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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.
GenAI synthesis of histopathological images from Raman imaging for intraoperative tongue squamous cell carcinoma assessment
The presence of a positive deep surgical margin in tongue squamous cell carcinoma (TSCC) significantly elevates the risk of local recurrence. Therefore, a prompt and precise intraoperative assessment of margin status is imperative to ensure thorough tumor resection. In this study, we integrate Raman imaging technology with an artificial intelligence (AI) generative model, proposing an innovative approach for intraoperative margin status diagnosis. This method utilizes Raman imaging to swiftly and non-invasively capture tissue Raman images, which are then transformed into hematoxylin-eosin (H&E)-stained histopathological images using an AI generative model for histopathological diagnosis. The generated H&E-stained images clearly illustrate the tissue’s pathological conditions. Independently reviewed by three pathologists, the overall diagnostic accuracy for distinguishing between tumor tissue and normal muscle tissue reaches 86.7%. Notably, it outperforms current clinical practices, especially in TSCC with positive lymph node metastasis or moderately differentiated grades. This advancement highlights the potential of AI-enhanced Raman imaging to significantly improve intraoperative assessments and surgical margin evaluations, promising a versatile diagnostic tool beyond TSCC.
The closing longevity gap between battery electric vehicles and internal combustion vehicles in Great Britain
Electric vehicles are increasingly being adopted in Great Britain and other parts of the world, driven by the perception that they offer a cost-effective alternative to internal combustion engine vehicles while reducing emissions. However, a key element that underpins this perception is the longevity of electric vehicles, which remains relatively under researched. Here we show that although early battery electric vehicles (BEVs) exhibited lower reliability than internal combustion engine vehicles, rapid technological advancements have allowed newer BEVs to achieve comparable lifespans, even under more intensive use. Longevity is also found to be impacted by engine size, location and make of vehicle. We provide parameter estimates for life mileage that can be used to update life cycle assessment and total cost of ownership studies of different vehicle powertrains. Our results also shed light on BEV diffusion patterns, fleet replacement strategies and end-of-life treatment planning, including the increasingly important debate around BEV battery recycling and second-life options.
Genetic architectures of childhood maltreatment and causal influence of childhood maltreatment on health outcomes in adulthood
Childhood maltreatment is increasingly recognized as a pivotal risk factor for adverse health outcomes. However, comprehensive analyses of its long-term impact are scarce. This study aims to fill this gap by examining the genetic architectures of childhood maltreatment and its influence on adult health and socioeconomic outcomes. Utilizing data from the UK Biobank (N = 129,017), we conducted sex-combined and sex-stratified genome-wide association studies to identify genomic loci associated with five childhood maltreatment subtypes. We then performed genetic correlation and Mendelian randomization (MR) analyses to assess the effects of childhood maltreatment on high-burden diseases, healthcare costs, lifespan, and educational attainment. We identified several novel loci for childhood maltreatment, including one locus for sexual abuse in sex-combined analysis, one novel locus for sexual abuse in males, one locus for emotional neglect in females, and one locus for sexual abuse in females. The pairwise genetic correlations between subtypes of childhood maltreatment were moderate to high, and similar patterns of genetic correlations between childhood maltreatment subtypes were observed in males and females. Childhood maltreatment was genetically correlated with ten out of 16 high-burden diseases significantly after multiple testing correction. Moreover, MR analyses suggest childhood maltreatment may increase the risk of age-related and other hearing loss, low back pain, major depressive disorder, and migraine in adulthood, and reduce the lifespan. Our study elucidates the genetic architecture of specific childhood maltreatment subtypes and the influence of childhood maltreatment on health outcomes in adulthood, highlighting the enduring influence of childhood maltreatment on lifelong health consequences. It is important to develop prevention strategies to lower the incidence of childhood maltreatment and provide support and care for victims of childhood maltreatment for better long-term health outcomes in the population.
A reform of value-added taxes on foods can have health, environmental and economic benefits in Europe
Fiscal policies can provide important incentives for encouraging the dietary changes needed to achieve global policy targets. Across Europe, the foods relevant to health and the environment often incur reduced but non-zero value-added tax (VAT) rates at about half the maximum rates, which allows for providing both incentives and disincentives. Integrating economic, health and environmental modelling, we show that reforming VAT rates on foods, including increasing rates on meat and dairy, and reducing VAT rates on fruits and vegetables can improve diets and result in health, environmental and economic benefits in most European countries. The health improvements were primarily driven by reductions in VAT rates on fruits and vegetables, whereas most of the environmental and revenue benefits were driven by increased rates on meat and dairy. Our findings suggest that differentiating VAT rates based on health and environmental considerations can support changes towards healthier and more sustainable diets in Europe.
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