Analysis of nearly 3000 archaeal genomes from terrestrial geothermal springs sheds light on interconnected biogeochemical processes.

Terrestrial geothermal springs are physicochemically diverse and host abundant populations of Archaea. However, the diversity, functionality, and geological influences of these Archaea are not well understood. Here we explore the genomic diversity of Archaea in 152 metagenomes from 48 geothermal springs in Tengchong, China, collected from 2016 to 2021. Our dataset is comprised of 2949 archaeal metagenome-assembled genomes spanning 12 phyla and 392 newly identified species, which increases the known species diversity of Archaea by ~48.6%. The structures and potential functions of the archaeal communities are strongly influenced by temperature and pH, with high-temperature acidic and alkaline springs favoring archaeal abundance over Bacteria. Genome-resolved metagenomics and metatranscriptomics provide insights into the potential ecological niches of these Archaea and their potential roles in carbon, sulfur, nitrogen, and hydrogen metabolism. Furthermore, our findings illustrate the interplay of competition and cooperation among Archaea in biogeochemical cycles, possibly arising from overlapping functional niches and metabolic handoffs. Taken together, our study expands the genomic diversity of Archaea inhabiting geothermal springs and provides a foundation for more incisive study of biogeochemical processes mediated by Archaea in geothermal ecosystems.

Nernst and seebeck effects inα-T3lattice.

By using the tight-binding Hamiltonian and non-equilibrium Green's function methods, the Seebeck and Nernst effects ofα-T3lattice are investigated, in which the lattice interpolates between graphene and the dice lattice via the parameterα. Forα= 0 (graphene), flat bands are always present in the band structure. The Seebeck and Nernst coefficients are consistent with those in graphene. Whenαis non-zero at zero magnetic field, the Seebeck coefficient is an odd function of the Fermi energy. It produces a very large and wide first peak within the band gap for the zigzag boundary. Under the influence of magnetic fields, the first peak of the Seebeck coefficient in the gap region increases withαincreasing. The Nernst effect occurs under the influence of a magnetic field. The height of the zeroth peak of the Nernst coefficient increases withαincreasing. Whenαreaches a certain value, the zeroth peak splits. The post-split peak decreases withαincreasing for the zigzag boundary, but continues to become wider and higher for the armchair boundary.

CD39hi identifies an exhausted tumor-reactive CD8+ T cell population associated with tumor progression in human gastric cancer.

The ectonucleotidase CD39 has been regarded as a promising immune checkpoint in solid tumors. However, the expression of CD39 by tumor-infiltrating CD8+ T cells as well as their potential roles and clinical implications in human gastric cancer (GC) remain largely unknown. Here, we found that GC-infiltrating CD8+ T cells contained a fraction of CD39hi cells that constituted about 6.6% of total CD8+ T cells in tumors. These CD39hi cells enriched for GC-infiltrating CD8+ T cells with features of exhaustion in transcriptional, phenotypic, metabolic and functional profiles. Additionally, GC-infiltrating CD39hiCD8+ T cells were also identified for tumor-reactive T cells, as these cells expanded in vitro were able to recognize autologous tumor organoids and induced more tumor cell apoptosis than those of expanded their CD39int and CD39-CD8+ counterparts. Furthermore, CD39 enzymatic activity controlled GC-infiltrating CD39hiCD8+ T cell effector function, and blockade of CD39 efficiently enhanced their production of cytokines IFN-γ and TNF-α. Finally, high percentages of GC-infiltrating CD39hiCD8+ T cells correlated with tumor progression and independently predicted patients' poor overall survival. These findings provide novel insights into the association of CD39 expression level on CD8+ T cells with their features and potential clinical implications in GC, and empowering those exhausted tumor-reactive CD39hiCD8+ T cells through CD39 inhibition to circumvent the suppressor program may be an attractive therapeutic strategy against GC.

CD39 expression defines exhausted CD4+ T cells associated with poor survival and immune evasion in human gastric cancer.

