Enhancing Hi-C contact matrices for loop detection with Capricorn: a multiview diffusion model.

MOTIVATION: High-resolution Hi-C contact matrices reveal the detailed three-dimensional architecture of the genome, but high-coverage experimental Hi-C data are expensive to generate. Simultaneously, chromatin structure analyses struggle with extremely sparse contact matrices. To address this problem, computational methods to enhance low-coverage contact matrices have been developed, but existing methods are largely based on resolution enhancement methods for natural images and hence often employ models that do not distinguish between biologically meaningful contacts, such as loops and other stochastic contacts. RESULTS: We present Capricorn, a machine learning model for Hi-C resolution enhancement that incorporates small-scale chromatin features as additional views of the input Hi-C contact matrix and leverages a diffusion probability model backbone to generate a high-coverage matrix. We show that Capricorn outperforms the state of the art in a cross-cell-line setting, improving on existing methods by 17% in mean squared error and 26% in F1 score for chromatin loop identification from the generated high-coverage data. We also demonstrate that Capricorn performs well in the cross-chromosome setting and cross-chromosome, cross-cell-line setting, improving the downstream loop F1 score by 14% relative to existing methods. We further show that our multiview idea can also be used to improve several existing methods, HiCARN and HiCNN, indicating the wide applicability of this approach. Finally, we use DNA sequence to validate discovered loops and find that the fraction of CTCF-supported loops from Capricorn is similar to those identified from the high-coverage data. Capricorn is a powerful Hi-C resolution enhancement method that enables scientists to find chromatin features that cannot be identified in the low-coverage contact matrix. AVAILABILITY AND IMPLEMENTATION: Implementation of Capricorn and source code for reproducing all figures in this paper are available at https://github.com/CHNFTQ/Capricorn.

Identification of COQ2 as a regulator of proliferation and lipid peroxidation through genome-scale CRISPR-Cas9 screening in myeloma cells.

Multiple myeloma (MM) is the second most common malignant haematological disease with a poor prognosis. The limit therapeutic progress has been made in MM patients with cancer relapse, necessitating deeper research into the molecular mechanisms underlying its occurrence and development. A genome-wide CRISPR-Cas9 loss-of-function screening was utilized to identify potential therapeutic targets in our research. We revealed that COQ2 plays a crucial role in regulating MM cell proliferation and lipid peroxidation (LPO). Knockout of COQ2 inhibited cell proliferation, induced cell cycle arrest and reduced tumour growth in vivo. Mechanistically, COQ2 promoted the activation of the MEK/ERK cascade, which in turn stabilized and activated MYC protein. Moreover, we found that COQ2-deficient MM cells increased sensitivity to the LPO activator, RSL3. Using an inhibitor targeting COQ2 by 4-CBA enhanced the sensitivity to RSL3 in primary CD138+ myeloma cells and in a xenograft mouse model. Nevertheless, co-treatment of 4-CBA and RSL3 induced cell death in bortezomib-resistant MM cells. Together, our findings suggest that COQ2 promotes cell proliferation and tumour growth through the activation of the MEK/ERK/MYC axis and targeting COQ2 could enhance the sensitivity to ferroptosis in MM cells, which may be a promising therapeutic strategy for the treatment of MM patients.

A Bioinspired Single-Atom Fe Nanozyme with Excellent Laccase-Like Activity for Efficient Aflatoxin B1 Removal.

The applications of natural laccases are greatly restricted because of their drawbacks like poor biostability, high costs, and low recovery efficiency. M/NC single atom nanozymes (M/NC SAzymes) are presenting as great substitutes due to their superior enzyme-like activity, excellent selectivity and high stability. In this work, inspired by the catalytic active center of natural enzyme, a biomimetic Fe/NC SAzyme (Fe-SAzyme) with O2-Fe-N4 coordination is successfully developed, exhibiting excellent laccase-like activity. Compared with their natural counterpart, Fe-SAzyme has shown superior catalytic efficiency and excellent stability under a wide range of pH (3.0-9.0), temperature (4-80 °C) and NaCl strength (0-300 mm). Interestingly, density functional theory (DFT) calculations reveal that the high catalytic performance is attributed to the activation of O2 by O2-Fe-N4 sites, which weakened the O─O bonds in the oxygen-to-water oxidation pathway. Furthermore, Fe-SAzyme is successfully applied for efficient aflatoxin B1 removal based on its robust laccase-like catalytic activity. This work provides a strategy for the rational design of laccase-like SAzymes, and the proposed catalytic mechanism will help to understand the coordination environment effect of SAzymes on laccase-like catalytic processes.

