bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Transcriptional Pattern Related to Immune Cell Infiltration With Gene Co-Expression Network in Papillary Thyroid Cancer
Authors: Li Meiye , Zhang Jimei , Zhang Zongjing , Qian Ying , Qu Wei , Jiang Zhaoshun , Zhao Baochang
Published: February 2022

Background

A growing body of evidence suggests that immune cell infiltration in cancer is closely related to clinical outcomes. However, there is still a lack of research on papillary thyroid cancer (PTC).

Methods

Based on single-sample gene set enrichment analysis (SSGSEA) algorithm and weighted gene co-expression network analysis (WGCNA) tool, the infiltration level of immune cell and key modules and genes associated with the level of immune cell infiltration were identified using PTC gene expression data from The Cancer Genome Atlas (TCGA) database. In addition, the co-expression network and protein-protein interactions network analysis were used to identify the hub genes. Moreover, the immunological and clinical characteristics of these hub genes were verified in TCGA and GSE35570 datasets and quantitative real-time polymerase chain reaction (PCR). Finally, receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value of hub genes.

Results

Activated B cell, activated dendritic cell, CD56bright natural killer cell, CD56dim natural killer cell, Eosinophil, Gamma delta T cell, Immature dendritic cell, Macrophage, Mast cell, Monocyte, Natural killer cell, Neutrophil and Type 17 T helper cell were significantly changed between PTC and adjacent normal groups. WGCNA results showed that the black model had the highest correlation with the infiltration level of activated dendritic cells. We found 14 hub genes whose expression correlated to the infiltration level of activated dendritic cells in both TCGA and GSE35570 datasets. After validation in the TCGA dataset, the expression level of only 5 genes (C1QA, HCK, HLA-DRA, ITGB2 and TYROBP) in 14 hub genes were differentially expressed between PTC and adjacent normal groups. Meanwhile, the expression levels of these 5 hub genes were successfully validated in GSE35570 dataset. Quantitative real-time PCR results showed the expression of these 4 hub genes (except C1QA) was consistent with the results in TCGA and GSE35570 dataset. Finally, these 4 hub genes had diagnostic value to distinguish PTC and adjacent normal controls.

Conclusions

HCK, HLA-DRA, ITGB2 and TYROBP may be key diagnostic biomarkers and immunotherapy targets in PTC.
Serum Cystatin C Levels Are Associated With Obesity in Adolescents Aged 14–17 Years
Authors: Huo Ying-Xiang , Wei Wei , Liu Yang , Ma Ya-Nan , Tao Jun-Min , Wang Ning-Ning , Li Xiao-Feng , Chen Xin
Published: February 2022

Background

The association between serum cystatin C levels and obesity has not been fully explored in adolescents. This study aimed to explore the association between serum cystatin C levels and obesity in adolescents of different sexes.

Methods

We conducted a cross-sectional study including 481 adolescents aged 14−17 years. Cystatin C level was measured by immunoassay. Health examinations data, biochemical parameters, and questionnaire information were collected. The restricted cubic spline model analyzed the association between cystatin C levels and obesity in boys and girls.

Results

Boys exhibited significantly higher cystatin C levels than girls, with a mean level of 0.97 ± 0.10 mg/L in boys and 0.86 ± 0.09 mg/L in girls (P < 0.001). The restricted cubic spline model suggested that low or high cystatin C levels were associated with an increased risk of obesity in boys, whereas only higher cystatin C levels were associated with an increased risk of obesity in girls.

Conclusions

A U-shaped correlation was observed between serum cystatin C levels and the risk of obesity in boys. However, in girls, the risk of obesity showed a trend of initially increase and then decrease with increasing cystatin C levels. Longitudinal studies should be conducted to further investigate the diagnostic potential of cystatin C in the progression of early obesity in adolescents of different sexes.
PLL-Free Voltage Oriented Control Strategy for Voltage Source Converters Tied to Unbalanced Utility Grids
Authors: Xiong Liansong , Wu Binbing , Liu Xiaokang , Xiu Liancheng , Wang Dongjie
Published: February 2022

Asymmetrical working conditions of the utility grid introduce the large-amplitude negative-sequence component to the output current of the voltage source converter (VSC), causing power semiconductor devices to suffer from thermal fatigue and thermal damage. Though the conventional phase-locked loop (PLL) based voltage oriented control (VOC) solution can suppress the steady-state negative-sequence current effectively, it has a weak suppression ability of transient overload current, and even aggravates the transient current asymmetry and causes more severe transient impact to the VSC. This paper first analyzes the transient performance of the conventional VOC strategy, especially its dynamic response time and the main factors for performance limitation. On this basis, the PLL-free VOC strategy for VSCs tied to unbalanced grids is proposed, and its critical parts, namely, the reference current calculation and the fast detection of the grid voltage sequence components, are implemented. Besides, to improve the frequency adaptability, a high-performance grid frequency detection strategy is developed based on the difference-frequency phase caused by the frequency variation. Finally, experiments are performed to verify the effectiveness and advancement of the proposed method. Specifically, the results proved the rapidity, accuracy, and frequency adaptability of the proposed method in suppressing the VSC negative-sequence current, both in transient and steady-state conditions.
Wind Power Prediction Based on a Hybrid Granular Chaotic Time Series Model
Authors: Wang Yanyang , Xiong Wei , E. Shiping , Liu Qingguo , Yang Nan , Fu Ping , Gong Kang , Huang Yu
Published: February 2022

