bluuebunny/crossref_metadata_2025 huggingface dataset:
8-Gene signature related to CD8+ T cell infiltration by integrating single-cell and bulk RNA-sequencing in head and neck squamous cell carcinoma
Authors: Zhang Shoujing , Zhang Wenyi , Zhang Jian
Published: July 2022

Background: CD8+ T cells, a critical component of the tumor immune microenvironment, have become a key target of cancer immunotherapy. Considering the deficiency of robust biomarkers for head and neck squamous cell carcinoma (HNSCC), this study aimed at establishing a molecular signature associated with CD8+T cells infiltration.

Methods: Single-cell RNA sequencing data retrieved from the Gene Expression Omnibus (GEO) database was analyzed to obtain the different cell types. Next, the cell proportions were investigated through deconvolution of RNA sequencing in the Cancer Genome Atlas (TCGA) database, and then the immune-related genes (IRGs) were identified by weighted gene co-expression network analysis (WGCNA). LASSO-Cox analysis was employed to establish a gene signature, followed by validation using a GEO dataset. Finally, the molecular and immunological properties, and drug responses between two subgroups were explored by applying “CIBERSORT”, “ESTIMATE”, and single sample gene set enrichment analysis (ssGSEA) methods.

Results: A total of 215 differentially expressed IRGs were identified, of which 45 were associated with the overall survival of HNSCC. A risk model was then established based on eight genes, including DEFB1, AICDA, TYK2, CCR7, SCARB1, ULBP2, STC2, and LGR5. The low-risk group presented higher infiltration of memory activated CD4+ T cells, CD8+ T cells, and plasma cells, as well as a higher immune score, suggesting that they could benefit more from immunotherapy. On the other hand, the high-risk group showed higher abundance of activated mast cells and M2 macrophages, as well as a lower immune score.

Conclusion: It was evident that the 8-gene signature could accurately predict HNSCC prognosis and thus it may serve as an index for clinical treatment.
Hypoxia–Immune-Related Gene SLC19A1 Serves as a Potential Biomarker for Prognosis in Multiple Myeloma
Authors: Li Wenjin , Yuan Peng , Liu Weiqin , Xiao Lichan , Xu Chun , Mo Qiuyu , Xu Shujuan , He Yuchan , Jiang Duanfeng , Wang Xiaotao
Published: July 2022

Background

Multiple myeloma (MM) remains an incurable malignant tumor of plasma cells. Increasing evidence has reported that hypoxia and immune status contribute to the progression of MM. In this research, the prognostic value of the hypoxia–immune-related gene SLC19A1 in MM was evaluated by bioinformatics analysis.

Method

RNA-sequencing (RNA-seq) data along with clinical information on MM were downloaded from the Gene Expression Omnibus (GEO) database. Consistent clustering analysis and ESTIMATE algorithms were performed to establish the MM sample subgroups related to hypoxia and immune status, respectively, based on the GSE24080 dataset. The differentially expressed analysis was performed to identify the hypoxia–immune-related genes. Subsequently, a hypoxia–immune-gene risk signature for MM patients was constructed by univariate and multivariate Cox regression analyses, which was also verified in the GSE4581 dataset. Furthermore, the mRNA expression of SLC19A1 was determined using qRT-PCR in 19 MM patients, and the correlations between the genetic expression of SLC19A1 and clinical features were further analyzed.

Result

A total of 47 genes were identified as hypoxia–immune-related genes for MM. Among these genes, SLC19A1 was screened to construct a risk score model that had better predictive power for MM. The constructed prognostic signature based on SLC19A1 was verified in the GSE4581 dataset. All independent prognostic factors (age, β2-microglobulin, LDH, albumin, MRI, and gene risk score) were used to develop a nomogram that showed a better performance for predicting the survival probability of MM patients for 1–5 years. Furthermore, SLC19A1 was highly expressed in newly diagnosed and relapsed MM patients, and high expression of SLC19A1 is correlated with higher bone marrow aspiration plasma cells and β2-microglobulin levels in MM patients.

Conclusion

In conclusion, our results suggest that SLC19A1 is aberrantly expressed in MM and highly expressed SLC19A1 might be a biomarker correlated with inferior prognosis. More importantly, we identified SLC19A1 as a hypoxia–immune-related gene in MM. Future functional and mechanistic studies will further clarify the roles of SLC19A1 in MM.
Immunological risk factors for nonalcoholic fatty liver disease in patients with psoriatic arthritis: New predictive nomograms and natural killer cells
Authors: Li Baochen , Su Rui , Yan Huanhuan , Liu Juanjuan , Gao Chong , Li Xiaofeng , Wang Caihong
Published: July 2022

Objective

To search for the immunological risk factors of Psoriatic arthritis (PsA) combined with nonalcoholic fatty liver disease (NAFLD), development and assessment of predictive nomograms for NAFLD risk in patients with PsA, and to further explore the correlation between risk factors and dyslipidemia.

Methds

A total of 127 patients with PsA (46 with NAFLD and 81 without NAFLD) were included in this retrospective study. The clinical and serological parameters of the patients were collected. The percentage and the absolute number of lymphocytes and CD4+T cells were determined by Flow cytometry. Univariate and multivariate binary logistic regression analysis was used to screen independent risk factors of PsA complicated with NAFLD in the model population, and a nomogram prediction model was developed and assessed.

