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Autoimmune diseases are conditions characterized by aberrant B-cell and T-cell reactivity against self-antigens. Autoantibodies are serological biomarkers of autoimmune diseases, as such, autoantibody testing is a key step for diagnosing and classifying many autoimmune diseases, as well as monitoring disease activity and devising a treatment strategy. Considering the rising number of people affected by autoimmune diseases worldwide, it is even more important to have efficient techniques that combine high sensitivity and specificity with reduced sample processing times and an automated high-throughput workflow. In this context, the identification and validation of new autoantigens and autoantibodies, together with the implementation of technological advancements, has led, in the last decades, to an improvement in patient diagnosis and stratification. Here, we review the major antigens of some of the most common autoimmune diseases, and the most widely used assays employed in diagnostic laboratories for the detection of their cognate antibody, confronting more traditional platforms with emerging ones in selected cases of study.
The ethynyl radical cation, CCH+ (3Π), offers a unique system for fundamental spectroscopic studies of nonadiabatic effects due to its open-shell linear structure and the presence of a low-lying 3Σ- state, which induces notable perturbations in the (ro-)vibrational spectrum. To probe these effects, we recorded the broadband vibrational spectrum of CCH+ from 350-3450 cm-1 using leak-out spectroscopy. The spectrum reveals a complex splitting pattern in the CCH bending mode attributed to Renner-Teller and pseudo-Jahn-Teller coupling effects between the 3Π and 3Σ- electronic states. A three-state diabatic model, validated here against high-resolution IR data of the CH stretching mode, facilitated assignments within the broadband infrared (IR) spectrum, including an additional Π vibronic feature observed in the aforementioned high-resolution spectrum. Our results highlight a pronounced sensitivity of the splitting pattern to the Π-Σ energy gap, with couplings so large that even the zero-point vibrational motion of the bending vibration is sufficient to disrupt the vibronic structure of this ion. This compact ion, with strong coupling effects and high-quality spectroscopic data, serves as an exemplary system for evaluating nonadiabatic models.
In 2024, Garg and co-workers reported that norborn-1-enes, a class of anti-Bredt olefins, can be systematically prepared and trapped. This finding has prompted us to combine multistate, multiconfigurational quantum chemical gradients and multiscale modeling to simulate the light-induced dynamics and chemistry of norborn-1-ene in acetonitrile. The results predict the existence of an excited state intermediate with a unique electronic structure consisting of a zwitterion incorporating a nonclassical cationic moiety. A set of 200 room-temperature quantum-classical trajectories were propagated to show that such intermediate decay through a unique conical intersection leads to the simultaneous formation of a carbene and a diradical as primary photoproducts. A third zwitterionic photoproduct is instead predicted to have a transient existence. Thus, our simulation not only uncovers a new type of photochemical funnel but also points to novel chemistries only accessible when anti-Bredt olefins are prepared or trapped under illumination conditions.
Spermatogenesis relies on the highly specialized interaction between germ cells and a supportive somatic niche, yet replicating this environment in vitro remains a major challenge. Primary human Sertoli cells (hSCs), key architects of this niche, often lose their phenotype under conventional culture conditions, limiting the establishment of a stable blood-testis barrier (BTB)-associated phenotype and their ability to support germ cells. Here, we present a structurally organized, human ECM-derived connective tissue equivalent (CTE) designed to support long-term maintenance and organization of hSCs in vitro. The CTE, generated from fibroblast-secreted matrix enriched in laminin, fibronectin, and collagen IV, reproduces key biochemical and physical features of a supportive microenvironment. hSCs introduced into the CTE as single cells or pre-formed spheroids were evaluated for survival, structural organization, phenotypic stability, and ECM remodeling. Both configurations supported progressive expression and organization of BTB-associated proteins (ZO-1, OCLDN) together with upregulation of Sertoli cell-associated markers, including SOX9 and ABP, with the spheroid-based model showing improved structural cohesion, integration within the construct, and more evident junctional organization over time. Overall, this bioactive human-derived platform supports long-term maintenance of hSC phenotype and barrier-associated features in vitro, providing a promising basis for future human testis models and co-culture studies.
