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.
Background:
Epithelial-mesenchymal transition (EMT) is a critical process in tumor invasion and metastasis. EMT has been shown to significantly influence the invasion, metastasis, and poor prognosis ...in lung adenocarcinoma (LUAD). This study aimed to develop a novel EMT-related prognostic model capable of predicting overall survival (OS) in patients with LUAD.
Methods:
A total of
283
LUAD patients from TCGA RNA-seq dataset were assigned to a training cohort for model building, and 310 LUAD patients from GEO RNA-seq dataset were assigned to a validation cohort. EMT genes were acquired from MsigDB database and then prognosis-related EMT genes were identified by univariate Cox regression. Lasso regression was then performed to determine the genes and the corresponding variables to construct a prognosis risk model from the training cohort. Furthermore, characteristics of the tumor microenvironment (TME), mutation status and chemotherapy responses were analyzed to assess the differences between the two risk groups based on the prognostic model. In addition, RT-qPCR was employed to validate the expression patterns of the 6 genes derived from the risk model.
Results:
A six-gene EMT signature (PMEPA1, LOXL2, PLOD2, MMP14, SPOCK1 and DCN) was successfully constructed and validated. The signature assigned the LUAD patients into high-risk and low-risk groups. In comparison with the low-risk group, patients in the high-risk group had a significantly lower survival rate. ROC curves and calibration curves for the risk model demonstrated reliable stratification and predictive ability. The risk model was robustly correlated with multiple TME characteristics. Besides, the data showed that patients in the low-risk group had more immune activities, higher stemness scores and cytolytic activity scores and higher TMB. In addition, RT-qPCR results revealed that PMEPA1, LOXL2, PLOD2, MMP14, and SPOCK1 were notably upregulated in LUAD tissues, while DCN was downregulated.
Conclusion:
Our study successfully developed a novel EMT-related signature to predict prognosis of LUAD patients and guide treatment strategies. The six genes derived from the prediction signature might play a potential role in antitumor immunity and serve as promising therapeutic targets in LUAD.
Intrahepatic cholangiocarcinoma (ICC) with lymph node metastasis has a poor clinical prognosis. Comprehensive surgical treatment based on surgery is critical for improving the prognosis. Conversion ...therapy provides an opportunity for radical surgery in such patients but also increases the difficulty of surgery. The technical barrier to laparoscopic lymph node dissection is determining the extent of regional lymph node dissection after conversion therapy and formulating a suitable procedure to ensure the quality of lymph node dissection and oncological safety. One patient with initially unresectable left ICC underwent successful conversion therapy at another hospital. Then, we performed laparoscopic left hemihepatectomy with middle hepatic vein resection and regional lymph node dissection. Specific surgical techniques are used to reduce injury and bleeding, ultimately reducing the incidence of complications and promoting rapid recovery of patients. No postoperative complications were noted. The patient recovered well; no tumor recurrence was observed during the follow-up. Preoperatively planned regional lymph node dissection provides a reference for exploring the standard laparoscopic surgical treatment of ICC. Procedural regional lymph node dissection and artery protection techniques ensure quality and oncological safety in lymph node dissection. When selecting appropriate cases, as long as the laparoscopic surgical technique is mastered, laparoscopic surgery is safe and feasible with faster postoperative recovery and less trauma for left ICC.
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•Compounds 1–4 were isolated from Aspergillus cristatus.•Compound 1 is the first bicyclo2.2.2 diazaoctane indole alkaloid where the diketopiperazine structure is constructed from ...tryptophan and alanine.•Compound 4 exhibited moderate antibacterial activities against Bacillus subtilis and Staphylococcus aureus.
Three new indole diketopiperazine alkaloids, aspergillines A-C (1–3), together with one new polyketide, aspergillone A (4), were isolated from the solid cultures of an endophytic fungus Aspergillus cristatus. Aspergilline A is the first bicyclo2.2.2 diazaoctane indole alkaloid where the diketopiperazine structure is constructed from tryptophan and alanine. The structures were determined by spectroscopic analysis and their absolute configurations were determined through single-crystal X-ray diffraction and electronic circular dichroism (ECD) spectroscopy. Aspergillone A exhibited moderate antibacterial activities against Bacillus subtilis and Staphylococcus aureus with MIC50 values of 8.5 and 32.2 μg/mL, respectively.
TSP and 9-stage size-segregated samples were simultaneously collected in Xi'an during the spring of 2013 and analyzed for organic aerosols (OA) on a molecular level. n-Alkanes were the dominant ...compound class during the whole campaign, followed by fatty acids. High molecular weight (HMW) n-alkanes and fatty acids dominated in the coarse mode particles (>1.1 μm) during the dust event, indicating they were mostly originated from surface soil and plants in the upwind regions. Low-volatile anthropogenic compounds such as benzo(e)pyrene (BeP) and bisphenol A (BPA) dominated in the fine mode particles during the whole campaign. In contrast, semi-volatile anthropogenic compounds such as phenanthrene (Phe) and di-n-butyl phthalates (DBP) showed a bimodal size distribution with a significant increase in the coarse mode during the dust event due to their vaporization from the fine mode particles and the subsequent adsorption on the dust surface. Secondary organic aerosols (SOA) in Xi'an during the dust storm period were predominantly enriched on the coarse particles, which can be ascribed to the adsorption and subsequent oxidation of gas-phase hydrophilic organics on the aqueous-phase of hygroscopic dust surface (e.g., mirabilite). Our work suggested an important role of multiphase reaction in evolution of aerosol chemistry during the dust long-range transport process.
