LMP2 deficiency causes abnormal metabolism, oxidative stress, neuroinflammation, myelin loss and neurobehavioral dysfunctions.

BACKGROUND: Substantial evidence suggests that immunoproteasome is implicated in the various neurological diseases such as stroke, multiple sclerosis and neurodegenerative diseases. However, whether the immunoproteasome itself deficiency causes brain disease is still unclear. Therefore, the aim of this study was to explore the contribution of the immunoproteasome subunit low molecular weight protein 2 (LMP2) in neurobehavioral functions. METHODS: Male LMP2 gene completed knockout (LMP2-KO) and littermate wild type (WT) Sprague-Dawley (SD) rats aged 12-month-old were used for neurobehavioral testing and detection of proteins expression by western blotting and immunofluorescence. A battery of neurobehavioral test tools including Morris water maze (MWM), open field maze, elevated plus maze were used to evaluate the neurobehavioral changes in rats. Evans blue (EB) assay, Luxol fast blue (LFB) and Dihydroethidium (DHE) staining were applied to explore the blood-brain barrier (BBB) integrity, brain myelin damage and brain intracellular reactive oxygen species (ROS) levels, respectively. RESULTS: We firstly found that LMP2 gene deletion did not cause significantly difference in rats' daily feeding activity, growth and development as well as blood routine, but it led to metabolic abnormalities including higher levels of low-density lipoprotein cholesterol, uric acid and blood glucose in the LMP2-KO rats. Compared with the WT rats, LMP2-KO rats displayed obviously cognitive impairment and decreased exploratory activities, increased anxiety-like behavior and without strong effects on gross locomotor abilities. Furthermore, multiple myelin loss, increased BBB leakage, downregulation of tight junction proteins ZO-1, claudin-5 and occluding, and enhanced amyloid-ß protein deposition were observed in brain regions of LMP2-KO rats. In addition, LMP2 deficiency significantly enhanced oxidative stress with elevated levels of ROS, caused the reactivation of astrocytes and microglials and markedly upregulated protein expression levels of interleukin (IL)-1 receptor-associated kinase 1 (IRAK1), IL-6 and tumor necrosis factor-α (TNF-α) compared to the WT rats, respectively. CONCLUSION: These findings highlight LMP2 gene global deletion causes significant neurobehavioral dysfunctions. All these factors including metabolic abnormalities, multiple myelin loss, elevated levels of ROS, increased BBB leakage and enhanced amyloid-ß protein deposition maybe work together and eventually led to chronic oxidative stress and neuroinflammation response in the brain regions of LMP2-KO rats, which contributed to the initial and progress of cognitive impairment.

Characteristics and potential clinical applications of the extracellular vesicles of human pathogenic Fungi.

Extracellular vesicles (EVs) are a heterogeneous group of lipid membrane-enclosed compartments that contain different biomolecules and are released by almost all living cells, including fungal genera. Fungal EVs contain multiple bioactive components that perform various biological functions, such as stimulation of the host immune system, transport of virulence factors, induction of biofilm formation, and mediation of host-pathogen interactions. In this review, we summarize the current knowledge on EVs of human pathogenic fungi, mainly focusing on their biogenesis, composition, and biological effects. We also discuss the potential markers and therapeutic applications of fungal EVs.

Biomarkers for Immunotherapy in Driver-Gene-Negative Advanced NSCLC.

Outcome improvement in patients with driver-gene-negative advanced non-small cell lung cancer (NSCLC) has been significantly enhanced through targeting the immune system, specifically the PD-L1/PD-1 axis. Nevertheless, only a subset of patients with advanced NSCLC may derive benefits from immuno-monotherapy or immunotherapy combined with chemotherapy. Hence, in order to identify patients who will gain the maximum advantage from immunotherapy, it is crucial to investigate predictive biomarkers. This review provides a summary of the currently identified biomarkers associated with the extent of benefit from immuno-monotherapy or immunotherapy combined with chemotherapy in patients with advanced NSCLC. These biomarkers can be categorized into three groups: tumor-related, tumor-microenvironment-related, and host-factor-related.Tumor-related factors include PD-L1 expression, tumor mutational burden and specific genetic mutations, while tumor-microenvironment-related factors include extracellular vesicles and T-cell receptors, and host-related factors include systemic inflammation, circulating fatty acid profile, and the microbiome.