Computational vibrational spectroscopy beyond the harmonic approximation relies on the molecular potential and ideally dipole and possibly higher moments of charge distributions. In the past decade, there has been a paradigm shift in generating highly accurate Machine-Learned potentials (MLPs). These are precise fits to thousands of electronic energies, using modern methods of regression. With such MLPs, it is possible to combine these with a variety of post-harmonic quantum methods ranging from perturbation theory to full variational calculations. After a short review of these methods, we focus on vibrational self-consistent field and configuration interaction (VSCF + VCI) calculations, as implemented in the code MULTIMODE. Two applications of this software to complex parts of the infrared spectra of formic acid dimer and the protonated oxalate anion are presented. Two new interfaces to MULTIMODE are then given. One is a Python-based GUI to enable user-friendly input to MULTIMODE. The second interface, PyFort, which is written in Fortran, uses MLPs written in Python in MULTIMODE via a C wrapper. Demonstrations of this are given for a PhysNet potential of Meuwly and co-workers for protonated oxalate anion (C2O4H-) and for the "universal" force field MACE-OFF of Csányi and co-workers. MULTIMODE VSCF + VCI vibrational energies of C2O4H- using the PhysNet MLP agree well with those using a permutationally invariant potential, trained on the datasets used to train the PhysNet MLP. A test of the MACE-OFF interface is done for H2CO. The PyFort software for both these examples is provided in the supplementary material.
In recent years, the focus on luminescent solar concentrator (LSC) materials has been renewed thanks to their properties that support their integration into PV technologies in buildings and in the urban environment. In this work, three dyes bearing push-pull units and presenting anthracene (compound 1) or 2,1,3-benzothiadiazole (BTZ-P6t, compound 2, and TBTZ-P12t, compound 3) as the central chromophore module are investigated as luminophores for the LSCs based on polyacrylate. The optical and luminescence characterization of the dyes in solution and in polyacrylate panels has been carried out to examine the impact of medium polarity and stiffening on the photophysical behavior of the dyes. The photoluminescence quantum yield (PLQY), decay times, and radiative and nonradiative rate constants have been evaluated together with the overlap integral to rationalize the reabsorption phenomena. The photophysical parameters highlight that medium polarity and matrix stiffening have an impact on the photoluminescence properties. The evaluation of the photovoltaic performance, performed by placing an edge of dye panels in contact with a silicon PV device, shows that the panels act as LSCs. In particular, compound 3 exhibits the highest value of PLQY (81%), resulting in the highest value of PV light-to-energy conversion efficiencies (ηopt%, 2.8%). This study proposes a thorough and correlated examination of the photophysical characteristics of molecular systems when the media are switched from solution to acrylate panels in order to rationalize the photovoltaic performance of the prepared LSCs. Although the prepared dye-acrylate panels fall outside accepted standard dimensions for LSC size, this study is relevant to designing chromophore architecture for enhanced efficiencies for LSCs.
Controlling lattice-oxygen reactivity in earth-abundant OER catalysts requires precise tuning of defect chemistry in the oxide lattice. Here, we combine DFT + U calculations with plasma-assisted synthesis to show how O2 and H2O in the discharge govern vacancy formation, electronic structure, and catalytic predisposition in NiO thin films. Oxygen-rich plasmas generate isolated and clustered Ni vacancies that stabilize oxygen-ligand-hole states and produce shallow O 2p-Ni 3d hybrid levels, enhancing Ni-O covalency. In contrast, introducing H2O during growth drives local hydroxylation that compensates vacancy-induced Ni3+ centers, restoring Ni2+-like coordination, suppressing deep divacancy-derived in-gap states, and introducing shallow Ni-O-H-derived valence-band tails. EXAFS confirms that hydroxylation perturbs only the local environment while preserving the medium-range NiO lattice, and Ni L-edge spectroscopy shows a persistent but redistributed ligand-hole population. These complementary vacancy- and hydroxylation-driven pathways provide a plasma-controlled route to predefine electronic defect landscapes in NiO and to tune its activation toward OER-relevant NiOOH formation.
