Birinapant Reshapes the Tumor Immunopeptidome and Enhances Antigen Presentation.

Birinapant, an antagonist of the inhibitor of apoptosis proteins, upregulates MHCs in tumor cells and displays a better tumoricidal effect when used in combination with immune checkpoint inhibitors, indicating that Birinapant may affect the antigen presentation pathway; however, the mechanism remains elusive. Based on high-resolution mass spectrometry and in vitro and in vivo models, we adopted integrated genomics, proteomics, and immunopeptidomics strategies to study the mechanism underlying the regulation of tumor immunity by Birinapant from the perspective of antigen presentation. Firstly, in HT29 and MCF7 cells, Birinapant increased the number and abundance of immunopeptides and source proteins. Secondly, a greater number of cancer/testis antigen peptides with increased abundance and more neoantigens were identified following Birinapant treatment. Moreover, we demonstrate the existence and immunogenicity of a neoantigen derived from insertion/deletion mutation. Thirdly, in HT29 cell-derived xenograft models, Birinapant administration also reshaped the immunopeptidome, and the tumor exhibited better immunogenicity. These data suggest that Birinapant can reshape the tumor immunopeptidome with respect to quality and quantity, which improves the presentation of CTA peptides and neoantigens, thus enhancing the immunogenicity of tumor cells. Such changes may be vital to the effectiveness of combination therapy, which can be further transferred to the clinic or aid in the development of new immunotherapeutic strategies to improve the anti-tumor immune response.

Widely targeted metabolomic and KEGG analyses of natural deep eutectic solvent-based saponins extraction from Camellia oleifera Abel.: Effects on composition.

Camellia saponins are important by-products of Camellia Oleifer Abel. processing. In this study, an eco-friendly method based on natural deep eutectic solvents (NaDESs, proline and glycerol at a molar ratio of 2:5) was established to extract saponins from C.oleifera cakes. The content of saponin (702.22 ± 1.28 mg/g) obtained using NaDES was higher than those extracted using water or methanol. UPLC-Q-TOF MS analysis of chemical structure showed that the difference in the extraction technique alter individual saponins. A widely targeted metabolomic approach and KEGG metabolic pathway analysis showed that the upregulated metabolites in the NaDES-based extract mainly included flavonoids, alkaloids, and phenolic acids; and they were involved in arginine and proline metabolism, metabolic pathways, phenylpropanoid biosynthesis, biosynthesis of secondary metabolites, and flavonoid biosynthesis. The present study proposes a selective substitute for use in the extraction of camellia saponins with composition analysis.

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.

Sudapyridine (WX-081) antibacterial activity against Mycobacterium avium, Mycobacterium abscessus, and Mycobacterium chelonae in vitro and in vivo.

Sudapyridine (WX-081) is a structural analog of bedaquiline (BDQ), which shows anti-tuberculosis and non-tuberculous mycobacteria (NTM) activities but, unlike BDQ, did not prolong QT interval in animal model studies. This study evaluated the antibacterial activity of this novel compound against Mycobacterium avium, Mycobacterium abscessus, and Mycobacterium chelonae in vitro and in vivo. The minimum inhibitory concentration (MIC) of WX-081 against three kinds of non-tuberculous mycobacteria (NTM) clinical strains was determined using microplate-based alamarBlue assay (MABA), and the antibacterial activity of WX-081 against NTM in J774A.1 cells and mice was evaluated. MIC ranges of WX-081 against clinical strains of M. avium and M. abscessus were 0.05-0.94 µg/mL, 0.88-7.22 µg/mL (M. abscessus subsp. abscessus), and 0.22-8.67 µg/mL (M. abscessus subsp. massiliense), respectively, which were slightly higher than those of BDQ. For M. avium, M. abscessus, and M. chelonae, WX-081 can reduce the intracellular bacterial load by 0.13-1.18, 0.18-1.50, and 0.17-1.03 log10 colony forming units (CFU)/mL, respectively, in a concentration-dependent manner. WX-081 has bactericidal activity against three NTM species in mice. WX-081 exhibited anti-NTM activity to the same extent as BDQ both in vivo and in vitro. WX-081 is a promising clinical candidate and should be studied further in clinical trials. IMPORTANCE: Due to the rapidly increased cases globally, non-tuberculous mycobacteria (NTM) disease has become a significant public health problem. NTM accounted for 11.57% of all mycobacterial isolates in China, with a high detection rate of Mycobacterium abscessus, Mycobacterium avium, and Mycobacterium chelonae during 2000-2019. Treatment of NTM infection is often challenging, as natural resistance to most antibiotics is quite common among different NTM species. Hence, identifying highly active anti-NTM agents is a priority for potent regimen establishment. The pursuit of new drugs to treat multidrug-resistant tuberculosis may also identify some agents with strong activity against NTM. Sudapyridine (WX-081) is a structural analog of bedaquiline (BDQ), which was developed to retain the anti-tuberculosis efficacy but eliminates the severe side effects of BDQ. This study initially evaluated the antimicrobial activity of this novel compound against M. avium, M. abscessus, and M. chelonae in vitro, in macrophages and mice, respectively.

