabolism in a murine model of physiological exercise, which was compared to three modified formulations combining BCAAs with increasing concentrations of L-Alanine (ALA), an AA controlling BCAAs catabolism. RESULTS: A preliminary pharmacokinetic study confirmed the ability of ALA to boost up BCAAs bioavailability. After 4 weeks, mix 2 (BCAAs + 2ALA) had the best protective effect on mice force and fatigability, as well as on muscle morphology and metabolic indices. CONCLUSION: Our study corroborates the use of BCAAs + ALA to support muscle health during physiological exercise, underlining how the relative BCAAs/ALA ratio is important to control BCAAs distribution.

Catalyst-Free Synthesis of Polysubstituted 5-Acylamino-1,3-Thiazoles via Hantzsch Cyclization of α-Chloroglycinates.

A catalyst-free heterocyclization reaction of α-chloroglycinates with thiobenzamides or thioureas leading to 2,4-disubstituted-5-acylamino-1,3-thiazoles has been developed. The methodology provides straightforward access to valuable building blocks for pharmaceutically relevant compounds.

DF2726A, a new IL-8 signalling inhibitor, is able to counteract chemotherapy-induced neuropathic pain.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect of several anti-neoplastics and a main cause of sensory disturbances in cancer survivors, negatively impacting patients' quality of life. Peripheral nerve degeneration or small fibre neuropathy is generally accepted as the underlying mechanism in the development of CIPN. Recent evidence has contributed to clarify the determinant role of cytokines and chemokines in the process leading to neuronal hyperexcitability. Exposure to oxaliplatin triggers alterations in peripheral neuropathic pathways previously linked to IL-8 pathway. We investigated a novel selective inhibitor of IL-8 receptors, DF2726A, and showed its effects in counteracting CINP pathways, extending the relevance of the activation of IL-8 pathway to the class of platinum chemotherapeutics. Based on our results, we suggest that DF2726A might be a promising candidate for clinical treatment of CIPN conditions due to its efficacy and optimized pharmacokinetic/pharmacodynamic profile.