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There is growing evidence that extracellular vesicles (EVs) play a functional role in tissue repair and anti-aging by transferring the contents of donor cells to recipient cells. We hypothesized that Dauer (C. elegans), known as "ageless" nematodes, can also secrete extracellular vesicles and influence the lifespan of C. elegans. Here, we isolated EVs of dauer larvae (dauer EVs). Dauer EVs were characterized using transmission electron microscopy, nanoparticle tracking analysis (NTA), and Western blot analysis. Wild-type C. elegans were fed in the presence or absence of dauer EVs and tested for a range of phenotypes, including longevity, mobility and reproductive capacity. Results showed that dauer EVs increased the average lifespan of nematodes by 15.74%, improved mobility, slowed age-related pigmentation as well as body length, and reduced the accumulation of reactive oxygen species and lipids, while not impairing nematode reproductive capacity. These findings suggest that dauer EVs can extend the lifespan of C. elegans as well as the healthy lifespan by reducing ROS accumulation, with potential anti-aging capacity. [ABSTRACT FROM AUTHOR]

Purpose. Skin cutaneous melanoma (SKCM) is one of the most malignant and aggressive cancers with poor prognosis due to its rapid progression towards metastasis. Thus, finding clinically relevant biomarkers for early diagnosis, prognosis, and therapy prediction is essential. This study focused on the identification of SLC25A13 as a novel biomarker for SKCM and is aimed at investigating the biological functions of solute carrier family 25 member 13 (SLC25A13) in the development of SKCM. Methods. GEPIA was used to analyze the diagnostic and prognostic values of SLC25A13 in SKCM using the TCGA dataset. PrognoScan was used to validate the prognostic value of SLC25A13 and its coexpressed genes in SKCM. TISIDB was established to reveal the relationship between the expression of SLC25A13 and immune infiltration in SKCM. The protein expression of SLC25A13 in SKCM was evaluated by the Human Protein Atlas. The signaling pathways and biological functions of SLC25A13 in SKCM were analyzed by LinkOmics. Metascape was applied to analyze the functional enrichment analysis of SLC25A13. Protein-protein interaction analysis of SLC25A13 was performed by GeneMANIA. Results. The mRNA and protein levels of SLC25A13 in the SKCM were much higher than those in the normal tissue. Furthermore, the overexpression of SLC25A13 predicts worse outcomes of SKCM patients. Moreover, the SLC25A13 expression was negatively correlated with the immune infiltration level of SKCM. The overexpression of SLC25A13 coexpressed genes, such as ACLY and AFG3L2, and SCL25A13 interacting genes also predicted the unfavorable prognosis of SKCM patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of SLC25A13 coexpressed genes showed that these genes are enriched in ATPase activity, cell cycle, mTOR, and VEGFA-VEGFR2 signaling pathways, which were relevant to tumor development and angiogenesis. Gene set enrichment analysis (GSEA) demonstrated that the SLC25A13 expression was related to infiltrating immune cells in SKCM. Conclusion. Our findings revealed that SLC25A13 might be a potential prognostic and therapeutic biomarker for SKCM. [ABSTRACT FROM AUTHOR]

Providing constructive feedback is complex due to the interplay of emotional and motivational processes students experience when receiving such feedback. In the present study, we investigated constitutive elements of what would make feedback perceived to be constructive, and whether students' mastery approach goal orientation and writing self-efficacy influenced these perceptions of feedback on an imagined, writing assignment scenario. In Phase 1, college students were asked to rate 56 feedback statements on degree of specificity and friendliness. In Phase 2, different students rated the feedback statements from Phase 1 on levels of constructiveness. Feedback high in specificity was rated higher in constructiveness than unspecific feedback; however, feedback friendliness had no effect overall. Feedback high in specificity and friendliness received lower ratings of constructiveness. This pattern was more pronounced for students high in mastery approach goal orientation and students high in writing self-efficacy. [ABSTRACT FROM AUTHOR]