Results

(1) Univariate and multivariate logistic regression analysis of the modeling population showed that the percentage of peripheral blood T helper 1 cells (Th1%) (OR=1.12, P=0.001), body mass index (BMI) (OR=1.22, P=0.005) and triglycerides (TG) (OR=4.78, P=0.003) were independent risk factors for NAFLD in patients with PsA, which were incorporated and established a nomogram prediction model. The model has good discrimination and calibration, and also has certain clinical application value. (2) The number of peripheral blood NK cells in PsA patients was significantly positively correlated with serum triglyceride (TG) (r=0.489, P<0.001), cholesterol (CHOL) (r=0.314, P=0.003) and low-density lipoprotein (LDL) (r=0.362, P=0.001) levels.

Conclusions

Our study shows that the novel NAFLD nomogram could assess the risk of NAFLD in PsA patients with good efficiency. In addition, peripheral blood NK cell levels may be associated with dyslipidemia in patients with PsA.
ITGB4 Deficiency in Airway Epithelium Aggravates RSV Infection and Increases HDM Sensitivity
Authors: Du Xizi , Yuan Lin , Yao Ye , Yang Yu , Zhou Kai , Wu Xinyu , Wang Leyuan , Qin Ling , Li Wenkai , Xiang Yang , Qu Xiangping , Liu Huijun , Qin Xiaoqun , Yang Ming , Liu Chi
Published: July 2022

Background

The heterogeneity of RSV-infected pathology phenotype in early life is strongly associate with increased susceptibility of asthma in later life. However, the inner mechanism of this heterogeneity is still obscure. ITGB4 is a down-regulated adhesion molecular in the airway epithelia of asthma patients which may participate in the regulation of RSV infection related intracellular pathways.

Object

This study was designed to observe the involvement of ITGB4 in the process of RSV infection and the effect of ITGB4 deficiency on anti-RSV responses of airway epithelia.

Results

RSV infection caused a transient decrease of ITGB4 expression both in vitro and in vivo. Besides, ITGB4 deficiency induced not only exacerbated RSV infection, but also enhanced HDM sensitivity in later life. Moreover, IFN III (IFN-λ) was significantly suppressed during RSV infection in ITGB4 deficient airway epithelial cells. Furthermore, the suppression of IFN-λ were regulated by IRF-1 through the phosphorylation of EGFR in airway epithelial cells after RSV infection.

Conclusion

These results demonstrated the involvement of ITGB4 deficiency in the development of enhance RSV infection in early life and the increased HDM sensitivity in later life by down-regulation of IFN-λ through EGFR/IRF-1 pathway in airway epithelial cells.
Establishment of a circular RNA regulatory stemness-related gene pair signature for predicting prognosis and therapeutic response in colorectal cancer
Authors: Chen Qian , Tang Peng , Huang Huishen , Qiu Xiaoqiang
Published: July 2022

Background

Colorectal cancer (CRC) is a common malignant tumor of the digestive tract with a poor prognosis. Cancer stem cells (CSCs) affect disease outcomes and treatment responses in CRC. We developed a circular RNA (circRNA) regulatory stemness-related gene pair (CRSRGP) signature to predict CRC patient prognosis and treatment effects.

Methods

The circRNA, miRNA, and mRNA expression profiles and clinical information of CRC patients were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. CRSRGPs were established based on stemness-related genes in the competing endogenous RNA (ceRNA) network. A CRSRGP signature was generated using the least absolute shrinkage and selection operator (Lasso) and Cox regression analysis of TCGA training set. The prognosis was predicted by generating a nomogram integrating the CRSRGP signature and clinicopathologic features. The model was validated in an external validation set (GSE17536). The antitumor drug sensitivity and immunotherapy responses of CRC patients in the high-risk group (HRG) and low-risk group (LRG) were evaluated by the pRRophetic algorithm and immune checkpoint analysis.

Results

We established an 18-CRSRGP signature to predict the prognosis and treatment responses of CRC patients. In the training and external validation sets, risk scores were used to categorize CRC patients into the HRG and LRG. The Kaplan–Meier analysis showed a poor prognosis for patients in the HRG and that subgroups with different clinical characteristics had significantly different prognoses. A multivariate Cox analysis revealed that the CRSRGP signature was an independent prognostic factor. The nomogram integrating clinical features and the CRSRGP signature efficiently predicted CRC patient prognosis, outperformed the current TNM staging system, and had improved practical clinical value. Anticancer drug sensitivity predictions revealed that the tumors of patients in the HRG were more sensitive to pazopanib, sunitinib, gemcitabine, lapatinib, and cyclopamine. Analysis of immune checkpoint markers demonstrated that patients in the HRG were more likely to benefit from immunotherapy.

Conclusion

An efficient, reliable tool for evaluating CRC patient prognosis and treatment response was established based on the 18-CRSRGP signature and nomogram.
A New Thinking: Deciphering the Aberrance and Clinical Implication of IGF Axis Regulation Pattern in Clear Cell Renal Cell Carcinoma
Authors: Jiang Aimin , Wu Xiaofeng , Wang Desheng , Wang Anbang , Dong Kai , Liu Bing , Qu Le , Luo Peng , Wang Jian , Tong Qiang , Wang Linhui
Published: July 2022

Rationale

The recent research found that IGF regulator genes played a pivotal role in multiple biological processes, which may be developed for cancer treatment. However, the characteristics and implication of IGF regulators in cancers, especially in clear cell renal cell carcinoma (ccRCC), remain elusive.

Methods

We systematically analyzed the expression, prognostic valuation, genome variation, and functional implication at pan-cancer level from The Cancer Genome Atlas. According to expression levels of IGF regulator genes, ccRCC could be divided into three different subtypes via unsupervised cluster algorithm: IGF pattern cancer type1 (IPCS1), type2 (IPCS2), and type3 (IPCS3). The immune microenvironment, immunotherapy response, metabolic pattern, and tumor progression signature among the three subgroups were investigated. The clinical characteristics, genomic mutations, and potential drug sensitivity were further analyzed. IGF pattern–related risk model was constructed to predict RCC patients’ outcome. Finally, SHC1, a potential IGF axis target, was comprehensively investigated in ccRCC.