Integration of multiple terminology bases: a multi-view alignment method using the hierarchical structure.

MOTIVATION: In the medical field, multiple terminology bases coexist across different institutions and contexts, often resulting in the presence of redundant terms. The identification of overlapping terms among these bases holds significant potential for harmonizing multiple standards and establishing unified framework, which enhances user access to comprehensive and well-structured medical information. However, the majority of terminology bases exhibit differences not only in semantic aspects but also in the hierarchy of their classification systems. The conventional approaches that rely on neighborhood-based methods such as GCN may introduce errors due to the presence of different superordinate and subordinate terms. Therefore, it is imperative to explore novel methods to tackle this structural challenge. RESULTS: To address this heterogeneity issue, this paper proposes a multi-view alignment approach that incorporates the hierarchical structure of terminologies. We utilize BERT-based model to capture the recursive relationships among different levels of hierarchy and consider the interaction information of name, neighbors, and hierarchy between different terminologies. We test our method on mapping files of three medical open terminologies, and the experimental results demonstrate that our method outperforms baseline methods in terms of Hits@1 and Hits@10 metrics by 2%. AVAILABILITY AND IMPLEMENTATION: The source code will be available at https://github.com/Ulricab/Bert-Path upon publication.

Muricauda meishanensis sp. nov., a facultative anaerobic bacterium belonging to the family Flavobacteriaceae isolated from marine sediment in the East China Sea.

A facultative anaerobic, Gram-strain-negative, rod-shaped bacterium (strain NBU2970T) was isolated by using modified ichip in situ cultivation from a marine sediment sample collected from Meishan Island in the East China Sea. Strain NBU2970T grew optimally at 37 °C, with a NaCl concentration of 2.0 % (w/v) and at pH 7.0. The 16S rRNA gene sequence analyses revealed that strain NBU2970T represents a novel species with the genus Muricauda, sharing highest sequence identities with Muricauda beolgyonensis BB-My12T (96.1 %), Muricauda alvinocaridis SCR12T (96.0 %), Muricauda taeanensis 105T (96.0 %) and Muricauda ruestringensis B1T (95.6 %). Phylogenetic analyses also indicated that strain NBU2970T clustered with the genus Muricauda and was closely related to M. beolgyonensis BB-My12T and M. ruestringensis B1T. The draft genome sequence of strain NBU2970T was composed of six contigs with a size of 3.2 Mbp, containing 3045 protein-coding genes and 38 RNA genes. The DNA G+C content was 43.8 mol%. The average nucleotide identity and digital DNA-DNA hybridization values between strain NBU2970T and related species of the genus Muricauda were well below the threshold limit for prokaryotic species delineation. The major cellular fatty acids were iso-C15 : 0, iso-C15 : 1 G and iso-C17 : 0 3-OH. The only respiratory quinone was MK-6. The major polar lipid was phosphatidylethanolamine. Based on its phenotypic, chemotaxonomic and genotypic data, strain NBU2970T is considered to be a representative of a novel species in the genus Muricauda, for which the name Muricauda meishanensis sp. nov. is proposed. The type strain is NBU2970T (=KCTC 82915T=MCCC 1K06394T).