Objectives: CD4+ T cell helper and regulatory function in human cancers has been well characterised. However, the definition of tumor-infiltrating CD4+ T cell exhaustion and how it contributes to the immune response and disease progression in human gastric cancer (GC) remain largely unknown. Methods: A total of 128 GC patients were enrolled in the study. The expression of CD39 and PD-1 on CD4+ T cells in the different samples was analysed by flow cytometry. GC-infiltrating CD4+ T cell subpopulations based on CD39 expression were phenotypically and functionally assessed. The role of CD39 in the immune response of GC-infiltrating T cells was investigated by inhibiting CD39 enzymatic activity. Results: In comparison with CD4+ T cells from the non-tumor tissues, significantly more GC-infiltrating CD4+ T cells expressed CD39. Most GC-infiltrating CD39+CD4+ T cells exhibited CD45RA-CCR7- effector-memory phenotype expressing more exhaustion-associated inhibitory molecules and transcription factors and produced less TNF-α, IFN-γ and cytolytic molecules than their CD39-CD4+ counterparts. Moreover, ex vivo inhibition of CD39 enzymatic activity enhanced their functional potential reflected by TNF-α and IFN-γ production. Finally, increased percentages of GC-infiltrating CD39+CD4+ T cells were positively associated with disease progression and patients' poorer overall survival. Conclusion: Our study demonstrates that CD39 expression defines GC-infiltrating CD4+ T cell exhaustion and their immunosuppressive function. Targeting CD39 may be a promising therapeutic strategy for treating GC patients.

Temperature, pH, and oxygen availability contributed to the functional differentiation of ancient Nitrososphaeria.

Ammonia-oxidizing Nitrososphaeria are among the most abundant archaea on Earth and have profound impacts on the biogeochemical cycles of carbon and nitrogen. In contrast to these well-studied ammonia-oxidizing archaea (AOA), deep-branching non-AOA within this class remain poorly characterized because of a low number of genome representatives. Here, we reconstructed 128 Nitrososphaeria metagenome-assembled genomes from acid mine drainage and hot spring sediment metagenomes. Comparative genomics revealed that extant non-AOA are functionally diverse, with capacity for carbon fixation, carbon monoxide oxidation, methanogenesis, and respiratory pathways including oxygen, nitrate, sulfur, or sulfate, as potential terminal electron acceptors. Despite their diverse anaerobic pathways, evolutionary history inference suggested that the common ancestor of Nitrososphaeria was likely an aerobic thermophile. We further surmise that the functional differentiation of Nitrososphaeria was primarily shaped by oxygen, pH, and temperature, with the acquisition of pathways for carbon, nitrogen, and sulfur metabolism. Our study provides a more holistic and less biased understanding of the diversity, ecology, and deep evolution of the globally abundant Nitrososphaeria.

The chromosome-level assembly of the wild diploid alfalfa genome provides insights into the full landscape of genomic variations between cultivated and wild alfalfa.

Alfalfa (Medicago sativa L.) is one of the most important forage legumes in the world, including autotetraploid (M. sativa ssp. sativa) and diploid alfalfa (M. sativa ssp. caerulea, progenitor of autotetraploid alfalfa). Here, we reported a high-quality genome of ZW0012 (diploid alfalfa, 769 Mb, contig N50 = 5.5 Mb), which was grouped into the Northern group in population structure analysis, suggesting that our genome assembly filled a major gap among the members of M. sativa complex. During polyploidization, large phenotypic differences occurred between diploids and tetraploids, and the genetic information underlying its massive phenotypic variations remains largely unexplored. Extensive structural variations (SVs) were identified between ZW0012 and XinJiangDaYe (an autotetraploid alfalfa with released genome). We identified 71 ZW0012-specific PAV genes and 1296 XinJiangDaYe-specific PAV genes, mainly involved in defence response, cell growth, and photosynthesis. We have verified the positive roles of MsNCR1 (a XinJiangDaYe-specific PAV gene) in nodulation using an Agrobacterium rhizobia-mediated transgenic method. We also demonstrated that MsSKIP23_1 and MsFBL23_1 (two XinJiangDaYe-specific PAV genes) regulated leaf size by transient overexpression and virus-induced gene silencing analysis. Our study provides a high-quality reference genome of an important diploid alfalfa germplasm and a valuable resource of variation landscape between diploid and autotetraploid, which will facilitate the functional gene discovery and molecular-based breeding for the cultivars in the future.

Changes of putative pathogenic species within the water bacterial community in large-scale drinking water treatment and distribution systems.