For realizing high-accuracy short-term wind power prediction, a hybrid model considering physical features of data is proposed in this paper, with consideration of chaotic analysis and granular computing. First, considering the chaotic features of wind power time series physically, data reconstruction in chaotic phase space is studied to provide a low-dimensional input with more information in modeling. Second, considering that meteorological scenarios of wind development are various, complicated, and uncertain, typical chaotic time series prediction models and wind scenarios are analyzed correspondingly via granular computing (GrC). Finally, through granular rule-based modeling, a hybrid model combining reconstructed wind power data and different models is constructed for short-term wind power prediction. Data from real wind farms is taken for experiments, validating the feasibility and effectiveness of the proposed wind power prediction model.
High-Throughput Screening of Antimicrobial Resistance Genes and Their Association With Class 1 Integrons in Urban Rivers in Japan
Authors: Kasuga Ikuro , Nagasawa Kyoka , Suzuki Masato , Kurisu Futoshi , Furumai Hiroaki
Published: February 2022

Antimicrobial resistance (AMR) is a serious public health concern. Many countries have implemented AMR surveillance programs for humans and animals, but a scheme for monitoring AMR in the environment has not yet been established. Class 1 integrons, which can acquire antimicrobial resistance genes (ARGs) to gene cassettes, were proposed as a candidate to evaluate the anthropogenic impacts on AMR. However, the association between class 1 integrons and ARGs in aquatic environments is less studied and requires further elucidation. This study used high-throughput quantitative polymerase chain reaction (HT-qPCR) to characterize the pollution profiles of ARGs and mobile gene elements (MGEs) in 24 urban rivers in Tokyo and its surrounding area. The abundance of class 1 integron-integrase gene (intI1) and the array of class 1 integron gene cassettes were also determined. In total, 9–53 target genes were detected per sample, and their abundances increased following effluent discharge from wastewater treatment plants. The river and wastewater samples were categorized based on their HT-qPCR profiles, indicating that this method was useful for characterizing the pollution status in aquatic environments. The prevalence ofintI1in the rivers was observed. Some ARGs and MGEs were positively correlated withintI1, indicating thatintI1could be used as a proxy for monitoring these ARGs and MGEs in urban rivers. Long-read sequencing of class 1 integron gene cassettes revealed that one to three ARGs were present in the gene cassettes. Regardless of the sample type,blaGES-24,aadA2, andqacHwere dominant in the gene cassettes. The source and spread of class 1 integrons carrying these ARGs in aquatic environments should be further monitored.
Can the Natural Resources Capitalization Contribute to the Achievement of Carbon Neutrality? A Pilot Experiment Evidence From China
Authors: Ye Penghao , Xia Senmao , Xiong Yu , Li Yanan , Chen Lei
Published: February 2022

There has been renewed interest in assessing the pilot scheme for compiling the natural resources capitalization (NRC). A growing body of evidence highlights the good effects that the policy of NRC has on the construction of ecological civilization. No known empirical research has focused on exploring relationships between the policy of NRC and carbon emissions reduction. This paper employs the NRC as the ecological civilization policy to investigate whether the implementation of NRC has contributed to the carbon emissions reduction with a difference-in-differences (DID) method. The results showed that different variables of carbon emissions in four pilot cities can be effectively affected by the implementation of NRC. There were significant negative correlations between the carbon emissions per GDP (Gross Domestic Product) and the policy for Hulun Buir, Huzhou and Loudi cities, and a significant increase of carbon sequestration was found in Yan’an city. This research provides a timely and necessary study that the NRC policy could be a contributing factor to carbon emissions reduction. As a result of these investigations, suggestions were identified for future research. Further research should be undertaken to investigate the collaborative effects of multi-policies on environmental issues.
RNA Sequencing of Lake Charr Epidermal Mucus to Assess Molecular Effects of Diluted Bitumen Exposure in a Boreal Lake
Authors: Andrzejczyk Nicolette E. , Palace Vince P. , Hrenchuk Lee , Peters Lisa , Schlenk Daniel
Published: February 2022

Transport of diluted bitumen (dilbit) from Canada’s oil sands region poses risk for leaks and spills of petroleum-derived contaminants into the environment. Exposure of fish to dilbit is known to cause cardiotoxicity, developmental deformities, and impairment in swim performance. However, previous studies have examined the toxicity of dilbit in laboratory settings which does not account for environmental and biological food-web variables that may alter exposure and/or toxicity of dilbit. Moreover, most methods of assessing organism health following oil exposure require lethal sampling. This work is a part of a larger set of experiments where dilbit spills were simulated within enclosures on a lake; the present study assesses the impacts of residual levels of dilbit that may have entered the surrounding lake environment from the enclosures following model spill cleanup. In order to understand the impacts of residual dilbit in an ecosystem setting without use of lethal sampling, epidermal mucus was collected and sequenced from lake charr (Salvelinus namaycush) exposed to residual dilbit in a boreal lake. While concentrations reached a maximum of 2.29 μg/L total polycyclic aromatic compounds (ΣPAC) within surface waters, surface water ΣPAC concentrations generally remained below 1 μg/L. Results of RNA sequencing were compared to sequencing data from mucus collected prior to dilbit additions. Differential gene expression and pathway analyses indicated dysregulation of genes associated with intermediary and energy metabolism as well as a trend in upregulation of cyp1a3 in epidermal mucus following dilbit exposure. Thus, results of the present study suggest that lake charr undergo consistent biological responses after exposure to residual levels of dilbit following a model spill, and that mRNA-based analysis of mucus may be a viable method for non-lethal oil exposure assessment. Overall, the results provide insight on the response of wild fish to very dilute dilbit exposures after a model spill cleanup.
Comparative Analysis of the Complete Chloroplast Genomes of Nine Paphiopedilum Species
Authors: Sun Yin , Zou Peishan , Jiang Nannan , Fang Yifu , Liu Guofeng
Published: February 2022

