bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Monocyte-Derived Suppressor Cell Supernatant Induces Immunoregulatory Effects and Mitigates xenoGvHD
Authors: Gérard Claire , Thébault Marine , Lamarthée Baptiste , Genet Coraline , Cattin Florine , Brazdova Andréa , Janikashvili Nona , Cladière Claudie , Ciudad Marion , Ouandji Séthi , Ghesquière Thibault , Greigert Hélène , Tinel Claire , Adotevi Olivier , Saas Philippe , Samson Maxime , Audia Sylvain , Bonnotte Bernard
Published: March 2022

Recently developed cell-based therapies have shown potential for graft-versus-host disease (GvHD) mitigation. Our team previously developed a protocol to generate human monocyte-derived suppressor Cells (HuMoSC), a subpopulation of CD33+ suppressor cells of monocytic origin. CD33+HuMoSC successfully reduced xenoGvHD severity in NOD/SCID/IL-2Rγc-/- (NSG) mice. While CD33+ HuMoSC culture supernatant inhibits T cell activation and proliferation, the recovery of CD33+ HuMoSC immunosuppressive cells and the subsequent production of their supernatant is limited. An attractive solution would be to use both the CD33+ and the large number of CD14+ cells derived from our protocol. Here, we assessed the immunoregulatory properties of the CD14+HuMoSC supernatant and demonstrated that it inhibited both CD4 and CD8 T cell proliferation and decreased CD8 cytotoxicity. In vivo, injection of CD14+HuMoSC supernatant reduced xenoGvHD in NSG mice. Furthermore, CD14+HuMoSC supernatant maintained its immunoregulatory properties in an inflammatory environment. Proteomic and multiplex analyses revealed the presence of immunosuppressive proteins such as GPNMB, galectin-3 and IL-1R(A) Finally, CD14+HuMoSC supernatant can be produced using good manufacturing practices and be used as complement to current immunosuppressive drugs. CD14+HuMoSC supernatant is thus a promising therapy for preventing GvHD.
Comprehensive Metabolic Profiling of Inflammation Indicated Key Roles of Glycerophospholipid and Arginine Metabolism in Coronary Artery Disease
Authors: Zhu Qian , Wu Yonglin , Mai Jinxia , Guo Gongjie , Meng Jinxiu , Fang Xianhong , Chen Xiaoping , Liu Chen , Zhong Shilong
Published: March 2022

Background

Systemic immune inflammation is a key mediator in the progression of coronary artery disease (CAD), concerning various metabolic and lipid changes. In this study, the relationship between the inflammatory index and metabolic profile in patients with CAD was investigated to provide deep insights into metabolic disturbances related to inflammation.

Methods

Widely targeted plasma metabolomic and lipidomic profiling was performed in 1,234 patients with CAD. Laboratory circulating inflammatory markers were mainly used to define general systemic immune and low-grade inflammatory states. Multivariable-adjusted linear regression was adopted to assess the associations between 860 metabolites and 7 inflammatory markers. Least absolute shrinkage and selection operator (LASSO) logistic-based classifiers and multivariable logistic regression were applied to identify biomarkers of inflammatory states and develop models for discriminating an advanced inflammatory state.

Results

Multiple metabolites and lipid species were linearly associated with the seven inflammatory markers [false discovery rate (FDR) <0.05]. LASSO and multivariable-adjusted logistic regression analysis identified significant associations between 45 metabolites and systemic immune-inflammation index, 46 metabolites and neutrophil–lymphocyte ratio states, 32 metabolites and low-grade inflammation score, and 26 metabolites and high-sensitivity C-reactive protein states (P < 0.05). Glycerophospholipid metabolism and arginine and proline metabolism were determined as key altered metabolic pathways for systemic immune and low-grade inflammatory states. Predictive models based solely on metabolite combinations showed feasibility (area under the curve: 0.81 to 0.88) for discriminating the four parameters that represent inflammatory states and were successfully validated using a validation cohort. The inflammation-associated metabolite, namely, β-pseudouridine, was related to carotid and coronary arteriosclerosis indicators (P < 0.05).

Conclusions

This study provides further information on the relationship between plasma metabolite profiles and inflammatory states represented by various inflammatory markers in CAD. These metabolic markers provide potential insights into pathological changes during CAD progression and may aid in the development of therapeutic targets.
C5b-9 Membrane Attack Complex Formation and Extracellular Vesicle Shedding in Barrett’s Esophagus and Esophageal Adenocarcinoma
Authors: Kolka Cathryn M. , Webster Julie , Lepletier Ailin , Winterford Clay , Brown Ian , Richards Renee S. , Zelek Wioleta M. , Cao Yilang , Khamis Ramlah , Shanmugasundaram Karthik B. , Wuethrich Alain , Trau Matt , Brosda Sandra , Barbour Andrew , Shah Alok K. , Eslick Guy D. , Clemons Nicholas J. , Morgan B. Paul , Hill Michelle M.
Published: March 2022

