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Background Microbes produce diverse secondary metabolites (SMs) such as signaling molecules and antimicrobials that mediate microbe-microbe interaction. Archaea, the third domain of life, are a large and diverse group of microbes that not only exist in extreme environments but are abundantly distributed throughout nature. However, our understanding of archaeal SMs lags far behind our knowledge of those in bacteria and eukarya. Results Guided by genomic and metabolic analysis of archaeal SMs, we discovered two new lanthipeptides with distinct ring topologies from a halophilic archaeon of class Haloarchaea. Of these two lanthipeptides, archalan α exhibited anti-archaeal activities against halophilic archaea, potentially mediating the archaeal antagonistic interactions in the halophilic niche. To our best knowledge, archalan α represents the first lantibiotic and the first anti-archaeal SM from the archaea domain. Conclusions Our study investigates the biosynthetic potential of lanthipeptides in archaea, linking lanthipeptides to antagonistic interaction via genomic and metabolic analyses and bioassay. The discovery of these archaeal lanthipeptides is expected to stimulate the experimental study of poorly characterized archaeal chemical biology and highlight the potential of archaea as a new source of bioactive SMs.

Background:Cardiopulmonary bypass (CPB) can lead to lung injury and even acute respiratory distress syndrome (ARDS) through triggering systemic inflammatory response. The objective of this study was to investigate the impact of CPB time on clinical outcomes in patients with ARDS after cardiac surgery. Methods:Totally, patients with ARDS after cardiac surgery in Beijing Anzhen Hospital from January 2005 to December 2015 were retrospectively included and were further divided into three categories according to CPB time during operation. The primary endpoints were the ICU mortality and in-hospital mortality, and ICU and hospital stay. Restricted cubic spline (RCS), logistic regression, cox regression model, and receiver operating characteristic (ROC) curve were adopted to explore the relationship between CPB time and clinical endpoints. Results: Of the 54217 patients who underwent cardiac surgery during the above period, 210 patients developed ARDS after surgery and were finally included. The ICU mortality and in-hospital mortality were 21.0% and 41.9% in all ARDS patients after cardiac surgery respectively. Patients in category3 (CPB time ≥ 173 minutes) had longer ICU stay (P=0.011), higher ICU (PP=0.002) mortality compared with those in category1 (CPB=0). For each ten minutes increment in CPB time, the hazards of a worse outcome increased by 13.3% for ICU mortality and 9.3% for in-hospital mortality after adjusting for potential factors.ROC curves showed CPB time presented more satisfactory power to predict mortality compared with APCHEII score. The optimal cut-off value of CPB time were 160.5 minutes for ICU mortality and in-hospital mortality. Conclusion: Our findings firstly revealed the quantitative relationship between CPB time and clinical outcomes in patients with ARDS after cardiac surgery. Longer time of CPB was associated with poorer clinical outcomes, and could be served as an indicator to predict short-term mortality in patients with ARDS after cardiac surgery.

The evolution of a local strain of the Ti-6Al-4V alloy subjected to tensile loading was investigated in situ by using the digital image correlation technique. The results show that some local strain concentration areas have already appeared in the elastic deformation stage, which then connected and became concentrated in the gauge region when the specimen yielded. The strain compatibility of grains in the macroscopic region is kept constant. The deformation process is further divided into six parts based on the development of the maximum strain gradient, and the strain compatibility of each stage of the alloy is summarized and analyzed. The quasi-in situ experiment reveals that the primary α(αp) grains undertake the main deformation at the micro-scale.

