The future of integrated structural biology.

Instruct-ERIC, "the European Research Infrastructure Consortium for Structural biology research," is a pan-European distributed research infrastructure making high-end technologies and methods in structural biology available to users. Here, we describe the current state-of-the-art of integrated structural biology and discuss potential future scientific developments as an impulse for the scientific community, many of which are located in Europe and are associated with Instruct. We reflect on where to focus scientific and technological initiatives within the distributed Instruct research infrastructure.

Study of Chalcogen Aspirin Derivatives with Carbonic Anhydrase Inhibitory Properties for Treating Inflammatory Pain.

Carbonic anhydrase (CA) inhibitors represent intriguing tools for treating pain. This study aims at studying the pharmacological profile of chalcogen bioisosteres of aspirin, as inhibitors of CA isoforms (hCA I, II, IV, VII, IX, and XII). Our results show that selenoaspirin () displayed markedly superior inhibitory potency across all tested isoforms compared to thioaspirin () and aspirin, with a strong selectivity against the isoform CA IX.

Synthesis, biochemical screening and in-silico investigations of arylsulfonamides bearing linear and cyclic tails.

A small series of arylsulfonamide derivatives was designed and synthesized to study linear and cyclic inhibitors targeting human Carbonic Anhydrases (hCAs EC 4.2.1.

Hybrid lipid-AuNP clusters as highly efficient SERS substrates for biomedical applications.

Although Surface Enhanced Raman Scattering (SERS) is widely applied for ultrasensitive diagnostics and imaging, its potential is largely limited by the difficult preparation of SERS tags, typically metallic nanoparticles (NPs) functionalized with Raman-active molecules (RRs), whose production often involves complex synthetic approaches, low colloidal stability and poor reproducibility. Here, we introduce LipoGold Tags, a simple platform where gold NPs (AuNPs) clusters form via self-assembly on lipid vesicle. RRs embedded in the lipid bilayer experience enhanced electromagnetic field, significantly increasing their Raman signals.

Microplastic removal and risk assessment framework in a constructed wetland for the treatment of combined sewer overflows.

Combined sewer overflows (CSOs) release a significant amount of pollutants, including microplastics (MPs), due to the discharge of untreated water into receiving water bodies. Constructed Wetlands (CWs) offer a promising strategy for CSO treatment and have recently attracted attention as a potential solution for MP mitigation. Nevertheless, limited research on MP dynamics within CSO events and MP removal performance in full-scale CW systems poses a barrier to this frontier of application.

Study of the Preparation and Properties of Chemically Modified Materials Based on Rapeseed Meal.

In recent years, there has been increasing interest in developing novel materials based on natural biopolymers as a renewable alternative to petroleum-based plastics. The availability of proteins derived from agricultural by-products, along with their favourable properties, has fostered a renewed interest in protein-based materials, promoting research in innovative technologies. In this study, we propose the use of rapeseed protein-rich meal as the main ingredient for the preparation of novel sustainable materials combining excellent environmental properties such as biodegradability and renewability.

Physiological modeling of the metaverse of the Mycobacterium tuberculosis β-CA inhibition mechanism.

Tuberculosis (TB) is an infectious disease that primarily affects the lungs of humans and accounts for Mycobacterium tuberculosis (Mtb) bacteria as the etiologic agent. In this study, we introduce a computational framework designed to identify the important chemical features crucial for the effective inhibition of Mtb β-CAs. Through applying a mechanistic model, we elucidated the essential features pivotal for robust inhibition.

Sustainable and effective reconditioning of SPR gold chips functionalized with molecularly imprinted polynorepinephrine.

Surface Plasmon Resonance (SPR) technology has revolutionized the study of affinity-based biomolecular interactions, offering label-free and real-time analysis capabilities. However, traditional SPR gold chips have been viewed as disposable due to challenges in post-use reconditioning, leading to significant resource wastage and increased costs. To address this issue, we propose a novel approach utilizing polynorepinephrine-based (PNE) Molecularly Imprinted Bio-Polymers (MIBPs) as alternative receptors to conventional antibodies.

Novel Discrete and Imprinted Fluoride-Selective Sensors: Bridging the Gap from DMSO to Aqueous Samples.

Fluoride in drinking water has beneficial or harmful health effects depending on its concentration. This highlights the need for new low-cost and portable sensors capable of in situ monitoring of F ions. Unfortunately, achieving high levels of water compatibility and fluoride specificity remains a challenge.