The early complement components have emerged as mediators of pro-oncogenic inflammation, classically inferred to cause terminal complement activation, but there are limited data on the activity of terminal complement in cancer. We previously reported elevated serum and tissue C9, the terminal complement component, in esophageal adenocarcinoma (EAC) compared to the precursor condition Barrett’s Esophagus (BE) and healthy controls. Here, we investigate the level and cellular fates of the terminal complement complex C5b-9, also known as the membrane attack complex. Punctate C5b-9 staining and diffuse C9 staining was detected in BE and EAC by multiplex immunohistofluorescence without corresponding increase of C9 mRNA transcript. Increased C9 and C5b-9 staining were observed in the sequence normal squamous epithelium, BE, low- and high-grade dysplasia, EAC. C5b-9 positive esophageal cells were morphologically intact, indicative of sublytic or complement-evasion mechanisms. To investigate this at a cellular level, we exposed non-dysplastic BE (BAR-T and CP-A), high-grade dysplastic BE (CP-B and CP-D) and EAC (FLO-1 and OE-33) cell lines to the same sublytic dose of immunopurified human C9 (3 µg/ml) in the presence of C9-depleted human serum. Cellular C5b-9 was visualized by immunofluorescence confocal microscopy. Shed C5b-9 in the form of extracellular vesicles (EV) was measured in collected conditioned medium using recently described microfluidic immunoassay with capture by a mixture of three tetraspanin antibodies (CD9/CD63/CD81) and detection by surface-enhanced Raman scattering (SERS) after EV labelling with C5b-9 or C9 antibody conjugated SERS nanotags. Following C9 exposure, all examined cell lines formed C5b-9, internalized C5b-9, and shed C5b-9+and C9+EVs, albeit at varying levels despite receiving the same C9 dose. In conclusion, these results confirm increased esophageal C5b-9 formation during EAC development and demonstrate capability and heterogeneity in C5b-9 formation and shedding in BE and EAC cell lines following sublytic C9 exposure. Future work may explore the molecular mechanisms and pathogenic implications of the shed C5b-9+EV.
Identification of CD101 in Glioma: A Novel Prognostic Indicator Expressed on M2 Macrophages
Authors: Liu Yuyang , Yao Renqi , Shi Ying , Liu Yuxiao , Liu Hongyu , Liu Jialin , Guan Yunqian , Yao Yongming , Chen Ling
Published: March 2022

Glioma represents the most common primary intracranial malignancy worldwide, with low overall survival rates and limited therapeutic options. The protein CD101, mainly expressed on several immune cells, has been demonstrated to exert potent effects on blunting T cell immune responses across infectious and autoimmunity diseases. Nevertheless, the prognostic value of CD101 expression and its role in the immune microenvironment of various malignancies currently remains elusive. Herein, by adopting bioinformatics methodology, we comprehensively illustrated the potential function and predictive value of CD101 in stratifying clinical prognosis among patients with glioma, for which a high CD101 level predicted an unfavorable clinical outcome in glioma patients. Results from enrichment analyses manifested that CD101 predominantly expressed on the tumor-associated macrophages and was significantly associated with the immune regulatory processes, as evidenced by its positive correlation with immune-related genes and the putative infiltration of immune cells. Evidence provided byin-situmulticolor immunofluorescence staining further validated our findings at the protein level. Taken together, CD101 may serve as a novel biomarker in predicting clinical prognosis and immune status for glioma patients.
Living Inside a Jellyfish: The Symbiosis Case Study of Host-Specialized Dinoflagellates, “Zooxanthellae”, and the Scyphozoan Cotylorhiza tuberculata
Authors: Enrique-Navarro Angélica , Huertas Emma , Flander-Putrle Vesna , Bartual Ana , Navarro Gabriel , Ruiz Javier , Malej Alenka , Prieto Laura
Published: March 2022

The photosymbiosis with host-specific dinoflagellates is a widespread relationship in marine organisms. Despite the evidenced biodiversity of this kind of mutualism, most research focuses on the study of scleractinian corals, and there is a lack of knowledge about other symbiotic cnidarians such as jellyfishes. The Mediterranean jellyfish Cotylorhiza tuberculata (Rhizostomae, Scyphozoa) harbors an endosymbiotic dinoflagellate of the family Symbiodiniaceae. In this study, we examine the algae distribution within the host body as well as, the pigment content and cell density of the symbiont. Furthermore, the size, morphology and fluorescence of cultured symbionts were studied under light microscopy, Imaging Flow Cytometry (IFC), and Scanning Electron Microscopy (SEM). The C:N composition and optical properties of the medusa tissue were measured to evaluate their role in the symbiosis. The medusae body was divided into two different sections to investigate the distribution of symbionts in hospite: oral arms (OA) and umbrella (UM). C:N composition of C. tuberculata was and symbiont density was significantly higher in the OA section. Mean chlorophyll a concentration of the algae was 1.33 (± 0.83) pg Chl a cell–1. The study of the pigment composition by HPLC (High Performance Liquid Chromatography), revealed the presence of 13 different pigments, being the most representative chlorophyll a, chlorophyll c2, and peridinin typical pigments of Symbiodiniaceae. Cell diameter of algae freshly isolated from the host was 8.71 ± 0.97 μm and cell growth rate was 0.52 (± 0.09) 106 cell ml–1 d–1. The presence of vegetative coccoid cells, doublet and motile mastigotes were revealed within the Symbiodiniaceae cultures. A calcifying matrix typical of Symbiodiniaceae and formed in partner with bacteria, was also observed most cultures. The umbrella tissue of the medusa absorbed at ultraviolet radiation (UVR) region, suggesting that medusae tissue protects photosymbionts from the negative effect of the high energetic UVR and attenuates the light intensity reaching algae inside the host. The presence of a dense Symbiodiniaceae population and the protection to UVR and elevated environmental irradiance provided by medusae tissue, maintain symbionts in optimal light conditions for photosynthesis and may be a reason added to explain the population success of Cotylorhiza tuberculata.
Phytoplankton Species Diversity Patterns and Associated Driving Factors in China’s Jiulong River Estuary: Roles That Nutrients and Nutrient Ratios Play
Authors: Ge Feiyang , Ma Zhiyuan , Chen Bin , Wang Yu , Lu Xiaoqian , An Shenqun , Zhang Dian , Zhang Wanting , Yu Weiwei , Han Wenxuan , Yu Xingguang , Liu Zhenghua , Kuang Fangfang
Published: March 2022

