This study reveals the step-wise establishment of nuclear speckle-associated domains (SPADs) during mouse embryogenesis. Using optimized CUT&Tag, researchers found paternal SPADs dominate pre-ZGA stages, coordinating sequential gene expression and 3D genome reorganization. SPADs form two classes (primary and ZGA-dependent secondary), regulated by factors like Nipbl and Gata6, linking chromatin dynamics to developmental programming.

This study reported that pasteurized Akkermansia muciniphila (pAKK) promotes the differentiation of intestinal microfold cells (M cells) and increases the expression of the GP2 receptor via the TLR2-MyD88-NF-κB pathway, thereby enhancing the ability of Salmonella Typhimurium (STm) to invade Peyer's patches and leading to aggravated infection in mice. However, pAKK had no significant effect on the extracellular pathogen Citrobacter rodentium (Cr). Experiments showed that pre-treatment with pAKK significantly increased the expression of M cell markers and the number of gut lymphoid tissues, with effects depending on TLR2 signal activation mediated by the Amuc_1100 protein, independent of the canonical RANKL pathway. This study cautions that the application of probiotics should take pathogen specificity into account, as pAKK may increase the risk of infection by pathogens that rely on M cell invasion.

Low back pain (LBP) is the leading cause of musculoskeletal disability worldwide, affecting approximately 70% of the global population (Global Burden of Disease Study 2021). Aging is an independent risk factor for LBP, with nearly 40% of individuals over 65 developing LBP and exhibiting heightened susceptibility to lumbar disc herniation. Through single-nucleus RNA sequencing of human lumbar disc specimens, this study systematically compares cellular heterogeneity between aging and herniated discs. We identified senescence-associated secretory phenotype (SASP) in aged disc cells and IL-17-mediated immune activation in herniation, revealing distinct therapeutic targets. These findings advance mechanistic understanding of disc degeneration and offer mechanistically-informed strategies, such as SASP inhibition and IL-17 pathway modulation, for precision treatment of age-related LBP in elderly populations. 

This study reveals that neutrophil extracellular traps (NETs) drive macrophage-derived chemokine production (CXCL9/10/11) to promote CD8+ T cell infiltration in obstruction-induced renal fibrosis. Using unilateral ureteral obstruction (UUO) models, researchers demonstrated that NET inhibition via PAD4 deletion or DNase treatment attenuated fibrosis, while NET transfer exacerbated it. Mechanistically, NET-macrophage interactions via TLR2/4 signaling license chemokine secretion, fueling CD8+ T cell recruitment and granzyme B-mediated tubular injury. These findings establish NETs as central orchestrators of immune-fibrotic crosstalk, providing therapeutic targets for chronic kidney diseases.

Researchers are exploring how to produce more sustainable chemicals and fuels.

Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, is characterized by a high rate of metastasis and recurrence. Although lenvatinib is widely used as a first-line chemotherapy for advanced HCC, its clinical benefit is limited, owing to drug resistance. StAR-related lipid transfer protein 4 (STARD4), a protein regulated by the sterol-responsive element-binding protein 2 (SREBP-2), plays a crucial role in maintaining intracellular cholesterol homeostasis. However, its role and underlying mechanisms in HCC progression remain unclear.

Age-related macular degeneration (AMD), classified into dry and wet types, poses a significant threat to the vision of the elderly population globally. Despite its prevalence, the exact molecular mechanisms underlying the damage to retinal pigment epithelial cells (RPEs) and photoreceptor cells (PCs) in dry AMD remain poorly understood. Hence, there is a critical need for the development of human retinal models that can mimic dry AMD.

This study deciphers the genesis of the Huoshaoyun deposit, the world's largest carbonate-hosted Zn-Pb system, through ore characteristics, isotopes, and trace elements, revealing multi-stage mineralization linked to crust-mantle interaction and Jurassic volcanic-hydrothermal processes. 

This study presents a new 1.8-billion-year full-plate tectonic model, integrating geological and paleomagnetic data to reconstruct supercontinent cycles (Nuna, Rodinia, Pangea), revealing dynamic Proterozoic tectonics and challenging the “boring billion” hypothesis.