bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of core cuprotosis-correlated biomarkers in abdominal aortic aneurysm immune microenvironment based on bioinformatics
Authors: Hu Jiateng , Xue Song , Xu Zhijue , Wu Zhaoyu , Xu Xintong , Wang Xin , Liu Guang , Lu Xinwu , Li Bo , Liu Xiaobing
Published: April 2023

Background

The occurrence of abdominal aortic aneurysms (AAAs) is related to the disorder of immune microenvironment. Cuprotosis was reported to influence the immune microenvironment. The objective of this study is to identify cuprotosis-related genes involved in the pathogenesis and progression of AAA.

Methods

Differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) in mouse were identified following AAA through high-throughput RNA sequencing. The enrichment analyses of pathway were selected through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG). The validation of cuprotosis-related genes was conducted through immunofluorescence and western blot analyses.

Results

Totally, 27616 lncRNAs and 2189 mRNAs were observed to be differentially expressed (|Fold Change| ≥ 2 and q< 0.05) after AAA, including 10424 up-regulated and 17192 down-regulated lncRNAs, 1904 up-regulated and 285 down-regulated mRNAs. Gene ontology and KEGG pathway analysis showed that the DElncRNAs and DEmRNAs were implicated in many different biological processes and pathways. Furthermore, Cuprotosis-related genes (NLRP3, FDX1) were upregulated in the AAA samples compared with the normal one.

Conclusion

Cuprotosis-related genes (NLRP3,FDX1) involved in AAA immune environment might be critical for providing new insight into identification of potential targets for AAA therapy.
Mast cells selectively produce inflammatory mediators and impact the early response to Chlamydia reproductive tract infection
Authors: Mayavannan Animamalar , Shantz Emily , Haidl Ian D. , Wang Jun , Marshall Jean S.
Published: April 2023

Introduction

Chlamydia trachomatis (C. trachomatis) is a Gram-negative obligate intracellular bacterium that causes reproductive tract complications in women, including ectopic pregnancies and tubal factor infertility. We hypothesized that mast cells, which are common at mucosal barriers, may contribute to responses to Chlamydia infection and aimed to define human mast cell responses to C. trachomatis.

Methods

Human cord blood-derived mast cells (CBMCs) were exposed to C. trachomatis to assess bacterial uptake, mast cell degranulation, gene expression, and production of inflammatory mediators. The role of formyl peptide receptors and Toll-like receptor 2 (TLR2) were investigated using pharmacological inhibitors and soluble TLR2. Mast cell-deficient mice and littermate controls were used to examine the in vivo role of mast cells in influencing the immune response to Chlamydia infection in the female reproductive tract.

Results

C. trachomatis bacteria were taken up by human mast cells but did not replicate efficiently inside CBMCs. C. trachomatis-activated mast cells did not degranulate but maintained viability and exhibited cellular activation with homotypic aggregation and upregulation of ICAM-1. However, they significantly enhanced the gene expression of IL1B, CCL3, NFKB1, CXCL8, and IL6. Inflammatory mediators were produced, including TNF, IL-1β, IL-1RA, IL-6, GM-CSF, IL-23, CCL3, CCL5, and CXCL8. Endocytic blockade resulted in reduced gene expression of IL6, IL1B, and CCL3, suggesting C. trachomatis induced mast cell activation in both extracellular and intracellular locations. The IL-6 response to C. trachomatis was reduced when CBMCs were treated with C. trachomatis coated with soluble TLR2. Mast cells derived from TLR2-deficient mice also demonstrated a reduced IL-6 response to C. muridarum. Five days following C. muridarum infection, mast cell-deficient mice showed attenuated CXCL2 production and significantly reduced numbers of neutrophils, eosinophils, and B cells in the reproductive tract when compared with mast cell-containing littermates.

Discussion

Taken together, these data demonstrate that mast cells are reactive to Chlamydia spp. through multiple mechanisms that include TLR2-dependent pathways. Mast cells also play an important role in shaping in vivo immune responses in Chlamydia reproductive tract infection through both effector cell recruitment and modification of the chemokine microenvironment.
Solid phase extraction of ocean dissolved organic matter with PPL cartridges: efficiency and selectivity
Authors: Jerusalén-Lleó E. , Nieto-Cid M. , Fuentes-Santos I. , Dittmar Thorsten , Álvarez-Salgado X. A.
Published: April 2023

Our current knowledge of the chemical composition of ocean dissolved organic matter (DOM) is limited, mainly because of its extreme molecular diversity, low concentration of individual compounds and the elevated ionic strength of ocean waters. As a result, many analytical methods require a previous extraction step. The efficiency and selectivity of the extraction method defines the representativeness of the extracted DOM fraction. Nowadays, the most widespread procedure for concentrating DOM is solid phase extraction (SPE) using styrene divinyl benzene polymer cartridges (PPL). Here, we investigate the effect of SPE-PPL on DOM elemental and optical properties to assess the efficiency and selectivity of this extraction method on water samples from the main intermediate and deep water masses of Arctic, Mediterranean and Antarctic origin present in the Cape Vert Frontal Zone (CVFZ, NW Africa). Furthermore, North and South Atlantic Central waters converge in this area and coastal DOM is injected by the giant upwelling filament of Cape Blanc. On one side, the colored fraction of DOM (CDOM) presented extraction efficiencies comparable to that of the bulk dissolved organic carbon (DOC), but decreased significantly with increasing wavelength, suggesting an affinity of PPL cartridges for low molecular weight organic compounds. While the protein-like fluorescent fraction of DOM (FDOM) was also extracted with the same efficiency than DOC, the extraction efficiency of the humic-like fraction was comparatively much higher. On the other side, dissolved organic nitrogen (DON) extraction efficiencies were about half that of DOC. These contrasting extraction efficiencies of the different DOM pools indicated that the extracts were enriched in N-poor, low molecular weight and recalcitrant DOM, therefore showing less variability than the corresponding bulk DOM. Furthermore, DOC, DON, CDOM and FDOM extracted were not homogeneous through the water column but displayed certain significant differences among water masses in both efficiency and selectivity.
Biases and improvements of the boreal winter–spring equatorial undercurrent in the Indian Ocean in the CMIP5 and CMIP6 models
Authors: Li Junling , Xu Kang , Wang Weiqiang , He Zhuoqi , Huang Ke
Published: April 2023