Colloidal Synthesis of Carbon Dot-ZnSe Nanoplatelet Van der Waals Heterostructures for Boosting Photocatalytic Generation of Methanol-Storable Hydrogen.

Methanol is not only a promising liquid hydrogen carrier but also an important feedstock chemical for chemical synthesis. Catalyst design is vital for enabling the reactions to occur under ambient conditions. This study reports a new class of van der Waals heterojunction photocatalyst, which is synthesized by hot-injection method, whereby carbon dots (CDs) are grown in situ on ZnSe nanoplatelets (NPLs), i.e., metal chalcogenide quantum wells. The resultant organic-inorganic hybrid nanoparticles, CD-NPLs, are able to perform methanol dehydrogenation through CH splitting. The heterostructure has enabled light-induced charge transfer from the CDs into the NPLs occurring on a sub-nanosecond timescale, with charges remaining separated across the CD-NPLs heterostructure for longer than 500 ns. This resulted in significantly heightened H2 production rate of 107 µmole·g-1·h-1 and enhanced photocurrent density up to 34 µA cm-2 at 1 V bias potential. EPR and NMR analyses confirmed the occurrence of α-CH splitting and CC coupling. The novel CD-based organic-inorganic semiconductor heterojunction is poised to enable the discovery of a host of new nano-hybrid photocatalysts with full tunability in the band structure, charge transfer, and divergent surface chemistry for guiding photoredox pathways and accelerating reaction rates.

Wnt/ß-catenin signalling activates IMPDH2-mediated purine metabolism to facilitate oxaliplatin resistance by inhibiting caspase-dependent apoptosis in colorectal cancer.

BACKGROUND: Oxaliplatin resistance usually leads to therapeutic failure and poor prognosis in colorectal cancer (CRC), while the underlying mechanisms are not yet fully understood. Metabolic reprogramming is strongly linked to drug resistance, however, the role and mechanism of metabolic reprogramming in oxaliplatin resistance remain unclear. Here, we aim to explore the functions and mechanisms of purine metabolism on the oxaliplatin-induced apoptosis of CRC. METHODS: An oxaliplatin-resistant CRC cell line was generated, and untargeted metabolomics analysis was conducted. The inosine 5'-monophosphate dehydrogenase type II (IMPDH2) expression in CRC cell lines was determined by quantitative real-time polymerase chain reaction (qPCR) and western blotting analysis. The effects of IMPDH2 overexpression, knockdown and pharmacological inhibition on oxaliplatin resistance in CRC were assessed by flow cytometry analysis of cell apoptosis in vivo and in vitro. RESULTS: Metabolic analysis revealed that the levels of purine metabolites, especially guanosine monophosphate (GMP), were markedly elevated in oxaliplatin-resistant CRC cells. The accumulation of purine metabolites mainly arose from the upregulation of IMPDH2 expression. Gene set enrichment analysis (GSEA) indicated high IMPDH2 expression in CRC correlates with PURINE_METABOLISM and MULTIPLE-DRUG-RESISTANCE pathways. CRC cells with higher IMPDH2 expression were more resistant to oxaliplatin-induced apoptosis. Overexpression of IMPDH2 in CRC cells resulted in reduced cell death upon treatment with oxaliplatin, whereas knockdown of IMPDH2 led to increased sensitivity to oxaliplatin through influencing the activation of the Caspase 7/8/9 and PARP1 proteins on cell apoptosis. Targeted inhibition of IMPDH2 by mycophenolic acid (MPA) or mycophenolate mofetil (MMF) enhanced cell apoptosis in vitro and decreased in vivo tumour burden when combined with oxaliplatin treatment. Mechanistically, the Wnt/ß-catenin signalling was hyperactivated in oxaliplatin-resistant CRC cells, and a reciprocal positive regulatory mechanism existed between Wnt/ß-catenin and IMPDH2. Blocking the Wnt/ß-catenin pathway could resensitize resistant cells to oxaliplatin, which could be restored by the addition of GMP. CONCLUSIONS: IMPDH2 is a predictive biomarker and therapeutic target for oxaliplatin resistance in CRC.

Experimental Demonstration of Input-Output Indefiniteness in a Single Quantum Device.