Genomic Insights into the Origin and Evolution of Molluscan Red-Bloodedness in the Blood Clam Tegillarca granosa.

Blood clams differ from their molluscan kins by exhibiting a unique red-blood (RB) phenotype; however, the genetic basis and biochemical machinery subserving this evolutionary innovation remain unclear. As a fundamental step toward resolving this mystery, we presented the first chromosome-level genome and comprehensive transcriptomes of the blood clam Tegillarca granosa for an integrated genomic, evolutionary, and functional analyses of clam RB phenotype. We identified blood clam-specific and expanded gene families, as well as gene pathways that are of RB relevant. Clam-specific RB-related hemoglobins (Hbs) showed close phylogenetic relationships with myoglobins (Mbs) of blood clam and other molluscs without the RB phenotype, indicating that clam-specific Hbs were likely evolutionarily derived from the Mb lineage. Strikingly, similar to vertebrate Hbs, blood clam Hbs were present in a form of gene cluster. Despite the convergent evolution of Hb clusters in blood clam and vertebrates, their Hb clusters may have originated from a single ancestral Mb-like gene as evidenced by gene phylogeny and synteny analysis. A full suite of enzyme-encoding genes for heme synthesis was identified in blood clam, with prominent expression in hemolymph and resembling those in vertebrates, suggesting a convergence of both RB-related Hb and heme functions in vertebrates and blood clam. RNA interference experiments confirmed the functional roles of Hbs and key enzyme of heme synthesis in the maintenance of clam RB phenotype. The high-quality genome assembly and comprehensive transcriptomes presented herein serve new genomic resources for the super-diverse phylum Mollusca, and provide deep insights into the origin and evolution of invertebrate RB.

A case in subtropical climate city: Assessing the bioretention hydraulic performance on storm in response to poor permeability soil.

Bioretention has been widely used in China for the purpose of sponge city construction. In subtropical climate areas, the performance of bioretention cell under condition of low infiltration underlying soil and heavy storms is still poorly understood. This study aimed to assess the effects of low infiltration underlying soil and precipitation characteristics on the hydraulic performance of a bioretention cell using the Storm Water Management Model (SWMM). The hydraulic performance of a bioretention cell were investigated under a Typical year rainfall event (P(total) (total precipitation) = 1299.2 mm) and seven heavy storms (i.e., Ptotal range from 53.1 mm to 287.3 mm), at different SF(i) (seepage rates of the underlying soil) (i.e., range from 2.5 mm/h to 15 mm/h). Then, sensitivity of the optimal design to the different design parameters, including the hydraulic conductivity of soil medium layer and the berm height of surface layer, was examined. The results show that the increase in SF(i) was effective in increasing the ARVR(i) (annual runoff volume reduction) and RVR(i) (runoff volume reduction), while little effective in increasing PFR(i) (peak flow reduction). Moreover, the ARVR(i) could meet the designed goal of 70% when the SF(i) was more than 7.5 mm/h. For RVR(i), the key variable of precipitation characteristic changes from Ptotal to P4h(max) (maximum precipitation in 4 h) as SF(i) increases, while P4h(max) remains as the key variable for PFR(i) all the time. The sensitivity studies demonstrate that the hydraulic conductivity is more effective in increasing PFR(i) than the berm height. For the bioretention cell under condition of low infiltration underlying soil and heavy storms, in order to simultaneously achieve expected reduction goal of both peak flow and runoff volume, and make the best comprehensive performance of bioretention cell, it requires not only a maintenance action to increase the hydraulic conductivity of soil medium layer, but also a drain pipe to be added in the storage layer, and meanwhile other LID practices should be combined.

One-Year Clinical Outcome of Pulmonary Vein Isolation Using the Second-Generation Cryoballoon: A Meta-Analysis.