We assessed the performance of state-of-the-art coupled models in reproducing the equatorial undercurrent (EUC) in the Indian Ocean based on the outputs of the Coupled Model Intercomparison Project Phase 6 (CMIP6) models and compared with the Phase 5 (CMIP5) models. Our results showed that the CMIP6 models reproduced the boreal winter–spring Indian Ocean EUC more realistically than the CMIP5 models, although both generations of models underestimated the strength of the Indian Ocean EUC compared with the observations. This underestimation of the Indian Ocean EUC can be attributed to the excessively strong and westward-extended cold tongue in the equatorial Pacific. In the CMIP models, a stronger winter-mean cold tongue favors a stronger zonal sea surface temperature gradient, which forces a strong easterly wind bias over the equatorial western Pacific. This, in turn, contributes to an acceleration of the Walker circulation. This enhanced Walker circulation over the Indo-Pacific Ocean directly causes a lower level westerly wind bias over the equatorial Indian Ocean and drives a shallow west–deep east thermocline tilt bias, ultimately leading to an excessively weak EUC in the Indian Ocean via wind-induced thermocline processes. Compared with the CMIP5 models, the overall improvement in the strength of the winter–spring Indian Ocean EUC in the CMIP6 models can be traced back to the improvement in the degree of the strong and westward-extended cold tongue bias. Our results suggest that efforts should be made to reduce the bias in the mean-state equatorial Pacific sea surface temperature to further improve the simulation and projection of the atmospheric and oceanic circulations in the Indian Ocean.
Oxygen saturation targets for adults with acute hypoxemia in low and lower-middle income countries: a scoping review with analysis of contextual factors
Authors: Herbst Austin , Goel Swati , Beane Abi , Brotherton B. Jason , Dula Dingase , Ely E. Wesley , Gordon Stephen B. , Haniffa Rashan , Hedt-Gauthier Bethany , Limbani Felix , Lipnick Michael S. , Lyon Samuel , Njoki Carolyne , Oduor Peter , Otieno George , Pisani Luigi , Rylance Jamie , Shrime Mark G. , Uwamahoro Doris Lorette , Vanderburg Sky , Waweru-Siika Wangari , Twagirumugabe Theogene , Riviello Elisabeth
Published: April 2023

Knowing the target oxygen saturation (SpO2) range that results in the best outcomes for acutely hypoxemic adults is important for clinical care, training, and research in low-income and lower-middle income countries (collectively LMICs). The evidence we have for SpO2 targets emanates from high-income countries (HICs), and therefore may miss important contextual factors for LMIC settings. Furthermore, the evidence from HICs is mixed, amplifying the importance of specific circumstances. For this literature review and analysis, we considered SpO2 targets used in previous trials, international and national society guidelines, and direct trial evidence comparing outcomes using different SpO2 ranges (all from HICs). We also considered contextual factors, including emerging data on pulse oximetry performance in different skin pigmentation ranges, the risk of depleting oxygen resources in LMIC settings, the lack of access to arterial blood gases that necessitates consideration of the subpopulation of hypoxemic patients who are also hypercapnic, and the impact of altitude on median SpO2 values. This process of integrating prior study protocols, society guidelines, available evidence, and contextual factors is potentially useful for the development of other clinical guidelines for LMIC settings. We suggest that a goal SpO2 range of 90-94% is reasonable, using high-performing pulse oximeters. Answering context-specific research questions, such as an optimal SpO2 target range in LMIC contexts, is critical for advancing equity in clinical outcomes globally.
Lamellar macular defects: are degenerative lamellar macular holes truly degenerative?
Authors: Pertile Grazia , Iacovello Daniela , Maraone Giorgia , Bottega Elisa , Guerriero Massimo , Maggio Emilia
Published: April 2023

Purpose

To investigate morpho-functional changes after surgical treatment for ERM foveoschisis or lamellar macular hole (LMH), and to evaluate whether the two entities are associated with different healing processes and long-term outcomes.

Design

Retrospective interventional case series.

Methods

A total of 56 eyes, treated for lamellar macular defects and followed up for 24 months, were enrolled. The eyes were divided into two groups: 34 with ERM foveoschisis and 22 with LMH. Changes in the following features were evaluated and compared between the two groups: best-corrected visual acuity (BCVA), external limiting membrane (ELM) and ellipsoid zone (EZ) defects, central foveal thickness (CFT), and autofluorescence (FAF) diameter and area.

Results

After surgery, progressive BCVA improvement was observed with no significant difference between the two groups (p-value: 0.06). An increased number of eyes with intact outer-retinal layers was found both in the ERM foveoschisis and LMH groups. FAF diameter and area decreased significantly throughout the FU with no significant difference between the two groups (p-value: 0.2).

