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Bacteria-mediated treatments gained increasing attention as alternative therapies against tumors. An attenuated mutant strain of Salmonella enterica serovar Typhimurium (STMΔznuABC) has recently been considered as a potential new anti-cancer strategy. However, it is unclear whether this activity is tumor-induced or species-specific, and no data are available regarding STMΔznuABC on canine mammary tumors (CMTs). This study aimed to investigate the ability of STMΔznuABC in modulating the response of CMTs, focusing on cancer-associated fibroblasts. Four CMT cell lines (CF33, TM51, TM52 TM53) were treated with STMΔznuABC. Then, antiproliferative activity (MTT assay), bacterial invasion, and CMT cell lines gene expression analysis (RT-qPCR) of genes involved in immune response and cancer aggressiveness were evaluated. STMΔznuABC penetrated in TM51, TM52, TM53, and CF33 cell lines, causing a significant reduction of cell viability. Moreover, the expression of several genes was significantly modulated in all CMT cell lines: STMΔznuABC infection determined a significant up-regulation of CXCL8, IL18, IL10, TLR4 and RAD51, while CD14, IL6, CXCR4, P53, PTEN, STAT5, TLR5 and TGFB1 were downregulated in TM53. In CF33, CXCL8 and P53 were upregulated, while MYD88, MD2, IL18, TLR4,5, TGFB1 were downregulated. In TM52, CXCL8, CD44 and MD2 were upregulated and PTEN was downregulated, while in TM51 CXCL8, CD44 and ErbB2 were downregulated. We demonstrated the anti-proliferative and immuno-modulatory activity of STMΔznuABC in CMTs, paving the way for potential new anti-cancer treatments., Competing Interests: Declaration of competing interest The authors have no competing interests to declare. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The Pauli exclusion principle (PEP), a cornerstone of quantum mechanics and whole science, states that in a system, two fermions can not simultaneously occupy the same quantum state. Several experimental tests have been performed to place increasingly stringent bounds on the validity of PEP. Among these, the series of VIP experiments, performed at the Gran Sasso Underground National Laboratory of INFN, is searching for PEP-violating atomic X-ray transitions in copper. In this paper, the upgraded VIP-3 setup is described, designed to extend these investigations to higher-Z elements such as zirconium, silver, palladium, and tin. We detail the enhanced design of this setup, including the implementation of cutting-edge, 1 mm thick, silicon drift detectors, which significantly improve the measurement sensitivity at higher energies. Additionally, we present calculations of expected PEP-violating energy shifts in the characteristic lines of these elements, performed using the multi-configurational Dirac-Fock method from first principles. The VIP-3 realization will contribute to ongoing research into PEP violation for different elements, offering new insights and directions for future studies.

Introduction: Cancer is a leading cause of death in cats, and the rate of such disease has been increasing recently. Nonetheless, feline oncology represents an important area of study not only for the health and wellbeing of cats but also for human health since various types of cancer in cats share similarities to those found in humans. Therefore, epidemiological studies on feline oncology may suggest environmental and genetic factors contributing to cancer in cats, which can eventually be translated to improve human cancer care., Method: To provide an initial understanding of the epidemiology of feline neoplasms, a descriptive study was undertaken using a dataset documenting cases of feline cancer gathered from the Liguria region (northwest Italy) spanning from 2002 to 2022. The database includes tumor location, morphological codes of the International Classification of Diseases for Oncology, 3rd Edition (ICD-O-3), feline's breed, sex, neuter status, date of birth, date of diagnosis, national territorial unit code of the town of the owner's residence, and an alphanumeric string uniquely identifying the owner's surname., Results and Discussion: The dataset involves a population of 4,399 cats, including 3,195 females (1,425 neutered) and 1,204 males (750 neutered). Our results indicate that mammary gland tumors are the most represented tumors in the female population, while soft tissue and skin cancers appear to have a higher abundance in the male population during the periods investigated (2002-2022). Moreover, Poisson regression analysis showed that not neutered female cats have a significantly increased risk of developing mammary gland tumors compared to the neutered female population [proportional morbidity ratio (PMR) neutered vs. not neutered = 0.58, 95% CI: 0.47-0.72]; meanwhile, for both sexes, for soft tissue and skin tumors, being neutered appears to be a risk factor (PMR neutered vs. not neutered = 2.26, 95% CI: 1.86-2.73; PMR neutered vs. not neutered = 1.16, 95% CI: 0.89-1.51). Finally, the evaluation of the Ligurian municipalities pollution, based on wild boars data (i.e., biomonitors), which coexisted with cats, was correlated to cancer development for all the tumors investigated (in polluted areas, estimated PMRs ranged from 42.61 to 80.13, 95% CI: 29.94-105.11). Overall, the data presented here suggest the use of the feline population as a possible animal model for human health, i.e., sentinel., 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 © 2024 Giugliano, Dell'Anno, De Paolis, Crescio, Ciccotelli, Vivaldi and Razzuoli.)