Quantum theory allows information to flow through a single device in a coherent superposition of two opposite directions, resulting into situations where the input-output direction is indefinite. Here we introduce a theoretical method to witness input-output indefiniteness in a single quantum device, and we experimentally demonstrate it by constructing a photonic setup that exhibits input-output indefiniteness with a statistical significance exceeding 69 standard deviations. Our results provide a way to characterize input-output indefiniteness as a resource for quantum information and photonic quantum technologies and enable tabletop simulations of hypothetical scenarios exhibiting quantum indefiniteness in the direction of time.

Unlocking a Type-II CoO@BiVO4 Heterostructure for Wastewater Purification.

Developing a semiconductor-based heterostructure photoanode is crucial in improving the photoelectrocatalytic (PEC) efficiency for degrading refractory organic pollutants. Nevertheless, the PEC performance of the photoanodes is usually restricted by electron/hole pair recombination, oxygen evolution, and slow electron transfer. Herein, a novel CoO@BiVO4 nanowire array film (Ti/CoO@BiVO4) with n-type semiconductor characteristics was prepared via a straightforward hydrothermal method. The optimized Ti/CoO@BiVO4 electrode exhibited excellent PEC decolorization efficiency of active brilliant blue KN-R (∼92.8%) and long-term stability, outperforming recent reports. The insight reason for enhancing the PEC degradation efficiency of the Ti/CoO@BiVO4 electrodes can be attributed to the large electrochemical active area, low charge transfer resistance, and negative flat band potential. The formation of a type-II heterostructure was investigated between CoO and BiVO4 further to promote the generation and separation efficiency of electron/hole pairs, indicating that the optimized Ti/CoO@BiVO4 electrode has the potential for the water PEC degradation ability and superior service life.

Mno-miR164a and MnNAC100 regulate the resistance of mulberry to Botrytis cinerea.

Although microRNAs (miRNAs) regulate the defense response of a variety of plant species against a variety of pathogenic fungi, the involvement of miRNAs in mulberry's defense against Botrytis cinerea has not yet been documented. In this study, we identified responsive B. cinerea miRNA mno-miR164a in mulberry trees. After infection with B. cinerea, the expression of mno-miR164a was reduced, which was fully correlated with the upregulation of its target gene, MnNAC100, responsible for encoding a transcription factor. By using transient infiltration/VIGS mulberry that overexpressed mno-miR164a or knocked-down MnNAC100, our study revealed a substantial enhancement in mulberry's resistance to B. cinerea when mno-miR164a was overexpressed or MnNAC100 expression was suppressed. This enhancement was accompanied by increased catalase (CAT) activity and reduced malondialdehyde (MDA) content. In addition, mno-miR164a-mediated inhibition of MnNAC100 enhanced the expression of a cluster of defense-related genes in transgenic plants upon exposure to B. cinerea. Meanwhile, MnNAC100 acts as a transcriptional repressor, directly suppressing the expression of MnPDF1.2. Our study indicated that the mno-miR164a-MnNAC100 regulatory module manipulates the defense response of mulberry to B. cinerea infection. This discovery has great potential in breeding of resistant varieties and disease control.

Exclusive Coordination between Melem and Silver(I) Ions: From Irregular Aggregates to Nanofibers to Crystal Cubes.

There is growing focus on metal-free molecules and polymers owing to their potential applications in various energy and catalysis-related applications. Melem (2,5,8-triamino-s-heptazine, C6H6N10) has emerged as a metal-free material for solar-to-fuel conversion. However, its reactivity with metal ions or organic molecules has never been reported although it possesses multiple supramolecular interaction sites. In this work, we report on the synthesis of a novel metal-organic coordination framework (melem-Ag) by simply introducing Ag+ into the aqueous suspension of aggregated melem particles. Notably, as the reaction progresses, the melem disappears, and the morphology of the newly formed complex spontaneously evolves from nanofibers to single-crystalline blocks, which possess the same chemical structure, indicating that the morphology evolution is driven by Ostwald ripening. The structure of melem-Ag displays infinite nanocages of triangular pyramids consisting of melem molecules and Ag+, linked via Ag-N coordinate bonding and Ag-Ag argentophilic interactions. It is noteworthy that Ag+ is the only transition-metal cation that reacts with melem suspensions, even in the presence of other transition-metal cations (Co2+, Ni2+, Cu2+, and Zn2+). The coordination of Ag+ to melem results in metal-to-ligand charge transfer (MLCT), resulting in a quenched photoluminescence and enhanced light absorption. Exposing the melem-Ag crystals to UV light for varying time intervals results in the formation of colorful powders, which may be used for Ag-decorated photocatalysts.

