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Affiliation around tensions: strategies for aligning with putative readers through counter-expectation resources in media editorials

One important feature of newspaper editorials concerns the presentation of opposing values towards one ideational entity. This study aims to explore affiliation around contrasting values in media discourse, with a particular focus on the role of counter-expectation resources in dynamically managing these values and creating ambient affiliation between writers and putative readers. The analyses were undertaken with reference to the discourse semantic systems of ideation and appraisal in systemic functional linguistics. Based on close qualitative analysis of a corpus of editorials collected from The Australian, this study identified four recurrent rhetorical strategies used to override positive assessments of the Labor Party. The analysis develops the affiliation framework by exploring alignment around opposing values and provides guidelines for widening the study of persuasion in media discourse by focusing on the rhetorical functions of counter-expectation resources.

Single-cell immune aging clocks reveal inter-individual heterogeneity during infection and vaccination

Aging affects human immune system functionality, increasing susceptibility to immune-mediated diseases. While gene expression programs accurately reflect immune function, their relationship with biological immune aging and health status remains unclear. Here we developed robust, cell-type-specific aging clocks (sc-ImmuAging) for the myeloid and lymphoid immune cell populations in circulation within peripheral blood mononuclear cells, using single-cell RNA-sequencing data from 1,081 healthy individuals aged from 18 to 97 years. Application of sc-ImmuAging to transcriptome data of patients with COVID-19 revealed notable age acceleration in monocytes, which decreased during recovery. Furthermore, inter-individual variations in immune aging induced by vaccination were identified, with individuals exhibiting elevated baseline interferon response genes showing age rejuvenation in CD8+ T cells after BCG vaccination. sc-ImmuAging provides a powerful tool for decoding immune aging dynamics, offering insights into age-related immune alterations and potential interventions to promote healthy aging.

Pathogen stress heightens sensorimotor dimensions in the human collective semantic space

Infectious diseases have been major causes of death throughout human history and are assumed to broadly affect human psychology. However, whether and how conceptual processing, an internal world model central to various cognitive processes, adapts to such salient stress variables remains largely unknown. To address this, we conducted three studies examining the relationship between pathogen severity and semantic space, probed through the main neurocognitive semantic dimensions revealed by large-scale text analyses: one cross-cultural study (across 43 countries) and two historical studies (over the past 100 years). Across all three studies, we observed that increasing pathogen severity was associated with an enhancement of the sensory-motor dimension in the collective semantic space. These patterns remained robust after controlling for the effects of sociocultural variables, including economic wealth and societal norms of tightness. These results highlight the universal dynamic mechanisms of collective semantics, such that pathogen stress potentially drives sensorially oriented semantic processing.

Integrating single-cell RNA and T cell/B cell receptor sequencing with mass cytometry reveals dynamic trajectories of human peripheral immune cells from birth to old age

A comprehensive understanding of the evolution of the immune landscape in humans across the entire lifespan at single-cell transcriptional and protein levels, during development, maturation and senescence is currently lacking. We recruited a total of 220 healthy volunteers from the Shanghai Pudong Cohort (NCT05206643), spanning 13 age groups from 0 to over 90 years, and profiled their peripheral immune cells through single-cell RNA-sequencing coupled with single T cell and B cell receptor sequencing, high-throughput mass cytometry, bulk RNA-sequencing and flow cytometry validation experiments. We revealed that T cells were the most strongly affected by age and experienced the most intensive rewiring in cell–cell interactions during specific age. Different T cell subsets displayed different aging patterns in both transcriptomes and immune repertoires; examples included GNLY+CD8+ effector memory T cells, which exhibited the highest clonal expansion among all T cell subsets and displayed distinct functional signatures in children and the elderly; and CD8+ MAIT cells, which reached their peaks of relative abundance, clonal diversity and antibacterial capability in adolescents and then gradually tapered off. Interestingly, we identified and experimentally verified a previously unrecognized ‘cytotoxic’ B cell subset that was enriched in children. Finally, an immune age prediction model was developed based on lifecycle-wide single-cell data that can evaluate the immune status of healthy individuals and identify those with disturbed immune functions. Our work provides both valuable insights and resources for further understanding the aging of the immune system across the whole human lifespan.

Sex-specific and cell-type-specific changes in chaperone-mediated autophagy across tissues during aging

Aging leads to progressive decline in organ and tissue integrity and function, partly due to loss of proteostasis and autophagy malfunctioning. A decrease with age in chaperone-mediated autophagy (CMA), a selective type of lysosomal degradation, has been reported in various organs and cells from rodents and humans. Disruption of CMA recapitulates features of aging, whereas activating CMA in mice protects against age-related diseases such as Alzheimer’s, retinal degeneration and/or atherosclerosis. However, sex-specific and cell-type-specific differences in CMA with aging remain unexplored. Here, using CMA reporter mice and single-cell transcriptomic data, we report that most organs and cell types show CMA decline with age, with males exhibiting a greater decline with aging. Reduced CMA is often associated with fewer lysosomes competent for CMA. Transcriptional downregulation of CMA genes may further contribute to CMA decline, especially in males. These findings suggest that CMA differences may influence organ vulnerability to age-related degeneration.

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