•n-Alkanes were the dominant organic compound class during the whole campaign.•Low-volatile anthropogenic compounds dominated in the fine mode particles.•SOA were predominantly enriched on the coarse particles during the dust storm.•Multiphase reaction has an important role in evolution of aerosol chemistry.
Polo-like kinase 4 (PLK4), a key regulator of centriole biogenesis, is frequently overexpressed in cancer cells. However, roles and the mechanism of PLK4 in the leukemiagenesis of acute myeloid ...leukemia (AML) remain unclear. In this study, the PLK4 inhibitor Centrinone and the shRNA knockdown were used to investigate roles and the mechanism of PLK4 in the leukemiagenesis of AML. Our results indicated that Centrinone inhibited the proliferation of AML cells in a dose- and time-dependent manner
via
reduced the expression of PLK4 both in the protein and mRNA levels. Moreover, colony formation assay revealed that Centrinone reduced the number and the size of the AML colonies. Centrinone induced AML cell apoptosis by increasing the activation of Caspase-3/poly ADP-ribose polymerase (PARP). Notably, Centrinone caused the G2/M phase cell cycle arrest by decreasing the expression of cell cycle-related proteins such as Cyclin A2, Cyclin B1, and Cyclin-dependent kinase 1 (CDK1). Consistent with above results, knockdown the expression of PLK4 also inhibited cell proliferation and colony formation, induced cell apoptosis, and caused G2/M phase cell cycle arrest without affecting cell differentiation. All in all, this study suggested that PLK4 inhibited the progression of AML
in vitro
, and these results herein may provide clues in roles of PLK4 in the leukemiagenesis of AML.
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.
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.
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.
Purpose
FLT3 mutations occurred in approximately one third of patients with acute myeloid leukemia (AML). FLT3-ITD mutations caused the constitutive activation of the RAS/MAPK signaling pathway. ...Ribosomal S6 Kinases (RSKs) were serine/threonine kinases that function downstream of the Ras/Raf/MEK/ERK signaling pathway. However, roles and mechanisms of RSKs inhibitor LJH-685, and combinational effects of LJH-685 and FLT3 inhibitor FF-10101 on AML cells were till unclear.
Methods
Cell viability assay, CFSE assay, RT-qPCR, Colony formation assay, PI stain, Annexin-V/7-AAD double stain, Western blot, and Xenogeneic transplantation methods were used to used to investigate roles and mechanisms of LJH-685 in the leukemogenesis of AML.
Results
LJH-685 inhibited the proliferation and clone formation of AML cells, caused cell cycle arrest and induced the apoptosis of AML cells via inhibiting the RSK-YB-1 signaling pathway. MV4-11 and MOLM-13 cells carrying FLT3-ITD mutations were more sensitive to LJH-685 than that of other AML cell lines. Further studies suggested that LJH-685 combined with Daunorubicin or FF- 10101 synergistically inhibited the cell viability, promoted the apoptosis and caused cycle arrest of AML cells carrying FLT3-ITD mutations. Moreover, in vivo experiments also indicated that LJH-685 combined with FF-10101 or Daunorubicin prolonged the survival time of NSG mice and reduced the leukemogenesis of AML.
Conclusion
Thus, these observations demonstrated combination of RSK inhibitor LJH-685 and FLT3 inhibitor FF-10101 showed synergism anti-leukemia effects in AML cell lines with FLT3-ITD mutations via inhibiting MAPK-RSKs-YB-1 pathway and provided new targets for therapeutic intervention especially for AML with FLT3-ITD mutations and Daunorubicin-resistant AML.
Rapeseed(Brassica napus L.) is the main source of edible vegetable oil in China, and increasing seed oil content is the most effective way to increase the supply of rapeseed oil. In this study, 43 ...genes related to lipid synthesis were selected by analyzing the seed transcriptome data of 4 rapeseed inbred lines 25, 35, and 45 days after pollination. Among them, 33 genes were continuously up-expressed and 10 genes were continuously down-expressed from 25 to 45 days of seed development. The main genes included BnLEC1, BnABI5, Bn OLEO4, and BnOBAP1a. At the same time, combined with the resequencing data of 50semi-winter Brassica napus, 3 SNPs and 9 SNPs significantly related to oil content were detected to BnOBAP1a-A10 and BnABI5-A05, respectively, and the oil content of BnOBAP1A-A10__Hap1 was significantly higher than Hap2. The oil content of BnABI5-A05__Hap1 was significantly higher than Hap3. In addition, WGCNA was used to construct gene networks, and we found that BnOBAP1a and BnABI5 were indirectly connected
Atomic-scale oxidation dynamics of Cu2O nanocrystallines （NCs） are directly observed by in situ high-resolution transmission electron microscopy. A two-stage oxidation process is observed： （1）The ...initial oxidation stage is dominated by the dislocation-mediated oxidation behavior of Cu2O NCs via solid-solid transformations, leading to the formation of a new intermediate CuOx phase. The possible crystal structure of the CuOx phase is discussed. （2） Subsequently, CuOx is transformed into CuO by layer-by-layer oxidation. These results will help in understanding the oxidation mechanisms of copper oxides and pave the way for improving their structural diversity and exploiting their potential industrial applications.