Occurrence, distribution, and ecological risk assessment of pharmaceuticals and personal care products in the surface water of Lipu River, China.

Pharmaceuticals and Personal Care Products (PPCPs) are inadvertently released into the aquatic environment, causing detrimental effects on aquatic ecosystem. There is an urgent need of an in-deep investigation on contamination information of PPCPs in aquatic environment as well as the ecological risks to the aquatic ecosystem. This study was carried out in Lipu River basin, China, to investigate the distribution pattern and ecological risks of PPCPs. Results showed that PPCPs pollution is ubiquitous, 29 out of 30 targeted PPCPs were detected in Lipu River. Fourteen PPCPs were detected with a frequency of 100% in all water samples, and ten PPCPs were detected with a frequency of more than 80%. The cumulated PPCPs concentrations ranged from 33.30 ng/L to 99.60 ng/L, with a median value of 47.20 ng/L in Lipu River. Caffeine, flumequine, nifedipine, and lomefloxacin were the predominant PPCPs in study area. Caffeine showed high ecological risk, five and seven individual PPCP showed medium and low ecological risk to algae.

Serum apolipoprotein A-I depletion is causative to silica nanoparticles-induced cardiovascular damage.

The rapid development of nanotechnology has greatly benefited modern science and engineering and also led to an increased environmental exposure to nanoparticles (NPs). While recent research has established a correlation between the exposure of NPs and cardiovascular diseases, the intrinsic mechanisms of such a connection remain unclear. Inhaled NPs can penetrate the air-blood barrier from the lung to systemic circulation, thereby intruding the cardiovascular system and generating cardiotoxic effects. In this study, on-site cardiovascular damage was observed in mice upon respiratory exposure of silica nanoparticles (SiNPs), and the corresponding mechanism was investigated by focusing on the interaction of SiNPs and their encountered biomacromolecules en route. SiNPs were found to collect a significant amount of apolipoprotein A-I (Apo A-I) from the blood, in particular when the SiNPs were preadsorbed with pulmonary surfactants. While the adsorbed Apo A-I ameliorated the cytotoxic and proinflammatory effects of SiNPs, the protein was eliminated from the blood upon clearance of the NPs. However, supplementation of Apo A-I mimic peptide mitigated the atherosclerotic lesion induced by SiNPs. In addition, we found a further declined plasma Apo A-I level in clinical silicosis patients than coronary heart disease patients, suggesting clearance of SiNPs sequestered Apo A-I to compromise the coronal protein's regular biological functions. Together, this study has provided evidence that the protein corona of SiNPs acquired in the blood depletes Apo A-I, a biomarker for prediction of cardiovascular diseases, which gives rise to unexpected toxic effects of the nanoparticles.

DNA demethylase TET2-mediated reduction of HADHB expression contributes to cadmium-induced malignant progression of colorectal cancer.

Environmental exposure to the cadmium (Cd) has been shown to be a risk factor for colorectal cancer (CRC) progression, but the exact mechanism has not been fully elucidated. In this study, we found that chronic Cd (3 µM) exposure promoted the proliferation, adhesion, migration, and invasion of CRC cells in vitro, as well as lung metastasis in vivo. RNA-seq and TCGA-COAD datasets revealed that decreased hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta (HADHB) expression may be a crucial factor in Cd-induced CRC progression. Further analysis using qRT-PCR and tissue microarrays from CRC patients showed that HADHB expression was significantly reduced in CRC tissues compared to adjacent normal tissues, and low HADHB expression was associated with adverse clinical features and poor overall survival, either directly or through TNM stage. Furthermore, HADHB was found to play an important role in the Cd-induced malignant metastatic phenotype of CRC cells and lung metastasis in mice. Mechanistically, we discovered that chronic Cd exposure resulted in hypermethylation of the HADHB promoter region via inhibition of DNA demethylase tet methylcytosine dioxygenase 2 (TET2), which then led to decreased HADHB expression and activation of the FAK signaling pathway, and ultimately contributed to CRC progression. In conclusion, this study provided a new potential insight and evaluable biomarker for Cd exposure-induced CRC progression and treatment.