Introduction: Nasal extranodal natural killer (NK)/T cell lymphoma, nasal type (ENKTCL) is a high-grade Epstein-Barr virus (EBV)-associated malignancy with poor outcomes. There are few biomarkers for the accurate diagnosis and prognostic prediction of the disease. The aim of this study was to investigate the clinicopathological significance of prohibitin (PHB) expression in nasal ENKTCL. Methods: The expression level of PHB was detected via immunohistochemical staining in 49 nasal ENKTCL tissues and age- and sex-matched controls of 30 nasal mucosa-reactive lymphoid hyperplasia (NRLH) tissues. The correlations between the PHB expression and clinicopathological features of patients with nasal ENKTCL were evaluated. Results: The results indicated a significantly decreased expression of PHB in nasal ENKTCL tissues compared with in NRLH tissues. Low-level PHB expression was significantly associated with younger age and fever (p = 0.008 and 0.018, respectively). The Kaplan-Meier analysis showed that the cytoplasm expression level of PHB in nasal ENKTCL was inversely related to overall survival (p = 0.046). Conclusions: PHB may be a potential diagnostic marker and prognostic predictor of nasal ENKTCL. [ABSTRACT FROM AUTHOR]

Following publication of the original article [1], the author reported two errors in the authors affiliations: [ABSTRACT FROM AUTHOR]

Background: Aberrant expression of the RON receptor tyrosine kinase is a pathogenic feature and a validated drug target in various types of cancers. Currently, therapeutic antibodies targeting RON for cancer therapy are under intensive evaluation. Here we report the development and validation of a novel humanized anti-RON antibody-drug conjugate for cancer therapy. Methods: Antibody humanization was achieved by grafting sequences of complementarity-determining regions from mouse monoclonal antibody Zt/g4 into human IgG1/κ acceptor frameworks. The selected humanized Zt/g4 subclone H1L3 was conjugated with monomethyl auristatin E using a dipeptide linker to form H-Zt/g4-MMAE. Pharmacokinetic analysis of H-Zt/g4-MMAE was determined using hydrophobic interaction chromatography and a MMAE ADC ELISA kit. Biochemical and biological assays were used for measuring RON expression, internalization, cell viability and death. Therapeutic efficacies of H-Zt/g4-MMAE were validated in vivo using three pancreatic cancer xenograft models. Toxicological activities of H-Zt/g4-MMAE were determined in mouse and cynomolgus monkey. Results: H-Zt/g4-MMAE had a drug to antibody ratio of 3.77:1 and was highly stable in human plasma with a dissociation rate less than 5% within a 20 day period. H-Zt/g4-MMAE displayed a favorable pharmacokinetic profile in both mouse and cynomolgus monkey. In vitro, H-Zt/g4-MMAE induced RON internalization, which results in killing of pancreatic cancer cells with IC50 values at 10–20 nM. In vivo, H-Zt/g4-MMAE inhibited pancreatic cancer xenograft growth with tumoristatic concentrations at 1~3 mg/kg bodyweight. Significantly, H-Zt/g4-MMAE eradicated tumors across multiple xenograft models regardless their chemoresistant and metastatic statuses. Moreover, H-Zt/g4-MMAE inhibited and eradicated xenografts mediated by pancreatic cancer stem-like cells and by primary cells from patient-derived tumors. Toxicologically, H-Zt/g4-MMAE is well tolerated in mice up to 60 mg/kg. In cynomolgus monkey, H-Zt/g4-MMAE up to 30 mg/kg had a manageable and reversible toxicity profile. Conclusions: H-Zt/g4-MMAE is superior in eradication of pancreatic cancer xenografts with favorable pharmacokinetic profiles and manageable toxicological activities. These findings warrant the transition of H-Zt/g4-MMAE into clinical trials in the future. [ABSTRACT FROM AUTHOR]