Although the management of microbes in drinking water is of paramount importance for public health, there remain challenges in comprehensively examining pathogenic bacteria in the water supply system at the species level. In this study, high-throughput sequencing of nearly full-length 16S rRNA genes was performed to investigate the changes of the water bacterial community in three large-scale drinking water treatment plants (DWTPs) and their corresponding distribution systems during winter and summer. Our findings revealed significant differences in the bacterial community structure between winter and summer water samples for each DWTP and its distribution management area (DMA). In the groundwater-fed DWTP, selective enrichment of mycobacterial species was observed in both seasons, and the subsequent DMA also exhibited strong selection for specific mycobacterial species. In one of the surface water-fed DWTPs, certain Legionella species present in the source water in winter were selectively enriched in the bacterial community after pre-oxidation, although they were susceptible to the subsequent purification steps. A variety of putative pathogenic species (n = 83) were identified based on our pathogen identification pipeline, with the dominant species representing opportunistic pathogens commonly found in water supply systems. While pathogen removal primarily occurred during the purification processes of DWTPs, especially for surface water-fed plants, the relative abundance of pathogenic bacteria in the DMA water flora was lower than that in the DWTP effluent flora, indicating a diminished competitiveness of pathogens within the DMA ecosystem.

Sweroside attenuates podocyte injury and proteinuria in part by activating Akt/BAD signaling in mice.

In this study, we investigated the effects of sweroside on podocyte injury in diabetic nephropathy (DN) mice and elucidated its molecular mechanisms. We conducted in vivo experiments using a C57BL/6 mice model of DN to explore the effects of sweroside on proteinuria and podocyte injury in DN mice. In in vitro experiments, conditionally immortalized mouse podocytes were treated with high glucose and sweroside, and the protective effects of sweroside on podocyte injury were analyzed. In vitro, Akt/BAD pathways were detected using gene siRNA silencing assays and found to be involved in the protective roles of sweroside in high glucose-mediated podocyte injury. In vivo, sweroside significantly decreased albuminuria in DN mice (p < 0.01). periodic acid-Schiff staining showed that sweroside alleviated the glomerular volume and mesangium expansion in DN mice. Consistently, western blot and reverse transcription-polymerase chain reaction analyses showed that the profibrotic molecule expression in the glomeruli declined in sweroside-treated DN mice. Immunofluorescent results showed that sweroside preserved nephrin and podocin expression, and transmission electron microscopy showed that sweroside attenuated podocyte injury. In DN mice, sweroside decreased podocyte apoptosis, and increased nephrin, podocin expression and decreased desmin and HIF1α expression. These results confirmed that sweroside ameliorated albuminuria, glomerulomegaly, and glomerulosclerosis in these mice. Experiments in vitro revealed that sweroside improved HG-induced podocyte injury and apoptosis. Sweroside stimulated activation of the Akt/BAD pathway and upregulated Bcl-2-associated death promoter (BAD) and p-Akt. Overall, sweroside protected podocytes from injury and prevented the progression of DN, providing a novel strategy for the treatment of DN.

Sweroside alleviates hepatic steatosis in part by activating AMPK/mTOR-mediated autophagy in mice.

In this study, we investigated the effect of sweroside (SOS) on hepatic steatosis in mice and elucidated its molecular mechanisms. We conducted in vivo experiments using a C57BL/6 mice model of nonalcohol fatty liver disease (NAFLD) to explore the effect of SOS on hepatic steatosis in NAFLD mice. In in vitro experiments, primary mouse hepatocytes were treated with palmitic acid and SOS, and the protective effects of SOS on inflammation, lipogenesis, and fat deposition were analyzed. Autophagy-related protein levels and their related signaling pathways were evaluated in both in vivo and in vitro experiments. The results demonstrated that SOS decreased the high-fat-induced intrahepatic lipid content both in vivo and in vitro. The autophagy level in the liver was decreased in NAFLD mice but was reactivated following SOS intervention. SOS intervention was found to partially activate autophagy via the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway. Consequently, when the AMPK/mTOR pathway was suppressed or autophagy was inhibited, the beneficial effects of SOS intervention on hepatic steatosis were diminished. These results indicate that SOS intervention attenuates hepatic steatosis by promoting autophagy in the liver of NAFLD mice, in part by activating the AMPK/mTOR signaling pathway.

LncRNA CASC11 upregulation promotes HDAC4 to alleviate oxidized low-density lipoprotein-induced injury of cardiac microvascular endothelial cells.

