RESUMEN
Purpose: Idiosyncratic deals (I-deals), a novel human resource management implement, has significantly contributed to attracting, retaining and motivating personnel to enhance creativity. Building upon self-categorization theory, this study investigates the impact of I-deals on creativity and the moderating role of psychological safety in this process by perceived insider status. Participants and Methods: To mitigate common method bias and causal lag effects, this study was conducted in three phases with a half-month interval for data collection. In this study, a total of 331 employees from six enterprises in China were selected to test the hypotheses using Bootstrap and Johnson-Neyman methods. Results: Results show that I-deals have a positive influence on creativity. Perceived insider status acts as intermediary between I-deals and creativity; Psychological safety strengthens the influence of I-deals on perceived insider status and further enhances the indirect influence of I-deals on creativity through perceived insider status. Conclusion: This study demonstrates that organizations can leverage the unique characteristics of I-deals to fully showcase the diverse talents of their personnel, while simultaneously enhancing their psychological security. This, in turn, empowers employees to confidently propose new ideas and methods, thus catalyzing the generation of creativity.
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The widespread use of chemical disinfectants and antibiotics poses a major threat to food safety and human health. However, the mechanisms of co-transmission of antimicrobial resistance genes (ARGs) and biocides and metal resistance genes (BMRGs) of foodborne pathogens in the food chain is still unclear. This study isolated 343 E. coli strains from animal-derived foods in Beijing and incorporated online data of human-derived E. coli strains from NCBI. Our results demonstrated a relatively uniform distribution of strains from various regions in Beijing, indicating a lack of region-specific clustering. Additionally, predominant sequence types varied between food- and human-derived strains, suggesting a preference for different hosts and environments. Phenotypic association analysis showed that the chlorine disinfectants peroxides had a significant positive correlation with tetracyclines. Many more ARGs and BMRGs were enriched in human-associated E. coli compared with those in chicken- and pork-origin. The quaternary ammonium compounds (QACs) resistance gene qacEΔ1 had a strong correlation with aminoglycoside resistance gene aadA5, folate pathway antagonist resistance gene dfrA17, sul1 and macrolide resistance gene mph(A). The correlation results indicated a significant association between the copper resistance gene cluster pco and the silver resistance gene cluster sil. Coexistence of many resistance genes was observed within the qacEΔ1 gene structure, with qacEΔ1-sul1 being the most common combination. Our findings demonstrated that the epidemiological spread of resistance is affected by a combination of heavy metals, disinfectants and antibiotic use, suggesting that the prevention and control strategies of antimicrobial resistance need to be multifaceted and comprehensive.
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Antibacterianos , Desinfectantes , Escherichia coli , Desinfectantes/farmacología , Antibacterianos/farmacología , Humanos , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Beijing , Farmacorresistencia Bacteriana/genética , Microbiología de Alimentos , Animales , ChinaRESUMEN
The carryover of trace allergens in complex food matrices poses challenges for detection techniques. Here, we demonstrate an accurate UPLC-MS/MS quantification assay for the shrimp allergen tropomyosin with a full-length isotope-labelled recombinant tropomyosin (TM-I) internal standard in complex food matrices. The TM-I, expressed based on the SILAC technique, exhibited a high isotope labelling ratio (>99%), purity, and alignment with the natural sequence. This method determined the tropomyosin ranging from 0.2 to 100 ng/mL. Mean recoveries ranged from 89 to 116%, with intra- and inter-day RSDs below 12%, for three signature peptides across three types of commercially processed food matrices. The limits of quantitation were 1 µg/g in pop food and sauce, and 10 µg/g in surimi product, respectively. This study supports the use of recombinant full-length isotope-labelled proteins rather than stable-isotope labelling peptides as internal standards to achieve more accurate quantitation of food allergens as the digestion error is corrected.
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Hipersensibilidad a los Alimentos , Espectrometría de Masas en Tándem , Animales , Espectrometría de Masas en Tándem/métodos , Cromatografía Liquida , Tropomiosina , Cromatografía Líquida con Espectrometría de Masas , Alérgenos , Crustáceos , Péptidos , Proteínas Recombinantes , IsótoposRESUMEN
Current treatment approaches for renal cell carcinoma (RCC) face challenges in achieving durable tumor responses due to tumor heterogeneity and drug resistance. Combination therapies that leverage tumor molecular profiles could offer an avenue for enhancing treatment efficacy and addressing the limitations of current therapies. To identify effective strategies for treating RCC, we selected ten drugs guided by tumor biology to test in six RCC patient-derived xenograft (PDX) models. The multitargeted tyrosine kinase inhibitor (TKI) cabozantinib and mTORC1/2 inhibitor sapanisertib emerged as the most effective drugs, particularly when combined. The combination demonstrated favorable tolerability and inhibited tumor growth or induced tumor regression in all models, including two from patients who experienced treatment failure with FDA-approved TKI and immunotherapy combinations. In cabozantinib-treated samples, imaging analysis revealed a significant reduction in vascular density, and single-nucleus RNA sequencing (snRNA-seq) analysis indicated a decreased proportion of endothelial cells in the tumors. SnRNA-seq data further identified a tumor subpopulation enriched with cell-cycle activity that exhibited heightened sensitivity to the cabozantinib and sapanisertib combination. Conversely, activation of the epithelial-mesenchymal transition pathway, detected at the protein level, was associated with drug resistance in residual tumors following combination treatment. The combination effectively restrained ERK phosphorylation and reduced expression of ERK downstream transcription factors and their target genes implicated in cell-cycle control and apoptosis. This study highlights the potential of the cabozantinib plus sapanisertib combination as a promising treatment approach for patients with RCC, particularly those whose tumors progressed on immune checkpoint inhibitors and other TKIs. SIGNIFICANCE: The molecular-guided therapeutic strategy of combining cabozantinib and sapanisertib restrains ERK activity to effectively suppress growth of renal cell carcinomas, including those unresponsive to immune checkpoint inhibitors.