Understanding diversity patterns and associated driving factors are the critical topics in macroecology and conservation biology. Phytoplankton are highly susceptible to environmental changes in estuaries, particularly eutrophication. This study examined phytoplankton alpha and beta diversity using investigation data in May (springtime), August (summer) and November (autumn) 2009 in China’s Jiulong River estuary, where it was easily polluted because of considerable discharge from a highly dense human population and low self-purification capacity with its limited river basin area, potentially resulting in eutrophication and then influencing phytoplankton diversity. Potential influencing factors were also explored, including dissolved oxygen, salinity, nutrients, nutrient ratios, geographic and hydrologic distance, and so on. The results indicated that Shannon’s index (H’) and Pielou’s index (J) decreased from the estuary’s upper to middle and then increased from middle to lower reaches, Simpson’s (D) observed the opposite trend and species number (S) gradually increased from the estuary’s upper to lower reaches. For beta diversity, all the indices showed a gradual decrease trend from the estuary’s upper to lower reaches, where also, turnover dominated beta diversity for all seasons. It is noteworthy that the significant roles that nutrients and nutrient ratios played in shaping phytoplankton diversity patterns and the nutrient balance were characterized by excess nitrogen (N) and silicon (Si) and limited phosphorus (P), which could potentially cause diatom blooms. Findings also showed that decreasing Si concentrations can help to reduce overall pollution levels as well as the restoration of the estuary’s ecosystem better than just reducing N alone. Accordingly, this study advocates for the protection of the entire estuary system with particular emphasis on its upper reaches. Moreover, greater attention should also be paid to impacts associated with N input and nutrient ratio trade-offs to the prospective watershed management of this estuary. This study provides a practical approach to explore estuarine diversity in a comprehensive way, which can inform effective biodiversity conservation and also be applied to other marine ecosystems to better guide sustainable management and conservation practices.
Hadal Biodiversity, Habitats and Potential Chemosynthesis in the Java Trench, Eastern Indian Ocean
Authors: Jamieson Alan J. , Stewart Heather A. , Weston Johanna N. J. , Lahey Patrick , Vescovo Victor L.
Published: March 2022

The Java Trench is the only subduction trench in the Indian Ocean that extends to the hadal zone (> 6,000 m water depth), and except for sevenbenthic trawls acquired around the 1950s, there has been little to no sampling at hadal depths undertaken since. In 2019, we undertook a 5-day expedition comprising a scientific dive using a full ocean depth-rated submersible, the DSV Limiting Factor, seven hadal-lander deployments, and high-resolution bathymetric survey. The submersible performed a video transect from the deepest point of the trench, up a 150 m high near-vertical escarpment located on the forearc, and then across a plateau at a depth of ∼7,050 m to make in situ observations of the habitat heterogeneity and biodiversity inhabiting these hadal depths. We found the Java Trench hadal community to be diverse and represented by 10 phyla, 21 classes, 34 orders and 55 families, with many new records and extensions in either depth or geographic range, including a rare encounter of a hadal ascidian. The submersible transect revealed six habitats spanning the terrain. The deepest trench axis comprised fine-grained sediments dominated by holothurians, whereas evidence of active rock slope failure and associated talus deposits were prevalent in near-vertical and vertical sections of the escarpment. Sediment pockets and sediment pouring down the steep wall in “chutes” were commonly observed. The slope terrain was dominated by two species in the order Actiniaria and an asteroid, as well as 36 instances of orange, yellow, and white bacterial mats, likely exploiting discontinuities in the exposed bedrock, that may indicate a prevalence of chemosynthetic input into this hadal ecosystem. Near the top of the escarpment was an overhang populated by > 100 hexactinellid (glass) sponges. The substrate of the plateau returned to fine-grained sediment, but with a decreased density and diversity of epifauna relative to the trench floor. By providing the first visual insights of the hadal habitats and fauna of the Java Trench, this study highlights how the habitat heterogeneity influences patchy species distributions, and the great benefit of using a hadal-rated exploratory vehicle to comprehensively assess the biodiversity of hadal ecosystems.
Electrochemical Properties of Diluted Al-Mg Alloys With Columnar-To-Equiaxed Transition
Authors: Román Alejandra Silvina , Ibañez Edgar Rolando , Méndez Claudia Marcela , Pedrozo Marianela , Kramer Gustavo Raúl , Zadorozne Natalia Silvina , Alonso Paula Regina , Ares Alicia Esther
Published: March 2022

The objective of the present research is to study the corrosion susceptibility of two Al-Mg diluted alloys (Al-0.5wt.%Mg and Al-2wt.%Mg) with different grains structures obtained by directional solidification (columnar, equiaxed and columnar-to-equiaxed transition, CET) in 0.5% NaCl solution, at room temperature. The corrosion resistance is analyzed by potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) techniques in both longitudinal and transversal sections of the samples. The columnar grain zone presents higher corrosion resistance than the equiaxed grain zone. In addition, the transversal section shows higher corrosion resistance than the longitudinal section of the samples. Then, the Al-0.5wt.% Mg alloy displays higher corrosion resistance than the Al-2wt.% Mg alloy. The values of the polarization resistance are used as a basic criterion for the evaluation of the corrosion resistance of both alloys. In this way, when the polarization resistance decreases with the increasing in the distance from the base, the grain size, secondary dendritic arm spacings and hardness increases. In addition, when the polarization resistance increases, the critical temperature gradient decreases.
Effect of Serum Phosphate on the Prognosis of Septic Patients: A Retrospective Study Based on MIMIC-IV Database
Authors: Li Zhaoyang , Shen Tingwen , Han Yi
Published: March 2022

Objective

To assess the effect of serum inorganic phosphate (Pi) on the prognosis of patients with sepsis.

