Organoid-based high-throughput screening (HTS) is revolutionizing pharmaceutical development. However, the complexity of handling extracellular matrix (ECM) components with traditional HTS devices leads to the use of suspension cultures for organoids during HTS, which alters their transcriptomic landscape and drug responses. Although automated generation techniques for 3D ECM-encapsulated organoids have been established, limitations in operational simplicity and time efficiency remain barriers to achieving high throughput. Here, we develop a whole-process 3D ECM-encapsulated organoid-based automated HTS (wp3D-OAHTS) platform, which achieves superior throughput compared to existing reported systems for 3D organoid drug screening. Utilizing this automated platform, we generated more than 10,000 homogeneous 3D organoid domes of neuroendocrine cervical cancer (NECC) and evaluated their drug responses to 2802 compounds in 13 days. This highly efficient and reproducible approach finally enabled the identification of 5 top hits that significantly inhibited NECC organoids in vitro with half-maximal inhibitory concentration (IC₅₀) of lower than 10 nM. The representative candidate, Quisinostat 2HCl, demonstrated significantly stronger anti-tumor efficacy than clinically used agents in vivo. This platform significantly improves the rapidity and efficiency of 3D ECM-encapsulated organoid drug screening and facilitates new drug discovery for rare diseases.

Adipose tissue serves as a crucial energy storage and metabolic organ in the human body. With the surging of elderly population in China comes significant challenges in preventing and managing age-associated diseases, while adipose tissue aging represents one of the pivotal initiating events for multi-organ senescence. To address these challenges, the Aging China Biomarkers Consortium (ABC) has established an expert consensus on biomarkers of adipose tissue aging by digesting literature and collecting insights from scientists and clinicians. This consensus provides a comprehensive evaluation of the key changes and characteristics, as well as biomarkers related to adipose tissue aging and proposes a systematic framework categorizing these biomarkers into functional, structural and humoral dimensions. Within each dimension, the ABC recommends clinically and empirically validated biomarkers and parameters for assessing both physiological and pathological changes in adipose tissue during aging, which aims to establish a foundation for future prediction, diagnosis, early warning and treatment for adipose tissue aging and its related diseases, with the ultimate goal of improving adipose tissue health and promoting healthy aging in elderly populations both in China and worldwide.

Once viewed primarily as an energy reservoir, adipose tissue (AT) is now recognized as a key endocrinal organ in regulating systemic aging. With age, AT undergoes significant remodeling, marked by altered fat distribution, visceral fat expansion, impaired thermogenesis, and chronic low-grade inflammation, which disrupts metabolic and immune homeostasis. Emerging insights from single-cell and spatial transcriptomics highlight the critical roles of adipose progenitors, immune cells, and senescent cells in driving local dysfunction and systemic decline. Through inflammatory and metabolic signaling, dysfunctional AT actively contributes to age-related pathologies. This review explores how AT functions as both an early sensor and driver of aging and discusses therapeutic opportunities targeting adipose dysfunction to promote healthy aging.

Activated phosphoinositide 3-kinase delta syndrome (APDS) is a primary immunodeficiency characterized by hyperactivated lymphocytes and recurrent infections. This study presents a 2.5-year-old patient with a novel PIK3CD gene mutation (c.1309C>T; p. R437C) derived from his mother. We explored the immunological consequences of this mutation in both the patient and his mother, revealing defects in T cell differentiation, B cell maturation, and mitochondrial function. Notably, we found that the elevated CD38 expression on B cells is a key factor driving B cell senescence, mitochondrial dysfunction, and increased transitional B cell proportion, contributing to the observed immunodeficiency, such as diminished serum antibodies. Further investigations of the PI3K/AKT/mTOR pathway highlight a preferential activation of mTORC2 over mTORC1. We also demonstrate that the transcription factor FOXO1, a downstream molecule of PI3K/AKT signaling, regulates CD38 expression by binding to the promotor of the CD38 gene, linking this pathway to B cell dysfunction. This novel mutation expands the spectrum of PIK3CD mutations associated with APDS and provides new insights into the molecular mechanisms underlying B-cell senescence and other immune dysregulation. Moreover, targeting the AKT-FOXO1 axis could offer therapeutic potential to reverse B-cell dysfunction and improve immune responses in patients with PIK3CD mutations.