The Microtubule End Binding Protein Mal3 Is Essential for the Dynamic Assembly of Microtubules during Magnaporthe oryzae Growth and Pathogenesis.

Cytoskeletal microtubules (MTs) play crucial roles in many aspects of life processes in eukaryotic organisms. They dynamically assemble physiologically important MT arrays under different cell conditions. Currently, aspects of MT assembly underlying the development and pathogenesis of the model plant pathogenic fungus Magnaporthe oryzae (M. oryzae) are unclear. In this study, we characterized the MT plus end binding protein MoMal3 in M. oryzae. We found that knockout of MoMal3 results in defects in hyphal polar growth, appressorium-mediated host penetration and nucleus division. Using high-resolution live-cell imaging, we further found that the MoMal3 mutant assembled a rigid MT in parallel with the MT during hyphal polar growth, the cage-like network in the appressorium and the stick-like spindle in nuclear division. These aberrant MT organization patterns in the MoMal3 mutant impaired actin-based cell growth and host infection. Taken together, these findings showed that M. oryzae relies on MoMal3 to assemble elaborate MT arrays for growth and infection. The results also revealed the assembly mode of MTs in M. oryzae, indicating that MTs are pivotal for M. oryzae growth and host infection and may be new targets for devastating fungus control.

Inactivation of pathogenic microorganisms in water by electron beam excitation multi-wavelength ultraviolet irradiation: Efficiency, influence factors and mechanism.

Due to the limitations of traditional ultraviolet (UV) in microbial inactivation in water, it is necessary to explore a more suitable and efficient UV disinfection method. In this study, an electron beam excitation multi-wavelength ultraviolet (EBE-MW-UV) system was established and aims to analyze its differential microbial inactivation capabilities in comparison to single-wavelength UV-LEDs in waterborne applications. Furthermore, the inactivation mechanisms of this system on microorganisms were explored. The results showed that EBE-MW-UV had significantly higher inactivation effects on the Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis and Candida albicans in water compared to UV-LEDs (p＜0.05), and the inactivation effect of EBE-MW-UV on Escherichia coli and Pseudomonas aeruginosa at the same UV dose was 3.8 and 1.9 log higher than that of UV-LEDs, respectively, EBE-MW-UV exhibited better inactivation effects on Gram-negative bacteria. Further research found that, under the majority of irradiation doses, neither EBE-MW-UV nor UV-LEDs were significantly affected by the concentration of suspended solids (5 and 20 mg/L) or humic acids (2 and 5 mg/L) in the water. Mechanism analysis revealed that during the disinfection process of EBE-MW-UV, microbial DNA and proteins were initially damaged, which prevented the occurrence of dark repair and led to bacterial inactivation. In addition, UV irradiation led to the production of additional reactive oxygen species (ROS) inside the cells, increasing cell membrane permeability and exacerbating membrane damage. This was accompanied by a decrease in energy metabolism and depletion of ATP, ultimately resulting in microbial inactivation. Therefore, EBE-MW-UV demonstrated more effective disinfection than single-wavelength UV-LEDs, showing great potential. Our research gives new insights into the characteristics of multiple wavelength ultraviolet, and provides scientific basis for the selection of new light sources in the field of ultraviolet disinfection.

Effects of Central Metal Ion on Binuclear Metal Phthalocyanine-Based Redox Mediator for Lithium Carbonate Decomposition.

Li2CO3 is the most tenacious parasitic solid-state product in lithium-air batteries (LABs). Developing suitable redox mediators (RMs) is an efficient way to address the Li2CO3 issue, but only a few RMs have been investigated to date, and their mechanism of action also remains elusive. Herein, we investigate the effects of the central metal ion in binuclear metal phthalocyanines on the catalysis of Li2CO3 decomposition, namely binuclear cobalt phthalocyanine (bi-CoPc) and binuclear cobalt manganese phthalocyanine (bi-CoMnPc). Density functional theory (DFT) calculations indicate that the key intermediate peroxydicarbonate (*C2O62-) is stabilized by bi-CoPc2+ and bi-CoMnPc3+, which is accountable for their excellent catalytic effects. With one central metal ion substituted by manganese for cobalt, the bi-CoMnPc's second active redox couple shifts from the second Co(II)/Co(III) couple in the central metal ion to the Pc(-2)/Pc(-1) couple in the phthalocyanine ring. In artificial dry air (N2-O2, 78:22, v/v), the LAB cell with bi-CoMnPc in electrolyte exhibited 261 cycles under a fixed capacity of 500 mAh g-1carbon and current density of 100 mA g-1carbon, significantly better than the RM-free cell (62 cycles) and the cell with bi-CoPc (193 cycles).