Results

We found that IGF regulator genes were specifically upregulated in various cancer tissues, which were correlated with copy number variations and dysregulated pathways. IPCS1, IPCS2, and IPCS3 exhibited different clinical profiles and biological characteristics in ccRCC. IPCS3 subtype indicated a higher clinical stage and a worse survival. IPSC3 ccRCC displayed activated metabolic signatures to fuel the cancer progression. IPCS3 subgroup holds a higher tumor mutation burden and lower immune activities, which resulted in a low ICI therapy response and tumor immunity dysfunction state. The genome copy numbers of IPCS2/3, including arm gain and arm loss, were significantly higher than IPCS1. Besides, the drug sensitivity profiles were different among the three subgroups. The prognostic risk model based on subtype’s biomarker exerted a promising performance both in training and validation cohorts. Finally, upregulated expression of SHC1 partly induced poorer immunotherapy response and shorter survival of ccRCC patients.

Conclusion

Targeting IGF regulators may be functioned as a treatment approach among multi-cancers. IGF regulator–related signature could reshape the tumor immune microenvironment via activating multi-step immune programs. The inhibition of SHC1 may enhance the efficacy of immunotherapy, and SHC1 could be a suitable target for ccRCC therapy.
Use of gliptins reduces levels of SDF-1/CXCL12 in bullous pemphigoid and type 2 diabetes, but does not increase autoantibodies against BP180 in diabetic patients
Authors: Nätynki Antti , Leisti Päivi , Tuusa Jussi , Varpuluoma Outi , Huilaja Laura , Izumi Kentaro , Herukka Sanna-Kaisa , Ukkola Olavi , Junttila Juhani , Kokkonen Nina , Tasanen Kaisa
Published: July 2022

The use of dipeptidyl peptidase 4 (DPP4) inhibitors, (also known as gliptins), is associated with an increased risk of bullous pemphigoid (BP), an autoimmune blistering skin disease. To explore the mechanism behind gliptin-associated BP we investigated circulating autoantibodies against the major BP autoantigen BP180 in serum samples from patients with type 2 diabetes (T2D) with preceding gliptin medication (n = 136) or without (n = 136). Sitagliptin was the most frequently prescribed gliptin (125/136 patients). Using an ELISA assay, we showed that IgG autoantibodies against the immunodominant NC16A domain of BP180 were found in 5.9% of gliptin treated and in 6.6% of non-gliptin treated T2D patients. We found that 28% of gliptin treated patients had IgG autoantibodies recognizing the native full-length BP180 in ELISA, but among non-gliptin treated the seropositivity was even higher, at 32%. Further ELISA analysis of additional serum samples (n = 57) found no major changes in the seropositivity against BP180 during a follow-up period of about nine years. In immunoblotting, full-length BP180 was recognized by 71% of gliptin treated and 89% of non-gliptin treated T2D patients, but only by 46% of the age-and sex-matched controls. The chemokine stromal derived factor-1(SDF-1/CXCL12) is one of the major substrates of DPP4. Immunostainings showed that the expression of SDF-1 was markedly increased in the skin of BP patients, but not affected by prior gliptin treatment. We found that the use of gliptins decreased the serum level of SDF-1α in both BP and T2D patients. Our results indicate that the autoantibodies against the linear full-length BP180 are common in patients with T2D, but seropositivity is unaffected by the use of sitagliptin.
The protective capability of Hedyotis diffusa Willd on lupus nephritis by attenuating the IL-17 expression in MRL/lpr mice
Authors: Li Ying , Ding Tao , Chen Jing , Ji Jinjun , Wang Weijie , Ding Bin , Ge Weihong , Fan Yongsheng , Xu Li
Published: July 2022

Lupus nephritis (LN), the most severe organ manifestation of systemic lupus erythematosus (SLE), is generally treated with glucocorticoids (GC) in clinical practice, leading to drug resistance and adverse effects in the long term. Fortunately, the combination of GC and traditional Chinese medical prescriptions can attenuate the adverse effects and improve therapeutic efficiency. Hedyotis diffusa Willd (HDW) is one of the most commonly used herbal compounds for LN treatment, which exhibits “heat-clearing” and “detoxification” effects. However, the underlying pharmacological mechanism remains unclear. The present study identified the chemical compounds in HDW extract with UPLC-Q-TOF-MS/MS. A total of 49 components were identified in the HDW extract, and the IL-17 signaling pathway was highly enriched by network pharmacological analysis. MRL/lpr model mice, reflecting the spontaneous development of LN, were used to evaluate the protective activity and investigate the underlying mechanism of the combination treatment. The white blood cell content (WBC), including lymphocytes and neutrophils, cytokines (IL-6, MCP-1, TNF-a), and various autoantibodies (ANA, ab-dsDNA, ab-snRNP/sm) in the blood of MRL/lpr mice were significantly improved by the intragastric administration of HDW. Additionally, the expression of STAT3, IL-17, Ly6G, and MPO in the kidney and neutrophil NETosis were ameliorated with HDW treatment. The pathological and morphological analysis suggested that HDW application could reduce urinary protein levels and inflammatory cell infiltration and inhibit glomerular interstitial cell proliferation. Hence, HDW might ameliorate lupus nephritis by inhibiting IL-6 secretion and STAT3-induced IL-17 expression. The active compounds in HDW were predictively selected with computational methods. The docking affinity of asiatic acid, neoandrographolide to IL-6, glycyrrhetinic acid, oleanolic acid, ursolic acid, and wilforlide A to STAT3 are extremely high. In conclusion, the IL-6 and STAT3/IL-17signaling pathways could be critical regulative targets of HDW on LN.
Capabilities of hepatitis B surface antigen are divergent from hepatitis B virus DNA in delimiting natural history phases of chronic hepatitis B virus infection
Authors: Zhang Zhanqing , Lu Wei , Huang Dan , Zhou Xinlan , Ding Rongrong , Li Xiufen , Wang Yanbing , Lin Weijia , Zeng Dong , Feng Yanling
Published: July 2022

Objective

Quantitative hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA in the natural history of chronic HBV infection have not been rationally evaluated. This study aimed to re-characterize quantitative HBsAg and HBV DNA in the natural history phases.