Meniscal injuries are one of the most frequent orthopedic injuries and often lead to joint degeneration and osteoarthritis if left untreated. Current meniscus prostheses are limited by inadequate mechanical properties and poor integration with native tissue, leading to high failure rates and limited long-term success. The field of meniscus replacement aims to develop scaffolds that mimic the native meniscus's complex structure and mechanical properties while promoting tissue regeneration and integration (when targeting a tissue-engineered meniscus). However, traditional fabrication methods, such as fused deposition modeling (FDM) 3D printing, are limited by the narrow range of compatible materials and insufficient resolution for producing highly porous and biocompatible scaffolds. To overcome these challenges, this study introduces a novel injection molding setup designed to fabricate scaffolds using hydrogel building blocks, AUP4K DA and AUP4K HA, specifically engineered for meniscus replacement applications. The scaffolds were characterized to assess their suitability for meniscus replacement. Microscopic analysis and SEM analysis revealed an interconnected porous network with uniform pore distribution and the absence of traces of the applied negative mold used to fabricate the scaffold. Swelling degree and gel fraction were evaluated to confirm the high hydrogels' water retention and cross-linking efficiency, respectively. Mechanical properties were analyzed through compression testing and texture profile analysis (TPA), demonstrating that the scaffolds exhibit compressive strength and viscoelastic behavior in the range of native human meniscal tissue. By addressing the material and structural limitations of FDM printing, the injection molding setup presents a versatile platform for fabricating hydrogel-based scaffolds with a large range of mechanical properties. This study thus provides a promising solution for meniscus replacement, paving the way for the development of hydrogel scaffolds that mimic the native meniscal tissue.
Recent trends in food packaging for reducing the use of petroleum-based plastics and waste focus on the development of sustainable protecting films based on metal nanostructure embedded biopolymers. However, the safety of such bionanocomposites if human ingested has been poorly explored so far. In this work, crosslinked alginate films embedding ZnO nanostructures (Alg/ZnO) were prepared and analyzed as a case study. A dynamic flow-through approach mimicking human digestion by simulated gastric fluid (SGF) extraction was assembled. It consisted of an automatic sequential injection analysis (SIA) setup that enabled evaluating the zinc oral bioaccessibility from the as-prepared composites. The temporal release of Zn2+ from 50 mg of Alg/ZnO films was monitored on-line by pumping SGF across film fragments in a flow-through container. Under fluidized-bed conditions, a quantitative retrieval of overall bioaccessible Zn2+ was achieved using only 12 mL of extractant (6 cycles of 2 mL SGF each), resulting in a cumulative extraction time of 30 min. For every extraction cycle, 50 μL aliquot of the gastric extract was automatically aspirated and mixed on-line with buffered Zincon colorimetric reagent for the on-line spectrophotometric detection of bioaccessible Zn2+. The gastric bioaccessible zinc fraction from Alg/ZnO films was about 70%. In the event of ingestion of 0.4 g of high-content Alg/ZnO films, a human daily intake of 0.52 mg Zn was estimated. This value is significantly lower than the maximum tolerable daily intake of 40 mg/day for adults. The proposed approach represents an interesting solution for the assessment of metal ion human bioaccessibility in antimicrobial-containing packaging without using cell tests.
Protonated species play a key role in ion-molecule chemistry relevant to astrochemical environments. In this work, we present a high-level theoretical characterization of the low-lying isomers of the [H,H,C,N,O]+ system. The exploration of the ground-state potential energy surface, using coupled-cluster (CC) theory, led to the identification of ten protonated isomers. Equilibrium structures and relative energies have been determined using composite schemes rooted in CC theory and accounting for extrapolation to the complete basis set limit and the effects of core correlation. H2NCO+ and HNCOH+ are confirmed as the two most stable forms. For all isomers, rotational spectroscopy parameters together with fundamental vibrational frequencies and infrared intensities are accurately predicted. Proton affinities of the HNCO isomers are evaluated to elucidate preferred protonation sites. In addition, the patterns of the lowest singlet and triplet electronic states of these species, which exhibit strong valence-Rydberg character, are also presented. This work is expected to help in the identification of these protonated species in laboratory and astrophysical media.
The effects on human health of chemical compounds, which might be present in the environment due to natural or anthropogenic causes, are a fundamental aspect to be considered for the protection of public health and workers' health and in the evaluation of industrial processes in terms of health protection and sustainability. Investigations focused on lesser known effects that have recently drawn more attention on potential human target proteins. Due to the complexity of biochemical interactions, it is not straightforward to determine the biological response resulting from exposure to a specific chemical. In this article, we tackle this issue by combining chemoinformatics tools and atomistic modeling to perform target identification for several compounds. The study was carried out using a publicly available database that collects relationships between chemicals, genes, and phenotypes and resulting diseases to validate the results of the target identification pipeline. Small molecules that may occur in occupational and nonoccupational settings were investigated. Finally, we discuss the potentialities and limitations of using these fast, computationally inexpensive methods in early-stage target identification, both with and without performing a literature search for experimental data.