BACKGROUND: The second-generation cryoballoon (CB-2G) is a promising technique to treat atrial fibrillation (AF). It is necessary to summarize and analyze the available data on 1-year clinical outcome of pulmonary vein isolation (PVI) with CB-2G. METHODS: PubMed and the Web of Science were searched in May 2015. Studies that reported the 1-year clinical success rates after PVI using CB-2G were included. The 1-year clinical success rates were pooled using the random-effect model. Complication rates and acute success rates were also analyzed. Subgroup analyses were conducted based on AF type and ablation strategy. RESULTS: Fifteen studies involving 2,363 AF patients met the inclusion criteria. The overall clinical success rate of PVI using CB-2G was 81%. A total of 82% of paroxysmal AF patients and 70% of persistent AF patients were in stable sinus rhythm 1 year after the procedure. The clinical success rates of the "no-bonus" strategy were 81% in all patients, 82% in paroxysmal AF patients, and 73% in persistent AF patients. The corresponding success rates of the "bonus" strategy were 81%, 83%, and 63%. Acute success rate was high. The overall rates of phrenic nerve palsy (PNP) and other procedure-related complications were 5.8% and 1.5%, respectively. Compared with "bonus" strategy, there was a trend of fewer PNPs in "no-bonus" strategy (4.6% vs 6.5%). CONCLUSIONS: CB-2G is highly effective in the treatment of both paroxysmal AF and persistent AF. The "no-bonus" strategy is as effective as the "bonus" strategy in terms of 1-year clinical outcome.

Exendin-4 attenuates cardiac hypertrophy via AMPK/mTOR signaling pathway activation.

Diabetes mellitus is a prominent risk factor for cardiovascular diseases. Diabetic cardiomyopathy is an important complication of the heart independent of hypertension and coronary artery disease and is accompanied by cardiac hypertrophy. Cardiac hypertrophy easily leads to heart failure, which is a leading cause of morbidity and mortality. Glucagon-like peptide 1 (GLP-1) is an incretin hormone, which has various beneficial roles in the cardiovascular system, and exendin-4 is a highly potent glucagon-like peptide 1 receptor agonist. However, the role of GLP-1 in cardiac hypertrophy remains unknown. Our study revealed that exendin-4 treatment ameliorated phenylephrine (PE)-induced cardiac hypertrophy, which presented as decreased cardiac hypertrophic markers (ANP, BNP, and ß-MHC) and cell surface area. This condition was significantly reversed upon treatment with the GLP-1 receptor antagonist exendin9-39. We also discovered that Erk1/2 and AMPK signaling pathways were involved in this process. Furthermore, our data demonstrate that the AMPK inhibitor compound C inhibited the anti-hypertrophic effect of exendin-4, which is associated with the mTOR/p70S6K/4-EBP1 signaling pathway. Finally, exendin-4 enhanced the anti-hypertrophic effect of rapamycin. In summary, our study disclosed that exedin-4 inhibits cardiac hypertrophy by upregulating GLP-1 receptor expression and activating the AMPK/mTOR signaling pathway.

Soil microbial community structure, function and network along a mangrove forest restoration chronosequence.

Mangrove forests have high ecological, social and economic values, but due to environmental changes and human activities, natural mangrove forests have experienced serious degradations and reductions in distribution area worldwide. In the coastal zones of southern China, an introduced mangrove species, Sonneratia apetala, has been extensively used for mangrove restoration because of its rapid growth and strong environmental adaptability. However, little is known about how soil microorganisms vary with the restoration stages of the afforested mangrove forests. Here, we examined the changes in soil physicochemical properties and microbial biomass, community structure and function, and network in three afforested S. apetala forests with restoration time of 7, 12, and 18 years and compared them with a bare flat and a 60-year-old natural Kandelia obovata forest in a mangrove nature reserve. Our results showed that the contents of soil salinity, organic carbon, total nitrogen, ammonium nitrogen, and microbial biomass increased, while soil pH and bacterial alpha diversity decreased with afforestation age. Soil microbial community structure was significantly affected by soil salinity, organic carbon, pH, total nitrogen, ammonium nitrogen, available phosphorus, and available kalium, and susceptibility to environmental factors was more pronounced in bacterial than fungal community structure. The relative abundances of aerobic chemoheterotrophy were significantly higher in 12- and 18-year-old S. apetala than in K. obovata forest, while that of sulfate-reducing bacteria showed a decreasing trend with afforestation age. The abundance of dung saprotroph was significantly higher in 12- and 18-year-old S. apetala forests than in the natural forest. With the increasing afforestation age, the modularity of microbial networks increased, while stability and robustness decreased. Our results suggest that planting S. apetala contributes to improving soil fertility and microbial biomass but may make soil microbial networks more vulnerable.