Background Lactic acid bacteria (LAB) produce various bioactive secondary metabolites (SMs), which endow LAB with a protective role for the host. However, the biosynthetic potentials of LAB-derived SMs remain elusive, particularly in their diversity, abundance, and distribution in the human microbiome. Thus, it is still unknown to what extent LAB-derived SMs are involved in microbiome homeostasis. Results Here, we systematically investigate the biosynthetic potential of LAB from 31,977 LAB genomes, identifying 130,051 secondary metabolite biosynthetic gene clusters (BGCs) of 2,849 gene cluster families (GCFs). Most of these GCFs are species-specific or even strain-specific and uncharacterized yet. Analyzing 748 human-associated metagenomes, we gain an insight into the profile of LAB BGCs, which are highly diverse and niche-specific in the human microbiome. We discover that most LAB BGCs may encode bacteriocins with pervasive antagonistic activities predicted by machine learning models, potentially playing protective roles in the human microbiome. Class II bacteriocins, one of the most abundant and diverse LAB SMs, are particularly enriched and predominant in the vaginal microbiome. We utilized metagenomic and metatranscriptomic analyses to guide our discovery of functional class II bacteriocins. Our findings suggest that these antibacterial bacteriocins have the potential to regulate microbial communities in the vagina, thereby contributing to the maintenance of microbiome homeostasis. Conclusions Our study systematically investigates LAB biosynthetic potential and their profiles in the human microbiome, linking them to the antagonistic contributions to microbiome homeostasis via omics analysis. These discoveries of the diverse and prevalent antagonistic SMs are expected to stimulate the mechanism study of LAB’s protective roles for the microbiome and host, highlighting the potential of LAB and their bacteriocins as therapeutic alternatives.

Neddylation is a posttranslational modification in which NEDD8 is conjugated to a target substrate by cellular processes similar to those involved in ubiquitination. Recent studies have identified PSD-95 and cofilin as substrates for neddylation in the brain and have shown that neddylation modulates the maturation and stability of dendritic spines in developing neurons. However, the precise substrates and functional consequences of neddylation at presynaptic terminals remain elusive. Here, we provide evidence that the mGlu7 receptor is a target of neddylation in heterologous cells and rat primary cultured neurons. We found that mGlu7 neddylation is reduced by agonist treatment and is required for the clustering of mGlu7 in the presynaptic active zone. In addition, we observed that neddylation is not required for the endocytosis of mGlu7, but it facilitates the ubiquitination of mGlu7 and stabilizes mGlu7 protein expression. Finally, we demonstrate that neddylation is necessary for the maturation of excitatory presynaptic terminals, providing a key role for neddylation in synaptic function., Nervous system: Nerve cell development New insights into the role of a regulatory protein in nerve development and activity in the brain will increase understanding of the maturation of nerve cells and the pathology of neurodevelopmental disorders. Young Ho Suh and colleagues at Seoul National University College of Medicine in South Korea studied cultured rat nerve cells to investigate a process called neddylation, mediated by the protein NEDD8. Neddylation occurs when NEDD8 is attached to other proteins in a manner that regulates the cell proliferation, but details of neddylation’s effects have been elusive in nerve cells. The authors have now identified a specific receptor protein in nerve cell membranes as a target for neddylation. This process seems to be required for the maturation and activity of nerve endings called pre-synapses, which release neurotransmitters to send signals to other nerve cells.

Metabotropic glutamate receptor 7 (mGlu7) is an inhibitory heterotrimeric G-protein-coupled receptor that modulates neurotransmitter release and synaptic plasticity at presynaptic terminals in the mammalian central nervous system. Recent studies have shown that rare mutations in glutamate receptors and synaptic scaffold proteins are associated with neurodevelopmental disorders (NDDs). However, the role of presynaptic mGlu7 in the pathogenesis of NDDs remains largely unknown. Recent whole-exome sequencing (WES) studies in families with NDDs have revealed that several missense mutations (c.1865G>A:p.R622Q; c.461T>C:p.I154T; c.1972C>T:p.R658W and c.2024C>A:p.T675K) or a nonsense mutation (c.1757G>A:p.W586X) in theGRM7gene may be linked to NDDs. In the present study, we investigated the mechanistic links betweenGRM7point mutations and NDD pathology. We find that the pathogenic GRM7 I154T and R658W/T675K mutations lead to the degradation of the mGlu7 protein. In particular, the GRM7 R658W/T675K mutation results in a lack of surface mGlu7 expression in heterologous cells and cultured neurons isolated from male and female rat embryos. We demonstrate that the expression of mGlu7 variants or exposure to mGlu7 antagonists impairs axon outgrowth through the mitogen-activated protein kinase (MAPK)-cAMP-protein kinase A (PKA) signaling pathway during early neuronal development, which subsequently leads to a decrease in the number of presynaptic terminals in mature neurons. Treatment with an mGlu7 agonist restores the pathologic phenotypes caused by mGlu7 I154T but not by mGlu7 R658W/T675K because of its lack of neuronal surface expression. These findings provide evidence that stable neuronal surface expression of mGlu7 is essential for neural development and that mGlu7 is a promising therapeutic target for NDDs.SIGNIFICANCE STATEMENTNeurodevelopmental disorders (NDDs) affect brain development and function by multiple etiologies. Metabotropic glutamate receptor 7 (mGlu7) is a receptor that controls excitatory neurotransmission and synaptic plasticity. Since accumulating evidence indicates that theGRM7gene locus is associated with NDD risk, we analyzed the functional effects of humanGRM7variants identified in patients with NDDs. We demonstrate that stable neuronal surface expression of mGlu7 is essential for axon outgrowth and presynaptic terminal development in neurons. We found that mitogen-activated protein kinase (MAPK)-cAMP-protein kinase A (PKA) signaling and subsequent cytoskeletal dynamics are defective because of the degradation of mGlu7 variants. Finally, we show that the defects caused by mGlu7 I154T can be reversed by agonists, providing the rationale for proposing mGlu7 as a potential therapeutic target for NDDs.