Secondary Atomization and Micro-Explosion Effect Induced by Surfactant and Nanoparticles on Enhancing the Combustion Performance of Al/JP-10/OA Nanofluid Fuel.

Aluminum/tetrahydrodicyclopentadiene/oleic acid (Al/JP-10/OA) nanofluid fuel is considered a potential fuel for aircraft powered by aviation turbine engines. However, an optimized formula for an Al/JP-10/OA system inducing a secondary atomization and micro-explosion effect and improving the burning performance needs to be developed. With this aim, in this work, the combustion characteristics of pure JP-10, JP-10/OA, JP-10/Al, and Al/JP-10/OA were experimentally tested, and a comparative analysis was conducted. Specifically, the influence of the surfactant and nanoparticle concentrations on the combustion characteristics of Al/JP-10/OA nanofluid fuel, including the flame structure, the flame temperature, the burning rate, the secondary atomization and micro-explosion effect, etc., were evaluated in detail. The results demonstrate that the addition of OA surfactant and Al nanoparticles had a significant effect on the burning rate of fuel droplets. The OA had an inhibition effect, while the Al nanoparticles had a promotion effect. As both OA and Al nanoparticles were added to the JP-10, the synergetic effect had to be considered. At the optimum ratio of OA to Al for the best suspension stability, there is a critical Al concentration of 1.0 wt.% from promotion to inhibition with increases in the Al concentration. The addition of OA and Al nanoparticles induced the secondary atomization and micro-explosion, resulting in an unsteady combustion and chaotic flame structure. The transient flame temperature of hundreds of Kelvins increased, the high-temperature flame zone widened, and thus, the energy release was elevated. Therefore, the combustion performance and energy release of Al/JP-10/OA nanofluid fuel can be improved through the secondary atomization and micro-explosion effect induced by the surfactant and nanoparticles.

The actin motor protein OsMYA1 associates with OsExo70H1 and contributes to rice secretory defense by modulating OsSyp121 distribution.

Magnaporthe oryzae (M. oryzae) is a devastating hemibiotrophic pathogen. Its biotrophic invasive hyphae (IH) are enclosed in the extrainvasive hyphal membrane produced by plant cells, thus generating a front line of the battlefield between the pathogen and the host plants. In plants, defense-related complexes such as proteins, callose-rich materials and vesicles, are directionally secreted to this interface to confer defense responses, but the underlying molecular mechanism is poorly understood. In this study, we found that a Myosin gene, Myosin A1 (OsMYA1), contributed to rice defense. The OsMYA1 knockout mutant exhibited decreased resistance to M. oryzae infection. OsMYA1 localizes to the actin cytoskeleton and surrounds the IH of M. oryzae. OsMYA1 interacts with an exocyst subunit, OsExo70H1, and regulates its accumulation at the plasma membrane (PM) and pathogen-plant interface. Furthermore, OsExo70H1 interacted with the rice syntaxin of the plants121 protein (OsSyp121), and the distribution of OsSyp121 to the PM or the pathogen-plant interface was disrupted in both the OsMYA1 and OsExo70H1 mutants. Overall, these results not only reveal a new function of OsMYA1 in rice blast resistance, but also uncover a molecular mechanism by which plants regulate defense against M. oryzae by OsMYA1-initiated vesicle secretory pathway, which originates from the actin cytoskeleton to the PM.

The genome of a vestimentiferan tubeworm (Ridgeia piscesae) provides insights into its adaptation to a deep-sea environment.