Methods

A total of 595 and 651 hepatitis B e antigen (HBeAg)-positive patients and 485 and 705 HBeAg-negative patients were assigned to the early and late cohorts, respectively. Based on the ‘S-shape’ receiver operating characteristic (ROC) curves, the HBeAg-positive sub-cohorts with possibly high HBV replication (PHVR) and possibly low HBV replication (PLVR) and the HBeAg-negative sub-cohorts with possibly high HBsAg expression (PHSE) and possibly low HBsAg expression (PLSE) were designated.

Results

The areas under the ROC curve (AUCs) of HBsAg and HBV DNA in predicting HBeAg-positive significant hepatitis activity (SHA) in the early cohort, sub-cohort with PHVR, and sub-cohort with PLVR were 0.655 and 0.541, 0.720 and 0.606, and 0.553 and 0.725, respectively; those in the late cohort, sub-cohort with PHVR, and sub-cohort with PLVR were 0.646 and 0.501, 0.798 and 0.622, and 0.603 and 0.674, respectively. The AUCs of HBsAg and HBV DNA in predicting HBeAg-negative SHA in the early cohort, sub-cohort with PHSE, and sub-cohort with PLSE were 0.508 and 0.745, 0.573 and 0.780, and 0.577 and 0.729, respectively; those in the late cohort, sub-cohort with PHSE, and sub-cohort with PLSE were 0.503 and 0.761, 0.560 and 0.814, and 0.544 and 0.722, respectively. The sensitivity and specificity of HBsAg ≤4.602 log10 IU/ml in predicting HBeAg-positive SHA in the early cohort were 82.6% and 45.8%, respectively; those in the late cohort were 87.0% and 44.1%, respectively. The sensitivity and specificity of HBV DNA >3.301 log10 IU/ml in predicting HBeAg-negative SHA in the early cohort were 73.4% and 60.8%, respectively; those in the late cohort were 73.6% and 64.1%, respectively.

Conclusion

Quantitative HBsAg and HBV DNA are valuable, but their capabilities are divergent in delimiting the natural history phases.
Comparative immunogenicity of an mRNA/LNP and a DNA vaccine targeting HIV gag conserved elements in macaques
Authors: Valentin Antonio , Bergamaschi Cristina , Rosati Margherita , Angel Matthew , Burns Robert , Agarwal Mahesh , Gergen Janina , Petsch Benjamin , Oostvogels Lidia , Loeliger Edde , Chew Kara W. , Deeks Steven G. , Mullins James I. , Pavlakis George N. , Felber Barbara K.
Published: July 2022

Immunogenicity of HIV-1 mRNA vaccine regimens was analyzed in a non-human primate animal model. Rhesus macaques immunized with mRNA in lipid nanoparticle (mRNA/LNP) formulation expressing HIV-1 Gag and Gag conserved regions (CE) as immunogens developed robust, durable antibody responses but low adaptive T-cell responses. Augmentation of the dose resulted in modest increases in vaccine-induced cellular immunity, with no difference in humoral responses. The gag mRNA/lipid nanoparticle (LNP) vaccine provided suboptimal priming of T cell responses for a heterologous DNA booster vaccination regimen. In contrast, a single immunization with gag mRNA/LNP efficiently boosted both humoral and cellular responses in macaques previously primed by a gag DNA-based vaccine. These anamnestic cellular responses were mediated by activated CD8+ T cells with a phenotype of differentiated T-bet+ cytotoxic memory T lymphocytes. The heterologous prime/boost regimens combining DNA and mRNA/LNP vaccine modalities maximized vaccine-induced cellular and humoral immune responses. Analysis of cytokine responses revealed a transient systemic signature characterized by the release of type I interferon, IL-15 and IFN-related chemokines. The pro-inflammatory status induced by the mRNA/LNP vaccine was also characterized by IL-23 and IL-6, concomitant with the release of IL-17 family of cytokines. Overall, the strong boost of cellular and humoral immunity induced by the mRNA/LNP vaccine suggests that it could be useful as a prophylactic vaccine in heterologous prime/boost modality and in immune therapeutic interventions against HIV infection or other chronic human diseases.
Metabolic regulation of T cell development
Authors: Zhang Mengdi , Lin Xiaoxi , Yang Zhou , Li Xia , Zhou Zhiguang , Love Paul E. , Huang Jiaqi , Zhao Bin
Published: July 2022

