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Abstract Vaccination against an airborne pathogen is very effective if it induces also the development of mucosal antibodies that can protect against infection. The mRNA‐based vaccine‐encoding SARS‐CoV‐2 full‐length spike protein (BNT162b2, Pfizer/BioNTech) protects also against infection despite being administered systemically. Here, we show that upon vaccination, cognate IgG molecules are also found in the saliva and are more abundant in SARS‐CoV‐2 previously exposed subjects, paralleling the development of plasma IgG. The antibodies titer declines at 3 months from vaccination. We identified a concentration of specific IgG in the plasma above which the relevant IgG can be detected in the saliva. Regarding IgA antibodies, we found only protease‐susceptible IgA1 antibodies in plasma while they were present at very low levels in the saliva over the course of vaccination of SARS‐CoV‐2‐naïve subjects. Thus, in response to BNT162b2 vaccine, plasma IgG can permeate into mucosal sites and participate in viral protection. It is not clear why IgA1 are detected in low amount, they may be proteolytically cleaved.

Background and Aims: The SARS-CoV-2 pandemic has overwhelmed the treatment capacity of the health care systems during the highest viral diffusion rate. Patients reaching the emergency department had to be either hospitalized (inpatients) or discharged (outpatients). Still, the decision was taken based on the individual assessment of the actual clinical condition, without specific biomarkers to predict future improvement or deterioration, and discharged patients often returned to the hospital for aggravation of their condition. Here, we have developed a new combined approach of omics to identify factors that could distinguish coronavirus disease 19 (COVID-19) inpatients from outpatients. Methods: Saliva and blood samples were collected over the course of two observational cohort studies. By using machine learning approaches, we compared salivary metabolome of 50 COVID-19 patients with that of 270 healthy individuals having previously been exposed or not to SARS-CoV-2. We then correlated the salivary metabolites that allowed separating COVID-19 inpatients from outpatients with serum biomarkers and salivary microbiota taxa differentially represented in the two groups of patients. Results: We identified nine salivary metabolites that allowed assessing the need of hospitalization. When combined with serum biomarkers, just two salivary metabolites (myo-inositol and 2-pyrrolidineacetic acid) and one serum protein, chitinase 3-like-1 (CHI3L1), were sufficient to separate inpatients from outpatients completely and correlated with modulated microbiota taxa. In particular, we found Corynebacterium 1 to be overrepresented in inpatients, whereas Actinomycetaceae F0332, Candidatus Saccharimonas, and Haemophilus were all underrepresented in the hospitalized population. Conclusion: This is a proof of concept that a combined omic analysis can be used to stratify patients independently from COVID-19.

The physiological bone-ligament junction is composed of four zones: ligament, fibrocartilage, calcified fibrocartilage and bone. It plays a very important part in the distribution of mechanical loads applied to ligaments so as to diminish stress concentration or shearing at the interface. This paper examines types of bone and neoligament insertion after anterior cruciate ligament (ACL) reconstruction with a Dacron prothesis, the Leeds-Keio scaffold ligament (LK), patellar tendon with LAD augmentation (PT+LAD) and bone patellar tendon bone alone (PT). The anterior cruciate reconstructions were implanted in 16 sheep via double-isometric bone tunnels without postoperative knee immobilization. Histological examination of the new insertions (using haematoxylin-eosin, Giemsa, Masson, and Mallory stains) was performed following animal sacrifice after 2, 3, 6 and 9 months. A layer of fibrocartilage between the bone and the ligament was observed with PT, followed by a nearly normal insertion after 6 months. With PT, followed by PT+LAD, the augmentation was surrounded by fibrous tissue (also noted inside the LAD). The PT insertion was virtually physiological after 3-6 months. With the LK scaffold, fibrous tissue was noted in and around the scaffold, even after 6 and 9 months. With the Dacron prosthesis, fibrous tissue around the ligament was unaccompanied by ingrowth into the prosthesis. Nerve endings (pacinian corpuscles) were only present in the PT. These findings show that even after 9 months artificial ligaments are separated from bone by fibrous tissue and devoid of the histological and biomechanical features of a physiological junction.(ABSTRACT TRUNCATED AT 250 WORDS) [ABSTRACT FROM AUTHOR]

