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C4d, a high-affinity LilrB2 ligand, is elevated in Alzheimer's disease and mediates synapse pruning

9 months ago
Synapse pruning sculpts neural circuits throughout life. The human Leukocyte immunoglobulin-like receptor type B2 (LilrB2)/murine Paired immunoglobulin receptor B (PirB) receptors expressed in neurons and complement protein C4 have been separately implicated in pruning. Here, we report that C4d, a C4 cleavage product with unknown function, binds LilrB2/PirB with nanomolar affinity. C4d and LilrB2 colocalize at excitatory synapses in the human cerebral cortex as well as with beta amyloid in...
Barbara K Brott

ZBP1 pathway promotes tumor immunogenicity in the combination of anti-HER2 therapy and epigenetic therapy

9 months ago
Z-form DNA (Z-DNA)-binding protein 1 (ZBP1)-mediated RNA sensing plays a critical role in tumor immunogenicity. However, how to augment ZBP1 signaling-mediated immunogenic tumor cell death to boost targeted therapy is yet unknown. Here, we demonstrated that epigenetic modulation by 5-aza-2'-deoxycytidine (5AZA) facilitated antitumor effects of anti-HER2 therapy, which requires antitumor CD8^(+) T cell responses initiated by ZBP1-mediated tumor immunogenicity. Moreover, the combination of...
Qishan Wang

Gut metagenome and plasma metabolome profiles in older adults suggest pyruvate metabolism as a link between sleep quality and frailty

9 months ago
Poor sleep quality is associated with increased frailty in older adults, but the role of the gut microbiome in this relationship remains unclear. Here, gut metagenome and plasma metabolome were profiled in 1,225 individuals aged 62-96 years. Poor sleep quality was associated with reduced abundances of potential probiotics such as Faecalibacterium prausnitzii and elevated abundances of pathobionts. A gut microbiome sleep quality index (GMSI) was developed to quantify microbial balance related to...
Yanni Pu

Negative wealth shock and epigenetic aging in middle-aged and older adults

9 months ago
CONCLUSIONS: Our study identifies a significant relationship between negative wealth shocks and biological aging in middle-aged and older adults. This suggests that socioeconomic factors, particularly sudden economic losses and fluctuations, should be considered in strategies for promoting healthy longevity and aging interventions. Additionally, there is a need for unemployment protection policies or measures to help stabilize medical and food consumption for households or individuals during...
Zhuo Li

Genomic diversity of the African malaria vector Anopheles funestus

9 months ago
Science, Volume 389, Issue 6766, September 2025.
Marilou Boddé, Joachim Nwezeobi, Petra Korlević, Alex Makunin, Ousman Akone-Ella, Sonia Barasa, Mahamat Gadji, Lee Hart, Emmanuel W. Kaindoa, Katie Love, Eric R. Lucas, Ibra Lujumba, Mara Máquina, Sanjay C. Nagi, Joel O. Odero, Brian Polo, Claire…