Long noncoding RNAs (LncRNAs) are essential to regulate the pathogenesis of coronary artery disease (CAD). This study was conducted to analyze the functionality of long noncoding RNA cancer susceptibility candidate 11 (lncRNA CASC11) in oxidized low-density lipoprotein (ox-LDL)-induced injury of cardiac microvascular endothelial cells (CMECs). CMECs were treated with ox-LDL to induce the CAD cell model. The cellular expression levels of CASC11 and histone deacetylase 4 (HDAC4) were determined by real-time quantitative polymerase chain reaction or Western blot assay. Cell absorbance, apoptosis, angiogenesis, and inflammation were evaluated by cell counting kit-8, flow cytometry, tube formation, and enzyme-linked immunosorbent assays. The subcellular localization of CASC11 was examined by the nuclear/cytoplasmic fractionation assay. The binding of human antigen R (HuR) to CASC11 and HDAC4 was analyzed by RNA immunoprecipitation. HDAC4 stability was determined after actinomycin D treatment. CASC11 was found to be decreased in the CAD cell model. CASC11 upregulation increased cell viability and angiogenesis and reduced apoptosis and inflammation. CASC11 bound to HuR and improved HDAC4 expression. HDAC4 downregulation counteracted the protective role of CASC11 overexpression in CMECs. In summary, CASC11 alleviated ox-LDL-induced injury of CMECs by binding to HuR and stabilizing HDAC4.

Metagenomic Discovery of "Candidatus Parvarchaeales"-Related Lineages Sheds Light on Adaptation and Diversification from Neutral-Thermal to Acidic-Mesothermal Environments.

"Candidatus Parvarchaeales" microbes, representing a DPANN archaeal group with limited metabolic potential and reliance on hosts for their growth, were initially found in acid mine drainage (AMD). Due to the lack of representatives, however, their ecological roles and adaptation to extreme habitats such as AMD as well as how they diverge across the lineage remain largely unexplored. By applying genome-resolved metagenomics, 28 Parvarchaeales-associated metagenome-assembled genomes (MAGs) representing two orders and five genera were recovered. Among them, we identified three new genera and proposed the names "Candidatus Jingweiarchaeum," "Candidatus Haiyanarchaeum," and "Candidatus Rehaiarchaeum," with the former two belonging to a new order, "Candidatus Jingweiarchaeales." Further analyses of the metabolic potentials revealed substantial niche differentiation between Jingweiarchaeales and Parvarchaeales. Jingweiarchaeales may rely on fermentation, salvage pathways, partial glycolysis, and the pentose phosphate pathway (PPP) for energy conservation reservation, while the metabolic potentials of Parvarchaeales might be more versatile. Comparative genomic analyses suggested that Jingweiarchaeales favor habitats with higher temperatures and that Parvarchaeales are better adapted to acidic environments. We further revealed that the thermal adaptation of these lineages, especially Haiyanarchaeum, might rely on genomic features such as the usage of specific amino acids, genome streamlining, and hyperthermophile featured genes such as rgy. Notably, the adaptation of Parvarchaeales to acidic environments was possibly driven by horizontal gene transfer (HGT). The reconstruction of ancestral states demonstrated that both may have originated from thermal and neutral environments and later spread to mesothermal and acidic environments. These evolutionary processes may also be accompanied by adaptation to oxygen-rich environments via HGT. IMPORTANCE "Candidatus Parvarchaeales" microbes may represent a lineage uniquely distributed in extreme environments such as AMD and hot springs. However, little is known about the strategies and processes of how they adapted to these extreme environments. By the discovery of potential new order-level lineages, "Ca. Jingweiarchaeales," and in-depth comparative genomic analysis, we unveiled the functional differentiation of these lineages. Furthermore, we show that the adaptation of these lineages to high-temperature and acidic environments was driven by different strategies, with the former relying more on genomic characteristics such as genome streamlining and amino acid compositions and the latter relying more on the acquisition of genes associated with acid tolerance. Finally, by the reconstruction of the ancestral states of the optimal growth temperature (OGT) and isoelectric point (pI), we showed the potential evolutionary process of Parvarchaeales-related lineages with regard to the shift from the high-temperature environment of their common ancestors to low-temperature (potentially acidic) environments.

Panguiarchaeum symbiosum, a potential hyperthermophilic symbiont in the TACK superphylum.