The bone-ligament junction is one of the most complex biological tissues. Its key function is distribution of mechanical loads applied to the ligament in such a way as to diminish the concentration of stresses or shearing at the interface. This paper reports an experimental assessment of the extent to which a nearly normal junction is formed following reconstruction of the anterior cruciate ligament (ACL) with patellar tendon in 20 New Zealand white rabbits sacrificed after 2-38 weeks. A histological comparison was also made with cadaver ACLs. After 5 weeks the new ligament was still separate from the tunnel wall, inflammation was no longer present, and there was no junction tissue. A thin fibrocartilage layer was observed between the bone and the ligament after 12 weeks and was thicker 6 weeks later. After 28 weeks, there was a substantial layer of fibrocartilage. The new junction was virtually "physiological" by the 38th week, with all four layers present. Many fibrocartilaginous cells were also visible between the collagen fibres. The bone-ligament insertion was almost normal. These findings indicate that tendon reconstruction results in the formation of a structure very similar to a physiological junction, and thus ensures better load distribution over a greater ligament insertion area. [ABSTRACT FROM AUTHOR]

Due to conflicting reports regarding the solvatochromism of p-extended pyridinium-phenolate dyes, the choice of base (N,N,N',N'-tetramethylguanidine or 1M tetrabutylammonium hydroxide in methanol) used to deprotonate the dyes was investigated. Three known dyes were synthesized and their UV-vis absorbance spectra were measured in a range of solvent using the two bases and the zwitterionic forms of the dyes. It was found that the methanolic tetrabutylammonium hydroxide could cause the appearance of inverted solvatochromism in negatively solvatochromic dyes when used in solvents of sufficiently low polarity. This was attributed to the presence of the polar, hydrogen bond donating methanol which preferentially solvates the dye, increasing the polarity it observes. Informed by these results, recommendations are presented for the methods used to compare solvatochromic dyes., (© 2025 Wiley‐VCH GmbH.)

Three new pyridinium-phenolate dyes based on the benchmark solvatochromic dye Betaine 30 were synthesised. The dyes contained phenylene spacers between the donor and acceptor groups. Their UV-Vis absorption spectra were measured, with the dyes showing strong negative solvatochromic behaviour comparable to that of Betaine 30. These results stood in contrast to the behaviour of the π-extended dye Betaine 21, originally reported in 1963. This dye was synthesised and found to be significantly more solvatochromic than previously reported but prone to degrade. All π-extended dyes synthesised were found to be unstable in certain solvents. Although the increased distance between donor and acceptor did not enhance solvatochromism to the extent predicted, it was still determined that the reduced planarity caused by a phenylene spacer is not as detrimental as believed., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Thymic epithelial tumors (TETs) are rare mediastinal cancers originating from the thymus, classified in two main histotypes: thymoma and thymic carcinoma (TC). TETs affect a primary lymphoid organ playing a critical role in keeping T-cell homeostasis and ensuring an adequate immunological tolerance against "self". In particular, thymomas and not TC are frequently associated with autoimmune diseases (ADs), with Myasthenia Gravis being the most common AD present in 30% of patients with thymoma. This comorbidity, in addition to negatively affecting the quality and duration of patients' life, reduces the spectrum of the available therapeutic options. Indeed, the presence of autoimmunity represents an exclusion criteria for the administration of the newest immunotherapeutic treatments with checkpoint inhibitors. The pathophysiological correlation between TETs and autoimmunity remains a mystery. Several studies have demonstrated the presence of a residual and active thymopoiesis in adult patients affected by thymomas, especially in mixed and lymphocytic-rich thymomas, currently known as type AB and B thymomas. The aim of this review is to provide the state of art in regard to the histological features of the different TET histotype, to the role of the different immune cells infiltrating tumor microenvironments and their impact in the break of central immunologic thymic tolerance in thymomas. We discuss here both cellular and molecular immunologic mechanisms inducing the onset of autoimmunity in TETs, limiting the portfolio of therapeutic strategies against TETs and greatly impacting the prognosis of associated autoimmune diseases., Competing Interests: PAZ reports outside the submitted work personal fees for advisory role, speaker engagements and travel and accommodation expenses from Merck Sharp & Dohme (MSD), Astellas, Janssen, Sanofi, Ipsen, Pfizer, Novartis, Bristol Meyer Squibb, Amgen, Astrazeneca, Roche, and Bayer. AS reports outside the submitted work personal fees for consultant or advisory role for SArqule, Sanofi, BMS, Servier, Gilead, Pfizer, Eisai, Bayer, Merck Sharp & Dohme (MSD). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Perrino, Voulaz, Balin, Cazzato, Fontana, Franzese, Defendi, De Vincenzo, Cordua, Tamma, Borea, Aliprandi, Airoldi, Cecchi, Fazio, Alloisio, Marulli, Santoro, Di Tommaso, Ingravallo, Russo, Da Rin, Villa, Della Bella, Zucali and Mavilio.)