Methods

A retrospective analysis of patients with sepsis selected from the Medical Information Mart for Intensive Care (MIMIC)-IV database was performed. Sepsis was diagnosed according to the Third International Consensus Definition for sepsis and septic shock (Sepsis-3). The time-weighted values of the serum Pi measurements within the first 24 h of sepsis were analyzed. The association between serum Pi and in-hospital mortality was evaluated with a generalized linear model (log-binomial model).

Results

The analysis of 11,658 patients from six intensive care units (ICUs) showed a nearly linear correlation between serum Pi and in-hospital mortality in all patients with sepsis, especially in those with acute kidney injury (AKI). The increase of serum Pi was related to a higher risk of AKI, higher norepinephrine doses, ICU mortality, and in-hospital mortality. The generalized linear model showed that serum Pi was an independent predictor for in-hospital mortality in all patients with sepsis even within the normal range. The adjusted risk ratios (RRs) were also significant in subgroup analyses according to kidney function, gender, respiratory infection, vasopressor use, and Sequential Organ Failure Assessment (SOFA) score.

Conclusion

Higher levels of serum Pi, even within the normal range, were significantly associated with a higher risk of in-hospital mortality in patients with sepsis regardless of kidney function, gender, respiratory infection, vasopressor use, and SOFA score.
Perspective: Drawing on Findings From Critical Illness to Explain Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Authors: Stanculescu Dominic , Bergquist Jonas
Published: March 2022

We propose an initial explanation for how myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) could originate and perpetuate by drawing on findings from critical illness research. Specifically, we combine emerging findings regarding (a) hypoperfusion and endotheliopathy, and (b) intestinal injury in these illnesses with our previously published hypothesis about the role of (c) pituitary suppression, and (d) low thyroid hormone function associated with redox imbalance in ME/CFS. Moreover, we describe interlinkages between these pathophysiological mechanisms as well as “vicious cycles” involving cytokines and inflammation that may contribute to explain the chronic nature of these illnesses. This paper summarizes and expands on our previous publications about the relevance of findings from critical illness for ME/CFS. New knowledge on diagnostics, prognostics and treatment strategies could be gained through active collaboration between critical illness and ME/CFS researchers, which could lead to improved outcomes for both conditions.
Socioeconomic Inequalities in COVID-19 Incidence During Different Epidemic Phases in South Korea
Authors: Yoo Dae-sung , Hwang Minji , Chun Byung Chul , Kim Su Jin , Son Mia , Seo Nam-Kyu , Ki Myung
Published: March 2022

Objective

Area-level socioeconomic status (SES) is associated with coronavirus disease 2019 (COVID-19) incidence. However, the underlying mechanism of the association is context-specific, and the choice of measure is still important. We aimed to evaluate the socioeconomic gradient regarding COVID-19 incidence in Korea based on several area-level SES measures.

Methods

COVID-19 incidence and area-level SES measures across 229 Korean municipalities were derived from various administrative regional data collected between 2015 and 2020. The Bayesian negative binomial model with a spatial autocorrelation term was used to estimate the incidence rate ratio (IRR) and relative index of inequality (RII) of each SES factor, with adjustment for covariates. The magnitude of association was compared between two epidemic phases: a low phase (<100 daily cases, from May 6 to August 14, 2020) and a rebound phase (>100 daily cases, from August 15 to December 31, 2020).

Results

Area-level socioeconomic inequalities in COVID-19 incidence between the most disadvantaged region and the least disadvantaged region were observed for nonemployment rates [RII = 1.40, 95% credible interval (Crl) = 1.01–1.95] and basic livelihood security recipients (RII = 2.66, 95% Crl = 1.12–5.97), but were not observed for other measures in the low phase. However, the magnitude of the inequalities of these SES variables diminished in the rebound phase. A higher area-level mobility showed a higher risk of COVID-19 incidence in both the low (IRR = 1.67, 95% Crl = 1.26–2.17) and rebound phases (IRR = 1.28, 95% Crl = 1.14–1.44). When SES and mobility measures were simultaneously adjusted, the association of SES with COVID-19 incidence remained significant but only in the low phase, indicating they were mutually independent in the low phase.

Conclusion

The level of basic livelihood benefit recipients and nonemployment rate showed social stratification of COVID-19 incidence in Korea. Explanation of area-level inequalities in COVID-19 incidence may not be derived only from mobility differences in Korea but, instead, from the country's own context.
Analysis of Conjunctival Sac Microbiome in Dry Eye Patients With and Without Sjögren's Syndrome
Authors: Song Hang , Xiao Kang , Chen Zhengyu , Long Qin
Published: March 2022

Purpose

To analyze the conjunctival sac microbial communities in patients with Sjögren's syndrome-associated dry eyes (SSDE) and non-Sjögren's syndrome-associated dry eyes (NSSDE), compared with normal controls (NC).

