资源环境科技发展态势分析平台

Neuronal activities in the central amygdala and paraventricular nucleus are transmitted via the splenic nerve to increase plasma cell formation after immunization, and this process can be behaviourally enhanced in mice.

The initiation of an intestinal tumour is a probabilistic process that depends on the competition between mutant and normal epithelial stem cells in crypts(1). Intestinal stem cells are closely associated with a diverse but poorly characterized network of mesenchymal cell types(2,3). However, whether the physiological mesenchymal microenvironment of mutant stem cells affects tumour initiation remains unknown. Here we provide in vivo evidence that the mesenchymal niche controls tumour initiation in trans. By characterizing the heterogeneity of the intestinal mesenchyme using single-cell RNA-sequencing analysis, we identified a population of rare pericryptal Ptgs2-expressing fibroblasts that constitutively process arachidonic acid into highly labile prostaglandin E-2 (PGE(2)). Specific ablation of Ptgs2 in fibroblasts was sufficient to prevent tumour initiation in two different models of sporadic, autochthonous tumorigenesis. Mechanistically, single-cell RNA-sequencing analyses of a mesenchymal niche model showed that fibroblast-derived PGE(2) drives the expansion omicron f a population of Sca-1(+) reserve-like stem cells. These express a strong regenerative/tumorigenic program, driven by the Hippo pathway effector Yap. In vivo, Yap is indispensable for Sca-1(+) cell expansion and early tumour initiation and displays a nuclear localization in both mouse and human adenomas. Using organoid experiments, we identified a molecular mechanism whereby PGE(2) promotes Yap dephosphorylation, nuclear translocation and transcriptional activity by signalling through the receptor Ptger4. Epithelial-specific ablation of Ptger4 misdirected the regenerative reprogramming of stem cells and prevented Sca-1(+) cell expansion and sporadic tumour initiation in mutant mice, thereby demonstrating the robust paracrine control of tumour-initiating stem cells by PGE(2)-Ptger4. Analyses of patient-derived organoids established that PGE(2)-PTGER4 also regulates stem-cell function in humans. Our study demonstrates that initiation of colorectal cancer is orchestrated by the mesenchymal niche and reveals a mechanism by which rare pericryptal Ptgs2-expressing fibroblasts exert paracrine control over tumour-initiating stem cells via the druggable PGE(2)-Ptger4-Yap signalling axis.

Single-cell RNA-sequencing analysis of intestinal mesenchyme identified a population of fibroblasts that produce prostaglandin E-2, which, when disrupted, prevented initiation of intestinal tumours.

Spin-based logic architectures provide nonvolatile data retention, near-zero leakage, and scalability, extending the technology roadmap beyond complementary metal-oxide-semiconductor logic(1-13). Architectures based on magnetic domain walls take advantage of the fast motion, high density, non-volatility and flexible design of domain walls to process and store information(1,3,14-16). Such schemes, however, rely on domain-wall manipulation and clocking using an external magnetic field, which limits their implementation in dense, large-scale chips. Here we demonstrate a method for performing all-electric logic operations and cascading using domain-wall racetracks. We exploit the chiral coupling between neighbouring magnetic domains induced by the interfacial Dzyaloshinskii-Moriya interaction(17-20), which promotes non-collinear spin alignment, to realize a domain-wall inverter, the essential basic building block in all implementations of Boolean logic. We then fabricate reconfigurable NAND and NOR logic gates, and perform operations with current-induced domain-wall motion. Finally, we cascade several NAND gates to build XOR and full adder gates, demonstrating electrical control of magnetic data and device interconnection in logic circuits. Our work provides a viable platform for scalable all-electric magnetic logic, paving the way for memory-in-logic applications.