Increases in synthetic drug production and distribution pose significant risks to public health and safety. Traditional detection methods often fail to accurately identify these complex chemicals, particularly when they are mixed. Accordingly, Herein, an advanced density functional theory spectroscopy integrated identification method (D‐SIIM) comprising a combination of experimental and theoretical analyses is introduced. D‐SIIM is helpful in correcting the erroneous information provided by gas chromatography–mass spectrometry during the analysis of a mixture of three synthetic drug stimulants. Furthermore, the application of a denoising mechanism to the experimental Raman data considerably aligns experimental results with theoretical predictions, thereby augmenting the accuracy and reliability of D‐SIIM. Moreover, the potential of employing hyperpolarized nuclear magnetic resonance (NMR) spectroscopy to enhance NMR signals at low concentrations is explored. Current approach provides a robust and adaptable framework for identifying synthetic drugs in complex mixtures and will play critical roles in forensic investigations and drug enforcement strategies.

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• Pub. Date : 2025
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Context.— In 2018, an evidence-based guideline was published by the College of American Pathologists to develop recommendations for the testing, application, interpretation, and reporting of high-risk human papillomavirus and surrogate marker tests in head and neck carcinomas. Substantial new evidence has prompted a review, including data on human papillomavirus (HPV) in nonoropharyngeal anatomic sites, HPV global rates, p16 immunohistochemistry, and HPV testing performance in cytology specimens, and performance of p16 immunohistochemistry as a surrogate marker. Objective.— To assess research published since the release of the original 2018 guideline and to update evidence-based recommendations for HPV testing in head and neck carcinomas. Design.— The College of American Pathologists convened a panel of experts to update the guideline following the standards established by the National Academy of Medicine for developing trustworthy clinical practice guidelines. The expert panel defined the key questions and performed a systematic review of the literature. Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, recommendations were updated on the basis of available evidence, certainty of that evidence, and key judgments. Results.— Seven strong recommendations, 4 conditional recommendations, and 5 good practice statements are offered in the guideline update. Conclusions.— The updated guideline statements provide direction on the nature of HPV testing in various head and neck specimens (including key updates based on new research on sinonasal squamous cell carcinoma) and expanded guidance on specific scenarios and practice settings. The goal is to improve and standardize, where possible, HPV testing across diverse pathology practice settings and different countries.

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• Pub. Date : 2025
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• Pub. Date : 2025
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Abstract Non-coding RNAs (ncRNAs) are finely tuned cellular regulators important for human cell growth and cancer progression. DUBR (Dppa2 upstream binding RNA, also known as linc00883) is a nuclear ncRNA first discovered in mice for its role in regulating myoblast differentiation through interactions with chromatin and DNA methyltransferases. High expression levels of this ncRNA are predictive of poor patient outcome in colon adenocarcinoma, suggesting that DUBR may be involved in controlling cancer growth. To elucidate its function, we used RAP-MS and RNA immunoprecipitation techniques which revealed its interaction with epigenetic maintenance proteins in the human colon cancer cell line HCT116. Further, ATAC-seq and RNA-seq were used to address its function in regulating the epigenome and transcriptome of HCT116 cells. Here we report that DUBR is a regulator of human colon cancer cell line HCT116 survival. Additionally, we find that the ncRNA DUBR regulates AP-1 transcription factor binding site accessibility at enhancers of genes involved in differentiation and morphogenesis through interactions with epigenetic proteins such as NuRD complex members HDAC1 and CHD4.

