In Europe, there is a growing concern for animal welfare, encompassing both their rights and health. Consequently, identifying biomarkers that predict serious pathological conditions has become crucial in veterinary medicine. The Buccal Micronucleus Cytome (BMCyt) assay is a minimally invasive method that uses biomarkers to evaluate DNA damage and chromosomal instability, using exfoliated buccal cells. A rising frequency of anomalies, such as micronuclei formation, strongly indicates an elevated risk of cancer, neurodegenerative diseases, or accelerated aging, potentially originating from exposure to genotoxins and cytotoxins. This method has been validated in humans, but very little research has been conducted on animals. This work aims to provide a detailed description of an optimized method for collecting buccal exfoliated cells in dogs and to characterize a biomarker related to genomic damage using optical and fluorescent microscopy. Samples from dogs in breeding kennels, including pregnant animals, were tested for chromosomal instability. By following procedures similar to those used in humans, we were able to detect and count major nuclear abnormalities. The percentage of micronuclei was higher compared to other studies. Technical aspects, such as avoiding artifacts and ensuring prior training of the operator, must be taken into account. This work validated the BMCyt method for collecting and processing samples in dogs, potentially enhancing the understanding of micronuclei as biomarkers for pre-pathological states in canines.

• Book : 15(3)
• Pub. Date : 2025
• Page : pp.382-382
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316LN austenitic stainless steel is extensively utilized within the domain of nuclear power, where its susceptibility to high-temperature fatigue and thermomechanical fatigue has emerged as a pivotal area of research for this material. Nevertheless, prior investigations have predominantly concentrated on axial loading outcomes, with a notable absence of studies examining its fatigue failure behavior under torsional loading conditions. The present study undertakes isothermal fatigue testing at temperatures of 450 °C, 550 °C, and 650 °C, along with thermomechanical fatigue testing across a temperature range of 350–550 °C, with strain amplitudes of 0.6%, 0.8%, and 1.2%. The findings reveal that secondary hardening observed under conditions of small deformation is primarily attributed to the enhancement of frictional stress, stemming from the accumulation of planar slip. Furthermore, as the temperature escalates, variations are observed in the intensity of the dynamic strain aging and the dislocation density within the material.

• Book : 18(3)
• Pub. Date : 2025
• Page : pp.541-541
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• Pub. Date : 2025
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Abstract Cellular senescence is a phenotypic state that contributes to the progression of age-related disease through secretion of pro-inflammatory factors known as the senescence-associated secretory phenotype (SASP). Understanding the process by which healthy cells become senescent and develop SASP factors is critical for improving the identification of senescent cells and, ultimately, understanding tissue dysfunction. Here, we reveal how the duration of cellular stress modulates the SASP in distinct subpopulations of senescent cells. We used multiplex, single-cell imaging to build a proteomic map of senescence induction in human epithelial cells induced to senescence over the course of 31 days. We map how the expression of SASP proteins increases alongside other known senescence markers such as p53, p21, and p16INK4a. The aggregated population of cells responded to etoposide with an accumulation of stress response factors over the first 11 days, followed by a plateau in most proteins. At the single-cell level, however, we identified two distinct senescence cell populations, one defined primarily by larger nuclear area and the second by higher protein concentrations. Trajectory inference suggested that cells took one of two discrete molecular paths from unperturbed healthy cells, through a common transitional subpopulation, and ending at the discrete terminal senescence phenotypes. Our results underscore the importance of using single-cell proteomics to identify the mechanistic pathways governing the transition from senescence induction to a mature state of senescence characterized by the SASP.

