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BACKGROUND: Gallbladder cancer (GBC) is a highly aggressive biliary epithelial malignancy. The median survival time of GBC patients was less than 1 year. Tumor invasion and metastasis are the major cause of high mortality of GBC patients. However, the molecular mechanisms involved in GBC metastases are still unclear. METHODS: We performed 10X genomics single-cell RNA sequencing (scRNA-seq) on GBC liver metastasis tissue to evaluate the characteristics of the GBC liver metastasis microenvironment. RESULTS: In this study, 8 cell types, a total of 7,788 cells, including T cells, B cells, malignant cells, fibroblasts, endothelial cells, macrophages, dendritic cells (DCs), and mast cells were identified. Malignant cells displayed a high degree of intratumor heterogenicity, while neutrophils were found to promote GBC cell proliferation, migration, and invasion. Furthermore, cytotoxic cluster of differentiation (CD8(+)) T cells became exhausted and CD4(+) regulatory T cells (Tregs) exhibited immunosuppressive characteristics. Macrophages played an important role in the tumor microenvironment (TME). We identified three distinct macrophage subsets and emergent M2 polarization. We also found that cancer-associated fibroblasts exhibited heterogeneity and may be associated with GBC metastasis. CONCLUSIONS: Although preliminary in nature, our study provides a landscape view at the single-cell level. These results offer a unique perspective into understanding the liver metastasis of GBC.

Summary Nuclear-erythroid-2-related factor 2 (Nrf2) is involved in the pathogenesis of different liver diseases. Herein, we first demonstrated that Nrf2 expression was diminished in nonalcoholic steatohepatitis (NASH) liver macrophages. In myeloid Nrf2-deficiency mice, aggravated liver steatosis and inflammation in high-fat-diet (HFD)-fed mice were observed compared with the chow-diet group. Moreover, the increasing inflammatory cytokines influenced the lipid metabolism in hepatocytes in vivo and in vitro. Further study showed Nrf2 regulated reactive-oxygen-species-mediated Hippo-yes-associated protein (YAP) signaling, which in turn modulated the NLRP3 inflammasome activation. Administration of YAP activator also significantly ablated the lipid accumulation and inhibited the NLRP3 activation in the Nrf2 deletion condition both in vitro and vivo. Overexpression Nrf2 in liver macrophages effectively alleviated steatohepatitis in wild-type mice fed with an HFD . Our data support that by modulating YAP-mediated NLRP3 inflammasome activity, macrophage Nrf2 slows down NASH progression., Graphical abstract, Highlights • Kupffer cells Nrf2 was downregulated in both human and mouse NASH livers • Myeloid Nrf2 deficiency aggravates liver steatosis and inflammation in HFD-induced NASH • Nrf2 controls the NLRP3 activation in a ROS-mediated Hippo-YAP signaling manner, Immunology; Physiology; Endocrine System Physiology; Human Metabolism

Clonal integration facilitates the growth and reproduction of clonal plants by providing the ability to share resources among ramets in heterogeneous environments. The benefits of clonal integration for plant growth may depend on a contrast in resource availability and may encounter costs, especially when a young part of the clone is growing across a border between richer and poorer conditions than the old part. We studied a clonal amphibian plant growing across a border between an aquatic and a terrestrial ecosystem, which typically differ in the availability of resources. We asked whether the young part of the clone is supporting the old part with phosphorus and whether this support has costs. We performed an experiment with Alternanthera philoxeroides where plants grow from water to a terrestrial habitat. The terrestrial habitat had either a low or high phosphorus supply, and the connection between the old and young parts of the clone was either left intact or split. We determined that the young part of the clone growing in a terrestrial habitat supported the old part with phosphorus when growing on a substrate rich in phosphorus. We have found no cost of this resource translocation; on the contrary, whole clones increased not only their accumulation of phosphorus, but also of nitrogen. Our study shows how an amphibian plant may profit from heterogeneous habitats by resource sharing in a clonal network.

Clonal integration can contribute to the invasiveness of amphibious plant, Alternanthera philoxeroides, but whether this differs between life-forms and whether such difference is underlying their biological control efficacy have scarcely been addressed. We aimed to determine whether clonal integration differs between life-forms and whether terrestrial form with lower biological control efficacy shows greater capacity of clonal integration in response to defoliation. In a greenhouse experiment, we subjected terrestrial and aquatic A. philoxeroides to four levels of experimental defoliation, i.e., 0 (control), 20% (mild), 50% (moderate), and 80% (heavy) leaf clipping, with the stolon connections being either severed or intact. The results showed that clonal integration greatly improved the growth and clonal propagation of both life-forms, especially under heavier defoliation. The shoot/root ratios of both life-forms were significantly increased by clonal integration under heavy defoliation. Moreover, higher level of resource sharing and greater division of labor promoted the terrestrial form to perform better than the aquatic form. These results supported our hypotheses that terrestrial A. philoxeroides can benefit from clonal integration more than aquatic form under herbivory, which may be an alternative mechanism accounted for the low efficacy of biological control of A. philoxeroides in the terrestrial habitats.