Methods

Conjunctival sac swab samples from 23 eyes of SSDE, 36 eyes of NSSDE, and 39 eyes of NC were collected. The V3–V4 region of the 16S ribosomal RNA (rRNA) gene high-throughput sequencing was performed on an Illumina MiSeq platform and analyzed using Quantitative Insights Into Microbial Ecology (QIIME). Alpha diversity was employed to analyze microbiome diversity through Chao1 and Shannon indexes. Beta diversity was demonstrated by the principal coordinates analysis (PCoA) and Partial Least Squares Discrimination Analysis (PLS-DA). The relative abundance was bioinformatically analyzed at the phylum and genus levels.

Results

The alpha diversity was lower in patients with dry eye disease (Shannon index: NC vs. SSDE: P = 0.020, NC vs. NSSDE: P = 0.029). The beta diversity showed divergent microbiome composition in different groups (NC vs. SSDE: P = 0.001, NC vs. NSSDE: P = 0.001, NSSDE vs. SSDE: P = 0.005). The top 5 abundant phyla were Firmicutes, Proteobacteria, Actinobacteriota, Bacteroidota, and Cyanobacteria in all three groups. The top five abundant genera included Acinetobacter, Staphylococcus, Bacillus, Corynebacterium, and Clostridium_sensu_stricto_1. The relative microbiome abundance was different between groups. The Firmicutes/Bacteroidetes (F/B) ratio was 6.42, 7.31, and 9.71 in the NC, NSSDE, and SSDE groups, respectively (NC vs. SSDE: P = 0.038, NC vs. NSSDE: P = 0.991, SSDE vs. NSSDE: P = 0.048).

Conclusion

The diversity of conjunctival sac microbiome in patients with NSSDE and SSDE was diminished compared with NC. The main microbiome at the phylum and genus level were similar between groups, but the relative abundance had variations. The Firmicutes/Bacteroidetes ratio was higher in the SSDE group.
The Saprophytic Lifestyle of Listeria monocytogenes and Entry Into the Food-Processing Environment
Authors: Lourenco Antonio , Linke Kristina , Wagner Martin , Stessl Beatrix
Published: March 2022

Listeria monocytogenes is an environmentally adapted saprophyte that can change into a human and animal bacterial pathogen with zoonotic potential through several regulatory systems. In this review, the focus is on the occurrence of Listeria sensu stricto and sensu lato in different ecological niches, the detection methods, and their analytical limitations. It also highlights the occurrence of L. monocytogenes genotypes in the environment (soil, water, and wildlife), reflects on the molecular determinants of L. monocytogenes for the saprophytic lifestyle and the potential for antibiotic resistance. In particular, the strain-specific properties with which some genotypes circulate in wastewater, surface water, soil, wildlife, and agricultural environments are of particular interest for the continuously updating risk analysis.
Intestinal Candida albicans Promotes Hepatocarcinogenesis by Up-Regulating NLRP6
Authors: Liu Zherui , Li Yinyin , Li Chen , Lei Guanglin , Zhou Lin , Chen Xiangling , Jia Xiaodong , Lu Yinying
Published: March 2022

Hepatocellular carcinoma (HCC), a primary liver cancer, is closely associated with the gut microbiota. However, the role of gut fungi in the development of HCC remains unclear. The aim of this study was to explore the influence of intestinalCandida albicanson HCC. Here, We found that patients with HCC showed significantly decreased diversity of the gut mycobiome and increased abundance ofC. albicans, compared to the patients with liver cirrhosis. The gavage ofC. albicansin the WT models increased the tumor size and weight and influenced the plasma metabolome, which was indicated by alterations in 117 metabolites, such as L-carnitine and L-acetylcarnitine, and several KEGG enriched pathways, such as phenylalanine metabolism and citrate cycle. Moreover, the expression of nucleotide oligomerization domain-like receptor family pyrin domain containing 6 (NLRP6) in the intestinal tissues and primary intestinal epithelial cells of the WT mice interacted withC. albicansincreased. Notably, the colonization ofC. albicanshad no effect on tumor growth inNlrp6–/–mice. In conclusion, the abnormal colonization ofC. albicansreprogrammed HCC metabolism and contributed to the progression of HCC dependent on NLRP6, which provided new targets for the treatment of HCC.
Integration of Interleukin-6 Improves the Diagnostic Precision of Metagenomic Next-Generation Sequencing for Infection in Immunocompromised Children
Authors: Wang Di , Lai Min , Song Hua , Zhang Jing-Ying , Zhao Fen-Ying , Liang Juan , Xu Wei-Qun , Tang Yong-Min , Xu Xiao-Jun
Published: March 2022