T cell development in the thymus is tightly controlled by complex regulatory mechanisms at multiple checkpoints. Currently, many studies have focused on the transcriptional and posttranslational control of the intrathymic journey of T-cell precursors. However, over the last few years, compelling evidence has highlighted cell metabolism as a critical regulator in this process. Different thymocyte subsets are directed by distinct metabolic pathways and signaling networks to match the specific functional requirements of the stage. Here, we epitomize these metabolic alterations during the development of a T cell and review several recent works that provide insights into equilibrating metabolic quiescence and activation programs. Ultimately, understanding the interplay between cellular metabolism and T cell developmental programs may offer an opportunity to selectively regulate T cell subset functions and to provide potential novel therapeutic approaches to modulate autoimmunity.
HTLV-1 intragenic viral enhancer influences immortalization phenotype in vitro, but is dispensable for persistence and disease development in animal models
Authors: Maksimova Victoria , Smith Susan , Seth Jaideep , Phelps Cameron , Niewiesk Stefan , Satou Yorifumi , Green Patrick L. , Panfil Amanda R.
Published: July 2022

Human T-cell leukemia virus type 1 (HTLV-1) is the causative infectious agent of adult T-cell leukemia/lymphoma (ATL) and chronic neurological disease. The disparity between silenced sense transcription versus constitutively active antisense (Hbz) transcription from the integrated provirus is not fully understood. The presence of an internal viral enhancer has recently been discovered in the Tax gene near the 3’ long terminal repeat (LTR) of HTLV-1. In vitro, this enhancer has been shown to bind SRF and ELK-1 host transcription factors, maintain chromatin openness and viral gene transcription, and induce aberrant host gene transcription near viral integration sites. However, the function of the viral enhancer in the context of early HTLV-1 infection events remains unknown. In this study, we generated a mutant Enhancer virus (mEnhancer) and evaluated its effects on HTLV-1-mediated in vitro immortalization, establishment of persistent infection with an in vivo rabbit model, and disease development in a humanized immune system (HIS) mouse model. The mEnhancer virus was able to establish persistent infection in rabbits, and there were no significant differences in proviral load or HTLV-1-specific antibody responses over a 25-week study. However, rabbits infected with the mEnhancer virus had significantly decreased sense and antisense viral gene expression at 12-weeks post-infection. HIS mice infected with wt or mEnhancer virus showed similar disease progression, proviral load, and viral gene expression. While mEnhancer virus was able to sufficiently immortalize primary T-lymphocytes in cell culture, the immortalized cells had an altered phenotype (CD8+ T-cells), decreased proviral load, decreased sense and anti-sense gene expression, and altered cell cycle progression compared to HTLV-1.wt immortalized cells (CD4+ T-cells). These results suggest that the HTLV-1 enhancer element alone does not determine persistence or disease development but plays a pivotal role in regulating viral gene expression.
Type II alveolar epithelial cell aryl hydrocarbon receptor protects against allergic airway inflammation through controlling cell autophagy
Authors: Wang Ji , Zhao Yilin , Zhang Xin , Tu Wei , Wan Rongjun , Shen Yingchun , Zhang Yan , Trivedi Ruchik , Gao Peisong
Published: July 2022

Rationale

Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, has been considered as an important regulator for immune diseases. We have previously shown that AhR protects against allergic airway inflammation. The underlying mechanism, however, remains undetermined.

Objectives

We sought to determine whether AhR specifically in type II alveolar epithelial cells (AT2) modulates allergic airway inflammation and its underlying mechanisms.

Methods

The role of AhR in AT2 cells in airway inflammation was investigated in a mouse model of asthma with AhR conditional knockout mice in AT2 cells (Sftpc-Cre;AhRf/f). The effect of AhR on allergen-induced autophagy was examined by both in vivo and in vitro analyses. The involvement of autophagy in airway inflammation was analyzed by using autophagy inhibitor chloroquine. The AhR-regulated gene profiling in AT2 cells was also investigated by RNA sequencing (RNA-seq) analysis.

Results

Sftpc-Cre;AhRf/f mice showed exacerbation of allergen-induced airway hyperresponsiveness and airway inflammation with elevated Th2 cytokines in bronchoalveolar lavage fluid (BALF). Notably, an increased allergen-induced autophagy was observed in the lung tissues of Sftpc-Cre;AhRf/f mice when compared with wild-type mice. Further analyses suggested a functional axis of AhR-TGF-β1 that is critical in driving allergic airway inflammation through regulating allergen-induced cellular autophagy. Furthermore, inhibition of autophagy with autophagy inhibitor chloroquine significantly suppressed cockroach allergen–induced airway inflammation, Th2 cytokines in BALFs, and expression of autophagy-related genes LC3 and Atg5 in the lung tissues. In addition, RNA-seq analysis suggests that autophagy is one of the major pathways and that CALCOCO2/NDP52 and S1009 are major autophagy-associated genes in AT2 cells that may contribute to the AhR-mediated cockroach allergen–induced airway inflammation and, subsequently, allergic asthma.

Conclusion

These results suggest that AhR in AT2 cells functions as a protective mechanism against allergic airway inflammation through controlling cell autophagy.
Molecular Characteristics of Scylla paramamosain Ubiquitin-Conjugating Enzyme E2 and Expression Analysis During Oogenesis
Authors: Han Kunhuang , Dai Yanbin , Zhang Ziping , Rao Congwen , Zhou Li , Wang Yilei
Published: July 2022

