Spatial structure, chemotaxis and quorum sensing shape bacterial biomass accumulation in complex porous media.

Biological tissues, sediments, or engineered systems are spatially structured media with a tortuous and porous structure that host the flow of fluids. Such complex environments can influence the spatial and temporal colonization patterns of bacteria by controlling the transport of individual bacterial cells, the availability of resources, and the distribution of chemical signals for communication. Yet, due to the multi-scale structure of these complex systems, it is hard to assess how different biotic and abiotic properties work together to control the accumulation of bacterial biomass. Here, we explore how flow-mediated interactions allow the gut commensal Escherichia coli to colonize a porous structure that is composed of heterogenous dead-end pores (DEPs) and connecting percolating channels, i.e. transmitting pores (TPs), mimicking the structured surface of mammalian guts. We find that in presence of flow, gradients of the quorum sensing (QS) signaling molecule autoinducer-2 (AI-2) promote E. coli chemotactic accumulation in the DEPs. In this crowded environment, the combination of growth and cell-to-cell collision favors the development of suspended bacterial aggregates. This results in hot-spots of resource consumption, which, upon resource limitation, triggers the mechanical evasion of biomass from nutrients and oxygen depleted DEPs. Our findings demonstrate that microscale medium structure and complex flow coupled with bacterial quorum sensing and chemotaxis control the heterogenous accumulation of bacterial biomass in a spatially structured environment, such as villi and crypts in the gut or in tortuous pores within soil and filters.

Integrated analysis of 14 lymphoma datasets revealed high expression of CXCL14 promotes cell migration in mantle cell lymphoma.

Lymphoma is accompanied by the impairment of multiple immune functions. Cytokines play an important role in a variety of immune-related functions and affect the tumor microenvironment. However, the exact regulatory mechanisms between them remain unclear. This study aimed to explore the cytokines expression and function in Hodgkin's lymphoma (HL), diffuse large B-cell lymphoma (DLBCL), and mantle cell lymphoma (MCL). We performed a transcriptome integration analysis of 14 lymphoma datasets including 240 Hodgkin's lymphoma, 891 diffuse large B-cell lymphoma, 216 mantle cell lymphoma, and 64 health samples. The results showed that multiple immune functions and signal pathway damage were shared by all three types of lymphoma, and these functions were related to cytokines. Furthermore, through co-expression network and functional interaction network analysis, we identified CXCL14 as a key regulator and it affects cell chemotaxis and migration functions. The functional experiment showed that CXCL14 knockdown inhibited cell migration in MCL cell lines. This study suggested that high expression of CXCL14 may aggravate MCL via promoting cell migration. Our findings provide novel insights into the biology of this disease and would be helpful for the pathogenesis study and drug discovery of lymphomas.

Phenylboronic acid-conjugated chitosan nanoparticles for high loading and efficient delivery of curcumin.

In order to achieve high loading and efficient delivery of curcumin, phenylboronic acid-conjugated chitosan nanoparticles were prepared by a simple desolvation method. These nanoparticles exhibited a regular spherical shape with the average size about 200-230 nm and narrow size distribution, which were kinetically stable under physiological condition. Due to boronate ester formation between curcumin and phenylboronic acid groups in the nanoparticles, and the hydrogen bonding interactions between curcumin and nanocarriers, curcumin was successfully loaded into the nanoparticles with high drug loading content. These curcumin-loaded nanoparticles showed pH and reactive oxygen species (ROS)-triggered drug release behavior. In vitro cell experiments revealed that the blank nanoparticles were completely nontoxic to cultured cells, and the curcumin-loaded nanoparticles exhibited efficient antitumor efficiency against cancer cells. Moreover, the drug-loaded nanoparticles performed an enhanced growth inhibition in three-dimensional multicellular tumor spheroids. Thus, these nanocarriers would be a promising candidate for curcumin delivery in tumor treatment.

ß-catenin regulates myocardial ischemia/reperfusion injury following heterotopic heart transplantation in mice by modulating PTEN pathways.

Ischemia reperfusion (I/R) injury, an inevitable event accompanying heart transplantation, is the primary factor leading to organ failure and graft rejection. In order to prevent I/R injury, we established murine heart transplantation model with I/R and cell culture system to determine whether ß-catenin is a mediate factor in preventing I/R injury in heart transplantation. After successfully established heterotopic heart transplantation mice model, the I/R injury was induced, and two dynamic temporal were studied during different I/R phases. With the increase of ischemia and reperfusion time, heart damage was more severe. In the initial study, we observed that ß-catenin was significantly decreased, while ROCK1 and PTEN increased during the perfusion phase from day 0 to day 1, and remain the same level until 3 days later. The similar pattern that ß-catenin was down-regulated while ROCK1 and PTEN were up-regulated was also observed in the dynamic temporal ischemia study. To further investigate the role of ß-catenin signaling in I/R injury in vitro, ß-catenin over-expressing plasmid was transfected into HL-1 cells, a cardiac cell line. We noted that ß-catenin over-expressing cardiomyocytes showed decreased ROCK1/PTEN expression both at mRNA and protein levels. In addition, cobalt dichloride (CoCl2) -induced oxidative stress model was further established to mimic cardiac I/R injury. We observed that CoCl2-induced activation of ROCK1/PTEN signaling pathway were attenuated by transient transfection of a ß-catenin over-expressing plasmid. Taken together, our results suggest that cardiac transplant induced IR injury is closely associated with the down-regulation of ß-catenin and up-regulation of ROCK1 and PTEN expression.