Mitigating Ni and Cu ecotoxicity in the ecological restoration material and ornamental Primula forbesii Franch. with exogenous 24-epibrassinolide and melatonin.

Nickel (Ni) and copper (Cu) contamination have become major threats to plant survival worldwide. 24-epibrassinolide (24-EBR) and melatonin (MT) have emerged as valuable treatments to alleviate heavy metal-induced phytotoxicity. However, plants have not fully demonstrated the potential mechanisms by which these two hormones act under Ni and Cu stress. Herein, this study investigated the impact of individual and combined application of 24-EBR and MT on the growth and physiological traits of Primula forbesii Franch. subjected to stress (200 µmol L-1 Ni and Cu). The experiments compared the effects of different mitigation treatments on heavy metal (HM) stress and the scientific basis and practical reference for using these exogenous substances to improve HM resistance of P. forbesii in polluted environments. Nickel and Cu stress significantly hindered leaf photosynthesis and nutrient uptake, reducing plant growth and gas exchange. However, 24-EBR, MT, and 24-EBR + MT treatments alleviated the growth inhibition caused by Ni and Cu stress, improved the growth indexes of P. forbesii, and increased the gas exchange parameters. Exogenous MT effectively alleviated Ni stress, and 24-EBR + MT significantly alleviated the toxic effects of Cu stress. Unlike HM stress, MT and 24-EBR + MT activated the antioxidant enzyme activity (by increasing superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT)), significantly reduced reactive oxygen species (ROS) accumulation, and regulated ascorbate and glutathione cycle (AsA-GSH) efficiency. Besides, the treatments enhanced the ability of P. forbesii to accumulate HMs, shielding plants from harm. These findings conclusively illustrate the capability of 24-EBR and MT to significantly bolster the tolerance of P. forbesii to Ni and Cu stress.

Tannic acid/Mg2+-based versatile coating to manipulate the osteoimmunomodulation of implants.

Instead of directly stimulating osteogenesis, endowing an implant surface with a favourable osteoimmunomodulatory (OIM) function has emerged as a new effective strategy to enhance osteointegration. Though metal-phenolic coatings have demonstrated to possess an immunomodulatory function, their potential application in manipulating an osteoimmune response has not been well explored. Herein, in order to develop a simple, rapid and universal coating method to impart excellent OIM to hard tissue implants, tannic acid (TA) and Mg2+ were selected to form a coating on Ti plate based on metal-phenolic chemistry. Besides its virtues of simplicity, ultrafastness, low-cost, and versatility, another merit for the coating method is that it can easily combine the unique functions of metal ions and phenolic ligands. The chelated Mg2+ can not only activate macrophage polarization towards the anti-inflammatory phenotype but also directly stimulate the osteogenic differentiation of bone marrow-derived stem cells (BMSCs). TA motifs rendered the coating with an excellent reactive oxygen species (ROS) scavenging capacity. TA and Mg2+ showed synergistic effects on regulating macrophage biological behaviour, suppressing its polarization towards the M1 phenotype, and promoting its polarization towards the M2 phenotype. In vivo histological analysis also demonstrated that the TA/Mg2+ coating could effectively inhibit the host response. Finally, the formed osteoimmune environment obviously enhanced the osteogenic differentiation of BMSCs. The above results demonstrated that the designed TA/Mg2+ coating not only possessed the function of directly stimulating osteogenesis but also the function of manipulating OIM to a desired one. Hence, it has great potential to be applied on advanced hard tissue implants to enhance osteointegration.

Integrated analyses of miRNA and mRNA profiles in leukocytes and serums in traditional Chinese medicine (TCM)-defined Pi-qi-deficiency syndrome and Pi-wei damp-heat syndrome resulting from chronic atrophic gastritis.