Conclusion

In the present study, significant functional and microstructural improvements were observed after surgery for both ERM foveoschisis and LMH, demonstrating considerable repair potential in both types of lamellar defects. These findings question the true “degenerative” nature of LMH.
Proteomics Reveal the Effect of Exogenous Electrons on Electroactive Escherichia coli
Authors: Feng Jiao , Feng Jia , Li Chunqiu , Xu Sheng , Wang Xin , Chen Kequan
Published: April 2023

Microbial cells utilizing electricity to produce high-value fuels and chemicals are the foundation of the biocathodic bioelectrochemical system. However, molecular mechanisms of electron transfer and utilization have not been elucidated. In this work, Escherichia coli engineered by introducing the Mtr pathway from Shewanella oneidensis exhibited stronger electrochemical activity than control and could utilize exogenous electrons to stimulate metabolite profiles and boost succinate production in the bioelectrochemical system. Proteomic analysis and real-time PCR were performed to investigate the effect of exogenous electrons on electroactive E. coli. Bioinformatics analysis suggested that the proteins of molecular function associated with oxidoreductase activity, 4 iron, 4 sulfur([4Fe-4S]) cluster binding, iron-sulfur cluster binding, and metal cluster binding were positively affected by exogenous electrons. Moreover, mapping to the Kyoto Encyclopedia of Genes and Genomes pathway database showed that the up-regulated proteins were mainly involved in metabolic pathways of tricarboxylic acid cycle, pyruvate metabolism, and nitrogen metabolism pathway, providing support for the metabolic balance of microbial cells shifting toward reduced end-products due to electron utilization. Using a biochemical method, the ompF-overexpressed strain was employed to investigate the function of the channel protein. These findings provided a theoretical basis for further improving electron transfer and utilization efficiency, and contributed to the potential applications of the bioelectrochemical system.
Rapid Discrimination of Clinically Important Pathogens Through Machine Learning Analysis of Surface Enhanced Raman Spectra
Authors: Tang Jia-Wei , Li Jia-Qi , Yin Xiao-Cong , Xu Wen-Wen , Pan Ya-Cheng , Liu Qing-Hua , Gu Bing , Zhang Xiao , Wang Liang
Published: April 2023

With its low-cost, label-free and non-destructive features, Raman spectroscopy is becoming an attractive technique with high potential to discriminate the causative agent of bacterial infections and bacterial infections per se. However, it is challenging to achieve consistency and accuracy of Raman spectra from numerous bacterial species and phenotypes, which significantly hinders the practical application of the technique. In this study, we analyzed surfaced enhanced Raman spectra (SERS) through machine learning algorithms in order to discriminate bacterial pathogens quickly and accurately. Two unsupervised machine learning methods, K-means Clustering (K-Means) and Agglomerative Nesting (AGNES) were performed for clustering analysis. In addition, eight supervised machine learning methods were compared in terms of bacterial predictions via Raman spectra, which showed that convolutional neural network (CNN) achieved the best prediction accuracy (99.86%) with the highest area (0.9996) under receiver operating characteristic curve (ROC). In sum, machine learning methods can be potentially applied to classify and predict bacterial pathogens via Raman spectra at general level.
A westernized diet changed the colonic bacterial composition and metabolite concentration in a dextran sulfate sodium pig model for ulcerative colitis
Authors: Panah Farhad M. , Nielsen Katrine D. , Simpson Gavin L. , Schönherz Anna , Schramm Andreas , Lauridsen Charlotte , Nielsen Tina S. , Højberg Ole , Fredborg Marlene , Purup Stig , Canibe Nuria
Published: April 2023

Introduction

Ulcerative colitis (UC) is characterized by chronic inflammation in the colonic epithelium and has a blurred etiology. A western diet and microbial dysbiosis in the colon were reported to play a role in UC development. In this study, we investigated the effect of a westernized diet, i.e., increasing fat and protein content by including ground beef, on the colonic bacterial composition in a dextran sulfate sodium (DexSS) challenged pig study.

Methods

The experiment was carried out in three complete blocks following a 2×2 factorial design including 24 six-week old pigs, fed either a standard diet (CT) or the standard diet substituted with 15% ground beef to simulate a typical westernized diet (WD). Colitis was induced in half of the pigs on each dietary treatment by oral administration of DexSS (DSS and WD+DSS, respectively). Samples from proximal and distal colon and feces were collected.

Results and discussion

Bacterial alpha diversity was unaffected by experimental block, and sample type. In proximal colon, WD group had similar alpha diversity to CT group and the WD+DSS group showed the lowest alpha diversity compared to the other treatment groups. There was a significant interaction between western diet and DexSS for beta diversity, based on Bray-Curtis dissimilarly. The westernized diet and DexSS resulted in three and seven differentially abundant phyla, 21 and 65 species, respectively, mainly associated with the Firmicutes and Bacteroidota phyla followed by Spirochaetota, Desulfobacterota, and Proteobacteria. The concentration of short-chain fatty acids (SCFA) was lowest in the distal colon. Treatment had a slight effect on the estimates for microbial metabolites that might have valuable biological relevance for future studies. The concentration of putrescine in the colon and feces and that of total biogenic amines was highest in the WD+DSS group. We conclude that a westernized diet could be a potential risk factor and an exacerbating agent for UC by reducing the abundance of SCFA-producing bacteria, increasing the abundance of pathogens such asHelicobacter trogontum, and by increasing the concentration of microbial proteolytic-derived metabolites in the colon.
Primer design for the amplification of the ammonium transporter genes from the uncultured haptophyte algal species symbiotic with the marine nitrogen-fixing cyanobacterium UCYN-A1
Authors: Salas Krystal , Cabello Ana M. , Turk-Kubo Kendra A. , Zehr Jonathan P. , Cornejo-Castillo Francisco M.
Published: April 2023