BACKGROUND: Vestimentifera (Polychaeta, Siboglinidae) is a taxon of deep-sea worm-like animals living in deep-sea hydrothermal vents, cold seeps, and organic falls. The morphology and lifespan of Ridgeia piscesae, which is the only vestimentiferan tubeworm species found in the hydrothermal vents on the Juan de Fuca Ridge, vary greatly according to endemic environment. Recent analyses have revealed the genomic basis of adaptation in three vent- and seep-dwelling vestimentiferan tubeworms. However, the evolutionary history and mechanism of adaptation in R. piscesae, a unique species in the family Siboglinidae, remain to be investigated. RESULT: We assembled a draft genome of R. piscesae collected at the Cathedral vent of the Juan de Fuca Ridge. Comparative genomic analysis showed that vent-dwelling tubeworms with a higher growth rate had smaller genome sizes than seep-dwelling tubeworms that grew much slower. A strong positive correlation between repeat content and genome size but not intron size and the number of protein-coding genes was identified in these deep-sea tubeworm species. Evolutionary analysis revealed that Ridgeia pachyptila and R. piscesae, the two tubeworm species that are endemic to hydrothermal vents of the eastern Pacific, started to diverge between 28.5 and 35 million years ago. Four genes involved in cell proliferation were found to be subject to positive selection in the genome of R. piscesae. CONCLUSION: Ridgeia pachyptila and R. piscesae started to diverge after the formation of the Gorda/Juan de Fuca/Explorer ridge systems and the East Pacific Rise. The high growth rates of vent-dwelling tubeworms might be derived from their small genome sizes. Cell proliferation is important for regulating the growth rate in R. piscesae.

Transforming growth factor-ß receptor type 2 is required for heparin-binding protein-induced acute lung injury and vascular leakage for transforming growth factor-ß/Smad/Rho signaling pathway activation.

Heparin-binding protein (HBP), as a granule protein secreted by polymorphonuclear neutrophils, participates in the pathophysiological process of sepsis. It has been reported that HBP is a biomarker of sepsis related to the severity of septic shock and organ dysfunction. HBP binds to vascular endothelial cells as a primary target site. However, it is still unclear whether HBP-binding protein receptors exist on the surface of endothelial cells. The effect of HBP on vascular permeability in sepsis and its mechanism needs to be explored. We conducted in vivo and in vitro studies and demonstrated that HBP binds to transforming growth factor-ß receptor type 2 (TGF-ß-R2) as a ligand. Glutathione S-transferase pull-down analysis revealed that HBP mainly interacts with the extracellular domain of TGF-ß-R2. HBP induces acute lung injury and vascular leakage via activation of the TGF-ß/SMAD2/3 signaling pathway. A permeability assay suggested that TGF-ß-R2 is necessary for HBP-induced increased permeability. We also defined the role of HBP and its potential membrane receptor TGF-ß-R2 in the blood-gas barrier in the pathogenesis of HBP-related acute lung injury.

Parapedobacter tibetensis sp. nov., isolated from shore soil of saline lake in Tibet of China and its genome mining of secondary metabolite.

Five aerobic, Gram-stain-negative, non-motile, non-spore-forming, short rod bacteria strains, designated as C3-1-R+6T, C3-2-M9, B3-2-R-7, B3-2-R-21 and C3-2-M2, were isolated from shore soil of LungmuCo Lake in Tibet of China. The 16S rRNA gene sequence comparisons confirmed their affiliation to the genus Parapedobacter of the family Sphingobacteriaceae, and showed that they were most closely related to Parapedobacter lycopersici KACC 18788T with 94.26 % similarities. The average nucleotide identity (ANI), average amino acid identity (AAI) and digital DNA-DNA hybridization (dDDH) values between them and the validly published Parapedobacter species were all below the thresholds for delineating species, supporting that they were novel species of genus Parapedobacter. The ANI, AAI and dDDH values between strains C3-1-R+6T and Parapedobacter lycopersici KACC 18788T were 72, 75, and 18% respectively. Meanwhile, the ANI/AAI and dDDH values between these five isolates were higher than the threshold values, showing that they belonged to the same species of Parapedobacter. According to genome comparison, the novel isolates have some special biosynthetic gene clusters of secondary metabolites including bacteriton, aryl-polyene, lantipeptide and t1pks, which were absent from their most related phylogenetic neighbours P. lycopersici KACC 18788T and P. pyrenivorans CGMCC 1.12195T. The main polar lipids contained phosphatidylethanolamine, one unidentified phospholipid, one unidentified aminolipid, one unidentified glycolipid and five unidentified lipids. The predominant respiratory quinone was MK-7. The major cellular fatty acids were iso-C15 : 0, summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c) and iso-C17 : 0 3-OH. The genome size of strain C3-1-R+6T was 5 984 948 bp, and its genomic DNA G+C content was 46.21 mol%. To sum up, the five strains were identified as a novel species of the genus Parapedobacter, for which the name Parapedobacter tibetensis sp. nov. was proposed. The type strain was C3-1-R+6T (=CGMCC 1.19194T=KCTC 92150T).