Bioinspired and bioderived nanomedicine for inflammatory bowel disease.

Due to its chronic nature and complex pathophysiology, inflammatory bowel disease (IBD) poses significant challenges for treatment. The long-term therapies for patients, often diagnosed between the ages of 20 and 40, call for innovative strategies to target inflammation, minimize systemic drug exposure, and improve patients' therapeutic outcomes. Among the plethora of strategies currently pursued, bioinspired and bioderived nano-based formulations have garnered interest for their safety and versatility in the management of IBD.

Red stains on heritage marbles: application of micro-scale analyses to assess the presence and distribution of lead compounds.

Stone cultural heritage buildings are frequently affected by different alteration phenomena and in particular, on heritage marbles the presence of chromatic discolouration, as the red stains, is one of the most widespread. In this paper, small fragments of red stains originated on marble exposed to different environmental contexts were analysed to reveal the presence and distribution of lead compounds at the micro-scale level. The samples come from slabs of historical religious buildings in Florence (Santa Maria del Fiore Cathedral and the San Giovanni Baptistery) and from the monumental fountains conserved in the Medicean Villa La Petraia (Florence).

Network analysis to reveal the most commonly detected compounds in predator-prey pairs in freshwater and marine mammals and fish in Europe.

Marine and freshwater mammalian predators and fish samples, retrieved from environmental specimen banks (ESBs), natural history museum (NHMs) and other scientific collections, were analysed by LIFE APEX partners for a wide range of legacy and emerging contaminants (2545 in total). Network analysis was used to visualize the chemical occurrence data and reveal the predominant chemical mixtures for the freshwater and marine environments. For this purpose, a web tool was created to explore these chemical mixtures in predator-prey pairs.

Microfluidic Detection of SPIONs and Co-Ferrite Ferrofluid Using Amorphous Wire Magneto-Impedance Sensor.

The detection of magnetic nanoparticles in a liquid medium and the quantification of their concentration have the potential to improve the efficiency of several relevant applications in different fields, including medicine, environmental remediation, and mechanical engineering. To this end, sensors based on the magneto-impedance effect have attracted much attention due to their high sensitivity to the stray magnetic field generated by magnetic nanoparticles, their simple fabrication process, and their relatively low cost. To improve the sensitivity of these sensors, a multidisciplinary approach is required to study a wide range of soft magnetic materials as sensing elements and to customize the magnetic properties of nanoparticles.

A First-in-Class Pyrazole-isoxazole Enhanced Antifungal Activity of Voriconazole: Synergy Studies in an Azole-Resistant Strain, Computational Investigation and in Vivo Validation in a Fungal Infection Model.

The widespread and irrational use of azole antifungal agents has led to an increase of azole-resistant strains with an urgent need for combination drug therapy, enhancing the treatment efficacy. Here, we report the discovery of a first-in-class pyrazole-isoxazole, namely, , that showed remarkable growth inhibition against the . ATCC 10231 strain in combination with voriconazole, acting as a downregulator of ERG 11 () gene expression with a significant reduction of the yeast-to-hypha morphological transition.

Isocoumarins incorporating chalcone moieties act as isoform selective tumor-associated carbonic anhydrase inhibitors.

A series of isocoumarin-chalcone hybrids were prepared and assays for the inhibition of four isoforms of human carbonic anhydrase (hCA; EC 4.2.1.

Exploiting CO laser to boost graphite inks electron transfer for fructose biosensing in biological fluids.

The possibility to print electronics by means of office tools has remarkedly increased the possibility to design affordable and robust point-of-care/need devices. However, conductive inks suffer from low electrochemical and rheological performances limiting their applicability in biosensors. Herein, a fast CO laser approach to activate printed carbon inks towards direct enzymatic bioelectrocatalysis (3 generation) is proposed and exploited to build biosensors for D-fructose analysis in biological fluids.

Organoselenium-Catalyzed Enantioselective Synthesis of 2-Oxazolidinones from Alkenes.

An operationally simple method for generating enantioenriched 2-oxazolidinones from -Boc amines and mono- or disubstituted alkenes via chiral organoselenium catalysis is described. Critical to the success of the transformation was the inclusion of triisopropylsilyl chloride (TIPSCl), likely because it sequestered fluoride generated by the oxidant (-fluorocollidinium tetrafluoroborate) throughout the reaction and suppressed side reactivity. The scope of both the amine and alkene substrates was explored, generating a variety of 2-oxazolidinones in modest to high yields with high enantioselectivities.