γδ T cells provide rapid cellular immunity against pathogens. Here, we conducted matched single-cell RNA-sequencing and γδ-TCR-sequencing to delineate the molecular changes in γδ T cells during a longitudinal study following mRNA SARS-CoV-2 vaccination. While the first dose of vaccine primes Vδ2 T cells, it is the second administration that significantly boosts their immune response. Specifically, the second vaccination uncovers memory features of Vδ2 T cells, shaped by the induction of AP-1 family transcription factors and characterized by a convergent central memory signature, clonal expansion, and an enhanced effector potential. This temporally distinct effector response of Vδ2 T cells was also confirmed in vitro upon stimulation with SARS-CoV-2 spike-peptides. Indeed, the second challenge triggers a significantly higher production of IFNγ by Vδ2 T cells. Collectively, our findings suggest that mRNA SARS-CoV-2 vaccination might benefit from the establishment of long-lasting central memory Vδ2 T cells to confer protection against SARS-CoV-2 infection., (© 2024. The Author(s).)

Introduction: Higher frequencies of mucosal-associated invariant T (MAIT) cells were associated with an increased adaptive response to mRNA BNT162b2 SARS-CoV-2 vaccine, however, the mechanistic insights into this relationship are unknown. In the present study, we hypothesized that the TNF response of MAIT cells supports B cell activation following SARS-CoV-2 immunization., Methods: To investigate the effects of repeated SARS-CoV-2 vaccinations on the peripheral blood mononuclear cells (PBMCs), we performed a longitudinal single cell (sc)RNA-seq and scTCR-seq analysis of SARS-CoV-2 vaccinated healthy adults with two doses of the Pfizer-BioNTech BNT162b2 mRNA vaccine. Collection of PBMCs was performed 1 day before, 3 and 17 days after prime vaccination, and 3 days and 3 months following vaccine boost. Based on scRNA/TCR-seq data related to regulatory signals induced by the vaccine, we used computational approaches for the functional pathway enrichment analysis (Reactome), dynamics of the effector cell-polarization (RNA Velocity and CellRank), and cell-cell communication (NicheNet)., Results: We identified MAIT cells as an important source of TNF across circulating lymphocytes in response to repeated SARS-CoV-2 BNT162b2 vaccination. The TNF high signature of MAIT cells was induced by the second administration of the vaccine. Notably, the increased TNF expression was associated with MAIT cell proliferation and efficient anti-SARS-CoV-2 antibody production. Finally, by decoding the ligand-receptor interactions and incorporating intracellular signaling, we predicted TNF high MAIT cell interplay with different B cell subsets. In specific, predicted TNF -mediated activation was selectively directed to conventional switched memory B cells, which are deputed to high-affinity long-term memory., Discussion: Overall, our results indicate that SARS-CoV-2 BNT162b2 vaccination influences MAIT cell frequencies and their transcriptional effector profile with the potential to promote B cell activation. This research also provides a blueprint for the promising use of MAIT cells as cellular adjuvants in mRNA-based vaccines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Marzano, Balin, Terzoli, Della Bella, Cazzetta, Piazza, Sandrock, Ravens, Tan, Prinz, Calcaterra, Di Vito, Cancellara, Calvi, Carletti, Franzese, Frigo, Darwish, Voza, Mikulak and Mavilio.)

A parasite-host list of cestodes parasitizing chondrichthyans in the Southwest Atlantic off Argentina and surrounding waters of Antarctica is compiled based on the available literature. The list is based on published descriptions and redescriptions of species, and newly collected worms during the current study. A total of 57 valid species belonging to 28 genera of the orders Cathetocephalidea, Diphyllidea, Gyrocotylidea, Lecanicephalidea, Onchoproteocephalidea, Phyllobothriidea, Rhinebothriidea, "Tetraphyllidea", and Trypanorhyncha is listed. Information on hosts, localities, specimens in collections and comments on tapeworms are also included. A host-parasite list including chimaeras (1 order, 1 genus), batoids (4 orders, 10 genera), and sharks (3 orders, 5 genera) is provided. Tapeworm diversity, distribution range, and host associations are discussed. The cestodes orders Phyllobothriidea and Rhinebothriidea exhibit the highest species richness, with 13 and 12 species, respectively. Onchoproteocephalideans and rhinebothriideans have the broadest geographic distribution in the study area. Regarding hosts, arhynchobatid skates are the group most frequently associated with cestodes. However, further collecting efforts are necessary to understand whether this data reflect the real diversity and host association of these parasites or is a result of a bias in sampling., (Sebastián Franzese, Guillermina García Facal, Adriana Menoret.)