Separation of isotopologues of various weak bases was studied by free solution capillary electrophoresis. In addition, the separation of isotopomers was successfully demonstrated for the first time based on the electrokinetic migration mechanism. It was shown that the difference in the charge density of the isotopologues of amphetamine, metamphetamine, and their analogues was not sufficient for their separation. Therefore, the only way to achieve the separations described in the present study was to exploit the minute differences in the pKa values of isotopologues, as well as of isotopomers. This study also illustrates the power of capillary electrophoresis to leverage pKa differences on the scale of 0.01 pH units in a reliable way. Such sensitivity to only marginal differences in pKa values has also been reported with advanced methods of NMR spectroscopy. However, the amount of sample required for such measurements in NMR spectroscopy is significantly (one to two orders) higher compared to capillary electrophoresis.
An accurate description of molecular structures is essential in several fields of chemistry and, in particular, in high-resolution molecular spectroscopy. The so-called "Lego-brick" approach has proven to provide near-spectroscopic accuracy at a fraction of the computational cost of high-level composite schemes, but its applicability has so far been mainly assessed for rather rigid systems. In this work, we systematically investigate the performance of the "Lego-brick" approach for strained and conformationally flexible cyclic molecules. A chemically diverse benchmark set of three-, four-, and five-membered rings, including heterocycles and species with multiple conformers, is considered. By comparing template-molecule (TM) and full "Lego-brick" (TM+LR) rotational constants with the experimental counterparts, the accuracy of corresponding equilibrium structures is analyzed. The results show that the "Lego-brick" approach retains good accuracy for small cyclic systems, although the data set turned out to be a challenging test case. Linear-regression (LR) corrections are found to be fundamental to achieve the aimed precision. Interestingly, the TM+LR geometries are so accurate that can be employed in the framework of the semiexperimental approach, thus allowing one to obtain equilibrium structures of experimental quality also when there is a lack of isotopic data. Overall, this study delineates the applicability limits of the "Lego-brick" approach for flexible systems, pointing out the ability of significantly improving the initial density functional theory results.
Hydrogen peroxide (H2O2) is a vital reactive oxygen species with significant roles in atmospheric and environmental chemistry. While its spontaneous generation in water microdroplets has gained attention, the abiotic pathways for its formation are still not fully understood. In this study, we demonstrate the rapid and spontaneous photochemical generation of H2O2 in pure water microdroplets on quartz surfaces under anoxic conditions. We show that H2O2 is efficiently formed through multiple pathways, including direct water photooxidation at the solid-water interface and, more significantly, reactions between water and quartz surface-bound peroxy radicals (≡Si-O-O·). The observed H2O2 production rate reached 2.5 × 1011 molecules cm- 2 s- 1 in microdroplets on quartz, exceeding that of bulk water photolysis by five orders of magnitude. This process occurs across various natural silicate minerals, suggesting that photochemical reactions in water microdroplets on silicate surfaces may represent a significant yet previously overlooked source of H2O2 in Earth's environment. Additionally, the solid-liquid interface reactions demonstrated in this study may offer a novel approach for the industrial-scale synthesis of H2O2, providing an efficient and sustainable alternative to traditional methods.
Parallel quasi-one-dimensional metals are known to experience strong dispersion (van der Waals, vdW) interactions that fall off unusually slowly with separation between the metals. Summation over atom pairs fails to reproduce this behavior. Examples include nanotube brushes, nano-wire arrays, and also common biological structures. In a many-stranded bundle, there are potentially strong multi-strand vdW interactions that go beyond a simple sum of negative (attractive) pairwise inter-strand energies. Perturbative analysis showed that these contributions alternate in sign, with the odd (triplet, quintuplet, …) terms being positive (repulsive). The triplet case led to the intriguing speculation that these strands may prefer to coalesce into even-numbered bundles, which could have implications for the formation kinetics of DNA, for example. Here we use a non-perturbative vdW energy analysis to show that this conjecture is not true in general. As our counter-example we consider 6 strands and show that 2 widely separated bundles of 3 strands have a more negative total vdW energy than 3 widely separated bundles of 2 strands (i.e. an odd-number preference). We also discuss a bundle of 6 strands and explore the relative importance of contributions beyond the sum of two-strand terms.