Iodine/Oxone® oxidative system for the synthesis of selenylindoles bearing a benzenesulfonamide moiety as carbonic anhydrase I, II, IX, and XII inhibitors.

A wide range of 3-selenylindoles were synthesized an eco-friendly approach that uses Oxone® as the oxidant in the presence of a catalytic amount of iodine. This mild and economical protocol showed broad functional group tolerance and operational simplicity. A series of novel selenylindoles bearing a benzenesulfonamide moiety were also synthesized and evaluated as carbonic anhydrase inhibitors of the human (h) isoforms hCa I, II, IX, and XII, which are involved in pathologies such as glaucoma and cancer.

Dual Inhibitors of P-gp and Carbonic Anhydrase XII (hCA XII) against Tumor Multidrug Resistance with Piperazine Scaffold.

A new series of piperazine derivatives were synthesized and studied with the aim of obtaining dual inhibitors of P-glycoprotein (P-gp) and carbonic anhydrase XII (hCA XII) to synergistically overcome the P-gp-mediated multidrug resistance (MDR) in cancer cells expressing the two proteins, P-gp and hCA XII. Indeed, these hybrid compounds contain both P-gp and hCA XII binding groups on the two nitrogen atoms of the heterocyclic ring. All compounds showed good inhibitory activity on each protein (P-gp and hCA XII) studied individually, and many of them showed a synergistic effect in the resistant HT29/DOX and A549/DOX cell lines which overexpress both the target proteins.

Saffron ( L.) and Its By-Products: Healthy Effects in Internal Medicine.

L., commonly known as saffron, is a precious spice coming from Asia, in particular from Iran, the country leader in its production. The spice is derived exclusively from dried stigmas and it is the most expensive one in the world.

The Many Lives of Auranofin: How an Old Anti-Rheumatic Agent May Become a Promising Antimicrobial Drug.

Auranofin (AF) is a gold-based compound with a well-known pharmacological and toxicological profile, currently used in the treatment of some severe forms of rheumatoid arthritis. Over the last twenty years, AF has also been repurposed as antiviral, antitumor, and antibacterial drug. In this review we focused on the antibacterial properties of AF, specifically researching the minimal inhibitory concentrations (MIC) of AF in both mono- and diderm bacteria reported so far in literature.

A green approach to encapsulate proteins and enzymes within crystalline lanthanide-based Tb and Gd MOFs.

In this work, bovine serum albumin (BSA) and sp. laccase (LC) were encapsulated within two lanthanide-based MOFs (TbBTC and GdBTC) through a green one-pot synthesis (almost neutral aqueous solution, = 25 °C, and atmospheric pressure) in about 1 h. Pristine MOFs and protein-encapsulated MOFs were characterized through wide angle X-ray scattering, scanning electron microscopy, thermogravimetric analysis, Fourier transform infrared and Raman spectroscopies.

Organocatalytic hydrogen bond donor/Lewis base (HBD/LB) synthesis and chiroptical properties of thiabridged [5]helicenes.

Thiabridged [5]helicenes are obtained from thioaryl--phthalimido benzo[]phenothiazines using a hydrogen bond donor/Lewis base organocatalytic approach. Resolution of [5]helicenes using either (1)-(-)-camphanic acid as a chiral auxiliary or CSP-HPLC is reported. Thiabridged [5]helicenes show an exceptional configurational stability with racemization energy barriers higher than 40 kcal mol.

Determination of persistent organic pollutants in urban and peri-urban wastewater sludge: environmental and carcinogenic human risk assessment in the case of land application.

The management of digested sludge derived from treatment water plants is a problem worldwide due to the possible transfer of contamination from sludge to amended soil and, in turn, to humans. Within this work, through a chemometric experimental design, a robust GC-MS method for the simultaneous determination of two classes of micropollutants of concern (polycyclic aromatic hydrocarbons-PAHs-and polychlorinated biphenyls-PCBs-including dioxin-like compounds) was developed using microwave-assisted extraction (MAE). The method, which showed interesting greenness features in compliance with the 12 principles of Green Chemistry, allowed PCB and PAH extraction with recoveries higher than 75% (RSD < 14%) with method detection limits between 4.