Background Despite advances in treatment strategies, acute respiratory distress syndrome (ARDS) after cardiac surgery remains associated with high morbidity and mortality. A method of screening patients for risk of ARDS after cardiac surgery is needed. Objectives To develop and validate an ARDS prediction score designed to identify patients at high risk of ARDS after cardiac or aortic surgery. Methods An ARDS prediction score was derived from a retrospective derivation cohort and validated in a prospective cohort. Discrimination and calibration of the score were assessed with area under the receiver operating characteristic curve and the Hosmer-Lemeshow goodness-of-fit test, respectively. A sensitivity analysis was conducted to assess model performance at different cutoff points. Results The retrospective derivation cohort consisted of 201 patients with and 602 patients without ARDS who had undergone cardiac or aortic surgery. Nine routinely available clinical variables were included in the ARDS prediction score. In the derivation cohort, the score distinguished patients with versus without ARDS with area under the curve of 0.84 (95% CI, 0.81-0.88; Hosmer-Lemeshow P = .55). In the validation cohort, 46 of 1834 patients (2.5%) had ARDS develop within 7 days after cardiac or aortic surgery. Area under the curve was 0.78 (95% CI, 0.71-0.85), and the score was well calibrated (Hosmer-Lemeshow P = .53). Conclusions The ARDS prediction score can be used to identify high-risk patients from the first day after cardiac or aortic surgery. Patients with a score of 3 or greater should be closely monitored. The score requires external validation before clinical use.

A Gram-stain-negative, non-spore-forming and rod-shaped bacterium, designated strain NS-102T, was isolated from herbicide-contaminated soil sampled in Nanjing, PR China, and its taxonomic status was investigated by a polyphasic approach. Cell growth of strain NS-102T occurred at 16–42 °C (optimum, 30 °C), at pH 5.0–8.0 (optimum, pH 6.0) and in the presence of 0–3.5 % (w/v) NaCl (optimum, without addition of NaCl). The 16S rRNA gene sequence of strain NS-102T shows high similarity to that of Agriterribacter humi YJ03T (96.9 % similarity), followed by Terrimonas terrae T16R-129T (93.8 %) and Terrimonas pekingensis QHT (93.6 %). Average nucleotide identity, average amino acid identity and digital DNA–DNA hybridization values between the draft genomes of strain NS-102T and A. humi YJ03T were 72.5, 69.4 and 18.6%, respectively. The only respiratory quinone was MK-7, and phosphatidylethanolamine and unidentified lipids were the major polar lipids. The major cellular fatty acids of strain NS-102T contained high amounts of iso-C15 : 0 (24.6 %), iso-C17 : 03-OH (24.1 %), iso-C15 : 0 G (16.6 %) and summed feature 3 (C16 : 1 ω6c and/or C16 : 1 ω7c) (15.6 %). The G+C content of the total DNA was determined to be 40.0 mol%. The morphological, physiological, chemotaxonomic and phylogenetic analyses clearly distinguished this strain from its closest phylogenetic neighbours. Thus, strain NS-102T represents a novel species of the genus Agriterribacter , for which the name Agriterribacter soli sp. nov. is proposed. The type strain is NS-102T (=CCTCC AB 2017249T=KCTC 62322T).