The revolutionary discovery by Abe & Kimura that H2S exerts a beneficial role in human body has renewed interest in this small molecule, long known for its toxicity. Understanding the (bio)-reactivity of H2S with biological and bioinorganic targets is therefore of increasing importance, yet studies on its interaction with nonheme metalloproteins remain limited. Here, we investigate the reactivity of HS- with two natural multicopper proteins, SLAC and NiR. We demonstrate that SLAC, a two-domain blue-copper oxidase, can function as a multiwavelength, multireadout fluorescent sensor for H2S in complex environments. Comparative studies on NiR support the proposed mechanism of H2S recognition via selective reduction of copper centers. Finally, we benchmark the performance of these multicopper proteins against Cu-azurin, previously reported as a H2S recognition element, highlighting the advantages of multicopper architectures in terms of sensitivity, selectivity, and reversibility. Our findings establish multicopper proteins as versatile platforms for H2S sensing with potential applications in biomedical and environmental monitoring.
Keratin, a structural protein with outstanding mechanical and biochemical properties, is abundant in animal-derived wastes such as feathers, wool, and hooves. However, these keratin-rich materials are still largely incinerated or landfilled, leading to environmental burdens and resource loss. This review introduces horse hoof trimmings as an unexploited, renewable, and cruelty-free keratin source generated through routine equine care. Unlike slaughter-derived materials, hoof trimmings provide a traceable and high-quality biopolymer feedstock with the potential for sustainable valorization. We summarize current knowledge on their chemical composition, structure, and physicochemical properties, highlighting correlations with nutrition, environment, and management practices. Furthermore, we critically assess green extraction methods and upcycling strategies for keratin recovery, identifying challenges and opportunities for scaling toward industrial applications. By focusing on this overlooked waste stream, this review aims to stimulate innovation in sustainable materials chemistry, biopolymer engineering, and circular resource management, advancing the principles of green and circular chemistry.
Purpose - Clinical imaging can resolve the main coronary arteries but not the smaller side branches that penetrate the heartwall. However, precise association between the main coronary branches and the myocardial mass they perfuse is crucial to achieve a correct description of haemodynamics from the large arteries to the cardiac tissue. In this work, we use ex-vivo detailed morphometric data of human coronary microcirculation to build and validate a tool for a personalized coronary-myocardium association, and we use it in a multiscale computational model of cardiac perfusion. Methods - From the digitalized dataset of an entire human coronary microcirculation, vascular beds associated to single branches are extracted and analysed to infer patterns in epicardial branching. 3D segmentations of the coronaries with and without this information are used to generate two different myocardial subdivisions, which are compared to the one obtained from the microcirculation data. The impact on haemodynamics is assessed through computational simulations. Results - Epicardial arteries exhibit characteristic patterns of transverse branching, with branching angles ≃ 90∘ and rate of branching, with respect to the distance along the vessel, depending on the core diameter. The addition of transverse outflows to the segmentations greatly increases accuracy in the myocardial subdivision, allowing discrimination between mass perfused by the proximal and distal arterial segments. Perfusion simulations including transverse outflows show more homogeneous blood flow across the myocardium, consistently with experimental findings. Conclusions - The inclusion of transverse outflows in 3D coronary segmentations is essential to correctly capture the coronary-myocardium association and the distribution of myocardial blood flow.
Excited state molecular dynamics simulations are a powerful computational tool for the study of photoinduced phenomena. These are often used in conjunction with linear response TD-DFT to get the excited state energy and its gradients. At each step of molecular dynamics simulation, the new molecular geometry is relatively close to the previous ones, suggesting that some extrapolation strategy can be applied, such that the results of the previous calculations, which are available for free, can be used to predict the result of the upcoming calculation. The prediction can then be used as a guess for the iterative solver to lower the number of iterations and thus the cost. In this contribution, we present an extension of the Grassmann extrapolation scheme to linear response TD-DFT, in which the knowledge about the manifold structure to which the solutions belong is used to make the extrapolation more accurate. The new extrapolation strategy is then tested on four systems, showing a significant acceleration of the excited state molecular dynamics.