Ubiquitination is an essential post-translational modification of proteins and involved in many physiological processes, including sperm differentiation, oocyte maturation, and embryonic development. Among them, the ubiquitin-conjugating enzyme E2 plays a crucial role in gametogenesis. However, the participation of E2 in the regulation of the gonad development of crustaceans is still very limited, especially for oogenesis. In this research, we isolated and identified full-length complementary DNA of ubiquitin-conjugating enzyme E2 from mud crab (Scylla paramamosain) (Sp-Ubc2), detected distribution in different tissues by real-time quantitative PCR, and described expression patterns during oogenesis by in situ hybridization. The results demonstrated that the deduced proteins with a ubiquitin-conjugating (UBC) catalytic domain was clustered with other arthropods. In addition, the Sp-Ubc2 was widely distributed in different tissues of female individuals and kept the highest expression level in the ovary. Moreover, the expression level of Sp-Ubc2 changed significantly during oogenesis and reached peak in secondary and tertiary vitellogenesis stages. At the same time, the Sp-Ubc2 signal in the ovary gradually concentrated in nuclei. These results indicated that Sp-Ubc2 might play important roles in the cell cycle of oogenesis. This study would provide insights into the regulatory mechanism of gonad development in S. paramamosain, and it also enriched the theoretical basis of ubiquitin family genes involved in crustacean gonad development.
A Screening Study on Effects Varying Dietary Macronutrient Composition on Gut Functions in Lumpfish (Cyclopterus lumpus)
Authors: Zhou Weiwen , Hamre Kristin , Chikwati Elvis , Kousoulaki Katerina , Lein Ingrid , Berge Gerd Marit , Sæle Øystein , Kortner Trond M. , Krogdahl Åshild
Published: July 2022

Cultivation of lumpfish (Cyclopterus lumpus) as lice cleaner fish for salmon is now expanding. For successful cultivation of a new species, understanding the basic biology of digestive functions is vital to facilitate and optimize diet formulation. This paper presents results from two experiments conducted to deepen our knowledge on lumpfish intestine physiology. Experiment 1 was a 42-day feeding trial in which lumpfish were fed twelve different diets in the following ranges of macronutrients: Protein 43-68%, lipid 4-17%, and carbohydrate 6-17%. Intestinal tissue, gut content and liver were sampled from 6 fish per tank. The results showed that with increasing lipid level and corresponding decrease in protein level, there was a linear decrease in several of the observed biomarkers, including activity of brush border membrane digestive enzymes, expression of genes related to nutrient digestion and transport, ion exchange, immune regulation, and cell remodeling. Increased intracellular accumulation of lipid (steatosis) was observed in gut and liver with increasing dietary lipid level. Fewer effects were observed for increased dietary carbohydrate and corresponding decreased protein level. Experiment 2 was a two-week feeding trial for estimation of macronutrient digestibility in which lumpfish were fed three diets, all containing 55% crude protein, with lipid to carbohydrate ratio of the low lipid diet of 7.5%/18.3%, the medium lipid diet of 13.8%/14.6%, and high lipid diet of 18.1%/9.5%. Fecal samples were collected as pooled samples per tank. These results showed that fatty acid digestibility’s increased as dietary lipid level increased. Of note, starch digestibility decreased greatly as starch level increased, whereas protein digestibility did not change as lipid or starch level varied. Taken together, the present studies indicated that increasing lipid level in the diet with corresponding decrease in protein level affects digestion, absorption, and immune responses in the lumpfish intestine. Variation in dietary carbohydrate to protein level showed less effects, possibly due to low starch digestibility which makes the variation in available carbohydrates much less than the variation in the analysed level of dietary carbohydrates.
Loss of coastal ecosystem services in Mexico: An approach to economic valuation in the face of sea level rise
Authors: Fernández-Díaz Violeta Z. , Canul Turriza Román A. , Kuc Castilla Angel , Hinojosa-Huerta Osvel
Published: July 2022

The economic valuation of coastal ecosystem services is a critical step for the design of sound public policies that support the preservation of the services that nature provides to society in the context of climate change. Using the value transfer method, we obtained the economic valuation that represents the loss of coastal ecosystem services caused by sea level rise in Mexico. Using the Bathtub method, digital elevation models and sea level data, we identified the areas in the country prone to flooding and the associated ecosystem impacts. In Mexico, the annual economic loss caused by the disappearance of coastal ecosystem services is estimated at $6,476,402,405 USD, where wetlands represent the greatest economic losses, since they represent the largest affected ecosystem by area. However, beaches and dunes are the most valued ecosystem due to the economic activities that occur in these areas. In the mangroves, the service as habitat, refuge and nursery is the most valued for its positive relationship with fisheries. The states with the most economic losses are Baja California Sur, Sinaloa and Campeche. The protection of the coastal zone in Mexico should be a priority in the development strategies in the country because its loss and/or rehabilitation imply high economic costs and compromises the wellbeing of society.
Recommendations for Plankton Measurements on OceanSITES Moorings With Relevance to Other Observing Sites
Authors: Boss Emmanuel , Waite Anya M. , Karstensen Johannes , Trull Tom , Muller-Karger Frank , Sosik Heidi M. , Uitz Julia , Acinas Silvia G. , Fennel Katja , Berman-Frank Ilana , Thomalla Sandy , Yamazaki Hidekatsu , Batten Sonia , Gregori Gerald , Richardson Anthony J. , Wanninkhof Rik
Published: July 2022

Measuring plankton and associated variables as part of ocean time-series stations has the potential to revolutionize our understanding of ocean biology and ecology and their ties to ocean biogeochemistry. It will open temporal scales (e.g., resolving diel cycles) not typically sampled as a function of depth. In this review we motivate the addition of biological measurements to time-series sites by detailing science questions they could help address, reviewing existing technology that could be deployed, and providing examples of time-series sites already deploying some of those technologies. We consider here the opportunities that exist through global coordination within the OceanSITES network for long-term (climate) time series station in the open ocean. Especially with respect to data management, global solutions are needed as these are critical to maximize the utility of such data. We conclude by providing recommendations for an implementation plan.
Effects of larval trematode parasitism on the reproductive capacity of Manila clam Ruditapes philippinarum in a sandy-mud tidal flat on the west coast of Korea
Authors: Cho Young-Ghan , Lee Hye-Mi , Kim Jeong-Hwa , Shin Jong-Seop , Jeung Hee-Do , Choi Kwang-Sik
Published: July 2022