Expanding catalytic promiscuity of a bifunctional terpene synthase through a single mutation-induced change in hydrogen-bond network within the catalytic pocket.

Fungal bifunctional terpene synthases (BFTSs) catalyze the formation of numerous di-/sester-/tri-terpenes skeletons. However, the mechanism in controlling the cyclization pattern of terpene scaffolds is rarely deciphered for further application of tuning the catalytic promiscuity of terpene synthases for expanding the chemical space. In this study, we expanded the catalytic promiscuity of Fusarium oxysporum fusoxypene synthase (FoFS) by a single mutation at L89, leading to the production of three new sesterterpenes. Further computational analysis revealed that the reconstitution of the hydrogen-bond (H-bond) network of second-shell residues around the active site of FoFS influences the orientation of the aromatic residue W69 within the first-shell catalytic pocket. Thus, the dynamic orientation of W69 alters the carbocation transport, leading to the production of diverse ring system skeletons. These findings enhance our knowledge on understanding the molecular mechanisms, which could be applied on protein engineering terpene synthases on regulating the terpene skeletons.

Amyloid hexapeptide prevent dental caries by antibiofilm formation.

OBJECTIVES: Biofilm formed by cariogenic microbes is the direct cause of dental caries, therefore, prevention of dental caries should be anti-biofilm-based. Previously, we found the amyloid hexapeptides efficiently inhibited biofilm formation by aggregating into amyloid fibrils agglutinating microbes. This study aimed to select the most stable amyloid hexapeptide GIDLKI (GI6) and study its anti-caries effect. METHODS: Biofilms of multi-species bacteria, derived from mixed saliva, were cultured to evaluate the anti-biofilm formation effect of GI6. And then, the primary cariogenic bacterium Streptococcus mutans (S.mutans) was cultured in BHI with various pH, gradient concentrations of sucrose, glucose, and calcium ions to evaluate the anti-biofilm formation effects of GI6. Then models of human enamel block caries and twenty male SPF-SD rat caries induced by S. mutans biofilm were constructed, and confocal laser scanning microscopy, scanning electron microscopy, and micro-computed tomography were applied to investigate the anti-biofilm formation, anti-caries effects and use safety of GI6. RESULTS: GI6 could inhibit the multi-species bacteria biofilm formation and remained effective in anti-biofilm activity against S. mutans in environments closely related to caries. GI6 suppressed S. mutans biofilm formation and thus prevented or alleviated the development of caries in human tooth blocks and rat teeth. GI6 did not affect the intestinal flora, serum biochemical parameters, and the pathological changes of various organs. CONCLUSIONS: Amyloid hexapeptides, including but not limited to GI6, are novel effective anti-caries agents that can be used to prevent dental caries safely. CLINICAL SIGNIFICANCE: This study explored the anti-biofilm formation and anti-caries effect of GI6 in vitro, highlighting the anti-biofilm formation therapy for dental caries and setting a foundation for the practical application of GI6 for the treatment of dental caries.

LncRNA RP4-639F20.1 interacts with THRAP3 to attenuate atherosclerosis by regulating c-FOS in vascular smooth muscle cells proliferation and migration.