Paphiopedilum is known as “lady’s or Venus” slipper orchids due to its prominent shoe-shaped labellum, with high ornamental value. Phylogenetic relationships among some species in Paphiopedilum genus cannot be effectively determined by morphological features alone or through the analysis of nuclear or chloroplast DNA fragments. In order to provide aid in understanding the evolutionary and phylogenetic relationship in Paphiopedilum at chloroplast (cp) genome-scale level, the complete cp genomes of six Paphiopedilum species were newly sequenced in this study, and three other published cp genome sequences of Paphiopedilum were included in the comparative analyses. The cp genomes of the six Paphiopedilum species ranged from 154,908 bp (P. hirsutissimum) to 161,300 bp (P. victoria-mariae) in size, all constituting four-part annular structures. Analyses of the nucleotide substitutions, insertions/deletions, and simple sequence repeats in the cp genomes were conducted. Ten highly variable regions that could serve as potential DNA barcodes or phylogenetic markers for this diverse genus were identified. Sequence variations in the non-coding regions were greater than that in the conserved protein-coding regions, as well as in the large single copy (LSC) and small single copy (SSC) regions than in the inverted repeat (IR) regions. Phylogenetic analysis revealed that all Paphiopedilum species clustered in one monophyletic clade in the Cypripedioideae subfamily and then subdivided into seven smaller branches corresponding to different subgenus or sections of the genus, with high bootstrap supports, indicate that cp genome sequencing can be an effective means in resolving the complex relationship in Paphiopedilum.
First Multi-Organ Full-Length Transcriptome of Tree Fern Alsophila spinulosa Highlights the Stress-Resistant and Light-Adapted Genes
Authors: Hong Yongfeng , Wang Zhen , Li Minghui , Su Yingjuan , Wang Ting
Published: February 2022

Alsophila spinulosa, a relict tree fern, is a valuable plant for investigating environmental adaptations. Its genetic resources, however, are scarce. We used the PacBio and Illumina platforms to sequence the polyadenylated RNA of A. spinulosa root, rachis, and pinna, yielding 125,758, 89,107, and 89,332 unigenes, respectively. Combining the unigenes from three organs yielded a non-redundant reference transcriptome with 278,357 unigenes and N50 of 4141 bp, which were further reconstructed into 38,470 UniTransModels. According to functional annotation, pentatricopeptide repeat genes and retrotransposon-encoded polyprotein genes are the most abundant unigenes. Clean reads mapping to the full-length transcriptome is used to assess the expression of unigenes. The stress-induced ASR genes are highly expressed in all three organs, which is validated by qRT-PCR. The organ-specific upregulated genes are enriched for pathways involved in stress response, secondary metabolites, and photosynthesis. Genes for five types of photoreceptors, CRY signaling pathway, ABA biosynthesis and transduction pathway, and stomatal movement-related ion channel/transporter are profiled using the high-quality unigenes. The gene expression pattern coincides with the previously identified stomatal characteristics of fern. This study is the first multi-organ full-length transcriptome report of a tree fern species, the abundant genetic resources and comprehensive analysis of A. spinulosa, which provides the groundwork for future tree fern research.
Independent Evolution of the MYB Family in Brown Algae
Authors: Zeng Qiangcheng , Liu Hanyu , Chu Xiaonan , Niu Yonggang , Wang Caili , Markov Gabriel V. , Teng Linhong
Published: February 2022

Myeloblastosis (MYB) proteins represent one of the largest families of eukaryotic transcription factors and regulate important processes in growth and development. Studies on MYBs have mainly focused on animals and plants; however, comprehensive analysis across other supergroups such as SAR (stramenopiles, alveolates, and rhizarians) is lacking. This study characterized the structure, evolution, and expression of MYBs in four brown algae, which comprise the biggest multicellular lineage of SAR. Subfamily 1R-MYB comprised heterogeneous proteins, with fewer conserved motifs found outside the MYB domain. Unlike the SHAQKY subgroup of plant 1R-MYB, THAQKY comprised the largest subgroup of brown algal 1R-MYBs. Unlike the expansion of 2R-MYBs in plants, brown algae harbored more 3R-MYBs than 2R-MYBs. At least ten 2R-MYBs, fifteen 3R-MYBs, and one 6R-MYB orthologs existed in the common ancestor of brown algae. Phylogenetic analysis showed that brown algal MYBs had ancient origins and a diverged evolution. They showed strong affinity with stramenopile species, while not with red algae, green algae, or animals, suggesting that brown algal MYBs did not come from the secondary endosymbiosis of red and green plastids. Sequence comparison among all repeats of the three types of MYB subfamilies revealed that the repeat of 1R-MYBs showed higher sequence identity with the R3 of 2R-MYBs and 3R-MYBs, which supports the idea that 1R-MYB was derived from loss of the first and second repeats of the ancestor MYB. Compared with other species of SAR, brown algal MYB proteins exhibited a higher proportion of intrinsic disordered regions, which might contribute to multicellular evolution. Expression analysis showed that many MYB genes are responsive to different stress conditions and developmental stages. The evolution and expression analyses provided a comprehensive analysis of the phylogeny and functions of MYBs in brown algae.
TRmir: A Comprehensive Resource for Human Transcriptional Regulatory Information of MiRNAs
Authors: Gao Yu , Feng Chenchen , Zhang Yuexin , Song Chao , Chen Jiaxin , Li Yanyu , Wei Ling , Qian Fengcui , Ai Bo , Liu Yuejuan , Zhu Jiang , Su Xiaojie , Li Chunquan , Wang Qiuyu
Published: February 2022