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• Pub. Date : 2025
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• Book : ()
• Pub. Date : 2025
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• Pub. Date : 2025
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Abstract Introduction Parathyroid carcinoma is a rare endocrine malignancy, accounting for a small fraction of primary hyperparathyroidism (PHPT) cases. Its rarity complicates diagnosis due to overlapping symptoms with benign conditions and challenges in pathological examination. Limited cases result in insufficient data on optimal treatment strategies and outcomes. Clinical Case A 49-year-old male with a history of symptomatic primary hyperparathyroidism (PHPT) four years earlier was referred due to recurring hypercalcemia. His initial imaging scans were unobtainable, however, he had a pathology report indicating that he had total thyroidectomy, left-sided cervical lymph node dissection (LND) and parathyroidectomy. A poorly differentiated thyroid carcinoma measuring 4.5x3.5 cm with positive surgical margins and cervical lymph node metastases (15/24) were reported. Additionally, three parathyroid glands were excised; with one reported to be a parathyroid adenoma with a Ki-67 index of 7-10%. The patient was asymptomatic for the following 4 years, except for a transient hypocalcemia early after surgery. However, recently, his symptoms of nausea, muscle weakness and fatigue returned due to recurrent PHPT. Two months before being referred to our center, he was assessed elsewhere (Serum Ca: 15.6 mg/dL, P: 1.9 mg/dL, creatinine: 1.2 g/dL, PTH: 1121 pg/mL), and given 5 mg intravenous zoledronic acid, followed by cinacalcet 30 mg daily. At the time of his presentation to our center, physical examination was unremarkable except surgical scars compatible with thyroidectomy and left-sided cervical LND, and a fixated left-sided supraclavicular lymph node of ∼2 cm. Upon presentation at our center, his labs showed Calcium: 12.07 mg/dL, phoshorus: 1.63 mg/dL, PTH: 1319 pg/mL, and imaging revealed multiple metastatic lymph nodes and lung metastases. A pathology re-evaluation confirmed parathyroid neoplasia, as the immunohistochemical evaluation of the specimens were positive for PTH but negative for thyroidal markers. Multidisciplinary treatment included cervical LND, surgical removal of lung and pleura metastases for reducing tumor load, followed by denosumab, and 16 cycles of paclitaxel and carboplatin, achieving stable disease. Sorafenib was then administered and continued for 18 months. The patient has an 8-year overall survival, with rather stable PTH levels (909-1626 pg/mL), with recent rapid PTH progression to 7897 pg/mL. Conclusion Management of parathyroid carcinoma requires a multidisciplinary approach, with a focus on meticulous metastatic assessment and calcium control. Surgical excision is advised for regional recurrences, while surgery for distant metastases is mainly palliative. Though rare, multikinase inhibitors may help manage hypercalcemia, but long-term survival data are lacking, warranting further research.

• Book : 3(Supplement_1)
• Pub. Date : 2025
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• Pub. Date : 2025
• Page : pp.1-1
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Background: Adopting appropriate noninvasive radiological method is crucial for periodic surveillance of liver metastases in colorectal cancer (CRC) patients after surgery, which is closely related to clinical management and prognosis. This study aimed to prospectively enroll stage II-III CRC patients for the surveillance of liver metastases, and compare the diagnostic performance of contrast-enhanced CT (CE-CT) and non-enhanced abbreviated MRI (NE-AMRI) during this process. Methods: 587 CRC patients undergoing radical resection of the primary tumor were evaluated by 1 to 3 rounds of surveillance tests, consisting of abdominal CE-CT and contrast-enhanced MRI (CE-MRI) within 7 days at 6-month intervals. Subsequently, images of NE-AMRI were extracted from the CE-MRI examination, paired CE-CT and NE-AMRI analysis were performed. The lesion-based detection rates between two protocols were compared and a subgroup analysis was performed in lesions with the size of ≤ 10 mm. The patient-based sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and the areas under the curves (AUCs) of CE-CT and NE-AMRI in each round were evaluated. Finally, the relationship between the diagnostic accuracy of two protocols and characteristics of patients was explored. Results: The lesion-based detection rates of NE-AMRI in three rounds were all significantly higher than that of CE-CT (p < 0.001, p < 0.001, p = 0.003, respectively). In the subgroup analysis of lesions ≤ 10 mm, NE-AMRI also performed better than CE-CT (p < 0.001, p = 0.002, p = 0.005, respectively). The patient-based sensitivities, specificities, NPVs, PPVs of NE-AMRI were higher than those of CE-CT in three rounds of surveillance. The AUCs for NE-AMRI were all significantly better than that for CE-CT in each round (p = 0.015, p = 0.045, p = 0.009, respectively). Furthermore, patient BMI and fatty liver disease had impacts on the diagnostic accuracy of CE-CT protocol, but not on NE-AMRI protocol. Conclusion: NE-AMRI may be a promising periodic surveillance tool for CRC patients after surgery to increase diagnostic accuracy of liver metastases, developing personalized clinical management and improving prognosis, simultaneously avoiding side-effects associated with ionizing radiation and contrast agents.

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• Pub. Date : 2025
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Abstract Radio-immunotherapy has antitumor activity but also causes toxicity, which limits its clinical application. JS-201 is a dual antibody targeting PD-1 and TGF-β signaling. We investigated the antitumour effect of JS-201 combined with radiotherapy and the effect on radiation-induced lung injury (RILI). Different tumor models were established to detect the antitumor effects of the combination of JS-201 and RT, and RILI models were established to observe the effects of JS-201. Transcriptome sequencing showed that JS-201 optimized the TME by inhibiting extracellular matrix formation and angiogenesis. Combining JS-201 with radiotherapy further increased the inflammatory response and immune infiltration and showed great abscopal effects in LLC-luc models. Single-cell sequencing demonstrated that JS-201 reduced fibroblast proliferation by inhibiting the TGF-β/Smad pathway and the release of neutrophil extracellular traps mediated by ROS, thereby relieving radiation-induced pulmonary fibrosis. In conclusion, the JS-201 and radiotherapy combination enhances antitumor effects while mitigating acute and chronic RILI, and it may have potential for translational investigation as a cancer treatment strategy.

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• Pub. Date : 2025
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