BACKGROUND AND AIMS: The aberrant proliferation and migration of vascular smooth muscle cells (VSMCs) play an essential role in the pathogenesis of atherosclerosis (AS). Long noncoding RNAs (lncRNAs) have been reported as important regulators in a number of diseases. However, very little is known regarding the functional role of lncRNAs in governing proliferation and migration of VSMCs and AS development. METHODS: Both in vitro and in vivo assays were performed to investigate the role of lncRNA in the pathophysiology of AS. Our previous lncRNA arrays revealed that lncRNA RP4-639F20.1 was significantly decreased in atherosclerotic plaques. Lentivirus overexpressing RP4-639F20.1 and lncRNA RP4-639F20.1 silencing vectors (Si-lnc-RP4-639F20.1) were constructed and transfected in VSMCs. The in vitro functions of lncRNA were analyzed by CCK-8 assays, EdU assays, scratch wound assays, transwell assays, qRT-PCR and Western blot analyses. RNA fluorescence in situ hybridization, immunoprecipitation and mRNA microarrays were used to explore the underlying mechanism. Adeno-associated-virus-9 (AAV9) overexpressing RP4-639F20.1 was constructed and injected intravenously into ApoE-/- mice to explore the role of lncRNA in vivo. RESULTS: In vitro experiments showed that lncRNA RP4-639F20.1 interacted with THRAP3 and downregulated c-FOS expression. Both increase of lncRNA RP4-639F20.1 expression and knockdown of c-FOS inhibited the expression of MMP10 and VEGF-α in VSMCs and suppressed VSMCs proliferation and migration. In vivo experiments using ApoE-/- mice fed a high-fat diet demonstrated that lncRNA RP4-639F20.1 overexpression deterred atherosclerosis and decreased lipid levels in atherosclerotic lesions. Patients with coronary artery disease were found to have higher c-FOS levels than healthy individuals and c-FOS expression was positively correlated with the SYNTAX score of patients. CONCLUSIONS: Overall, these data indicated that lncRNA RP4-639F20.1/THRAP3/c-FOS pathway protects against the development of atherosclerosis by suppressing VSMCs proliferation and migration. LncRNA RP4-639F20.1 and c-FOS could represent potential therapeutic targets to ameliorate atherosclerosis-related diseases.

Lactobacillus rhamnosus GG Regulates Host IFN-I Through the RIG-I Signalling Pathway to Inhibit Herpes Simplex Virus Type 2 Infection.

Numerous recent studies have demonstrated that the commensal microbiota plays an important role in host immunity against infections. During the infection process, viruses can exhibit substantial and close interactions with the commensal microbiota. However, the associated mechanism remains largely unknown. Therefore, in this study, we explored the specific mechanisms by which the commensal microbiota modulates host immunity against viral infections. We found that the expression levels of type I interferon (IFN-I) and antiviral priming were significantly downregulated following the depletion of the commensal microbiota due to treatment with broad-spectrum antibiotics (ABX). In addition, we confirmed a unique molecular mechanism underlying the induction of IFN-I mediated by the commensal microbiota. In vivo and in vitro experiments confirmed that Lactobacillus rhamnosus GG (LGG) can suppress herpes simplex virus type 2 (HSV-2) infection by inducing IFN-I expression via the retinoic acid-inducible gene-I (RIG-I) signalling pathway. Therefore, the commensal microbiota-induced production of IFN-I provides a potential therapeutic approach to combat viral infections. Altogether, understanding the complexity and the molecular aspects linking the commensal microbiota to health will help provide the basis for novel therapies already being developed.

Simulations of imaging Fabry-Perot interferometers for measuring upper-atmospheric temperatures and winds.

We apply an onion-peeling inversion to simulated imaging Fabry-Perot interferometer (FPI) observations for retrieving altitude profiles of neutral temperatures and winds in the thermosphere in order to investigate the effects of realistic gradients in thermospheric parameters on the retrieved parameters. A forward model is developed that simulates the interference spectrum observed by an FPI using the redline (630.0 nm) and greenline (557.7 nm) emissions simulated based on climatological models. This forward model is applicable to both ground- and satellite-based simulations and generates a two-dimensional interference ring pattern. We simulate both a single-band ground-based FPI and a dual-band satellite-based FPI in order to study the effects of realistic vertical and horizontal gradients on the retrieved parameters.

Spatiotemporal patterns and inequity of urban green space accessibility and its relationship with urban spatial expansion in China during rapid urbanization period.

