Explore the vast range of titles available.

During embryogenesis, the liver is the site of hepatogenesis and hematopoiesis and contains many cell lineages derived from the endoderm and mesoderm. However, the characteristics and developmental programs of many of these cell lineages remain unclear, especially in humans. Here, we performed single-cell RNA sequencing of whole human and mouse fetal livers throughout development. We identified four cell lineage families of endoderm-derived, erythroid, non-erythroid hematopoietic, and mesoderm-derived non-hematopoietic cells, and defined the developmental pathways of the major cell lineage families. In both humans and mice, we identified novel markers of hepatic lineages and an ID3 + subpopulation of hepatoblasts as well as verified that hepatoblast differentiation follows the “default-directed” model. Additionally, we found that human but not mouse fetal hepatocytes display heterogeneity associated with expression of metabolism-related genes. We described the developmental process of erythroid progenitor cells during human and mouse hematopoiesis. Moreover, despite the general conservation of cell differentiation programs between species, we observed different cell lineage compositions during hematopoiesis in the human and mouse fetal livers. Taken together, these results reveal the dynamic cell landscape of fetal liver development and illustrate the similarities and differences in liver development between species, providing an extensive resource for inducing various liver cell lineages in vitro.

Transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) is a member of the MAPK kinase kinase (MAPKKK) family and has been implicated in the regulation of a wide range of physiological and pathological processes. TAK1 functions through assembling with its binding partners TAK1-binding proteins (TAB1, TAB2, and TAB3) and can be activated by a variety of stimuli such as tumor necrosis factor α (TNFα), interleukin-1β (IL-1β), and toll-like receptor ligands, and they play essential roles in the activation of NF-κB and MAPKs. Numerous studies have demonstrated that post-translational modifications play important roles in properly controlling the activity, stability, and assembly of TAK1-TABs complex according to the indicated cellular environment. This review focuses on the recent advances in TAK1-TABs-mediated signaling and the regulations of TAK1-TABs complex by post-translational modifications.

As competitive HMG-CoA reductase (HMGCR) inhibitors, statins not only reduce cholesterol and improve cardiovascular risk, but also exhibit pleiotropic effects that are independent of their lipid-lowering effects. Among them, the anti-cancer properties of statins have attracted much attention and indicated the potential of statins as repurposed drugs for the treatment of cancer. A large number of clinical and epidemiological studies have described the anticancer properties of statins, but the evidence for anticancer effectiveness of statins is inconsistent. It may be that certain molecular subtypes of cancer are more vulnerable to statin therapy than others. Whether statins have clinical anticancer effects is still an active area of research. Statins appear to enhance the efficacy and address the shortcomings associated with conventional cancer treatments, suggesting that statins should be considered in the context of combined therapies for cancer. Here, we present a comprehensive review of the potential of statins in anti-cancer treatments. We discuss the current understanding of the mechanisms underlying the anti-cancer properties of statins and their effects on different malignancies. We also provide recommendations for the design of future well-designed clinical trials of the anti-cancer efficacy of statins.

Limited knowledge of cellular and molecular mechanisms underlying hematopoietic stem cell and multipotent progenitor (HSC/MPP) expansion within their native niche has impeded the application of stem cell-based therapies for hematological malignancies. Here, we constructed a spatiotemporal transcriptome map of mouse fetal liver (FL) as a platform for hypothesis generation and subsequent experimental validation of novel regulatory mechanisms. Single-cell transcriptomics revealed three transcriptionally heterogeneous HSC/MPP subsets, among which a CD93-enriched subset exhibited enhanced stem cell properties. Moreover, by employing integrative analysis of single-cell and spatial transcriptomics, we identified novel HSC/MPP ‘ p ocket- l ike’ u nit s (HSC PLUS), composed of niche cells (hepatoblasts, stromal cells, endothelial cells, and macrophages) and enriched with growth factors. Unexpectedly, macrophages showed an 11-fold enrichment in the HSC PLUS. Functionally, macrophage–HSC/MPP co-culture assay and candidate molecule testing, respectively, validated the supportive role of macrophages and growth factors (MDK, PTN, and IGFBP5) in HSC/MPP expansion. Finally, cross-species analysis and functional validation showed conserved cell–cell interactions and expansion mechanisms but divergent transcriptome signatures between mouse and human FL HSCs/MPPs. Taken together, these results provide an essential resource for understanding HSC/MPP development in FL, and novel insight into functional HSC/MPP expansion ex vivo.

As the most common type of refractive error, myopia has become one of the leading causes of visual impairment. With the increasing prevalence of myopia, there is a growing need to better understand the factors involved in its development. Inflammation, one of the most fundamental pathophysiological processes in humans, is a rapid response triggered by harmful stimuli and conditions. Although controlled inflammatory responses are necessary, over-activated inflammation is the common soil for many diseases. The impact of inflammation on myopia has received rising attention in recent years. Elevated inflammation may contribute to myopia progression either directly or indirectly by inducing scleral remodeling, and myopia development may also increase ocular inflammation. This article provides a comprehensive review of the interplay between inflammation and myopia and the potential biological mechanisms, which may present new targets for understanding the pathology of myopia and developing myopia therapies.