The multiple symbiotic partnerships between closely related species of the haptophyte algae Braarudosphaera bigelowii and the nitrogen-fixing cyanobacteria Candidatus Atelocyanobacterium thalassa (UCYN-A) contribute importantly to the nitrogen and carbon cycles in vast areas of the ocean. The diversity of the eukaryotic 18S rDNA phylogenetic gene marker has helped to identify some of these symbiotic haptophyte species, yet we still lack a genetic marker to assess its diversity at a finer scale. One of such genes is the ammonium transporter (amt) gene, which encodes the protein that might be involved in the uptake of ammonium from UCYN-A in these symbiotic haptophytes. Here, we designed three specific PCR primer sets targeting the amt gene of the haptophyte species (A1-Host) symbiotic with the open ocean UCYN-A1 sublineage, and tested them in samples collected from open ocean and near-shore environments. Regardless of the primer pair used at Station ALOHA, which is where UCYN-A1 is the pre-dominant UCYN-A sublineage, the most abundant amt amplicon sequence variant (ASV) was taxonomically classified as A1-Host. In addition, two out of the three PCR primer sets revealed the existence of closely-related divergent haptophyte amt ASVs (>95% nucleotide identity). These divergent amt ASVs had higher relative abundances than the haptophyte typically associated with UCYN-A1 in the Bering Sea, or co-occurred with the previously identified A1-Host in the Coral Sea, suggesting the presence of new diversity of closely-related A1-Hosts in polar and temperate waters. Therefore, our study reveals an overlooked diversity of haptophytes species with distinct biogeographic distributions partnering with UCYN-A, and provides new primers that will help to gain new knowledge of the UCYN-A/haptophyte symbiosis.
Variation in Sphingomonas traits across habitats and phylogenetic clades
Authors: Sorouri Bahareh , Rodriguez Cynthia I. , Gaut Brandon S. , Allison Steven D.
Published: April 2023

Whether microbes show habitat preferences is a fundamental question in microbial ecology. If different microbial lineages have distinct traits, those lineages may occur more frequently in habitats where their traits are advantageous. Sphingomonas is an ideal bacterial clade in which to investigate how habitat preference relates to traits because these bacteria inhabit diverse environments and hosts. Here we downloaded 440 publicly available Sphingomonas genomes, assigned them to habitats based on isolation source, and examined their phylogenetic relationships. We sought to address whether: (1) there is a relationship between Sphingomonas habitat and phylogeny, and (2) whether there is a phylogenetic correlation between key, genome-based traits and habitat preference. We hypothesized that Sphingomonas strains from similar habitats would cluster together in phylogenetic clades, and key traits that improve fitness in specific environments should correlate with habitat. Genome-based traits were categorized into the Y-A-S trait-based framework for high growth yield, resource acquisition, and stress tolerance. We selected 252 high quality genomes and constructed a phylogenetic tree with 12 well-defined clades based on an alignment of 404 core genes. Sphingomonas strains from the same habitat clustered together within the same clades, and strains within clades shared similar clusters of accessory genes. Additionally, key genome-based trait frequencies varied across habitats. We conclude that Sphingomonas gene content reflects habitat preference. This knowledge of how environment and host relate to phylogeny may also help with future functional predictions about Sphingomonas and facilitate applications in bioremediation.
A novel algicidal properties of fermentation products from Pseudomonas sp. Ps3 strain on the toxic red tide dinoflagellate species
Authors: Zheng Luwei , Lin Hong , Balaji-Prasath Barathan , Su Yuping , Wang Ying , Zheng Yi , Yu Guanglang
Published: April 2023

The viability of both China’s offshore fishing operations and the global marine fishing industry is threatened by the occurrence of red tides caused by Gymnodinium catenatum and Karenia mikimotoi. Effective control of these dinoflagellate-mediated red tides has become a pressing issue that requires immediate attention. In this study, High-efficiency marine alginolytic bacteria were isolated and underwent molecular biological identification to confirm their algicidal properties. Based on a combination of morphological, physiological, biochemical, and sequencing results, Strain Ps3 was identified as belonging to the species Pseudomonas sp. We examine the effects of algicidal bacteria on the red tide species G. catenatum and K. mikimotoi within an indoor experimental setting. Then gas chromatography– mass spectrometry (GC–MS) was used to analyze the structure of the algolytic active substances. This investigation demonstrated that with exposure to the algae-lysis experiment, the Ps3 strain has the best algae-lysis effect, with G. catenatum and K. mikimotoi reaching 83.0 and 78.3%. Our results from the sterile fermentation broth experiment showed that the inhibitory effect on the two red tide algae was positively correlated with the concentration of the treatment. At a treatment concentration of 2.0% (v/v), the 48 h lysis rates of G. catenatum and K. mikimotoi due to exposure to the Ps3 bacterial fermentation broth were 95.2 and 86.7%, respectively. The results of this study suggest that the algaecide may be a rapid and effective method to control dinoflagellate blooms, as evidenced by the observed changes in cellular morphology in all cases. In the ethyl acetate phase of Ps3 fermentation broth, the cyclic (leucine-leucine) dipeptide was the most abundant. The findings of this study contribute to our understanding of red tide prevention and control and provide a theoretical foundation for further research in this field.
Complex probiotics alleviate ampicillin-induced antibiotic-associated diarrhea in mice
Authors: Li Wenwen , Zhang Siyu , Wang Yanyan , Bian Hongsheng , Yu Shuang , Huang Lili , Ma Weiwei
Published: April 2023