BACKGROUND: To investigate the microRNA (miRNA)-gene interactions underlying leukocyte functions and characteristics, especially the potential serum biomarkers, implicated in the traditional Chinese medicine (TCM)-defined Pi-qi-deficiency syndrome (PQDS) and Pi-wei damp-heat syndrome (PDHS) resulting from chronic atrophic gastritis (CAG). METHODS: Using RNA/miRNA-sequencing approach, compared with healthy control population, we identified the PDHS- or PQDS-specific miRNAs and genes in leukocytes or serums, especially the Zheng (syndrome)-specific miRNA-gene interactions, and further decoded their functions and pathways. RESULTS: Despite being the TCM-defined Zhengs resulting from the same disease of CAG, the Zheng-specific genes and miRNAs were not same. The PDHS-specific leukocyte genes were mainly involved in defense and immune responses, including NOD-like receptor signaling and several synapses-related pathways. The expression upregulation of PDHS-specific genes enriched in the neutrophil degranulation pathway, indicated the enhanced leukocyte degranulation activation. The PQDS-specific genes in leukocytes were implicated in inflammatory response, extracellular matrix (ECM) organization and collagen catabolism. They could be enriched in MAPK and IL17 signaling and helper T cell differentiation pathways, especially the pathways associated with cell-to-cell adhesion/junction and communication such as cell adhesion molecules, ECM organization and ECM-receptor interaction, probably contributing to the characteristics and functions of leukocytes. Also, the experimentally-supported miRNA-gene interactions, concerned with COL4A2, COL26A1, SPP1 and PROCR, were implicated in the regulation of pathways related to cell-to-cell adhesion/junction and communication, suggesting the potential roles of the PQDS-specific miRNA-gene interactions for the characteristic and functional changes of leukocytes. Interestingly, the PQDS-specific miRNAs in the serums and the corresponding leukocytes, seemed to have the common roles in contributing to the characteristics and functions of leukocytes. Importantly, the hsa-miR-122-5p could be a potential biomarker, capable of being contained and carried in plasma exosomes and much higher expression in both the leukocytes and corresponding serums in the CAG patients with PQDS rather than PDHS. CONCLUSIONS: These results may provide new insights into the characteristic and functional changes of leukocytes in the two Zhengs, PDHS and PQDS, especially the miRNA-mediated gene regulation underlying leukocyte characteristics and functions, with potential leukocyte and serum biomarkers for future application in integrative medicine. Trial registration ClinicalTrials.gov, NCT02915393. Registered on September 17, 2016.

Integrated Analyses of lncRNA and mRNA Profiles Reveal Characteristic and Functional Changes of Leukocytes in Qi-Deficiency Constitution and Pi-Qi-Deficiency Syndrome of Chronic Superficial Gastritis.

METHODS: We adopted RNA-sequencing approach to identify differential lncRNAs and genes in leukocytes, clustered expression profiles, and analyzed biological functions and pathways of differential genes to decode their potential roles in contributing to characteristics and functions of leukocytes. In addition, interaction networks were created to detail the interactions between differential genes. In particular, we explored differential lncRNAs-mediated regulation of differential genes and predicted the subcellular location of lncRNAs to reveal their potential roles. RESULTS: Compared with TCM-defined balanced constitution (BC), 183 and 93 genes as well as 749 and 651 lncRNAs were differentially expressed (P < 0.05 and |log2 (fold change)| ≥1) in leukocytes of individuals from case populations 1 (QDC) and 2 (PQDS), respectively. Of them, 12 genes and 111 lncRNAs were common to each case population. Several networks were created to detail the interactions among case-specific genes, especially case-specific lncRNAs-mediated regulation of case-specific genes. Also, interaction networks were created for the common lncRNAs and genes. HCL analyses showed that differential genes and lncRNAs, especially the common genes and lncRNAs, kept similar expression patterns in both case populations. Furthermore, function enrichment analyses just indicated the common biological processes, namely, extracellular matrix organization and cell adhesion via plasma membrane adhesion molecules. In addition, most common genes underwent very tight and complex regulation of many trans- and cis-acting lncRNAs. In particular, of them, ADAMTSL5, COL26A1, COL27A1, MSH5, and LOC390937 could be regulated by multiple case-specific and common lncRNAs, including the means that directs binding of the common lncRNAs to their coded proteins. The common changes in the extracellular matrix and integral components of plasma membrane related to cell-cell adhesion/junction and communication may implicate the linkage between QDC and PQDS, contributing to alterations in characteristics and functions of leukocytes. CONCLUSIONS: These results may provide new insights into the characteristic and functional changes of leukocytes in QDC and PQDS, especially the mechanism underlying the linkage of QDC to PQDS, with potential leukocytes biomarkers for future application in integrative medicine.

LanceletDB: an integrated genome database for lancelet, comparing domain types and combination in orthologues among lancelet and other species.

Lancelet (amphioxus) represents the most basally divergent extant chordate (cephalochordates) that diverged from the other two chordate lineages (urochordates and vertebrates) more than half a billion years ago. As it occupies a key position in evolution, it is considered as one of the best proxies for understanding the chordate ancestral state. Thus, the construction of a database with multiple lancelet genomes and gene annotation data, including protein domains, is urgently needed to investigate the loss and gain of domains in orthologues among species, especially ancient domain types (non-vertebrate-specific domains) and novel domain combination, which is helpful for providing new insight into the chordate ancestral state and vertebrate evolution. Here, we present an integrated genome database for lancelet, LanceletDB, which provides reference haploid genome sequence and annotation data for lancelet (Branchiostoma belcheri), including gene models and annotation, protein domain types, gene expression pattern in embryogenesis, different expression sequence tag sets and alternative polyadenylation (APA) sites profiled by the sequencing APA sites method. Especially, LanceletDB allows comparison of domain types and combination in orthologues among type species so as to decode the ancient domain types and novel domain combination during evolution. We also integrated the released diploid lancelet genome annotation data (Branchiostoma floridae) to expand LanceletDB and extend its usefulness. These data are available through the search and analysis page, basic local alignment search tool page and genome browser to provide an integrated display.