• Book : 25(1)
• Pub. Date : 2025
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• Book : 25(1)
• Pub. Date : 2025
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• Book : 1075()
• Pub. Date : 2025
• Page : pp.170461-170461
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Waterpipe smoking (WPS) has adverse health effects that include endothelial dysfunction with mechanisms involving oxidative stress and inflammation. Nonetheless, there is a scarcity of data on the direct impact of WPS on endothelial function. In this study, we assessed the in vitro effects of waterpipe smoke extract (WPSE) on aortic endothelial cell lines, namely the TeloHAEC. The WPSE markedly caused concentration- and time-dependent decreases in cellular viability. When compared with the control, at a concentration of 20 % and an incubation period of 48 h, the WPSE significantly increased the levels of lactate dehydrogenase, and markers of oxidative stress including thiobarbituric acid reactive substances, superoxide dismutase, catalase, and reduced glutathione. Moreover, the concentrations of proinflammatory cytokine (tumor necrosis factor α), and adhesion molecules (E-selectin and intercellular adhesion molecule-1) were also significantly augmented. Likewise, WPSE triggered mitochondrial dysfunction, DNA oxidative damage, as well as apoptosis in TeloHAEC cells. Similarly, cells cultured with WPSE have shown increased expression of phosphorylated nuclear factor-κB and hypoxia-inducible factor 1-α (HIF-1α). In conclusion, our study showed that WPSE triggers endothelial inflammation, oxidative stress, DNA damage, mitochondrial dysfunction, and apoptosis via mechanisms involving the activation of nuclear factor-κB and HIF-1α.

• Book : (1/2025)
• Pub. Date : 2025
• Page : pp.69-78
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Amyotrophic lateral sclerosis (ALS) is a devastating neuromuscular disease characterized by progressive motor neuron degeneration and muscle atrophy, with no effective treatments available. Chronic inflammation, which impairs muscle regeneration and promotes proteolysis, is a key contributor to ALS-related muscle atrophy and a promising therapeutic target. Here, we applied extracellular vesicles (EVs) derived from regenerating skeletal muscles 14 days post-acute injury (CTXD14SkM-EVs), which possess a unique anti-inflammatory profile, to target muscle defects in ALS. We found that CTXD14SkM-EVs enhanced myoblast differentiation and fusion in a cellular muscle-wasting model induced by pro-inflammatory cytokine tumor necrosis factor alpha. Intramuscular administration of these EVs into an ALS mouse model mitigated muscle atrophy by promoting muscle regeneration, shifting macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 state, and suppressing the aberrant Nuclear Factor Kappa B (NF-κB) signaling, a key driver of muscle protein degradation. These results underscore the therapeutic potential of regenerating muscle-derived EVs for combating muscle atrophy in ALS.

• Book : 14(6)
• Pub. Date : 2025
• Page : pp.464-464
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AbstractDespite their diversity in habitats, nematodes are often considered to have a highly conserved neuroanatomy. This premise is based on only a subset of the nematode phylogenetic tree focused on the more diverged clades within the class Chromadorea, which includes the model organismCaenorhabditis elegans,thereby limiting our understanding of macroevolutionary trends in nervous system structure. To approach this problem, we used nuclear morphology to quantify the number of neurons in the nematode ventral nerve cord (VNC) to identify evolutionary patterns in neuroanatomical organization within the basal clades of Chromadorea and Enoplea. DAPI staining revealed significant VNC neuron count variations among families, with notable differences between the classes Enoplea and Chromadorea and among Enoplean species. These results may indicate a degree of evolutionary morphological stasis in later diverging Chromadorean clades. To further examine developmental patterns and potential variation in Enoplean nervous system architecture, we established an isogenic culture of the nematodeMononchus aquaticus.We found that whileM. aquaticuscontained four times as many VNC neuronal nuclei asC. elegans, the VNC had a similar developmental timeline during post-embryonic stages. However, dye-filling assays revealed an extensive distribution of neurons along the lateral body wall, which have no obvious homolog toC. elegans. We found thatM. aquaticusis capable of sustained movement following bisection that may imply a more distributed nervous system network. Our results provide a roadmap for understanding phylum-wide nervous system evolution and demonstrate large-scale differences between Enoplean and Chromodorean nervous systems.

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• Pub. Date : 2025
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• Pub. Date : 2025
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