Aim

Antibiotic-associated diarrhea (AAD) is a common side effect during antibiotic treatment, which can cause dysbacteriosis of the gut microbiota. Previous studies have shown beneficial effects in AAD treatment with Bifidobacterium lactis XLTG11, Lactobacillus casei Zhang, Lactobacillus plantarum CCFM8661, and Lactobacillus rhamnosus Probio-M9. However, no studies have been conducted on the immunomodulatory effects and protective intestinal barrier function of four complex probiotics. The aim of our study is to investigate the alleviation effects of complex probiotics on ampicillin-induced AAD.

Methods

Thirty-six BALB/c mice were randomly divided into six groups: normal control group (NC), model control group (MC), low-, medium-, and high-dose probiotics groups (LD, MD, and HD), and positive drug (Bifico, 1 × 107 cfu) control group (PDC; Bifico, also known as Bifidobacterium Triple Live Capsule, is composed of Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis). An AAD model was established by intragastric administration of ampicillin, by gavage of different doses of complex probiotics and Bifico. The weight gain, fecal water content, loose stool grade, intestinal permeability, total protein and albumin levels, intestinal barrier, cytokine levels, and gut microbiota were determined.

Results

The results showed that complex probiotics significantly decreased the fecal water content, loose stool grade, intestinal permeability, and ileum tissue damage. Their application increased the weight gain, SIgA, TP, and ALB levels. Additionally, complex probiotics significantly decreased the levels of pro-inflammatory cytokines and increased those of anti-inflammatory cytokines. Meanwhile, the mRNA expression levels of ZO-1, occludin, claudin-1, and MUC2 were significantly upregulated in the probiotic-treated group. Furthermore, the complex probiotics increased the gut microbiota diversity and modulated the changes in the gut microbiota composition caused by ampicillin. At the phylum level, the abundance of Proteobacteria in the HD group was lower than that in the MC group, whereas that of Bacteroidetes was higher. At the genus level, the abundances of Klebsiella and Parabacteroides in the HD group were lower, whereas those of Bacteroides, Muribaculaceae, and Lactobacillus were higher than those in the MC group. Moreover, Spearman’s correlation analysis also found that several specific gut microbiota were significantly correlated with AAD-related indicators.

Conclusion

We found that complex probiotics improved the diarrhea-related indexes, regulated gut microbiota composition and diversity, increased the expression levels of intestinal protective barrier-related genes, preserved the intestinal barrier function, and relieved inflammation and intestinal injury, thereby effectively improving AAD-associated symptoms.
A spitting image: molecular diagnostics applied to saliva enhance detection of Streptococcus pneumoniae and pneumococcal serotype carriage
Authors: Miellet Willem R. , van Veldhuizen Janieke , Litt David , Mariman Rob , Wijmenga-Monsuur Alienke J. , Nieuwenhuijsen Tessa , Christopher Jennifer , Thombre Rebecca , Eletu Seyi , Bosch Thijs , Rots Nynke Y. , van Houten Marianne Alice , Miller Elizabeth , Fry Norman K. , Sanders Elisabeth A. M. , Trzciński Krzysztof
Published: April 2023

Background

Despite strong historical records on the accuracy of saliva testing, oral fluids are considered poorly suited for pneumococcal carriage detection. We evaluated an approach for carriage surveillance and vaccine studies that increases the sensitivity and specificity of pneumococcus and pneumococcal serotype detection in saliva samples.

Methods

Quantitative PCR (qPCR)-based methods were applied to detect pneumococcus and pneumococcal serotypes in 971 saliva samples collected from 653 toddlers and 318 adults. Results were compared with culture-based and qPCR-based detection in nasopharyngeal samples collected from children and in nasopharyngeal and oropharyngeal samples collected from adults. Optimal Cq cut-offs for positivity in qPCRs were determined via receiver operating characteristic curve analysis and accuracy of different approaches was assessed using a composite reference for pneumococcal and for serotype carriage based on isolation of live pneumococcus from the person or positivity of saliva samples determined with qPCR. To evaluate the inter-laboratory reproducibility of the method, 229 culture-enriched samples were tested independently in the second center.

Results

In total, 51.5% of saliva samples from children and 31.8% of saliva samples from adults were positive for pneumococcus. Detection of pneumococcus by qPCR in culture-enriched saliva exhibited enhanced sensitivity and higher agreement with a composite reference compared to diagnostic culture of nasopharyngeal samples in children (Cohen’s κ: 0.69–0.79 vs. 0.61–0.73) and in adults (κ: 0.84–0.95 vs. 0.04–0.33) and culture of oropharyngeal samples in adults (κ: 0.84–0.95 vs. −0.12–0.19). Similarly, detection of serotypes with qPCR in culture-enriched saliva exhibited enhanced sensitivity and higher agreement with a composite reference compared to nasopharyngeal culture in children (κ: 0.73–0.82 vs. 0.61–0.73) and adults (κ: 0.90–0.96 vs. 0.00–0.30) and oropharyngeal culture in adults (κ: 0.90–0.96 vs. −0.13 to 0.30). However, results of qPCRs targeting serotype 4, 5, and 17F and serogroups 9, 12, and 35 were excluded due to assays’ lack of specificity. We observed excellent quantitative agreement for qPCR-based detection of pneumococcus between laboratories. After exclusion of serotype/serogroup-specific assays with insufficient specificity, moderate agreement (κ 0.68, 95% CI 0.58–0.77) was observed.