Gonad intrusion of the larval trematodes often results in substantial damage to the reproductive capacity of some economically important marine bivalves. Such detrimental impacts of the larval trematode infection are observed in Manila clam Ruditapes philippinarum in the coastal Yellow Sea, although the effects on the host’s reproduction are poorly understood. Accordingly, this study attempts to understand the impacts of parasitism on clam reproduction using histology. Of the 1,255 adult clams collected in early June from a tidal flat on the west coast of Korea, 68 individuals (5.4%) were infected by three different larval trematodes, including Cercaria tapidis, Cercaria pectinata, and Parvatrema duboisi. Histology revealed that the uninfected clams were in the late developing or ripe stage, exhibiting fully developed gametes in the expended follicles. In contrast, clams infected by the larval trematode showed retarded gonad maturation. Some of those clams remained sexually indifferent (13/68 infected clams) or early developing (9/68 infected clams). We categorized the infection level into uninfected (0), light (1), moderate (2), heavy (3), and very heavy (4), according to the area of sporocysts occupying the histology section. The image analysis indicated that approximately 50% of the infected clams were in “heavy” and “very heavy” conditions, and they occupied 16.7% and 26.9% of the total cross-section area, respectively. The nonparametric Kruskal–Wallis’s test and the post-hoc Tukey’s test indicated that the condition index (CI) of clams in heavy and very heavy infection were significantly lower than uninfected clams. In conclusion, the larval trematodes infected about 5.4% of the clam population in the tidal flat on the west coast of Korea, and we estimated that 32.4% of the infected clams might fail to reproduce during a spawning period due to the severe infection.
Two LRR-Only Proteins Involved in Antibacterial Defense and Prophenoloxidase System of Swimming Crab Portunus trituberculatus
Authors: Zhang Ao , Liu Yuan , Guo Na , Li Shihao , Li Fuhua
Published: July 2022

The leucine-rich repeat (LRR) motif is evolutionarily conserved in many pattern recognition receptors. Compared to the reported LRR proteins with multiple functional domains, the role of LRR-only proteins merely containing LRR motifs remain largely unexplored. In this study, two LRR-only proteins, PtLRR1 and PtLRR2, were identified from the swimming crab Portunus trituberculatus. Five LRR motifs with a consensus sequence LxxLxxLxLxxNxL were found in their encoded peptides. Both PtLRR1 and PtLRR2 were dominantly expressed in the hepatopancreas and showed a time-dependent response post bacteria and virus stimulation. The recombinant PtLRR1 could bind to various PAMPs, including LPS, PGN, and GLU. PtLRR1 and PtLRR2 displayed different regulatory activities in inducing the expression of inflammation and proPO system-related genes. Knockdown of PtLRR2 led to the decreased expression of the tested cytokines and adapter, while PtLRR1 knockdown enhanced the expression of serine proteases, serine protease homologues, and proPO genes. In addition, knockdown of PtLRR1 or PtLRR2 reduced the clearance activity of Vibrio but upregulated the expression levels of AMPs and key genes of Toll, IMD, and JNK pathways. These results suggest that PtLRR1 and PtLRR2 could act as potential immune receptors and regulate antibacterial immunity in crab.
Case Report: Subacute thyroiditis after receiving inactivated SARS-CoV-2 vaccine (BBIBP-CorV)
Authors: Pi Linhua , Lin Jian , Zheng Ying , Wang Zhen , Zhou Zhiguang
Published: July 2022

Background

Subacute thyroiditis, an inflammatory disease, has been reported caused by vaccines in rare cases. In the context of the coronavirus disease 19 pandemic, various SARS-CoV-2 vaccines have been developed and may be potential triggers for subacute thyroiditis.

Case presentation

We report a case of subacute thyroiditis 3 days after receiving the second dose of inactivated SARS-CoV-2 vaccine (BBIBP-CorV). The patient did not report a previous history of thyroid disease, upper respiratory tract infection, or COVID-19. Physical examination, laboratory testing, ultrasonography, and radioactive iodine uptake were consistent with subacute thyroiditis. During follow-up, the patient recovered from symptoms and signs, and imaging changes except for hypothyroidism, requiring an ongoing thyroxine replacement.

Conclusions

Inactivated SARS-CoV-2 vaccine may be a causal trigger leading to subacute thyroiditis. Clinicians should be aware of subacute thyroiditis as a possible thyroid-related side effect of an inactivated SARS-CoV-2 vaccine.
A prediction and interpretation machine learning framework of mortality risk among severe infection patients with pseudomonas aeruginosa
Authors: Cui Chen , Mu Fei , Tang Meng , Lin Rui , Wang Mingming , Zhao Xian , Guan Yue , Wang Jingwen
Published: July 2022