While much effort has gone into building predictive models of the COVID-19 pandemic, some have argued that early exponential growth combined with the stochastic nature of epidemics make the long-term prediction of contagion trajectories impossible. We conduct two complementary studies to assess model features supporting better long-term predictions. First, we leverage the diverse models contributing to the CDC repository of COVID-19 USA death projections to identify factors associated with prediction accuracy across different projection horizons. We find that better long-term predictions correlate with: (1) capturing the physics of transmission (instead of using black-box models); (2) projecting human behavioral reactions to an evolving pandemic; and (3) resetting state variables to account for randomness not captured in the model before starting projection. Second, we introduce a very simple model, SEIRb, that incorporates these features, and few other nuances, offers informative predictions for as far as 20-weeks ahead, with accuracy comparable with the best models in the CDC set. Key to the long-term predictive power of multi-wave COVID-19 trajectories is capturing behavioral responses endogenously: balancing feedbacks where the perceived risk of death continuously changes transmission rates through the adoption and relaxation of various Non-Pharmaceutical Interventions (NPIs).

Effective treatment of oily wastewater, which is toxic and harmful and causes serious environmental pollution and health risks, has become an important research field. Membrane separation technology has emerged as a key area of investigation in oil–water separation research due to its high separation efficiency, low costs, and user-friendly operation. This review aims to report on the advances in the research of various types of separation membranes around emulsion permeance, separation efficiency, antifouling efficiency, and stimulus responsiveness. Meanwhile, the challenges encountered in oil–water separation membranes are examined, and potential research avenues are identified.

Fanconi anemia (FA) is a devastating hereditary disease characterized by bone marrow failure (BMF) and acute myeloid leukemia (AML). As FA-deficient cells are hypersensitive to DNA interstrand crosslinks (ICLs), ICLs are widely assumed to be the lesions responsible for FA symptoms. Here, we show that FA-mutated cells are hypersensitive to persistent replication stress and that FA proteins play a role in the break-induced-replication (BIR)-like pathway for fork restart. Both the BIR-like pathway and ICL repair share almost identical molecular mechanisms of 53BP1–BRCA1-controlled signaling response, SLX4- and FAN1-mediated fork cleavage and POLD3-dependent DNA synthesis, suggesting that the FA pathway is intrinsically one of the BIR-like pathways. Replication stress not only triggers BMF in FA-deficient mice, but also specifically induces monosomy 7, which is associated with progression to AML in patients with FA, in FA-deficient cells. Cell-based, in vitro and in vivo assays reveal that Fanconi anemia factors function in a BRCA1-dependent BIR-like pathway to restart stalled replication forks and that persistent replication stress contributes to FA pathogenesis.

The pin-fin is one of the main technologies in enhancing heat transfer. The accelerated flow and vortex structures are produced, which can disrupt the development of the flow boundary layer. The configuration of the pin-fin is obvious for heat transfer and flow characteristics, including its shape, size, and arrangement in the cooling channel. This work provides a detailed introduction to the application of pin-fins in enhancing heat transfer and reducing flow resistance, including the conventional shapes, improved shapes based on circular pin-fins and irregular shapes. At the same time, the influence of the diameter, height and density of pin-fins on heat transfer and flow performance is studied, and the influence mechanism is analyzed from the perspective of boundary layers. In addition, some applications that combine pin-fins with other cooling methods to further improve performance are analyzed. In terms of the optimization technology, the structure optimization for pin-fin shape and the layout optimization for pin-fin array are summarized. Therefore, this review provides a wide range of literature for the design of internal cooling channel pin-fins.

Background One critical variable in the time series analysis is the change point, which is the point where an abrupt change occurs in chronologically ordered observations. Existing parametric models for change point detection, such as the linear regression model and the Bayesian model, require that observations are normally distributed and that the trend line cannot have extreme variability. To overcome the limitations of the parametric model, we apply a nonparametric method, the Mann-Kendall-Sneyers (MKS) test, to change point detection for the state-level COVID-19 case time series data of the United States in the early outbreak of the pandemic. Methods The MKS test is implemented for change point detection. The forward sequence and the backward sequence are calculated based on the new weekly cases between March 22, 2020 and January 31, 2021 for each of the 50 states. Points of intersection between the two sequences falling within the 95% confidence intervals are identified as the change points. The results are compared with two other change point detection methods, the pruned exact linear time (PELT) method and the regression-based method. Also, an open-access tool by Microsoft Excel is developed to facilitate the model implementation. Results By applying the MKS test to COVID-19 cases in the United States, we have identified that 30 states (60.0%) have at least one change point within the 95% confidence intervals. Of these states, 26 states have one change point, 4 states (i.e., LA, OH, VA, and WA) have two change points, and one state (GA) has three change points. Additionally, most downward changes appear in the Northeastern states (e.g., CT, MA, NJ, NY) at the first development stage (March 23 through May 31, 2020); most upward changes appear in the Western states (e.g., AZ, CA, CO, NM, WA, WY) and the Midwestern states (e.g., IL, IN, MI, MN, OH, WI) at the third development stage (November 19, 2020 through January 31, 2021). Conclusions This study is among the first to explore the potential of the MKS test applied for change point detection of COVID-19 cases. The MKS test is characterized by several advantages, including high computational efficiency, easy implementation, the ability to identify the change of direction, and no assumption for data distribution. However, due to its conservative nature in change point detection and moderate agreement with other methods, we recommend using the MKS test primarily for initial pattern identification and data pruning, especially in large data. With modification, the method can be further applied to other health data, such as injuries, disabilities, and mortalities.