The performance of metagenomic next-generation sequencing (mNGS) in identifying pathogens in immunocompromised children was not very clear. The purpose of this study is to assess the performance of mNGS in this population and to investigate whether the integration of serum cytokines and mNGS assay could improve diagnostic accuracy. We retrospectively collected the clinical data of pediatric patients who suffered febrile diseases and underwent mNGS determination simultaneously in the department of hematology/oncology between January 2019 and March 2021. Specimens were sent for conventional microbiological test (CMT), mNGS, and serum cytokine measurement in parallel. A total of 258 episodes of febrile diseases were enrolled, mNGS was positive in 224 cases, while CMT was positive in 78 cases. mNGS and CMT were both positive in 70 (27.1%) cases and were both negative in 26 (10.1%) cases. There were 154 (59.7%) cases positive by mNGS only while 8 (3.1%) were positive by CMT only. It was common that two or more pathogens were simultaneously detected by mNGS in a single specimen, with only 61 tests identified a single organism. Whether the organisms reported by mNGS were the microbiological etiology of infection was evaluated. Of the 224 cases with positive mNGS results, 135 (58.4%), 30 (13.0%), and 59 (28.6%) were considered as “probable,” “possible,” and “unlikely,” respectively. Patients with high IL-6 (≥ 390 pg/ml) were likely to be bacterial infection. Although mNGS reported mixed pathogens, 84.6% (33/39) and 83.3% (10/12) of patients presenting high IL-6 were confirmed as bacterial infection in the training and validation cohort, respectively. In conclusion, mNGS analysis demonstrates promising diagnostic potential in rapidly identifying clinically relevant pathogens. Given the detection of many clinically irrelevant organisms, the integration of IL-6 improves the precision of mNGS results interpretation.
Large-Scale Samples Based Rapid Detection of Ciprofloxacin Resistance in Klebsiella pneumoniae Using Machine Learning Methods
Authors: Wang Chunxuan , Wang Zhuo , Wang Hsin-Yao , Chung Chia-Ru , Horng Jorng-Tzong , Lu Jang-Jih , Lee Tzong-Yi
Published: March 2022

Klebsiella pneumoniae is one of the most common causes of hospital- and community-acquired pneumoniae. Resistance to the extensively used quinolone antibiotic, such as ciprofloxacin, has increased in Klebsiella pneumoniae, which leads to the increase in the risk of initial antibiotic selection for Klebsiella pneumoniae treatment. Rapid and precise identification of ciprofloxacin-resistant Klebsiella pneumoniae (CIRKP) is essential for clinical therapy. Nowadays, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) is another approach to discover antibiotic-resistant bacteria due to its shorter inspection time and lower cost than other current methods. Machine learning methods are introduced to assist in discovering significant biomarkers from MALDI-TOF MS data and construct prediction models for rapid antibiotic resistance identification. This study examined 16,997 samples taken from June 2013 to February 2018 as part of a longitudinal investigation done by Change Gung Memorial Hospitals (CGMH) at the Linkou branch. We applied traditional statistical approaches to identify significant biomarkers, and then a comparison was made between high-importance features in machine learning models and statistically selected features. Large-scale data guaranteed the statistical power of selected biomarkers. Besides, clustering analysis analyzed suspicious sub-strains to provide potential information about their influences on antibiotic resistance identification performance. For modeling, to simulate the real antibiotic resistance predicting challenges, we included basic information about patients and the types of specimen carriers into the model construction process and separated the training and testing sets by time. Final performance reached an area under the receiver operating characteristic curve (AUC) of 0.89 for support vector machine (SVM) and extreme gradient boosting (XGB) models. Also, logistic regression and random forest models both achieved AUC around 0.85. In conclusion, models provide sensitive forecasts of CIRKP, which may aid in early antibiotic selection against Klebsiella pneumoniae. The suspicious sub-strains could affect the model performance. Further works could keep on searching for methods to improve both the model accuracy and stability.
Linkages Among Dissolved Organic Matter Export, Dissolved Metabolites, and Associated Microbial Community Structure Response in the Northwestern Sargasso Sea on a Seasonal Scale
Authors: Liu Shuting , Longnecker Krista , Kujawinski Elizabeth B. , Vergin Kevin , Bolaños Luis M. , Giovannoni Stephen J. , Parsons Rachel , Opalk Keri , Halewood Elisa , Hansell Dennis A. , Johnson Rod , Curry Ruth , Carlson Craig A.
Published: March 2022

Deep convective mixing of dissolved and suspended organic matter from the surface to depth can represent an important export pathway of the biological carbon pump. The seasonally oligotrophic Sargasso Sea experiences annual winter convective mixing to as deep as 300 m, providing a unique model system to examine dissolved organic matter (DOM) export and its subsequent compositional transformation by microbial oxidation. We analyzed biogeochemical and microbial parameters collected from the northwestern Sargasso Sea, including bulk dissolved organic carbon (DOC), total dissolved amino acids (TDAA), dissolved metabolites, bacterial abundance and production, and bacterial community structure, to assess the fate and compositional transformation of DOM by microbes on a seasonal time-scale in 2016–2017. DOM dynamics at the Bermuda Atlantic Time-series Study site followed a general annual trend of DOC accumulation in the surface during stratified periods followed by downward flux during winter convective mixing. Changes in the amino acid concentrations and compositions provide useful indices of diagenetic alteration of DOM. TDAA concentrations and degradation indices increased in the mesopelagic zone during mixing, indicating the export of a relatively less diagenetically altered (i.e., more labile) DOM. During periods of deep mixing, a unique subset of dissolved metabolites, such as amino acids, vitamins, and benzoic acids, was produced or lost. DOM export and compositional change were accompanied by mesopelagic bacterial growth and response of specific bacterial lineages in the SAR11, SAR202, and SAR86 clades, Acidimicrobiales, and Flavobacteria, during and shortly following deep mixing. Complementary DOM biogeochemistry and microbial measurements revealed seasonal changes in DOM composition and diagenetic state, highlighting microbial alteration of the quantity and quality of DOM in the ocean.
Identification of a Novel Chromate and Selenite Reductase FesR in Alishewanella sp. WH16-1
Authors: Zhou Zijie , Zhu Lin , Dong Yixuan , You Lexing , Zheng Shixue , Wang Gejiao , Xia Xian
Published: March 2022