Pseudomonas aeruginosa is a ubiquitous opportunistic bacterial pathogen, which is a leading cause of nosocomial pneumonia. Early identification of the risk factors is urgently needed for severe infection patients with P. aeruginosa. However, no detailed relevant investigation based on machine learning has been reported, and little research has focused on exploring relationships between key risk clinical variables and clinical outcome of patients. In this study, we collected 571 severe infections with P. aeruginosa patients admitted to the Xijing Hospital of the Fourth Military Medical University from January 2010 to July 2021. Basic clinical information, clinical signs and symptoms, laboratory indicators, bacterial culture, and drug related were recorded. Machine learning algorithm of XGBoost was applied to build a model for predicting mortality risk of P. aeruginosa infection in severe patients. The performance of XGBoost model (AUROC = 0.94 ± 0.01, AUPRC = 0.94 ± 0.03) was greater than the performance of support vector machine (AUROC = 0.90 ± 0.03, AUPRC = 0.91 ± 0.02) and random forest (AUROC = 0.93 ± 0.03, AUPRC = 0.89 ± 0.04). This study also aimed to interpret the model and to explore the impact of clinical variables. The interpretation analysis highlighted the effects of age, high-alert drugs, and the number of drug varieties. Further stratification clarified the necessity of different treatment for severe infection for different populations.
Arbuscular Mycorrhizal Fungi Taxa Show Variable Patterns of Micro-Scale Dispersal in Prairie Restorations
Authors: Tipton Alice G. , Nelsen Donald , Koziol Liz , Duell Eric B. , House Geoffrey , Wilson Gail W. T. , Schultz Peggy A. , Bever James D.
Published: July 2022

Human land use disturbance is a major contributor to the loss of natural plant communities, and this is particularly true in areas used for agriculture, such as the Midwestern tallgrass prairies of the United States. Previous work has shown that arbuscular mycorrhizal fungi (AMF) additions can increase native plant survival and success in plant community restorations, but the dispersal of AMF in these systems is poorly understood. In this study, we examined the dispersal of AMF taxa inoculated into four tallgrass prairie restorations. At each site, we inoculated native plant species with greenhouse-cultured native AMF taxa or whole soil collected from a nearby unplowed prairie. We monitored AMF dispersal, AMF biomass, plant growth, and plant community composition, at different distances from inoculation. In two sites, we assessed the role of plant hosts in dispersal, by placing known AMF hosts in a “bridge” and “island” pattern on either side of the inoculation points. We found that AMF taxa differ in their dispersal ability, with some taxa spreading to 2-m in the first year and others remaining closer to the inoculation point. We also found evidence that AMF spread altered non-inoculated neighboring plant growth and community composition in certain sites. These results represent the most comprehensive attempt to date to evaluate AMF spread.
Temporal Dynamics of Endogenous Bacterial Composition in Rice Seeds During Maturation and Storage, and Spatial Dynamics of the Bacteria During Seedling Growth
Authors: Dutta Swarnalee , Choi Soo Yeon , Lee Yong Hoon
Published: July 2022

Seed endophytes are of interest because they are believed to affect seed quality, and ultimately, plant growth and fitness. A comprehensive understanding of the assembly of the seed microbiome during seed development and maturation, the fate of microbes during storage, and the migration of microbes during seedling growth are still lacking. In this study, to understand the assembly and fate of endogenous bacteria in rice seeds from the ripening stage to the storage and seedling stages, we employed culture-dependent and metagenomic analyses. Bacterial communities in rice seeds were composed of a few dominant taxa that were introduced at the milky and dough stages, and they persisted during seed maturation. The culturable bacterial population gradually increased during the ripening stage, whereas there was a gradual decrease during storage. Bacteria that persisted during storage proliferated after imbibition and were distributed and established in the shoots and roots of rice seedlings. The storage temperature influenced the abundance of bacteria, which consequently changed the bacterial composition in the shoots and roots of seedlings. Pantoea, Pseudomonas, and Allorhizobium were consistently abundant from seed development to the germination stage. Some endogenous bacterial strains significantly promoted the growth of Arabidopsis and rice plants. Overall, our results indicate that rice seeds are colonized by a few bacterial taxa during seed development, and their relative abundance fluctuates during storage and contributes significantly to the establishment of endophytes in the stems and roots of rice plants. The selected bacterial isolates can be used to improve the growth and health of rice plants. To the best of our knowledge, this is the first study to reveal the dynamics of bacterial populations during storage of rice seeds at different temperatures. The temporal dynamics of the bacterial community during seed storage provide clues for the manipulation of endogenous bacteria in rice plants.
Phenol-soluble modulin contributes to the dispersal of Staphylococcus epidermidis isolates from catheters
Authors: Jin Yixin , Wang Qichen , Zhang Haomin , Zhao Na , Yang Ziyu , Wang Hua , Li Min , Liu Qian
Published: July 2022

Staphylococcus epidermidis (S. epidermidis), a human commensal, has been implicated in invasive infection in humans due to their ability to form biofilm. It is assumed that when a biofilm is dispersed it will subsequently cause a more severe infection. The clinical significance of S. epidermidis isolated from sterile body fluid (BF) remains unclear, and might be related to dispersal from catheter-associated biofilm infection. To evaluate this relationship, we evaluated S. epidermidis isolates from catheters (CA) or BF in hospitalized patients. Sequence type 2 (ST2) is the most prevalent type isolated from infection sites. Although the specific STs were also observed in isolates from different sites, we observed that the main sequence type was ST2, followed by ST59, among all the 114 isolates from different infection sites. Interestingly, ST2 strains isolated from BF exhibited significantly thicker biofilm than those from CA. The thicker biofilm was due to the higher expression of accumulation-associated protein (aap) but not intercellular adhesion (ica) operon. Moreover, the transcription of PSMδ and PSMε were significantly increased in ST2 strains isolated from BF. Although the bacterial loads on catheters were similar infected by CA- or BF-originated strains in mouse biofilm-associated infection model, we observed a higher CFU in peri-catheter tissues infected by ST2 clones isolated from BF, suggesting that S. epidermidis with thicker biofilm formation might be able to disperse. Taken together, our data suggested that S. epidermidis originated from diverse infection sites exhibited different biofilm forming capacity. The major ST2 clone isolated from BF exhibited thicker biofilm by increasing the expression of Aap. The higher expression of PSM of these strains may contribute to bacteria dispersal from biofilm and the following bacterial spread.