The oxidation behavior of the selective laser melting (SLM)–fabricated Inconel 718 was investigated through isothermal oxidation testing at 650 °C for 500 h and compared with that of the as-cast and as-forged specimens at the same testing conditions. The effect of microstructure and surface roughness on the oxidation behavior of the SLM-fabricated, as-cast, and as-forged Inconel 718 specimens was examined. The result shows that Inconel 718 fabricated by SLM with the unique layer structure exhibited a better resistance to the 500 h oxidation at 650 °C compared with as-cast and as-forged 718 with coarse dendritic structure and uniform equiaxed grain microstructure, respectively. The influence of the surface roughness on the long-time oxidation resistance of SLM specimens is not pronounced compared with that of as-cast and as-forged specimens. The tiny dendrites instead of grain boundaries are a major influencing factor for the oxidation process of SLM specimens. The surface roughness has more evident influence on the oxidation resistance of as-forged specimens than that of the as-cast ones subjected to the 500 h oxidation at 650 °C.

Strain XY-J91T, a Gram-stain-negative, reddish orange, non-spore-forming and short-rod-shaped marine bacterium, was isolated from rhizosphere soil of the mangrove plant Kandelia candel (L.) Druce in Mai Po Nature Reserve, Hong Kong. The strain showed growth at 15–50 °C (optimum 40 °C), at pH 5.5–9.5 (optimum 7.0–8.0) and with 0–8 % (w/v) NaCl (optimum 1–2 %). The only respiratory quinone was MK-7 and the major fatty acids were iso-C15 : 0 and iso-C17 : 0 3-OH. The major polar lipids were phosphatidylethanolamine, an unidentified aminolipid and an unidentified phospholipid. The G+C content of strain XY-J91T was 40.4 mol%. Strain XY-J91T exhibited highest 16S rRNA gene sequence similarities to the type strains of Algoriphagus marincola SW-2T (96.66 %), Algoriphagus taiwanensis CC-PR-82T (96.21%), Algoriphagus ornithinivorans JC2052T (96.16%), Algoriphagus confluentis HJM-2T (95.73%) and Algoriphagus zhangzhouensis 12C11T (95.52 %). Based on the phylogenetic, phenotypic and chemotaxonomic evidence presented, strain XY-J91T represents a novel species of the genus Algoriphagus , for which the name Algoriphagus kandeliae sp. nov. is proposed. The type strain is XY-J91T (=MCCC 1K03612T=KCTC 72216T).

A novel bacterial strain, XY-99T, was isolated from the epidermis of a marine invertebrate of the genus Onchidium from seawater of the South China Sea. The cells of the strain were aerobic, Gram-stain-negative, non-motile, and oval-shaped (0.8–1.0 µm wide and 1.0–1.5 µm long) without a flagellum. The strain grew at temperatures of 15–37 °C (optimum, 35–37 °C), at pH 5.5–9.5 (optimum 7.5), and at NaCl concentrations of 0–12.0 % (w/v) (optimum 1.5–3.0 %). The major fatty acids (>10 %) were summed feature 8 (comprising C18 : 1ω7c and/or C18 : 1ω6c), C16 : 0 and 11-methyl C18 : 1ω7c. The predominant polar lipid was diphosphatidylglycerol. The respiratory quinone was Q-10. The closet phylogenetic neighbours were Pseudooceanicola flagellatus DY470T and Pseudooceanicola nitratireducens JLT1210T, showing 97.5 and 97.3 % of 16 s rRNA gene sequence similarity. The genome size of XY-99T was 3 673 499 bp, with 64.5 % DNA G+C content. The average nucleotide identity and digital DNA–DNA hybridization values between XY-99T and Pseudooceanicola flagellatus DY470T were 72.8 and 14.0 %, respectively, while they were 79.3 and 22.3 % between XY-99T and Pseudooceanicola nitratireducens JLT1210T. Characterization based on phylogenetic, phenotypic, chemotaxonomic and genomic evidence demonstrated that XY-99T represents a novel species of the genus Pseudooceanicola , for which the name Pseudooceanicola onchidii sp. nov. is proposed. The type strain is XY-99T (=KCTC 72211T=MCCC 1K03607T).