Composition and sources of suspended particles in the Pacific Arctic region.

During the 6th (2014) and 7th (2016) Chinese Arctic Expedition (CHINARE), samples of suspended particulate matter (SPM) were collected from both surface (depth: <1.0 m) and subsurface (depth: approximately between 10 and 150 m) waters over the northern shelf of the Bering Sea and in the western Arctic Ocean. To investigate the distribution and sources of organic matter in both the surface water and the vertical profile, the concentration and stable carbon isotopic composition of SPM, particulate organic carbon (POC), and particulate nitrogen (only in surface water samples) were determined, and some particle samples were selected for examination using scanning electron microscopy. Results showed apparent geographical partitioning and temporal variation in both the concentration and the composition of SPM. Higher SPM concentrations were observed in nearshore, shelf break, and sea ice edge areas; the distribution of POC concentration displayed a similar pattern, with higher values found from the northern part of the Bering Shelf to southern parts of the Chukchi Shelf. In surface water, SPM mainly comprised clay and detrital minerals with higher POC contents, lighter δ13C values, and higher POC/PN ratios, indicating organic matter predominantly derived from terrestrial sources in areas south of St. Lawrence Island and north of 73°N. The downward trend of heavier δ13C values, together with reduction in clay and detrital minerals, suggests that vertical transport of SPM is hindered by stratification, resulting in transport of terrestrial materials toward northern basin areas. In the Chukchi Slope and Canada Basin areas, extremely light δ13C values (as low as -33.41‰ PDB) were mainly observed at depths of 20-60 m, where the Polar Mixed Layer (PML) intersects with the Upper Halocline Layer (UHL). Under the condition of low sea ice extent in 2016, the POC-δ13C values were heavier in the PML than in the UHL in the Chukchi Slope and Canada Basin areas. These findings provide insights into the sources, transport, and fate of organic matter in the Pacific Arctic region, which have important implications for understanding the biogeochemical cycles and ecosystem dynamics in this remote and rapidly changing environment.

Pontibacter liquoris sp. nov. and Pontibacter vulgaris sp. nov., two novel bacteria isolated from the pit mud of Chinese liquor.

Two pink-pigmented bacterial strains, designated NBU2971T and NBU2972T, were isolated from the pit mud of a Chinese liquor. Phylogenetic analyses based on 16S rRNA gene sequences suggested that strains NBU2971T and NBU2972T formed a distinct lineage within the family Hymenobacteraceae and were closely related to members of the genus Pontibacter. 16S rRNA gene sequences revealed that strain NBU2971T showed highest similarity of 97.9 % to Pontibacter arcticus 2b14T, and strain NBU2972T showed the highest similarity of 96.9 % to Pontibacter deserti JC215T. The 16S rRNA gene sequence similarity, average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between the two novel strains were 95.2, 73.8 and 19.6 %, respectively, suggesting that they represent different species. The ANI and dDDH values between two novel strains and related species of genus Pontibacter were well below the threshold limit for prokaryotic species delineation. The genomic DNA G+C contents of strains NBU2971T and NBU2972T were 51.3 and 44.5 mol%, respectively. The major cellular fatty acids of the two novel strains were iso-C15 : 0 and summed feature 4 (iso-C17 : 1 I and/or anteiso-C17 : 1 B). The major polar lipid of both novel strains was phosphatidylethanolamine. The only respiratory quinone was MK-7. Combining results of phenotypic, chemotaxonomic and genotypic data, strains NBU2971T and NBU2972T are considered to be two representatives in the genus Pontibacter, which the name Pontibacter liquoris sp. nov. and Pontibacter vulgaris sp. nov. are proposed. The type strains of the new species are NBU2971T (=KCTC 82916T=MCCC 1K06395T) and NBU2972T (=KCTC 82917T=MCCC 1K06396T), respectively.

A targeted liquid cultivation method for previously uncultured non-colony forming microbes.