Background: Vulvar squamous cell carcinoma (VSCC) has been recently associated with Equus caballus papillomavirus type 2 (EcPV2) infection. Still, few reports concerning this disease are present in the literature., Objective: To describe a case of naturally occurring EcPV2-induced VSCC, by investigating tumour ability in undergoing the epithelial-to-mesenchymal transition (EMT)., Study Design: Case report., Methods: A 13-year-old Haflinger mare was referred for a rapidly growing vulvar mass. After surgical excision, the mass was submitted to histopathology and molecular analysis. Histopathological diagnosis was consistent with a VSCC. Real-time qPCR, real-time reverse transcriptase (RT)-qPCR and RNAscope were carried out to detect EcPV2 infection and to evaluate E6/E7 oncogenes expression. To highlight the EMT, immunohistochemistry (IHC) was performed. Expression of EMT-related and innate immunity-related genes was investigated through RT-qPCR., Results: Real-time qPCR, RT-qPCR and RNAscope confirmed EcPV2 DNA presence and expression of EcPV2 oncoproteins (E6 and E7) within the neoplastic vulvar lesion. IHC highlighted a cadherin switch together with the expression of the EMT-related transcription factor HIF1α. With RT-qPCR, significantly increased gene expression of EBI3 (45.0 ± 1.62, p < 0.01), CDH2 (2445.3 ± 0.39, p < 0.001), CXCL8 (288.7 ± 0.40, p < 0.001) and decreased gene expression of CDH1 (0.3 ± 0.57, p < 0.05), IL12A (0.04 ± 1.06, p < 0.01) and IL17 (0.2 ± 0.64, p < 0.05) were detected., Main Limitations: Lack of ability to generalise and danger of over-interpretation., Conclusion: The results obtained were suggestive of an EMT event occurring within the neoplastic lesion., (© 2023 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.)

Vulvo-vaginal epithelial tumors are uncommon in mares, and data on the epithelial-to-mesenchymal transition (EMT) and the tumor-immune microenvironment (TIME) are still lacking. This is a study investigating the equus caballus papillomavirus type 2 (EcPV2) infection state as well as the EMT process and the tumor microenvironment in vulvo-vaginal preneoplastic/ benign (8/22) or malignant (14/22) epithelial lesions in mares. To do this, histopathological, immunohistochemical, transcriptomic, in situ hybridization, and correlation analyses were carried out. Immunohistochemistry quantification showed that cytoplasmic E-cadherin and β-catenin expression as well as nuclear β-catenin expression were features of malignant lesions, while benign/preneoplastic lesions were mainly characterized by membranous E-cadherin and β-catenin expression. Despite this, there were no differences between benign and malignant equine vulvo-vaginal lesions in the expression of downstream genes involved in the canonical and noncanonical wnt/β-catenin pathways. In addition, malignant lesions were characterized by a lower number of cells with cytoplasmic cytokeratin expression as well as a slightly higher cytoplasmic vimentin immunolabeling. The TIME of malignant lesions was characterized by more numerous CD204 + M2-polarized macrophages. Altogether, our results support the hypothesis that some actors in TIME such as CD204 + M2-polarized macrophages may favor the EMT process in equine vulvo-vaginal malignant lesions providing new insights for future investigations in the field of equine EcPV2-induced genital neoplastic lesions., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Fermions are subject to the Pauli Exclusion Principle (PEP), which is grounded on the spin-statistics theorem and, hence, related to the very same structure of the underlying symmetries. The VIP-2 (VIolation of Pauli exclusion principle - 2) experiment has been performing extreme sensitivity tests of the PEP, up to its current and final configuration, exploiting several experimental setups designed to study different theoretical models of PEP violation, looking for a faint signal of physics Beyond the Standard Model.A current is introduced in the copper target to bring new electrons into the system and, hence, fulfill the requirements of the Messiah-Greenberg Super-Selection rule. The searched spin-statistics violating signal corresponds to X-rays emitted when the new electrons perform atomic transitions to the already filled fundamental level of copper. This work analyzes the set of the VIP-2 data corresponding to a test run of 68 days in a current modulated regime alternating no current with current data-taking in short periods (50 s each), instead the usual alternating months-long data-taking of each of these two phases. We propose an analysis method to improve the experiment's sensitivity: a spectral analysis constraint with the Discrete Fourier Transformation of the data. Compared to the spectrum-only analysis, about a factor of 1.5 of improvement to the limit for the probability of PEP violation for electrons was obtained., Competing Interests: Conflict of interestThe authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (© The Author(s) 2024.)