Conclusion

Molecular testing of culture-enriched saliva samples improves the sensitivity of overall surveillance of pneumococcal carriage in children and adults, but limitations of qPCR-based approaches for pneumococcal serotypes carriage detection should be considered.
Genomic analysis and characterization of phages infecting the marine Roseobacter CHAB-I-5 lineage reveal a globally distributed and abundant phage genus
Authors: Zhang Zefeng , Wu Zuqing , Liu He , Yang Mingyu , Wang Rui , Zhao Yanlin , Chen Feng
Published: April 2023

Marine phages play an important role in marine biogeochemical cycles by regulating the death, physiological metabolism, and evolutionary trajectory of bacteria. The Roseobacter group is an abundant and important heterotrophic bacterial group in the ocean, and plays an important role in carbon, nitrogen, sulfur and phosphorus cycling. The CHAB-I-5 lineage is one of the most dominant Roseobacter lineages, but remains largely uncultured. Phages infecting CHAB-I-5 bacteria have not yet been investigated due to the lack of culturable CHAB-I-5 strains. In this study, we isolated and sequenced two new phages (CRP-901 and CRP-902) infecting the CHAB-I-5 strain FZCC0083. We applied metagenomic data mining, comparative genomics, phylogenetic analysis, and metagenomic read-mapping to investigate the diversity, evolution, taxonomy, and biogeography of the phage group represented by the two phages. The two phages are highly similar, with an average nucleotide identity of 89.17%, and sharing 77% of their open reading frames. We identified several genes involved in DNA replication and metabolism, virion structure, DNA packing, and host lysis from their genomes. Metagenomic mining identified 24 metagenomic viral genomes closely related to CRP-901 and CRP-902. Genomic comparison and phylogenetic analysis demonstrated that these phages are distinct from other known viruses, representing a novel genus-level phage group (CRP-901-type). The CRP-901-type phages do not contain DNA primase and DNA polymerase genes, but possess a novel bifunctional DNA primase-polymerase gene with both primase and polymerase activities. Read-mapping analysis showed that the CRP-901-type phages are widespread across the world’s oceans and are most abundant in estuarine and polar waters. Their abundance is generally higher than other known roseophages and even higher than most pelagiphages in the polar region. In summary, this study has greatly expanded our understanding of the genetic diversity, evolution, and distribution of roseophages. Our analysis suggests that the CRP-901-type phage is an important and novel marine phage group that plays important roles in the physiology and ecology of roseobacters.
Effects of three different probiotics of Tibetan sheep origin and their complex probiotics on intestinal damage, immunity, and immune signaling pathways of mice infected with Clostridium perfringens type C
Authors: He Xi , Ye Guisheng , Xu Shuqin , Chen Xiaohui , He Xiaolong , Gong Zifeng
Published: April 2023

Tibetan sheep have unique intestinal microorganisms in their intestines that are adapted to the highland alpine and anoxic environment. To further clarify the probiotic properties of Tibetan sheep-derived probiotics, we selected three Tibetan sheep-derived probiotic isolates (Enterococcus faecalis EF1-mh, Bacillus subtilis BS1-ql, and Lactobacillus sakei LS-ql) to investigate the protective mechanisms of monocultures and their complex strains against Clostridium perfringens type C infection in mice. We established a model of C. perfringens type C infection and used histology and molecular biology to analyze the effects and mechanisms of different probiotic treatments on mice after C. perfringens type C infection. After supplementation with either probiotics or complex probiotics, mice were improved in terms of weight reduction and reduced the levels of cytokines in serum and increased the levels of intestinal sIgA, and supplementation with complex probiotics was effective. In addition, both probiotic and complex probiotic supplementation effectively improved the damage of intestinal mucosa and spleen tissue. The relative expressions of Muc 2, Claudin-1, and Occludin genes were increased in the ileum. The three probiotics and the compound probiotics treatment significantly reduced the relative mRNA expression of toll-like/MyD88/NF-κB/MAPK. The effect of probiotic treatment was similar to the results of engramycin treatment, but the effect of engramycin treatment on intestinal sIgA was not significant. Our results clarify the immunomodulatory effects of the three probiotic isolates and the complex probiotics on C. perfringens infection, and the repair of the intestinal mucosal barrier.
Abnormal prenatal brain development in Chiari II malformation
Authors: Masse Olivia , Kraft Emily , Ahmad Esha , Rollins Caitlin K. , Velasco-Annis Clemente , Yang Edward , Warfield Simon Keith , Shamshirsaz Alireza A. , Gholipour Ali , Feldman Henry A. , Estroff Judy , Grant Patricia Ellen , Vasung Lana
Published: April 2023

Introduction

The Chiari II is a relatively common birth defect that is associated with open spinal abnormalities and is characterized by caudal migration of the posterior fossa contents through the foramen magnum. The pathophysiology of Chiari II is not entirely known, and the neurobiological substrate beyond posterior fossa findings remains unexplored. We aimed to identify brain regions altered in Chiari II fetuses between 17 and 26 GW.

Methods

We used in vivo structural T2-weighted MRIs of 31 fetuses (6 controls and 25 cases with Chiari II).