A large number of microbes are not able to form colonies using agar-plating methods, which is one of the reasons that cultivation based on solid media leaves the majority of microbial diversity in the environment inaccessible. We developed a new Non-Colony-Forming Liquid Cultivation method (NCFLC) that can selectively isolate non-colony-forming microbes that exclusively grow in liquid culture. The NCFLC method involves physically separating cells using dilution-to-extinction (DTE) cultivation and then selecting those that could not grow on a solid medium. The NCFLC was applied to marine samples from a coastal intertidal zone and soil samples from a forest area, and the results were compared with those from the standard direct plating method (SDP). The NCFLC yielded fastidious bacteria from marine samples such as Acidobacteriota, Epsilonproteobacteria, Oligoflexia, and Verrucomicrobiota. Furthermore, 62% of the isolated strains were potential new species, whereas only 10% were novel species from SDP. From soil samples, isolates belonging to Acidobacteriota and Armatimonadota (which are known as rare species among identified isolates) were exclusively isolated by NCFLC. Colony formation capabilities of isolates cultivated by NCFLC were tested using solid agar plates, among which approximately one-third of the isolates were non-colony-forming, approximately half-formed micro-colonies, and only a minority could form ordinary size colonies. This indicates that the majority of the strains cultivated by NCFLC were previously uncultured microbial species unavailable using the SDP method. The NCFCL method described here can serve as a new approach to accessing the hidden microbial dark matter.

The distribution and enrichment of trace elements in surface and core sediments from the Changjiang River Estuary, China: Evidence for anthropogenic inputs and enhanced availability of rare earth elements (REE).

Huge amount of trace metals emitted through manmade activities are carried by the Changjiang River into the East China Sea. Most of them deposit in the Changjiang River Estuary and threaten the regional aquatic environment. In this study, major and trace elements of 34 archive surface sediments and two cores are examined. Sequential extraction procedures were also performed on surface sediments from 12 sites. We found that Tl, Tm, Er show distinct accumulation in surface sediments in the order of Tm > Tl > Er. Particularly, abnormally elevated HREE are observed mainly in those sites near the mouth of the estuary. Most elements exhibit an obvious reduction in the upper 30 cm of core B8, reflecting a decrease of sediment discharge from Changjiang River runoff. The increase of some trace elements recorded in the upper 20 cm of core C3 demonstrates a distinct local anthropogenic input in recent years.

Oricola nitratireducens sp. nov., a novel nitrate reducing bacterium isolated from marine sediment in East China Sea.

A novel strain designated NBU1457T, was isolated from marine sediment sampled on Meishan Island located in the East China Sea. Cells of strain NBU1457T was Gram-negative, facultatively anaerobic, non-motile and ovoid-shaped. Strain NBU1457T grew optimally at 37 °C, NaCl concentration of 2.0-3.0% (w/v) and pH 6.5-7.5. Catalase and oxidase activities, urease, nitrate reduction and H2S production were positive. Indole production, methyl red reaction, hydrolysis of starch, gelatin, casein, Tweens 20, 40, 60 and 80 were negative. Comparative analysis of the 16S rRNA gene sequence showed highest similarities to the species with validated name Oricola thermophila MEBiC13590T (98.8%), Oricola cellulosilytica CC-AMH-0 T (97.9%) and Oricola indica JL-62 T (97.9%). Phylogenetic analyses indicated that strain NBU1457T clustered with the genus Oricola and closely related to strains Oricola thermophila MEBiC13590T, Oricola cellulosilytica CC-AMH-0 T and Oricola indica JL-62 T. The average nucleotide identity and digital DNA-DNA hybridization values between strain NBU1457T and related species of genus Oricola were well below the threshold limit for prokaryotic species delineation. The DNA G + C content was 63.2%. The major cellular fatty acid was summed feature 8 (C18:1 ω7c and/or C18:1 ω6c). The major polar lipids were phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylmonomethylethanolamine, sulfoquinovosyldiacylglycerol and phosphatidylglycerol. The only respiratory quinone was ubiquinone-10 (Q-10). Combining results of our phenotypic, chemotaxonomic and genotypic data, strain NBU1457T is considered to be a representative in the genus Oricola, which the name Oricola nitratireducens sp. nov. is proposed. The type strain of the new species is NBU1457T (= KCTC 82225 T = MCCC 1K04764T).