A ferredoxin protein (AAY72_06850, named FesR) was identified to associate with chromate [Cr(VI)] resistance in Alishewanella sp. WH16-1. FesR and its similar proteins were phylogenetically separated from other reductase families. Unlike the reported Cr(VI) and selenite [Se(IV)] reductases, two 4Fe-4S clusters and one flavin adenine dinucleotide (FAD) -binding domain were found in the FesR sequence. The experiment in vivo showed that the mutant strain ΔfesR had lost partial Cr(VI) and Se(IV) reduction capacities compared to the wild-type and complemented strains. Furthermore, overexpression in Escherichia coli and enzymatic tests in vitro showed FesR were involved in Cr(VI) and Se(IV) reduction. 4Fe-4S cluster in purified FesR was detected by ultraviolet-visible spectrum (UV-VIS) and Electron Paramagnetic Resonance (EPR). The Km values of FesR for Cr(VI) and Se(IV) reduction were 1682.0 ± 126.2 and 1164.0 ± 89.4 μmol/L, and the Vmax values for Cr(VI) and Se(IV) reduction were 4.1 ± 0.1 and 9.4 ± 0.3 μmol min–1 mg–1, respectively. Additionally, site-directed mutagenesis and redox potential analyses showed that 4Fe-4S clusters were essential to FesR, and FAD could enhance the enzyme efficiencies of FesR as intracellular electron transporters. To the best of our knowledge, FesR is a novel Cr(VI) and Se(IV) reductase.
Foliar Herbivory Reduces Rhizosphere Fungal Diversity and Destabilizes the Co-occurrence Network
Authors: Shi Yu , Zhang Kaoping , Ma Tiantian , Zhang Zhongyue , Li Ping , Xing Zhenlong , Ding Jianqing
Published: March 2022

Insect herbivores can adversely impact terrestrial plants throughout ontogeny and across various ecosystems. Simultaneously, the effects of foliar herbivory may extend belowground, to the soil microbial community. However, the responses in terms of the diversity, assembly, and stability of rhizosphere fungi to aboveground herbivory remain understudied. Here, using high-throughput sequencing, the effects of foliar insect herbivory on rhizosphere fungal microbes were investigated in a common garden experiment that manipulated herbivory intensity and time from herbivore removal. The number of observed fungal species was reduced by a greater herbivory intensity, with some species evidently sensitive to herbivory intensity and time since herbivore removal. Rhizofungal assembly processes were altered by both herbivory intensity and time since herbivore removal. Further, we found evidence that both factors strongly influenced fungal community stability: a high intensity of herbivory coupled with a shorter time since herbivore removal resulted in low stability. These results suggest that foliar herbivory can adversely alter fungal diversity and stability, which would in turn be harmful for plant health. Fortunately, the effect seems to gradually diminish with time elapsed after herbivore removal. Our findings provide a fresh, in-depth view into the roles of rhizofungi in enhancing the adaption ability of plants under environmental stress.
The Critical Role of Potassium Efflux and Nek7 in Pasteurella multocida-Induced NLRP3 Inflammasome Activation
Authors: Wang Yu , Zeng Zheng , Ran Jinrong , Peng Lianci , Wu Xingping , Ye Chao , Dong Chunxia , Peng Yuanyi , Fang Rendong
Published: March 2022

Pasteurella multocida is a zoonotic pathogen causing respiratory infection in different animal species such as cattle, sheep, pigs, chickens and humans. Inflammasome is a complex assembled by multiple proteins in the cytoplasm and plays an important role in the host defense against microbial infection. Bovine Pasteurella multocida type A (PmCQ2) infection induces NLRP3 inflammasome activation and IL-1β secretion, but the mechanism of PmCQ2-induced activation of NLRP3 inflammasome is still unknown. Therefore, the underlying mechanism was investigated in this study. The results showed that potassium efflux mediated PmCQ2-induced IL-1β secretion and blocking potassium efflux attenuated PmCQ2-induced caspase-1 activation and ASC oligomerization. Furthermore, NIMA-related kinase 7 (Nek7) was also involved in PmCQ2-induced caspase-1 activation and IL-1β secretion. In addition, PmCQ2 infection promoted Nek7-NLRP3 interaction, which is dependent on potassium efflux. In conclusion, our results indicate the critical role of potassium efflux and Nek7 in Pasteurella multocida-induced NLRP3 inflammasome activation, which provides useful information about Pasteurella multocida-induced host immune response.
Increased Vascular Permeability Due to Spread and Invasion of Vibrio vulnificus in the Wound Infection Exacerbates Potentially Fatal Necrotizing Disease
Authors: Yamazaki Kohei , Kashimoto Takashige , Kado Takehiro , Yoshioka Kazuki , Ueno Shunji
Published: March 2022