Results

The results of our study indicated altered development of diencephalon and proliferative zones (ventricular and subventricular zones) in fetuses with a Chiari II malformation compared to controls. Specifically, fetuses with Chiari II showed significantly smaller volumes of the diencephalon and significantly larger volumes of lateral ventricles and proliferative zones.

Discussion

We conclude that regional brain development should be taken into consideration when evaluating prenatal brain development in fetuses with Chiari II.
Sensory organization of postural control after long term space flight
Authors: Shishkin Nikita , Kitov Vladimir , Sayenko Dimitry , Tomilovskaya Elena
Published: April 2023

Background

Alterations in motor control systems is an inevitable consequence of space flights of any duration. After the flight, the crew-members have significant difficulties with maintaining upright balance and locomotion, which last several days following landing. At the same time, the specific mechanisms of these effects remain unclear.

Objectives

The aim of the study was to assess effects of long-term space flight on postural control and to define the changes of sensory organization caused by microgravity.

Methods

33 cosmonauts of Russian Space Agency, the members of International Space Station (ISS) flights of duration between 166 and 196 days took part in this study. Computerized Dynamic Posturography (CDP) tests, which include assessment of visual, proprioceptive and vestibular function in postural stability, was performed twice before the flight and on the 3rd, 7th, and 10th days after landing. The video analysis of ankle and hip joints fluctuations was performed to investigate the basis of postural changes.

Results

Exposure to long-term space flight was followed by considerable changes of postural stability (−27% of Equilibrium Score value in the most complicated test, SOT5m). Changes in postural strategies to maintain balance were observed in the tests which provide the challenge for vestibular system. In particular, increased hip joint involvement (+100% in median value and +135% in 3rd quartile of hip angle fluctuation RMS in SOT5m) into postural control process was revealed.

Conclusion

Decrease of postural stability after long-term space flight was associated with alterations in vestibular system and biomechanically was revealed by increased hip strategy which is less accurate, but simpler in terms of the central control.
Intracranial electrophysiological recordings on a swine model of mesial temporal lobe epilepsy
Authors: Zhu Fengjun , Wang Hanwen , Li Lin , Bragin Anatol , Cao Dezhi , Cheng Yuan
Published: April 2023

Objective

To test the feasibility and reliability of intracranial electrophysiological recordings in an acute status epilepticus model on laboratory swine.

Method

Intrahippocampal injection of kainic acid (KA) was performed on 17 male Bama pigs (Sus scrofa domestica) weighing between 25 and 35 kg. Two stereoelectroencephalography (SEEG) electrodes with a total of 16 channels were implanted bilaterally along the sensorimotor cortex to the hippocampus. Brain electrical activity was recorded 2 h daily for 9–28 days. Three KA dosages were tested to evaluate the quantities capable of evoking status epilepticus. Local field potentials (LFPs) were recorded and compared before and after the KA injection. We quantified the epileptic patterns, including the interictal spikes, seizures, and high-frequency oscillations (HFOs), up to 4 weeks after the KA injection. Test–retest reliability using intraclass correlation coefficients (ICCs) were performed on interictal HFO rates to evaluate the recording stability of this model.

Results

The KA dosage test suggested that a 10 μl (1.0 μg/μl) intrahippocampal injection could successfully evoke status epilepticus lasting from 4 to 12 h. At this dosage, eight pigs (50% of total) had prolonged epileptic events (tonic-chronic seizures + interictal spikes n = 5, interictal spikes alone n = 3) in the later 4 weeks of the video-SEEG recording period. Four pigs (25% of total) had no epileptic activities, and another four (25%) had lost the cap or did not complete the experiments. Animals that showed epileptiform events were grouped as E + (n = 8) and the four animals showing no signs of epileptic events were grouped as E– (n = 4). A total of 46 electrophysiological seizures were captured in the 4-week post-KA period from 4 E + animals, with the earliest onset on day 9. The seizure durations ranged from 12 to 45 s. A significant increase of hippocampal HFOs rate (num/min) was observed in the E+ group during the post-KA period (weeks 1, 2,4, p < 0.05) compared to the baseline. But the E-showed no change or a decrease (in week 2, p = 0.43) compared to their baseline rate. The between-group comparison showed much higher HFO rates in E + vs. E – (F = 35, p < 0.01). The high ICC value [ICC (1, k) = 0.81, p < 0.05] quantified from the HFO rate suggested that this model had a stable measurement of HFOs during the four-week post-KA periods.

Significance

This study measured intracranial electrophysiological activity in a swine model of KA-induced mesial temporal lobe epilepsy (mTLE). Using the clinical SEEG electrode, we distinguished abnormal EEG patterns in the swine brain. The high test–retest reliability of HFO rates in the post-KA period suggests the utility of this model for studying mechanisms of epileptogenesis. The use of swine may provide satisfactory translational value for clinical epilepsy research.
Short-term effects of intravenous batroxobin in treatment of sudden sensorineural hearing loss: a propensity score-matched study
Authors: Jiang Mengzhu , Huang Huping , Mei Lingyun , He Chufeng , Cai Xinzhang , Jiang Lu , Wu Hong , Wang Xin , Wu Xuewen
Published: April 2023

Background

Sudden sensorineural hearing loss (SSNHL) can cause great panic in patients. Whether it is advantageous to add intravenous batroxobin in the treatment of SSNHL remains to be determined. This study aimed to compare the short-term efficacy of therapy combined with intravenous batroxobin and that without intravenous batroxobin in SSNHL patients.