Coverage of 13-Valent Pneumococcal Conjugate Vaccine Among Children 0-15 Months of Age - 9 Provinces, China, 2019-2021.

What is already known on this topic?: Limited data exist regarding the coverage of the 13-valent pneumococcal conjugate vaccine (PCV13) in China. A lack of official statistics, coupled with an insufficient body of published literature, hinders the accurate depiction of the current situation. What is added by this report?: This study investigated the utilization of PCV13 and estimated its coverage in nine provinces across eastern, central, and western China between 2019 and 2021. Despite an annual increase in PCV13 usage during this period, the overall coverage remained suboptimal. What are the implications for public health practice?: Consideration should be given to incorporating vaccines into the Expanded Program of Immunization, reducing vaccine prices, and addressing the vaccination coverage gap between eastern and western regions when there is an adequate supply of PCV13, particularly with domestic vaccines.

A co-adaptive duality-aware framework for biomedical relation extraction.

MOTIVATION: Biomedical relation extraction is a vital task for electronic health record mining and biomedical knowledge base construction. Previous work often adopts pipeline methods or joint methods to extract subject, relation, and object while ignoring the interaction of subject-object entity pair and relation within the triplet structure. However, we observe that entity pair and relation within a triplet are highly related, which motivates us to build a framework to extract triplets that can capture the rich interactions among the elements in a triplet. RESULTS: We propose a novel co-adaptive biomedical relation extraction framework based on a duality-aware mechanism. This framework is designed as a bidirectional extraction structure that fully takes interdependence into account in the duality-aware extraction process of subject-object entity pair and relation. Based on the framework, we design a co-adaptive training strategy and a co-adaptive tuning algorithm as collaborative optimization methods between modules to promote better mining framework performance gain. The experiments on two public datasets show that our method achieves the best F1 among all state-of-the-art baselines and provides strong performance gain on complex scenarios of various overlapping patterns, multiple triplets, and cross-sentence triplets. AVAILABILITY AND IMPLEMENTATION: Code is available at https://github.com/11101028/CADA-BioRE.

Efficacy of PBTZ169 and pretomanid against Mycobacterium avium, Mycobacterium abscessus, Mycobacterium chelonae, and Mycobacterium fortuitum in BALB/c mice models.

Objectives: We aimed to evaluate the activity of PBTZ169 and pretomanid against non-tuberculous mycobacteriosis (NTM) in vitro and in vivo. Methods: The minimum inhibitory concentrations (MICs) of 11 antibiotics, against slow-growing mycobacteria (SGMs) and rapid-growing mycobacteria (RGMs) were tested using the microplate alamarBlue assay. The in vivo activities of bedaquiline, clofazimine, moxifloxacin, rifabutin, PBTZ169 and pretomanid against four common NTMs were assessed in murine models. Results: PBTZ169 and pretomanid had MICs of >32 µg/mL against most NTM reference and clinical strains. However, PBTZ169 was bactericidal against Mycobacterium abscessus (3.33 and 1.49 log10 CFU reductions in the lungs and spleen, respectively) and Mycobacterium chelonae (2.29 and 2.24 CFU reductions in the lungs and spleen, respectively) in mice, and bacteriostatic against Mycobacterium avium and Mycobacterium fortuitum. Pretomanid dramatically decreased the CFU counts of M. abscessus (3.12 and 2.30 log10 CFU reductions in the lungs and spleen, respectively), whereas it showed moderate inhibition of M. chelonae and M. fortuitum. Bedaquiline, clofazimine, and moxifloxacin showed good activities against four NTMs in vitro and in vivo. Rifabutin did not inhibit M. avium and M. abscessus in mice. Conclusion: PBTZ169 appears to be a candidate for treating four common NTM infections. Pretomanid was more active against M. abscessus, M. chelonae and M. fortuitum than against M. avium.

The value of Pediatric Early Warning Score combined with SBAR in neonatal pneumonia nursing: A retrospective cohort study.