MicroRNAs (miRNAs) are small non-coding RNAs, which play important roles in regulating various biological functions. Many available miRNA databases have provided a large number of valuable resources for miRNA investigation. However, not all existing databases provide comprehensive information regarding the transcriptional regulatory regions of miRNAs, especially typical enhancer, super-enhancer (SE), and chromatin accessibility regions. An increasing number of studies have shown that the transcriptional regulatory regions of miRNAs, as well as related single-nucleotide polymorphisms (SNPs) and transcription factors (TFs) have a strong influence on human diseases and biological processes. Here, we developed a comprehensive database for the human transcriptional regulation of miRNAs (TRmir), which is focused on providing a wealth of available resources regarding the transcriptional regulatory regions of miRNAs and annotating their potential roles in the regulation of miRNAs. TRmir contained a total of 5,754,414 typical enhancers/SEs and 1,733,966 chromatin accessibility regions associated with 1,684 human miRNAs. These regions were identified from over 900 human H3K27ac ChIP-seq, ATAC-seq, and DNase-seq samples. Furthermore, TRmir provided detailed (epi)genetic information about the transcriptional regulatory regions of miRNAs, including TFs, common SNPs, risk SNPs, linkage disequilibrium (LD) SNPs, expression quantitative trait loci (eQTLs), 3D chromatin interactions, and methylation sites, especially supporting the display of TF binding sites in the regulatory regions of over 7,000 TF ChIP-seq samples. In addition, TRmir integrated miRNA expression and related disease information, supporting extensive pathway analysis. TRmir is a powerful platform that offers comprehensive information about the transcriptional regulation of miRNAs for users and provides detailed annotations of regulatory regions. TRmir is free for academic users and can be accessed at http://bio.liclab.net/trmir/index.html.
Determination of CSF GFAP, CCN5, and vWF Levels Enhances the Diagnostic Accuracy of Clinically Defined MS From Non-MS Patients With CSF Oligoclonal Bands
Authors: Probert Fay , Yeo Tianrong , Zhou Yifan , Sealey Megan , Arora Siddharth , Palace Jacqueline , Claridge Timothy D. W. , Hillenbrand Rainer , Oechtering Johanna , Kuhle Jens , Leppert David , Anthony Daniel C.
Published: February 2022

Background

Inclusion of cerebrospinal fluid (CSF) oligoclonal IgG bands (OCGB) in the revised McDonald criteria increases the sensitivity of diagnosis when dissemination in time (DIT) cannot be proven. While OCGB negative patients are unlikely to develop clinically definite (CD) MS, OCGB positivity may lead to an erroneous diagnosis in conditions that present similarly, such as neuromyelitis optica spectrum disorders (NMOSD) or neurosarcoidosis.

Objective

To identify specific, OCGB-complementary, biomarkers to improve diagnostic accuracy in OCGB positive patients.

Methods

We analysed the CSF metabolome and proteome of CDMS (n=41) and confirmed non-MS patients (n=64) comprising a range of CNS conditions routinely encountered in neurology clinics.

Results

OCGB discriminated between CDMS and non-MS with high sensitivity (85%), but low specificity (67%), as previously described. Machine learning methods revealed CCN5 levels provide greater accuracy, sensitivity, and specificity than OCGB (79%, +5%; 90%, +5%; and 72%, +5% respectively) while glial fibrillary acidic protein (GFAP) identified CDMS with 100% specificity (+33%). A multiomics approach improved accuracy further to 90% (+16%).

Conclusion

The measurement of a few additional CSF biomarkers could be used to complement OCGB and improve the specificity of MS diagnosis when clinical and radiological evidence of DIT is absent.
Indole-3-Acetic Acid Alters Intestinal Microbiota and Alleviates Ankylosing Spondylitis in Mice
Authors: Shen Jun , Yang Lianjun , You Ke , Chen Tao , Su Zhihai , Cui Zhifei , Wang Min , Zhang Weicong , Liu Bin , Zhou Kai , Lu Hai
Published: February 2022