The biology of Korarchaeia remains elusive due to the lack of genome representatives. Here, we reconstruct 10 closely related metagenome-assembled genomes from hot spring habitats and place them into a single species, proposed herein as Panguiarchaeum symbiosum. Functional investigation suggests that Panguiarchaeum symbiosum is strictly anaerobic and grows exclusively in thermal habitats by fermenting peptides coupled with sulfide and hydrogen production to dispose of electrons. Due to its inability to biosynthesize archaeal membranes, amino acids, and purines, this species likely exists in a symbiotic lifestyle similar to DPANN archaea. Population metagenomics and metatranscriptomic analyses demonstrated that genes associated with amino acid/peptide uptake and cell attachment exhibited positive selection and were highly expressed, supporting the proposed proteolytic catabolism and symbiotic lifestyle. Our study sheds light on the metabolism, evolution, and potential symbiotic lifestyle of Panguiarchaeum symbiosum, which may be a unique host-dependent archaeon within the TACK superphylum.

Characteristics and phylogenetic analysis of the complete chloroplast genome of Rubus chingii Hu 1925 from the family Rosaceae.

Rubus chingii Hu 1925 is an important medicinal vine shrub in the Rosaceae family, widely distributed in China and Japan. In this study, the complete chloroplast genome of R. chingii was sequenced and identified. The chloroplast genome was 155,563 bp in size with a total GC content of 37.06%. Two 25,749-bp inverted repeat (IRA and IRB) regions divided the genome as four sections, with the remainder forming a large single-copy (LSC, 85,322 bp) and a small single-copy (SSC, 18,743 bp) regions. This genome contained a total of 131 genes, of which 86 were protein-coding genes, 37 tRNA genes, and eight rRNA genes. The phylogenetic analysis showed that R. chingii, along with several other R. longisepalus, R. tsangii, R. hirsutus, R. taiwanicola, R. rubroangustifolius, and R. glandulosopunctatus, formed the monophylic group. Interestingly, the chloroplast genome structure we reported was different from the previously reported structure and provided richer phylogenetic analysis information in the Rubus genus compared to previous studies. The genome information reported in this paper will provide some useful information for further investigation on the evolution of the family Rosaceae.

Functional differentiation determines the molecular basis of the symbiotic lifestyle of Ca. Nanohaloarchaeota.

BACKGROUND: Candidatus Nanohaloarchaeota, an archaeal phylum within the DPANN superphylum, is characterized by limited metabolic capabilities and limited phylogenetic diversity and until recently has been considered to exclusively inhabit hypersaline environments due to an obligate association with Halobacteria. Aside from hypersaline environments, Ca. Nanohaloarchaeota can also have been discovered from deep-subsurface marine sediments. RESULTS: Three metagenome-assembled genomes (MAGs) representing a new order within the Ca. Nanohaloarchaeota were reconstructed from a stratified salt crust and proposed to represent a novel order, Nucleotidisoterales. Genomic features reveal them to be anaerobes capable of catabolizing nucleotides by coupling nucleotide salvage pathways with lower glycolysis to yield free energy. Comparative genomics demonstrated that these and other Ca. Nanohaloarchaeota inhabiting saline habitats use a "salt-in" strategy to maintain osmotic pressure based on the high proportion of acidic amino acids. In contrast, previously described Ca. Nanohaloarchaeota MAGs from geothermal environments were enriched with basic amino acids to counter heat stress. Evolutionary history reconstruction revealed that functional differentiation of energy conservation strategies drove diversification within Ca. Nanohaloarchaeota, further leading to shifts in the catabolic strategy from nucleotide degradation within deeper lineages to polysaccharide degradation within shallow lineages. CONCLUSIONS: This study provides deeper insight into the ecological functions and evolution of the expanded phylum Ca. Nanohaloarchaeota and further advances our understanding on the functional and genetic associations between potential symbionts and hosts. Video Abstract.

A common whole-genome paleotetraploidization in Cucurbitales.