To observe the effect of the Pediatric Early Warning System (PEWS) score combined with the situation-background-assessment-recommendation (SBAR) shift communication system in neonates with severe pneumonia in the pediatric intensive care unit. A total of 230 neonates admitted to the pediatric intensive care unit of our hospital from January 2018 to January 2021 were enrolled in this study. Participants were divided into an experimental group (110 patients, PEWS score combined with SBAR shift communication system) and a control group (120 patients, routine diagnosis and treatment and shift change). The early recognition rate, incidence of handover problems, and prognosis of critically ill children in the 2 groups were analyzed. Compared to the control group, the correct recognition rate of disease observation and early recognition rate of critically ill children in the experimental group were significantly higher, and the incidence of handover problems was significantly lower (P < .05). There was no significant difference in the incidence of asphyxia, heart failure, and toxic encephalopathy between both groups. The application of the PEWS score combined with the SBAR shift communication system can facilitate timely identification of deterioration of the condition of children with severe pneumonia, reduce handover problems, and help to implement interventions or rescue according to the changes in a patient's condition, which may be beneficial in improving the patient's prognosis.

Efficacy of Replacing Linezolid with OTB-658 in Anti-Tuberculosis Regimens in Murine Models.

Linezolid (LZD) was the first oxazolidinone approved for treating drug-resistant tuberculosis. A newly approved regimen combining LZD with bedaquiline (BDQ) and pretomanid (PMD) (BPaL regimen) is the first 6-month oral regimen that is effective against multidrug- and extensively drug-resistant tuberculosis. However, LZD toxicity, primarily due to mitochondrial protein synthesis inhibition, may undermine the efficacy of LZD regimens, and oxazolidinones with higher efficacy and lower toxicity during prolonged administration are needed. OTB-658 is an oxazolidinone anti-TB candidate derived from LZD that could replace LZD in TB treatment. We previously found that OTB-658 had better anti-TB activity and safety than LZD in vitro and in vivo. In the present work, two murine TB models were used to evaluate replacing LZD with OTB-658 in LZD-containing regimens. In the C3HeB/FeJ murine model, replacing 100 mg/kg LZD with 50 mg/kg OTB-658 in the BDQ + PMD backbone significantly reduced lung and spleen CFU counts (P < 0.05), and there were few relapses at 8 weeks of treatment. Replacing 100 mg/kg LZD with 50 or 100 mg/kg OTB-658 in the pyrifazimine (previously called TBI-166) + BDQ backbone did not change the anti-TB efficacy and relapse rate. In BALB/c mice, replacing 100 mg/kg LZD with 100 mg/kg OTB-658 in the TBI-166 + BDQ backbone resulted in no culture-positive lungs at 4 and 8 weeks of treatment, and there were no significant differences in relapses rate between the groups. In conclusion, OTB-658 is a promising clinical candidate that could replace LZD in the BPaL or TBI-166 + BDQ + LZD regimens and should be studied further in clinical trials.

How I do it? The surgical resection of the fourth ventricle choroid plexus papilloma.

BACKGROUND: The surgical resection of the large fourth ventricle choroid plexus papilloma (CPP) is complicated, where the challenge is to minimize the impairment of the vermis and the brainstem and restore the cerebrospinal fluid circulation. METHOD: We report a case of large CPP that wholly occluded the fourth ventricle, extended to the Luschka foramen, and underwent radical resection via telovelar approach. The intraoperative endoscope was applied to inspect the tumor residue and the aqueduct's opening. CONCLUSION: This case demonstrates the surgical nuance of the fourth ventricle CPP.

Estimating the influence of high temperature on hand, foot, and mouth disease incidence in China.

