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Cardiac regeneration involves the generation of new cardiomyocytes from cycling cardiomyocytes. Understanding cell-cycle activity of pre-existing cardiomyocytes provides valuable information to heart repair and regeneration. However, the anatomical locations and in situ dynamics of cycling cardiomyocytes remain unclear. Here we develop a genetic approach for a temporally seamless recording of cardiomyocyte-specific cell-cycle activity in vivo. We find that the majority of cycling cardiomyocytes are positioned in the subendocardial muscle of the left ventricle, especially in the papillary muscles. Clonal analysis revealed that a subset of cycling cardiomyocytes have undergone cell division. Myocardial infarction and cardiac pressure overload induce regional patterns of cycling cardiomyocytes. Mechanistically, cardiomyocyte cell cycle activity requires the Hippo pathway effector YAP. These genetic fate-mapping studies advance our basic understanding of cardiomyocyte cell cycle activity and generation in cardiac homeostasis, repair, and regeneration.

Abstract Background Risk stratification in non-ST segment elevation myocardial infarction (NSTEMI) determines the intervention time. Limited study compared two risk scores, the Thrombolysis in Myocardial Infarction (TIMI) and Global Registry of Acute Coronary Events (GRACE) risk scores in the current East Asian NSTEMI patients. Methods This retrospective observational study consecutively collected patients in a large academic hospital between 01/01 and 11/01/2017 and followed for 4 years. Patients were scored by TIMI and GRACE scores on hospital admission. In-hospital endpoints were defined as the in-hospital composite event, including mortality, re-infarction, heart failure, stroke, cardiac shock, or resuscitation. Long-term outcomes were all-cause mortality and cardiac mortality in 4-year follow-up. Results A total of 232 patients were included (female 29.7%, median age 67 years), with a median follow-up of 3.7 years. GRACE score grouped most patients (45.7%) into high risk, while TIMI grouped the majority (61.2%) into medium risk. Further subgrouping the TIMI medium group showed that half (53.5%) of the TIMI medium risk population was GRACE high risk (≥ 140). Compared to TIMI medium group + GRACE

Liver kinase B1 (Lkb1), encoded by serine/threonine kinase (Stk11), is a serine/threonine kinase and tumor suppressor that is strongly implicated in Peutz–Jeghers syndrome (PJS). Numerous studies have shown that mesenchymal‐specific Lkb1 is sufficient for the development of PJS‐like polyps in mice. However, the cellular origin and components of these Lkb1‐associated polyps and underlying mechanisms remain elusive. In this study, we generated tamoxifen‐inducible Lkb1flox/flox;Myh11‐Cre/ERT2 and Lkb1flox/flox;PDGFRα‐Cre/ERT2 mice, performed single‐cell RNA sequencing (scRNA‐seq) and imaging‐based lineage tracing, and aimed to investigate the cellular complexity of gastrointestinal polyps associated with PJS. We found that Lkb1flox/+;Myh11‐Cre/ERT2 mice developed gastrointestinal polyps starting at 9 months after tamoxifen treatment. scRNA‐seq revealed aberrant stem cell‐like characteristics of epithelial cells from polyp tissues of Lkb1flox/+;Myh11‐Cre/ERT2 mice. The Lkb1‐associated polyps were further characterized by a branching smooth muscle core, abundant extracellular matrix deposition, and high immune cell infiltration. In addition, the Spp1–Cd44 or Spp1–Itga8/Itgb1 axes were identified as important interactions among epithelial, mesenchymal, and immune compartments in Lkb1‐associated polyps. These characteristics of gastrointestinal polyps were also demonstrated in another mouse model, tamoxifen‐inducible Lkb1flox/flox;PDGFRα‐Cre/ERT2 mice, which developed obvious gastrointestinal polyps as early as 2–3 months after tamoxifen treatment. Our findings further confirm the critical role of mesenchymal Lkb1/Stk11 in gastrointestinal polyposis and provide novel insight into the cellular complexity of Lkb1‐associated polyp biology. © 2024 The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

This study develops three measures to optimize the junction-tree-based reinforcement learning (RL) algorithm, which will be used for network-wide signal coordination. The first measure is to optimize the frequency of running the junction-tree algorithm (JTA) and the intersection status division. The second one is to optimize the JTA information transmission mode. The third one is to optimize the operation of a single intersection. A test network and three test groups are built to analyze the optimization effect. Group 1 is the control group, group 2 adopts the optimizations for the basic parameters and the information transmission mode, and group 3 adopts optimizations for the operation of a single intersection. Environments with different congestion levels are also tested. Results show that optimizations of the basic parameters and the information transmission mode can improve the system efficiency and the flexibility of the green light, and optimizing the operation of a single intersection can improve the efficiency of both the system and the individual intersection. By applying the proposed optimizations to the existing JTA-based RL algorithm, network-wide signal coordination can perform better., 1. Introduction Signal control system is an important method of improving the operation of urban traffic. With the development of people's understanding on traffic and technology, urban traffic signal control [...]