Ankylosing spondylitis (AS) is a systemic, chronic, and inflammatory autoimmune disease associated with the disorder of intestinal microbiota. Unfortunately, effective therapies for AS are lacking. Recent evidence has indicated that indole-3-acetic acid (IAA), an important microbial tryptophan metabolite, can modulate intestinal homeostasis and suppress inflammatory responses. However, reports have not examined the in vivo protective effects of IAA against AS. In this study, we investigated the protective effects and underlying mechanisms through which IAA acts against AS. We constructed a proteoglycan (PG)-induced AS mouse model and administered IAA (50 mg/kg body weight) by intraperitoneal injection daily for 4 weeks. The effects of IAA on AS mice were evaluated by examining disease severity, intestinal barrier function, aryl hydrocarbon receptor (AhR) pathway, T-helper 17 (Th17)/T regulatory (Treg) balance, and inflammatory cytokine levels. The intestinal microbiota compositions were profiled through whole-genome sequencing. We observed that IAA decreased the incidence and severity of AS in mice, inhibited the production of pro-inflammatory cytokines (tumor necrosis factor α [TNF-α], interleukin [IL]-6, IL-17A, and IL-23), promoted the production of the anti-inflammatory cytokine IL-10, and reduced the ratios of pro-/anti- inflammatory cytokines. IAA ameliorated pathological changes in the ileum and improved intestinal mucosal barrier function. IAA also activated the AhR pathway, upregulated the transcription factor forehead box protein P3 (FoxP3) and increased Treg cells, and downregulated the transcription factors retinoic acid receptor–related orphan receptor gamma t (RORγt) and signal transducer and activator of transcription 3 (STAT3) and decreased Th17 cells. Furthermore, IAA altered the composition of the intestinal microbiota composition by increasing Bacteroides and decreasing Proteobacteria and Firmicutes, in addition to increasing the abundances of Bifidobacterium pseudolongum and Mucispirillum schaedleri. In conclusion, IAA exerted several protective effects against PG-induced AS in mice, which was mediated by the restoration of balance among the intestinal microbial community, activating the AhR pathway, and inhibiting inflammation. IAA might represent a novel therapeutic approach for AS.
Immune Response Is Key to Genetic Mechanisms of SARS-CoV-2 Infection With Psychiatric Disorders Based on Differential Gene Expression Pattern Analysis
Authors: Xia Jing , Chen Shuhan , Li Yaping , Li Hua , Gan Minghong , Wu Jiashuo , Prohaska Clare Colette , Bai Yang , Gao Lu , Gu Li , Zhang Dongfang
Published: February 2022

Existing evidence demonstrates that coronavirus disease 2019 (COVID-19) leads to psychiatric illness, despite its main clinical manifestations affecting the respiratory system. People with mental disorders are more susceptible to COVID-19 than individuals without coexisting mental health disorders, with significantly higher rates of severe illness and mortality in this population. The incidence of new psychiatric diagnoses after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is also remarkably high. SARS-CoV-2 has been reported to use angiotensin-converting enzyme-2 (ACE2) as a receptor for infecting susceptible cells and is expressed in various tissues, including brain tissue. Thus, there is an urgent need to investigate the mechanism linking psychiatric disorders to COVID-19. Using a data set of peripheral blood cells from patients with COVID-19, we compared this to data sets of whole blood collected from patients with psychiatric disorders and used bioinformatics and systems biology approaches to identify genetic links. We found a large number of overlapping immune-related genes between patients infected with SARS-CoV-2 and differentially expressed genes of bipolar disorder (BD), schizophrenia (SZ), and late-onset major depressive disorder (LOD). Many pathways closely related to inflammatory responses, such as MAPK, PPAR, and TGF-β signaling pathways, were observed by enrichment analysis of common differentially expressed genes (DEGs). We also performed a comprehensive analysis of protein–protein interaction network and gene regulation networks. Chemical–protein interaction networks and drug prediction were used to screen potential pharmacologic therapies. We hope that by elucidating the relationship between the pathogenetic processes and genetic mechanisms of infection with SARS-CoV-2 with psychiatric disorders, it will lead to innovative strategies for future research and treatment of psychiatric disorders linked to COVID-19.
S100A12 as Biomarker of Disease Severity and Prognosis in Patients With Idiopathic Pulmonary Fibrosis
Authors: Li Yupeng , He Yaowu , Chen Shibin , Wang Qi , Yang Yi , Shen Danting , Ma Jing , Wen Zhe , Ning Shangwei , Chen Hong
Published: February 2022

Background

Idiopathic pulmonary fibrosis (IPF) is one of interstitial lung diseases (ILDs) with poor prognosis. S100 calcium binding protein A12 (S100A12) has been reported as a prognostic serum biomarker in the IPF, but its correlation with IPF remains unclear in the lung tissue and bronchoalveolar lavage fluids (BALF).

Methods

Datasets were collected from the Gene Expression Omnibus (GEO) database. Person correlation coefficient, Kaplan–Meier analysis, Cox regression analysis, functional enrichment analysis and so on were used. And single cell RNA-sequencing (scRNA-seq) analysis was also used to explore the role of S100A12 and related genes in the IPF.

Results

S100A12 was mainly and highly expressed in the monocytes, and its expression was downregulated in the lung of patients with IPF according to scRNA-seq and the transcriptome analysis. However, S100A12 expression was upregulated both in blood and BALF of patients with IPF. In addition, 10 genes were found to interact with S100A12 according to protein–protein interaction (PPI) network, and the first four transcription factors (TF) targeted these genes were found according to hTFtarget database. Two most significant co-expression genes of S100A12 were S100A8 and S100A9. The 3 genes were significantly negatively associated with lung function and positively associated with the St. George’s Respiratory Questionnaire (SGRQ) scores in the lung of patients with IPF. And, high expression of the 3 genes was associated with higher mortality in the BALF, and shorter transplant-free survival (TFS) and progression-free survival (PFS) time in the blood. Prognostic predictive value of S100A12 was more superior to S100A8 and S100A9 in patients with IPF, and the composited variable [S100A12 + GAP index (gender, age, and physiological index)] may be a more effective predictive index.