The burden of disease caused by ambient high temperature has become a public health concern, but the associations between high temperature and hand, foot, and mouth disease (HFMD) remain indistinct. We used distributed lag non-linear model (DLNM) to estimate the burden of disease attribute to high temperature, adjusting for long-term trend and weather confounders. Total 18,167,455 cases were reported in 31 Chinese provinces, the incidence of HFMD showed a gradually increasing trend from 2008 to 2017 in China. Minimum morbidity temperature (MMT) was mainly concentrated at 17 to 23 °C in ≤ 5 years old group, 18 to 25 °C in 6 ~ 10 years old group and 19 to 27 °C in > 10 years old group. The greatest relative risk (RR) in age group ≤ 5 years old was 2.06 (95% CI: 1.85 ~ 2.30) in Heilongjiang, and the lowest RR was 1.02 (95% CI: 1.00 ~ 1.05) in Guangdong; the greatest RR in age group 6 ~ 10 years old was 2.24 (95% CI: 1.72 ~ 2.91) in Guizhou, and the lowest RR was 1.01 (95% CI: 0.97 ~ 1.12) in Tianjin; the greatest RR in the age group > 10 years old was 2.53 (95% CI: 1.66 ~ 3.87) in Heilongjiang, and the lowest RR was 1.02 (95% CI: 0.71 ~ 1.46) in Henan. We found the positive association between high temperature and HFMD in China.

Luteolibacter marinus sp. nov., a novel bacterium in the family Verrucomicrobiaceae, isolated from marine sediment.

A Gram-negative, rod-shaped, non-motile and strictly aerobic bacterium, designated NBU1238T, was isolated from marine sediment sampled on Meishan Island located in the East China Sea. Strain NBU1238T was able to grow optimally at 28-32 °C, at pH 7.5 and with no NaCl. Catalase and oxidase activities, H2S production and hydrolysis of Tweens 40 and 60 were positive. Methyl red reaction, Voges-Proskauer test and hydrolysis of starch, casein and Tweens 20 and 80 were negative. The major cellular fatty acids were iso-C14 : 0, C16 : 0, C16 : 1 ω9c and C14 : 0. The only respiratory quinone was menaquinone-9. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and phosphatidylmethylethanolamine. The 16S rRNA gene sequence of strain NBU1238T showed 95.6, 95.6, 94.8 and 93.8% sequence similarity to Luteolibacter flavescens GKXT, Luteolibacter luteus G-1-1-1T, Luteolibacter arcticus MC 3726T and Luteolibacter pohnpeiensis A4T-83T, respectively. Phylogenetic analyses indicated that strain NBU1238T clustered with the genus Luteolibacter and was closely related to strains L. flavescens GKXT, L. arcticus MC 3726T and L. luteus G-1-1-1T. The average nucleotide identity and digital DNA-DNA hybridization values between strain NBU1238T and related species of genus Luteolibacter were well below the threshold limit for prokaryotic species delineation. The DNA G+C content of the genomic DNA was 65.0 mol%. Based on its phenotypic, chemotaxonomic and genotypic data, strain NBU1238T is considered to be a representative of a novel species in the genus Luteolibacter, for which the name Luteolibacter marinus sp. nov. is proposed. The type strain is NBU1238T (=KCTC 82227T=MCCC 1K04772T).

Norditerpenoids biosynthesized by variediene synthase-associated P450 machinery along with modifications by the host cell Aspergillus oryzae.

The chemical diversity of terpenoids is typically established by terpene synthase-catalyzed cyclization and diversified by post-tailoring modifications. Fungal bifunctional terpene synthase (BFTS) associated P450 enzymes have shown significant catalytic potentials through the development of various new terpenoids with different biological activities. This study discovered the BFTS and its related gene cluster from the plant endophytic fungus Didymosphaeria variabile 17020. Heterologous expression of the BFTS in Saccharomyces cerevisiae resulted in the characterization of a major product diterpene variediene (1), along with two new minor products neovariediene and neoflexibilene. Further heterologous expression of the BFTS and one cytochrome P450 enzyme VndE (CYP6138B1) in Aspergillus oryzae NSAR1 led to the identification of seven norditerpenoids (19 carbons) with a structurally unique 5/5 bicyclic ring system. Interestingly, in vivo experiments suggested that the cyclized terpene variediene (1) was modified by VndE along with the endogenous enzymes from the host cell A. oryzae through serial chemical conversions, followed by multi-site hydroxylation via A. oryzae endogenous enzymes. Our work revealed that the two-enzymes biosynthetic system and host cell machinery could produce structurally unique terpenoids.