Vibrio vulnificus is known to cause necrotizing soft tissue infections (NSTIs). However, the pathogenic mechanism causing cellulitis, necrotizing fasciitis, muscle necrosis, and rapidly developing septicemia in humans have not been fully elucidated. Here, we report a multilayer analysis of tissue damage after subcutaneous bacterial inoculation as a murine model of V. vulnificus NSTIs. Our histopathological examination showed the progression of cellulitis, necrotizing fasciitis, and muscle necrosis worsening as the infection penetrated deeper into the muscle tissue layers. The increase in vascular permeability was the primary cause of the swelling and congestion, which are acute signs of inflammation in soft tissue and characteristic of human NSTIs. Most importantly, our sequential analysis revealed for the first time that V. vulnificus not only spreads along the skin and subcutaneous tissues or fascia but also invades deeper muscle tissues beyond the fascia as the crucial process of its lethality. Also, increased vascular permeability enabled V. vulnificus to proliferate in muscle tissue and enter the systemic circulation, escalating the bacterium’s lethality. Our finding may yield important clinical benefits to patients by helping physicians understand the impact of surgical debridement on the patient’s quality of life. Furthermore, this study provides a promising system to accelerate studies of virulence factors and eventually help establish new therapies.
Update on the Protein Homeostasis Network in Bacillus subtilis
Authors: Matavacas Judith , von Wachenfeldt Claes
Published: March 2022

Protein homeostasis is fundamental to cell function and survival. It relies on an interconnected network of processes involving protein synthesis, folding, post-translational modification and degradation as well as regulators of these processes. Here we provide an update on the roles, regulation and subcellular localization of the protein homeostasis machinery in the Gram-positive model organism Bacillus subtilis. We discuss emerging ideas and current research gaps in the field that, if tackled, increase our understanding of how Gram-positive bacteria, including several human pathogens, maintain protein homeostasis and cope with stressful conditions that challenge their survival.
Identifying SARS-CoV-2 Lineage Mutation Hallmarks and Correlating Them With Clinical Outcomes in Egypt: A Pilot Study
Authors: Agwa Sara H. A. , Elghazaly Hesham , El Meteini Mahmoud Shawky , Yahia Yahia A. , Khaled Radwa , Abd Elsamee Aya M. , Darwish Reham M. , Elsayed Shaimaa M. , Hafez Hala , Mahmoud Basma S. , EM Fouda , Matboli Marwa
Published: March 2022

The SARS-CoV-2 pandemic has led to over 4.9 million deaths as of October 2021. One of the main challenges of creating vaccines, treatment, or diagnostic tools for the virus is its mutations and emerging variants. A couple of variants were declared as more virulent and infectious than others. Some approaches were used as nomenclature for SARS-CoV-2 variants and lineages. One of the most used is the Pangolin nomenclature. In our study, we enrolled 35 confirmed SARS-CoV-2 patients and sequenced the viral RNA in their samples. We also aimed to highlight the hallmark mutations in the most frequent lineage. We identified a seven-mutation signature for the SARS-CoV-2 C36 lineage, detected in 56 countries and an emerging lineage in Egypt. In addition, we identified one mutation which was highly negatively correlated with the lineage. On the other hand, we found no significant correlation between our clinical outcomes and the C36 lineage. In conclusion, the C36 lineage is an emerging SARS-CoV-2 variant that needs more investigation regarding its clinical outcomes compared to other strains. Our study paves the way for easier diagnosis of variants of concern using mutation signatures.
Deciphering Key Foreign Body Reaction-Related Transcription Factors and Genes Through Transcriptome Analysis
Authors: Liu Wei , Xiong Shaoheng , Du Jing , Song Yajuan , Wang Tong , Zhang Yu , Dong Chen , Huang ZhaoSong , He Qiang , Yu Zhou , Ma Xianjie
Published: March 2022

Background: Silicone implants are widely used in the field of plastic surgery for wound repair and cosmetic augmentation. However, molecular mechanisms and signaling pathways underlying the foreign body reaction (FBR) of a host tissue to the silicone require further elucidation. The purpose of this study was to identify key FBR-related transcription factors (TFs) and genes through transcriptome analysis.

Methods: We used a rat model with a subcutaneous silicone implant in the scalp and performed high throughput sequencing to determine the transcriptional profiles involved in the FBR. The function was analyzed by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway-enrichment analysis. A protein-protein interaction (PPI) network of differentially expressed mRNAs (DEmRNAs) was constructed to identify the hub genes and key modules and to determine the regulatory TF-mRNA relationships. In addition, the hub gene and transcript expression levels were determined by Quantitative Reverse Transcription polymerase Chain Reaction (qRT-PCR). Myofibroblasts differentiation and macrophage recruitment were identified by immunofluorescence. The protein expression of MMP9 was detected by immunohistochemistry and Western blot.

Results: We identified ten hub genes (Fos, Spp1, Fn1, Ctgf, Tlr2, Itgb2, Itgax, Ccl2, Mmp9, and Serpine1) and 3 TFs (FOS, IRF4, and SPI1) that may be crucial (particularly FOS) for the FBR. Furthermore, we identified multiple differentially expressed genes involved in several important biological processes, including leukocyte migration, cytokine‒ cytokine receptor interaction, phagocytosis, extracellular matrix (ECM) organization, and angiogenesis. We also identified potentially significant signaling pathways, including cytokine‒cytokine receptor interaction, phagosome, ECM‒receptor interaction, complement and coagulation cascades, the IL-17 signaling pathway, and the PI3K‒Akt signaling pathway. In addition, qRT-PCR confirmed the expression patterns of the TFs and hub genes, Western blot and immunohistochemistry validated the expression patterns of MMP9.

Conclusion: We generated a comprehensive overview of the gene networks underlying the FBR evoked by silicone implants. Moreover, we identified specific molecular and signaling pathways that may perform key functions in the silicone implant-induced FBR. Our results provide significant insights into the molecular mechanisms underlying silicone-induced FBR and determine novel therapeutic targets to reduce complications related to silicone implantation.