Equitable access to urban green spaces (UGS) is an important component of social justice and can be quantified using indices such as urban green space accessibility (UGSA). However, the spatiotemporal patterns and inequity of UGSA among cities with different developments during rapid urbanization are unclear, especially lack evidence at a macroscopic national scale during rapid urbanization. Therefore, we evaluated the UGSA in 366 cities of China during 1990-2015 by the Gaussian-based two-step floating catchment area method (Gaussian-based 2SFCA). Then, the inequity pattern of UGSA among cities with different economic developments was analyzed by the concentration curve and concentration index. Finally, the relationship between UGSA and urban spatial expansion was explored quantitatively by the spatial econometric model. The results showed that: (1) The overall UGSA in China declined significantly by nearly 57.23% during 1990-2015. From the regional perspective, the UGSA in the southeastern region was always lower than that in the northwestern region, the Eastern zone presented a downward trend. From the perspective of different sizes cities, the UGSA of the megacities kept decreasing during 1990-2015, while UGSA of the large, medium, and small cities had turned to increase since 2010. (2) During rapid urbanization, the equity of UGSA among the cities gradually improved, while the cities with low economic developments tended to have higher UGSA. (3) Urban spatial expansion led to the decrease of UGSA during 1990-2015, while the impact had spatiotemporal heterogeneity, and UGSA had a positive spatial spillover effect. Our research provides a comparative baseline for the improvement of UGSA from a macroscopic perspective for China's urbanization policy in the future and novel insights into the green justice issue. The results can be compared with the development of UGS in other countries at different urbanization stages to promote UGS design and policy.

Outer membrane vesicles-transmitted virulence genes mediate the emergence of new antimicrobial-resistant hypervirulent Klebsiella pneumoniae.

Hypervirulent Klebsiella pneumoniae (hvKp) is a notorious clinical pathogen that is more likely to cause severe primary and metastatic abscesses. The dissemination of antimicrobial-resistant hvKp isolates has been reported worldwide, posing a great challenge and severe clinical threat. However, the mechanisms of antimicrobial-resistant hvKp isolates prevalent worldwide are not well precise. Outer membrane vesicles (OMVs) secreted from gram-negative bacteria are an important vehicle for delivering effector molecules inter- and intra-species. To explore whether OMVs as the vector of virulence genes horizontal transfer among Klebsiella pneumoniae and to explain the potential mechanism for the development of antimicrobial-resistant hvKp isolates, we isolated OMVs from hvKp and classical Klebsiella pneumoniae (cKp) by sequential differential centrifugation, respectively. Then, the characteristics and contents of hvKp-OMVs and cKp-OMVs were analyzed. These hvKp-OMVs contain virulence genes, which could be transferred from hvKp horizontally to extended-spectrum beta lactamase (ESBL)-producing cKp, leading to the production of antimicrobial-resistant hypervirulent transformants. Further experiments confirmed the transformants exhibited antimicrobial resistance and hypervirulent phenotypes in vitro and in vivo. In short, this work demonstrated that hvKp-OMVs facilitated virulence genes transfer, allowing an increase in the virulence level of ESBL-producing cKp and providing a new mechanism for the emergence of antimicrobial-resistant hvKp isolates.

Chemical control over the conversion between bicyclic and polycyclic terpenes by fungal bifunctional terpene synthases.

Fungal bifunctional terpene synthases (BFTSs) reportedly associate with a series of new skeletons of di/sesterterpenes. However, the molecular mechanisms underlying the variabilities in the ring system of BFTS-catalyzed products are not well understood. In this study, we identified a key site, S89/L89, that controls the conversion between bicyclic and polycyclic terpene skeletons catalyzed by two BFTSs, BsPS and FoFS. Our analysis revealed that a mutation on site 89 in the BFTSs alters the carbocation transportation pathway and redirects the competing reactions for previously unreported terpenes.

Simulation and analysis of a multi-order imaging Fabry-Perot interferometer for the study of thermospheric winds and temperatures.