Methods

This retrospective study harvested the data of SSNHL patients hospitalized in our department from January 2008 to April 2021. The hearing levels on the admitted day (before treatment) and the discharge day were considered pre-treatment hearing and post-treatment hearing, respectively. The hearing gain was the difference value of pre-treatment hearing and post-treatment hearing. We used Siegel's criteria and the Chinese Medical Association of Otolaryngology (CMAO) criteria to evaluate hearing recovery. The complete recovery rate, overall effective rate, and hearing gain at each frequency were considered outcomes. Propensity score matching (PSM) was conducted to balance the baseline characteristics between the batroxobin group and the non-batroxobin group. Sensitivity analysis was carried out in flat-type and total-deafness SSNHL patients.

Results

During the study period, 657 patients with SSNHL were admitted to our department. Among them, a total of 274 patients met the enrolled criteria of our study. After PSM, 162 patients (81 in each group) were included in the analysis. Once the hospitalized treatment was completed, the patients would be discharged the next day. Logistic regression analysis of the propensity score-matched cohort indicated that both the complete recovery rates [Siegel's criteria, OR: 0.734, 95% CI: 0.368–1.466, p = 0.381; CMAO criteria, OR: 0.879, 95% CI: 0.435–1.777, p = 0.720] and the overall effective rates [Siegel's criteria and CMAO criteria, OR: 0.741, 95% CI: 0.399–1.378, p = 0.344] were not significantly different between the two treatment groups. Sensitivity analysis has shown similar results. For flat-type and total-deafness SSNHL patients, no significant difference was found in post-treatment hearing gain at each frequency between the two groups after PSM.

Conclusion

There was no significant difference in short-term hearing outcomes between treatment with batroxobin and treatment without batroxobin in SSNHL patients by Siegel's and CMAO criteria after PSM. Future studies for better therapy regimens of SSNHL are still needed.
Tooth loss and the risk of cognitive decline and dementia: A meta-analysis of cohort studies
Authors: Li Liqing , Zhang Qi , Yang Di , Yang Sule , Zhao Yulan , Jiang Min , Wang Xiaofang , Zhao Ling , Liu Qi , Lu Zuxun , Zhou Xiaogang , Gan Yong , Wu Chunmei
Published: April 2023

Introduction

Epidemiological studies have shown that tooth loss may be associated with an increased risk of cognitive decline and dementia. However, some results do not show a significant association. Therefore, we performed a meta-analysis to evaluate this association.

Methods

Relevant cohort studies were searched in PubMed, Embase, Web of Science (up to May 2022), and the reference lists of retrieved articles. The pooled relative risk (RR) and 95% confidence intervals were computed using a random-effects model (CI). Heterogeneity was evaluated using the I2 statistic. Publication bias was evaluated using the Begg's and Egger's tests.

Results

Eighteen cohort studies met the inclusion criteria. Original studies with 356,297 participants with an average follow-up of 8.6 years (ranging from 2 to 20 years) were included in this study. The pooled RRs of tooth loss on dementia and cognitive decline were 1.15 (95% CI: 1.10–1.20; P < 0.01, I2 = 67.4%) and 1.20 (95% CI: 1.14–1.26; P = 0.04, I2 = 42.3%), respectively. The results of the subgroup analysis showed an increased association between tooth loss and Alzheimer's disease (AD) (RR = 1.12, 95% CI: 1.02–1.23) and vascular dementia (VaD) (RR = 1.25, 95% CI: 1.06–1.47). The results of the subgroup analysis also showed that pooled RRs varied by geographic location, sex, use of dentures, number of teeth or edentulous status, dental assessment, and follow-up duration. None of the Begg's and Egger's tests or funnel plots showed evidence of publication bias.

Discussion

Tooth loss is associated with a significantly increased risk of cognitive decline and dementia, suggesting that adequate natural teeth are important for cognitive function in older adults. The likely mechanisms mostly suggested include nutrition, inflammation, and neural feedback, especially deficiency of several nutrients like vitamin D.
Type 2 diabetes mellitus as a possible risk factor for myasthenia gravis: a case–control study
Authors: Liu Yu-Dong , Tang Fang , Li Xiao-Li , Liu Ya-Fei , Zhang Peng , Yang Chun-Lin , Du Tong , Li Heng , Wang Cong-Cong , Liu Ying , Yang Bing , Duan Rui-Sheng
Published: April 2023

Background

A certain number of myasthenia gravis (MG) patients clinically had type 2 diabetes mellitus (T2DM) prior to MG onset, which suggests that the onset of MG may correlate with the history of T2DM. This study aimed to examine the correlation between MG and T2DM.

Methods

In a single-center, retrospective, 1:5 matched case–control study, all 118 hospitalized patients with a diagnosis of MG from 8 August 2014 to 22 January 2019 were enrolled. In total, four datasets with different sources of the control group were retrieved from the electronic medical records (EMRs). Data were collected at the individual level. A conditional logistic regression analysis was used to test the risk of MG associated with T2DM.

Findings

The risk of MG was significantly associated with T2DM, and there were notable differences by sex and age. Whether compared to the general population, general hospitalized patients without autoimmune diseases (AIDs), or patients with other AIDs except MG, women aged over 50 years with T2DM had an increased risk of MG. The mean onset age of diabetic MG patients was more than that of the non-diabetic MG patients.

Interpretation

This study demonstrates that T2DM is strongly associated with the subsequent risk of MG and varies significantly by sex and age. It reveals that diabetic MG may be a unique subtype that is different from the conventional MG subgroup classification. More clinical and immunological features of diabetic MG patients need to be explored in further studies.