Conclusion

These results imply that S100A12 might be an efficient disease severity and prognostic biomarker in patients with IPF.
Joint Damage and Neuropathic Pain in Rats Treated With Lysophosphatidic Acid
Authors: McDougall Jason J. , Reid Allison R.
Published: February 2022

Joint pain is a complex phenomenon that involves multiple endogenous mediators and pathophysiological events. In addition to nociceptive and inflammatory pain, some patients report neuropathic-like pain symptoms. Examination of arthritic joints from humans and preclinical animal models have revealed axonal damage which is likely the source of the neuropathic pain. The mediators responsible for joint peripheral neuropathy are obscure, but lysophosphatidic acid (LPA) has emerged as a leading candidate target. In the present study, male and female Wistar rats received an intra-articular injection of LPA into the right knee and allowed to recover for 28 days. Joint pain was measured by von Frey hair algesiometry, while joint pathology was determined by scoring of histological sections. Both male and female rats showed comparable degenerative changes to the LPA-treated knee including chondrocyte death, focal bone erosion, and synovitis. Mechanical withdrawal thresholds decreased by 20-30% indicative of secondary allodynia in the affected limb; however, there was no significant difference in pain sensitivity between the sexes. Treatment of LPA animals with the neuropathic pain drug amitriptyline reduced joint pain for over 2 hours with no sex differences being observed. In summary, intra-articular injection of LPA causes joint degeneration and neuropathic pain thereby mimicking some of the characteristics of neuropathic osteoarthritis.
Human-Induced CD49a+ NK Cells Promote Fetal Growth
Authors: Du Xianghui , Zhu Huaiping , Jiao Defeng , Nian Zhigang , Zhang Jinghe , Zhou Yonggang , Zheng Xiaohu , Tong Xianhong , Wei Haiming , Fu Binqing
Published: February 2022

CD49a+ natural killer (NK) cells play a critical role in promoting fetal development and maintaining immune tolerance at the maternal-fetal interface during the early stages of pregnancy. However, given their residency in human tissue, thorough studies and clinical applications are difficult to perform. It is still unclear as to how functional human CD49a+ NK cells can be induced to benefit pregnancy outcomes. In this study, we established three no-feeder cell induction systems to induce human CD49a+ NK cells from umbilical cord blood hematopoietic stem cells (HSCs), bone marrow HSCs, and peripheral blood NK cells in vitro. These induced NK cells (iNKs) from three cell induction systems display high levels of CD49a, CD9, CD39, CD151 expression, low levels of CD16 expression, and no obvious cytotoxic capability. They are phenotypically and functionally similar to decidual NK cells. Furthermore, these iNKs display a high expression of growth-promoting factors and proangiogenic factors and can promote fetal growth and improve uterine artery blood flow in a murine pregnancy model in vivo. This research demonstrates the ability of human-induced CD49a+ NK cells to promote fetal growth via three cell induction systems, which could eventually be used to treat patients experiencing adverse pregnancy outcomes.
CCR2+ Macrophages Promote Orthodontic Tooth Movement and Alveolar Bone Remodeling
Authors: Xu Hao , Zhang Shuting , Sathe Adwait Amod , Jin Zhichun , Guan Jiani , Sun Wen , Xing Chao , Zhang Hanwen , Yan Bin
Published: February 2022

During mechanical force-induced alveolar bone remodeling, macrophage-mediated local inflammation plays a critical role. Yet, the detailed heterogeneity of macrophages is still unknown. Single-cell RNA sequencing was used to study the transcriptome heterogeneity of macrophages during alveolar bone remodeling. We identified macrophage subclusters with specific gene expression profiles and functions. CellChat and trajectory analysis revealed a central role of the Ccr2 cluster during development, with the CCL signaling pathway playing a crucial role. We further demonstrated that the Ccr2 cluster modulated bone remodeling associated inflammation through an NF-κB dependent pathway. Blocking CCR2 could significantly reduce the Orthodontic tooth movement (OTM) progression. In addition, we confirmed the variation of CCR2+ macrophages in human periodontal tissues. Our findings reveal that mechanical force-induced functional shift of the Ccr2 macrophages cluster mediated by NF-κB pathway, leading to a pro-inflammatory response and bone remodeling. This macrophage cluster may represent a potential target for the manipulation of OTM.
Comparison Between Different Composite Resins Used for Clear Aligner Attachments: An In-Vitro Study
Authors: Gazzani Francesca , Bellisario Denise , Quadrini Fabrizio , Parrinello Francesca , Pavoni Chiara , Cozza Paola , Lione Roberta
Published: February 2022

