Disclosing the composition of unknown historical drug formulations: an emblematic case from the Spezieria of St. Maria della Scala in Rome.

This paper reports a pioneering study of an unknown historical drug formulation preserved in the Spezieria of Santa Maria della Scala in Rome, founded at the end of the seventeenth century by the Discalced Carmelites. Due to limited literature related to pharmaceutical remedies and drugs of the Early Modern Era (between the XV and XVIII centuries) and the complexity in their formulations, the study of these drugs represents a great challenge. The untargeted nature of the selected drug required a multi-analytical approach with complementary techniques to formulate a compositional hypothesis: FT-IR spectroscopy, gas chromatography-associated/mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) were successfully employed to identify different organic compounds. Systematic archaeobotanical research was performed as well, allowing us to acquire data related to the possible genus of plants from which these natural compounds derive and their geographical origin. The unknown drug formulation turned out to be a complex mixture used as an ointment with an anti-inflammatory purpose. It mainly contains a mixture of Venetian turpentine; a Pine resin (colophony) from the Pinaceae family; an exudate of a plant from South America, whose identified components are triterpenic compounds such as alpha- and beta-amyrins, betulin and lupeol; and saturated fatty acids which act as carriers and/or to reduce the viscosity of abovementioned exudates and resins. The study of historical drugs is important not only in order to know the practices handed down by the speziali in the past but also to reconstruct historical recipes, which can inspire new dermatological, cosmetic, hygienic and current healing products.Graphical abstract.

Multidisciplinary long-term survey of Manila clam grown in farming sites subjected to different environmental conditions.

In recent years recurrent bivalve mass mortalities considerably increased around the world, causing the collapse of natural and farmed populations. Venice Lagoon has historically represented one of the major production areas of the Manila clam Ruditapes philippinarum in Europe. However, in the last 20 years a 75 % decrease in the annual production has been experienced. While climate change and anthropogenic interventions may have played a key role in natural and farmed stocks reductions, no studies investigated at multiple levels the environmental stressors affecting farmed Manila clam to date. In this work we carried out a long-term monitoring campaign on Manila clam reared in four farming sites located at different distances from the southern Venice Lagoon inlet, integrating (meta)genomic approaches (i.e. RNA-seq; microbiota characterization), biometric measurements and chemical-physical parameters. Our study allowed to characterize the molecular mechanisms adopted by this species to cope with the different environmental conditions characterizing farming sites and to propose hypotheses to explain mortality events observed in recent years. Among the most important findings, the disruption of clam's immune response, the spread of Vibrio spp., and the up-regulation of molecular pathways involved in xenobiotic metabolism suggested major environmental stressors affecting clams farmed in sites placed close to Chioggia's inlet, where highest mortality was also observed. Overall, our study provides knowledge-based tools for managing Manila clam farming on-growing areas. In addition, the collected data is a snapshot of the time immediately before the commissioning of MoSE, a system of mobile barriers aimed at protecting Venice from high tides, and will represent a baseline for future studies on the effects of MoSE on clams farming and more in general on the ecology of the Venice Lagoon.