We describe an analysis procedure for estimating the thermospheric winds and temperatures from the multi-order two-dimensional (2D) interferograms produced by an imaging Fabry-Perot interferometer (FPI) as imaged by a CCD detector. We also present a forward model describing the 2D interferograms. To investigate the robustness and accuracy of the analysis, we perform several Monte Carlo simulations using this forward model for an FPI that has recently been developed and deployed to northeastern Brazil. The first simulation shows that a slight cross-contamination at high temperatures exists between neighboring orders in the interferogram, introducing a bias in the estimated temperatures and increasing errors in both the estimated temperatures and winds when each order is analyzed in full. The second simulation investigates how using less than an entire order in the analysis reduces the cross contamination observed in the first set of simulations, improving the accuracy of the estimated temperatures. The last simulation investigates the effect of the signal-to-noise ratio on the errors in the estimated parameters. It is shown that, for the specific FPI simulated in this study, a signal-to-noise ratio of 1.5 is required to obtain thermospheric wind errors of 5 m/s and temperature errors of 20 K.

Hemoglobins from Scapharca subcrenata (Bivalvia: Arcidae) likely play an bactericidal role through their peroxidase activity.

Hemoglobin (Hb) is an iron-containing respiratory protein present in all vertebrates and some invertebrates. The blood clam Scapharca subcrenata is one of the few invertebrates that have Hb-containing red hemocytes. In this study, we purified Hb (Ss-Hb), including Ss-HbI and Ss-HbII, from S. subcrenata hemocytes using gel chromatography with a recovery rate of 70.71%, and then characterized their peroxidase activities. Both Ss-Hbs possessed peroxidase activity with high affinity to the substrates guaiacol and H2O2. Moreover, both Ss-Hbs had structural similarities, such as type b heme, proximal histidine (His), distal His, and heme pocket arginine (Arg), with other peroxidases. The optimal peroxidase activity of both Ss-Hbs was at pH 5 and 35 °C, but this was inhibited in the presence of Cu2+ and Fe2+. Ss-Hbs produced [Formula: see text] in the presence of H2O2. ß-phenylethylamine, a substrate of peroxidase, increased the [Formula: see text] generation, while Cu2+, an inhibitor of peroxidase, inhibited this reaction. These results indicated that the peroxidase cycle of Ss-Hb was involved in the production of [Formula: see text] . A large amount of [Formula: see text] may be generated by the peroxidase cycle if the substrate is sufficient. During the incubation of Ss-Hbs with Bacillus subtilis, it was speculated that trace H2O2, probably from autoxidation of Ss-Hbs or generated by B. subtilis, started the peroxidase cycle of Ss-Hb. and produced a large amount of [Formula: see text] in the presence of sufficient substrate in the culture medium. It is therefore reasonable to assume that Ss-Hbs played an antibacterial role owing to their peroxidase activity, which produced [Formula: see text] .

Benchmarking of Data-Driven Causality Discovery Approaches in the Interactions of Arctic Sea Ice and Atmosphere.

The Arctic sea ice has retreated rapidly in the past few decades, which is believed to be driven by various dynamic and thermodynamic processes in the atmosphere. The newly open water resulted from sea ice decline in turn exerts large influence on the atmosphere. Therefore, this study aims to investigate the causality between multiple atmospheric processes and sea ice variations using three distinct data-driven causality approaches that have been proposed recently: Temporal Causality Discovery Framework Non-combinatorial Optimization via Trace Exponential and Augmented lagrangian for Structure learning (NOTEARS) and Directed Acyclic Graph-Graph Neural Networks (DAG-GNN). We apply these three algorithms to 39 years of historical time-series data sets, which include 11 atmospheric variables from ERA-5 reanalysis product and passive microwave satellite retrieved sea ice extent. By comparing the causality graph results of these approaches with what we summarized from the literature, it shows that the static graphs produced by NOTEARS and DAG-GNN are relatively reasonable. The results from NOTEARS indicate that relative humidity and precipitation dominate sea ice changes among all variables, while the results from DAG-GNN suggest that the horizontal and meridional wind are more important for driving sea ice variations. However, both approaches produce some unrealistic cause-effect relationships. Additionally, these three methods cannot well detect the delayed impact of one variable on another in the Arctic. It also turns out that the results are rather sensitive to the choice of hyperparameters of the three methods. As a pioneer study, this work paves the way to disentangle the complex causal relationships in the Earth system, by taking the advantage of cutting-edge Artificial Intelligence technologies.