Attachments are specific features of clear aligner treatment designed to ensure the aligner’s retention and the predictability of tooth movements. The properties of composite resin used for their reproduction play a relevant role to preserve their integrity and shape over the time. Thus, the aim of the present evaluation was to compare the mechanical properties and the wear performance of two nanocomposite by means of mechanical and tribological tests. Twelve samples for both flowable nanocomposite (FNC) and conventional nanocomposite (CNC) were created. The two nanocomposites differ in terms of filler volume and viscosity of the mixture. The following tests were performed: thermal analysis and burning test; flat instrumented indentation test and a compression stress relaxation test; tribological analysis. Wear evaluation was performed by means of a contact probe surface profiler and a TayMap software for the 3D analysis. A customized step-sliding test was conducted to simulate the clinical application of materials with a polymethyl methacrylate (PMMA) ball used as counterpart. Wear evaluation of both resin surfaces and PMMA ball was performed. No differences were found in terms of polymeric nature and quantity of nanoparticles in the matrix. FNC showed lower density values (1.62 g/cm3 ± 0.02) and inorganic percentage residue (41%) than the CNC (respectively 1.95 g/cm3 ± 0.01 and 23%). Significant differences in terms of decrement of stress values, elastic modulus (1,114.12 ± 91.39 MPa), and stress relaxation rate (24.39% ± 3.23) were observed for the CNC when compared to the FNC (respectively, 835.04 ± 184.73 MPa and 40.19% ± 4.65). FNC showed higher values of dynamic friction coefficient (0.72 ± 0.017) and more worn and deeper profiles than the conventional ones. The step-sliding test with a PMMA ball confirmed a higher friction coefficient for FNC and a greater wear of the PMMA surfaces when used against flowable samples. Lower viscosity of FNC ensures a better adaptation during clinical attachment fabrication, whereas it has a negative impact on mechanical properties. CNC showed greater performance and resistance under mechanical stresses than the flowable ones, resulting in being more suitable for clinical needs.
Prevalence of Antibodies to SARS-CoV-2 Following Natural Infection and Vaccination in Irish Hospital Healthcare Workers: Changing Epidemiology as the Pandemic Progresses
Authors: Allen Niamh , Brady Melissa , Ni Riain Una , Conlon Niall , Domegan Lisa , Carrion Martin Antonio Isidro , Walsh Cathal , Doherty Lorraine , Higgins Eibhlin , Kerr Colm , Bergin Colm , Fleming Catherine
Published: February 2022

Background

In October 2020 SARS-CoV-2 seroprevalence among hospital healthcare workers (HCW) of two Irish hospitals was 15 and 4. 1%, respectively. We compare seroprevalence in the same HCW population 6 months later, assess changes in risk factors for seropositivity with progression of the pandemic and serological response to vaccination.

Methods

All staff of both hospitals (N= 9,038) were invited to participate in an online questionnaire and SARS-CoV-2 antibody testing in April 2021. We measured anti-nucleocapsid and anti-spike antibodies. Frequencies and percentages for positive SARS-CoV-2 antibodies were calculated and adjusted relative risks for participant characteristics were calculated using multivariable regression analysis.

Results

Five thousand and eighty-five HCW participated. Seroprevalence increased to 21 and 13%, respectively; 26% of infections were previously undiagnosed. Black ethnicity (aRR 1.7, 95% CI 1.3–2.2,p< 0.001), lower level of education (aRR 1.4 for secondary level education, 95% CI 1.1–1.8,p= 0.002), living with other HCW (aRR 1.2, 95% CI 1.0–1.4,p= 0.007) were significantly associated with seropositivity. Having direct patient contact also carried a significant risk being a healthcare assistant (aRR 1.8, 95% CI 1.3–2.3,p< 0.001), being a nurse (aRR 1.4, 95% CI 1.0–1.8,p= 0.022), daily contact with COVID-19 patients (aRR 1.4, 95% CI 1.1–1.7,p= 0.002), daily contact with patients without suspected or confirmed COVID-19 (aRR 1.3, 95% CI 1.1–1.5,p= 0.013). Breakthrough infection occurred in 23/4,111(0.6%) of fully vaccinated participants; all had anti-S antibodies.

Conclusion

The increase in seroprevalence reflects the magnitude of the third wave of the pandemic in Ireland. Genomic sequencing is needed to apportion risk to the workplace vs. the household/community. Concerted efforts are needed to mitigate risk factors due to ethnicity and lower level of education, even at this stage of the pandemic. The undiagnosed and breakthrough infections call for ongoing infection prevention and control measures and testing of HCW in the setting of close contact. Vaccinated HCW with confirmed infection should be actively assessed, including SARS-CoV-2 whole genome sequencing (WGS), serology testing and assessment of host determinants, to advance understanding of the reasons for breakthrough infection.
Disrupted Circadian Rest-Activity Cycles in Inflammatory Bowel Disease Are Associated With Aggressive Disease Phenotype, Subclinical Inflammation, and Dysbiosis
Authors: Swanson Garth R. , Kochman Nicole , Amin Jaimin , Chouhan Vijit , Yim Wesley , Engen Phillip A. , Shaikh Maliha , Naqib Ankur , Tran Laura , Voigt Robin M. , Forsyth Christopher B. , Green Stefan J. , Keshavarzian Ali
Published: February 2022