Cucurbitales are an important order of flowering plants known for encompassing edible plants of economic and medicinal value and numerous ornamental plants of horticultural value. By reanalyzing the genomes of two representative families (Cucurbitaceae and Begoniaceae) in Cucurbitales, we found that the previously identified Cucurbitaceae common paleotetraploidization that occurred shortly after the core-eudicot-common hexaploidization event is shared by Cucurbitales, including Begoniaceae. We built a multigenome alignment framework for Cucurbitales by identifying orthologs and paralogs and systematically redating key evolutionary events in Cucurbitales. Notably, characterizing the gene retention levels and genomic fractionation patterns between subgenomes generated from different polyploidizations in Cucurbitales suggested the autopolyploid nature of the Begoniaceae common tetraploidization and the allopolyploid nature of the Cucurbitales common tetraploidization and the Cucurbita-specific tetraploidization. Moreover, we constructed the ancestral Cucurbitales karyotype comprising 17 proto-chromosomes, confirming that the most recent common ancestor of Cucurbitaceae contained 15 proto-chromosomes and rejecting the previous hypothesis for an ancestral Cucurbitaceae karyotype with 12 proto-chromosomes. In addition, we found that the polyploidization and tandem duplication events promoted the expansion of gene families involved in the cucurbitacin biosynthesis pathway; however, gene loss and chromosomal rearrangements likely limited the expansion of these gene families.

Structural and functional dysbiosis of gut microbiota in Tibetan subjects with coronary heart disease.

The gut microbiota plays a crucial role in coronary heart disease (CHD). However, only a few studies focusing on the relationship between gut microbiota and CHD in ethnic populations are available. Here, we employed shotgun sequencing of the gut metagenome to analyze the taxonomic composition and functional annotation of the gut microbiota of 14 CHD patients, 13 patients with non-stenosis coronary heart disease (NCHD), and 18 healthy controls (HT) in Tibetan subjects. We found that the α-diversity of the gut microbiota was not significantly different among the three groups., whereas ß-diversity was significantly altered in the CHD group compared with HT. Based on the receiver operating characteristic curve (ROC) analysis, the relative abundance of Proteobacteria species effectively distinguished patients with CHD from the control group. Most of the enriched species belonged to Proteobacteria. The pathways that contributed the most to the differences between groups were amino acid metabolism-related pathways, especially lysine biosynthesis. The enzymes of the lysine biosynthesis pathway, including K01714 and K00821, were significantly decreased in the CHD group. Our findings increase the understanding of the association between CHD pathogenesis and gut microbiota in the Tibetan population, thus paving the way for the development of improved diagnostic methods and treatments for Tibetan patients with CHD.

Protective Effect of Galangin Methylation Modification Based on Cell Imaging on Inflammatory Lung Injury and Its Molecular Mechanism.

Background: Recently, inflammation has become a major threat to human health. Studies have confirmed that some Chinese traditional medicine ingredients may effectively interfere with the expression of inflammatory mediators through epigenetic modification, showing a great potential of the application. Objective: To investigate the role of the PPAR/DNMT3A pathway in the reversal of galangin-mediated inflammatory lung injury, promote the development of new anti-inflammatory drugs, reduce the side effects of chemical synthetic drugs on the body, and prove the effectiveness and safety of galangin in inhibiting inflammatory response and injury. Methods: 120 rats were randomly divided into 6 groups: (Group 1) LPS group; (Group 2) LPS + galangin group; (Group 3) LPS + galangin + GW9662 group; (Group 4) LPS + galangin + DNMT3A siRNA group; (Group 5) LPS + galangin + siRNA negative group; (Group 6) control group. The model of inflammatory lung injury was established by intrathecal instillation of LPS in the first five groups and NS in the control group. SD survival rate was recorded every 24 hours after modeling, lasting for 168 hours. The lung tissues were taken 168 hours after the establishment of the model. The pathological morphology of lung tissue was observed after the staining under the light microscope, and the lung dry/wet weight ratio was calculated after drying. After NS was perfused into lung tissue, the lavage fluid was collected and the levels of IL-6 and TNF-a were measured by ELISA. The contents of PPAR, DNMT3A, phosphorylated p65, and ERK in monocytes were detected by the WB method, and the binding contents of p65 and AP-1 in the promoter regions of IL-6 and TNF-a genes were detected by the Chip-qPCR method. Results: Intraperitoneal injection of galangin could inhibit the synthesis of alveolar inflammatory factors (TFs) in the SD model of lung injury induced by LPS, reduce the degree of pathological injury of lung tissue, and improve the survival rate of the SD model. GW9662 can completely reverse the protective effect, while DNMT3A interference can only partially block its protective effect. In addition, galangin could significantly inhibit the LPS-induced expression of p65 and AP-1 in alveolar monocytes and their binding content in the promoter region of inflammatory genes by activating PPAR/DNMT3A pathway. GW9662 could completely reverse the inhibitory effect of galangin. DNMT3A interference could restore the binding content of transcription factors at the promoter of the inflammatory gene but had no significant effect on its synthesis. Conclusion: Galangin can interfere with the binding of transcription factors to inflammatory gene promoters through the methylation modification induced by PPAR/DNMT3A pathway, so as to inhibit the synthesis of inflammatory molecules and reverse inflammatory lung injury.