Clonal traits can contribute to plant invasiveness, but little is known about the roles of division of labor (a key clonal trait) in homogeneous habitats. The hypothesis tested is that clonal integration allows division of labor and increases the overall performance of an invasive clonal plant, especially under higher soil nutrients. Clonal fragment pairs of aquatic invader Alternanthera philoxeroides (each with four ramets and a stolon apex) were grown in two homogenous habitats with high or low soil nutrient supply, and with stolon connections being either severed (clonal integration prevented) or kept intact (clonal integration allowed). Results showed that stolon connection allowed the division of labor within the clonal fragment, with basal ramets specializing in acquisition of belowground resources and apical ramets specializing in acquisition of aboveground expansion. Moreover, the capacity for division of labor was greater, which brought the clonal fragments of A. philoxeroides stronger clonal propagation and better performance in high nutrient habitats than in low nutrient habitats. The results supported our hypotheses that the developmentally programmed division of labor may facilitate the clonal expansion of this aggressive invader in some homogeneous habitats with high resource availability.

Clonal traits can contribute to plant invasiveness, but little is known about the roles of division of labor (a key clonal trait) in homogeneous habitats. The hypothesis tested is that clonal integration allows division of labor and increases the overall performance of an invasive clonal plant, especially under higher soil nutrients. Clonal fragment pairs of aquatic invader

Many notorious invasive plants are clonal, and clonal integration may improve their ability to cope with disturbances such as herbivory. We hypothesize that clonal integration positively affects the growth, physiology and biomass allocation of the invasive aquatic plant Eichhornia crassipes and thus improves its performance in response to defoliation. In a 7-week greenhouse experiment, we subjected E. crassipes ramets to three levels of experimental defoliation, i.e., 20 % (mild), 50 % (moderate) and 80 % (heavy) leaf clipping and an unclipped control, and the stolon connections to the mother plants were either severed or kept intact. Compared with the control, defoliation significantly decreased the growth (total biomass and ramet number), but increased the maximum quantum yield of photosystem II (F v/F m) and chlorophyll content of the target ramets. Stolon connection (clonal integration) greatly increased the growth, F v/F m and contents of non-structural carbohydrates (soluble sugar and total non-structural carbohydrates) of E. crassipes, and these effects were larger under heavier defoliation. Moreover, stolon connection significantly reduced the shoot/root ratio of E. crassipes ramets, and such effects were greater under heavier leaf clipping. These results support our hypothesis that E. crassipes can benefit from clonal integration in response to defoliation, suggesting that clonal integration may enhance the invasion potential of E. crassipes and potentially reduce the efficacy of biological control.

A series of novel self-dispreading phenoxy carboxylic acid derivatives were designed and synthesized by I 2 catalyzed one-step reaction. Their structures were confirmed by IR, NMR, and HRMS. The derivatives can self-spread and float on the water surface. Preliminary bioassays showed that some compounds, 3i – 3p , had excellent herbicidal activities against water hyacinth. This strategy provided a novel approach for the water hyacinth control.

Many notorious invasive plants are clonal, spreading mainly by vegetative propagules. Propagule pressure (the number of propagules) may affect the establishment, growth, and thus invasion success of these clonal plants, and such effects may also depend on habitat conditions. To understand how propagule pressure, habitat conditions and clonal integration affect the establishment and growth of the invasive clonal plants, an 8-week greenhouse with an invasive clonal plant, Alternanthera philoxeroides was conducted. High (five fragments) or low (one fragment) propagule pressure was established either in bare soil (open habitat) or dense native vegetation of Jussiaea repens (vegetative habitat), with the stolon connections either severed from or connected to the relatively older ramets. High propagule pressure greatly increased the establishment and growth of A. philoxeroides, especially when it grew in vegetative habitats. Surprisingly, high propagule pressure significantly reduced the growth of individual plants of A. philoxeroides in open habitats, whereas it did not affect the individual growth in vegetative habitats. A shift in the intraspecific interaction on A. philoxeroides from competition in open habitats to facilitation in vegetative habitats may be the main reason. Moreover, clonal integration significantly improved the growth of A. philoxeroides only in open habitats, especially with low propagule pressure, whereas it had no effects on the growth and competitive ability of A. philoxeroides in vegetative habitats, suggesting that clonal integration may be of most important for A. philoxeroides to explore new open space and spread. These findings suggest that propagule pressure may be crucial for the invasion success of A. philoxeroides, and such an effect also depends on habitat conditions.