Patients with inflammatory bowel disease (IBD)—Crohn's disease (CD), and ulcerative colitis (UC), have poor sleep quality. Sleep and multiple immunologic and gastrointestinal processes in the body are orchestrated by the circadian clock, and we recently reported that a later category or chronotype of the circadian clock was associated with worse IBD specific outcomes. The goal of this study was to determine if circadian misalignment by rest-activity cycles is associated with markers of aggressive disease, subclinical inflammation, and dysbiosis in IBD. A total of 42 patients with inactive but biopsy-proven CD or UC and 10 healthy controls participated in this prospective cohort study. Subjects were defined as having an aggressive IBD disease history (steroid dependence, use of biologic or immunomodulator, and/or surgery) or non-aggressive history. All participants did two weeks of wrist actigraphy, followed by measurement of intestinal permeability and stool microbiota. Wrist actigraphy was used to calculate circadian markers of rest-activity– interdaily stability (IS), intradaily variability (IV), and relative amplitude (RA). Aggressive IBD history was associated with decrease rest-activity stability (IS) and increased fragmentation compared to non-aggressive IBD and health controls at 0.39 ±.15 vs. 0.51 ± 0.10 vs. 0.55 ± 0.09 (P < 0.05) and 0.83 ± 0.20 vs. 0.72 ± 0.14 (P < 0.05) but not HC at 0.72 ± 0.14 (P = 0.08); respectively. There was not a significant difference in RA by IBD disease history. Increased intestinal permeability and increased TNF-α levels correlated with an increased rest activity fragmentation (IV) at R = 0.35, P < 0.05 and R = 0.37, P < 0.05, respectively; and decreased rest-activity amplitude (RA) was associated with increased stool calprotectin at R = 0.40, P < 0.05. Analysis of intestinal microbiota showed a significant decrease in commensal butyrate producing taxa and increased pro-inflammatory bacteria with disrupted rest-activity cycles. In this study, different components of circadian misalignment by rest-activity cycles were associated with a more aggressive IBD disease history, increased intestinal permeability, stool calprotectin, increased pro-inflammatory cytokines, and dysbiosis. Wrist activity allows for an easy non-invasive assessment of circadian activity which may be an important biomarker of inflammation in IB.
Periodontitis and Subsequent Risk of Cataract: Results From Real-World Practice
Authors: Yeh Li-Jen , Shen Te-Chun , Sun Kuo-Ting , Lin Cheng-Li , Hsia Ning-Yi
Published: February 2022

Background

Periodontitis can lead to systemic inflammation and oxidative stress, contributing to the development of various diseases. Periodontitis could also be associated with several ocular diseases.

Methods

We conducted a retrospective population-based cohort study using the National Health Insurance Research Database of Taiwan to evaluate the risk of cataract in people with and without periodontitis. We established a periodontitis cohort and a non-periodontitis cohort, which included 359,254 individuals between 2000 and 2012. Age, gender, and enrolled year were matched. All participants were monitored until the end of 2013. Cox proportional hazard models were applied to estimate hazard ratios (HRs) and confidence intervals (CIs).

Results

Patients with periodontitis had a significantly higher risk to develop cataract than those without periodontitis [10.7 vs. 7.91 per 1,000 person-years, crude HR = 1.35 (95% CI = 1.32–1.39), and adjusted HR = 1.33 (95% CI = 1.30–1.36)]. The significant levels remained the same after stratifying by age, gender, presence of comorbidity, and use of corticosteroid. In addition, we found that diabetes mellitus and hyperlipidemia had a synergistic effect in the interaction of periodontitis and cataract development.

Conclusion

Patients with periodontitis have a higher risk of cataract development than those without periodontitis. Such patients may request frequent ocular health check-up. Further studies should be performed to confirm the association and to understand the mechanisms.
Evaluation of Two Rapid Lateral Flow Tests and Two Surrogate ELISAs for the Detection of SARS-CoV-2 Specific Neutralizing Antibodies
Authors: Girl Philipp , Zwirglmaier Katrin , von Buttlar Heiner , Wölfel Roman , Müller Katharina
Published: February 2022

As vaccination against SARS-CoV-2 progresses rapidly around the world, reliable detection of SARS-CoV-2 specific neutralizing antibodies (NAb) has become an indispensable component of serological diagnostics. We evaluated the performance of four commercially available tests, i.e. two lateral flow assays (Coris BioConcept COVID-19 Sero NP/RBD and Concile InfectCheck COVID-19 NAb) and two surrogate ELISA (sELISA) tests (EUROIMMUN SARS-CoV-2 NeutraLISA and AdipoGen SARS-CoV-2 Neutralizing Antibodies Detection Kit) in comparison with an in-house SARS-CoV-2 micro neutralization test as reference. A total of 334 sera were tested, including 30 samples collected prior to the emergence of SARS-CoV-2, 128 sera from convalescent patients as well as 176 sera from partially or fully vaccinated individuals. The overall sensitivity of LFAs differed and was 71.6% for the Coris and 98.4% for the Concile. In contrast, overall sensitivity of the NeutraLISA was 86 and 98% for the AdipoGen. All test showed the highest sensitivity when testing samples from fully vaccinated individuals with both sELISA achieving 100% sensitivity. Overall specificity was 89.3% for the Coris and only 58.3% for the Concile. Similarly, significant differences were observed for both sELISA, with an overall specificity of 82.1% for the NeutraLISA and only 54.8% for the AdipoGen. All tests showed a 100% specificity when testing negative control samples while specificities were lowest when testing samples from only partially vaccinated individuals.
Genome-Scale Mining of Novel Anchor Proteins of Corynebacterium glutamicum
Authors: Lin Kerui , Zhao Nannan , Cai Youhua , Lin Ying , Han Shuangyan , Zheng Suiping
Published: February 2022

The display of recombinant proteins on the surfaces of bacteria is a research topic with many possible biotechnology applications—among which, the choice of host cell and anchoring motif is the key for efficient display. Corynebacterium glutamicum is a promising host for surface display due to its natural advantages, while single screening methods and fewer anchor proteins restrict its application. In this study, the subcellular localization (SCL) predictor LocateP and tied-mixture hidden Markov models were used to analyze all five known endogenous anchor proteins of C. glutamicum and test the accuracy of the predictions. Using these two tools, the SCLs of all proteins encoded by the genome of C. glutamicum 13032 were predicted, and 14 potential anchor proteins were screened. Compared with the positive controls NCgl1221 and NCgl1337, three anchoring proteins—NCgl1307, NCgl2775, and NCgl0717—performed better. This study also discussed the applicability of the anchor protein screening method used in this experiment to other bacteria.