Genome-Wide Analysis of the NAC Family Associated with Two Paleohexaploidization Events in the Tomato.

NAC transcription factors play an important regulatory role in tomato fruit ripening. We chose a novel perspective to explore the traces left by two paleopolyploidizations in the NAC family using a bioinformatics approach. We found that 85 (S. lycopersicum) and 88 (S. pennellii) members of the NAC family were present in two tomatoes, and most of them were amplified from two paleohexaploidizations. We differentiated NAC family members from the different paleohexaploidizations and found that the SWGT-derived NAC genes had more rearrangement events, so it was different from the DWGT-derived NAC genes in terms of physicochemical properties, phylogeny, and gene location. The results of selection pressure show that DWGT-derived NAC genes tended to be positively selected in S. lycopersicum and negatively selected in S. pennellii. A comprehensive analysis of paleopolyploidization and expression reveals that DWGT-derived NAC genes tend to promote fruit ripening, and are expressed at the early and middle stages, whereas SWGT-derived NAC genes tend to terminate fruit growth and are expressed at the late stages of fruit ripening. This study obtained NAC genes from different sources that can be used as materials for tomato fruit development, and the method in the study can be extended to the study of other plants.

GGDB: A Grameneae genome alignment database of homologous genes hierarchically related to evolutionary events.

The genomes of Gramineae plants have been preferentially sequenced owing to their economic value. These genomes are often quite complex, for example harboring many duplicated genes, and are the main source of genetic innovation and often the result of recurrent polyploidization. Deciphering these complex genome structures and linking duplicated genes to specific polyploidization events are important for understanding the biology and evolution of plants. However, efforts have been hampered by the complexity of analyzing these genomes. Here, we analyzed 29 well-assembled and up-to-date Gramineae genome sequences by hierarchically relating duplicated genes in collinear regions to specific polyploidization or speciation events. We separated duplicated genes produced by each event, established lists of paralogous and orthologous genes, and ultimately constructed an online database, GGDB (http://www.grassgenome.com/). Homologous gene lists from each plant and between plants can be displayed, searched, and downloaded from the database. Interactive comparison tools are deployed to demonstrate homology among user-selected plants and to draw genome-scale or local alignment figures and gene-based phylogenetic trees corrected by exploiting gene collinearity. Using these tools and figures, users can easily detect structural changes in genomes and explore the effects of paleo-polyploidy on crop genome structure and function. The GGDB will provide a useful platform for improving our understanding of genome changes and functional innovation in Gramineae plants.

Hydroxy-safflower yellow A composites: An effective strategy to enhance anti-myocardial ischemia by improving intestinal permeability.

Hydroxy-safflower yellow A (HSYA) is the chief component of safflower against myocardial ischemia (MI), and belongs to biopharmaceutics classification system (BCS) III drugs. Its structure contains multiple hydroxyl groups, contributing to its high polarity and poor oral bioavailability. The main objective of this study was to probe the potential of oral penetration enhancer n-[8-(2-hydroxybenzoyl) amino] sodium octanoate (SNAC) and cationic copolymer Eudragit®EPO (EPO) to promote absorption of HSYA. HSYA composites (SNAC-HSYA-EPO) were formed by hydrogen bonding and van der Waals force. SNAC-HSYA-EPO has biocompatibility, and can improve the membrane fluidity, uptake, transport, and penetration of Caco-2 cells. The mechanism of promoting of SNAC-HSYA-EPO may be related to energy and P-glycoprotein (P-gp) when compared with the inhibitor NaN3 and verapamil group. In the pharmacokinetic (PK) results, SNAC-HSYA-EPO significantly improved oral bioavailability. Pharmacodynamics (PD) results determined that SNAC-HSYA-EPO could improve the symptoms of MI. The mechanism of the SNAC-HSYA-EPO anti-MI is related to alleviating inflammation and anti-apoptosis to protect the heart. In summary, SNAC-HSYA-EPO prepared in this study possessed a complete appearance, high recombination rate and excellent oral permeability promoting ability. SNAC-HSYA-EPO has the potential to improve oral bioavailability and further enhance the anti-MI effect of HSYA.