bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antagonistic effects of Rhamnolipid biosurfactant on larval gut microbes and impact on the growth and development of the silkworm
Authors: Kannan Mani , Rahman Pattanathu , Arumugam Thangarasu , Suganya Thangaiyan , Arunprasanna Vimalanathan , Tettamanti Gianluca , Krishnan Muthukalingan 
Published: July 2022

The demand for bio-based insecticides has significantly increased during the last decade due to the contamination of the environment following massive pesticide use. The present study aims at evaluating the insecticidal activity of rhamnolipid (RL) biosurfactant (from
0.01 to 1 %) orally administered to fifth instar larvae of the silkworm, Bombyx mori, a model among Lepidoptera. The bioassay showed that above 0.5% RL caused significant mortality in the larvae and pupae of B.mori. To evaluate the mode of action of RL, we carried out
antibacterial activity assays against larval gut microbes of B.mori. Interestingly, a fall of the microbial population and a susceptibility of host beneficial bacterial species, like Bacillus megaterium, Bacterium IMBL3, Enterococcus mundtii and Bacillus cerus, towards RL were
observed by using plate sensitive assay and agar well diffusion assay, respectively. The results of the present study confirm that RL cause
the breakdown of beneficial interactions between the larval gut and microbes, leading to a high rate of larval mortality due to the digestive upset in the B. mori gut. This work provides a platform of knowledge to set up promising strategies for the biological control of insect pests.
Keywords: Rhamnolipid, antibacterial activity, Bombyx mori, insecticidal activity, gut microbes
The association between different hypoglycemic regimens and postoperative diabetic macular edema after vitrectomy in the Japanese patients with proliferative diabetic retinopathy
Authors: Lei Chunyan , Zhang Yun , Zhang Meixia 
Published: July 2022

PurposeTo study the association between different hypoglycemic regimens and postoperative diabetic macular edema (DME).MethodsA secondary analysis based on a retrospective cohort study.ResultsIn this secondary analysis, 124 eyes from patients with proliferative diabetic retinopathy (PDR) who underwent pars plana vitrectomy (PPV) between January 2008 and September 2012 were included. We found that compared with oral hypoglycemic medication, oral hypoglycemic medication plus insulin treatment revealed an insignificant relationship with postoperative DME (odds ratio [OR]=0.8, 95% confidence interval [CI]: 0.12-5.21, P=0.8167), only insulin treatment revealed a significant association with postoperative DME (OR=0.10, 95% CI: 0.01-0.84, P=0.0337) after adjusted age, sex. After adjusted age, sex, diabetes mellitus (DM) duration, glycosylated hemoglobin (HbA1c), the results did not have obvious changes (OR=0.61, 95% CI: 0.09-4.26, P=0.6187; OR=0.07, 95% CI: 0.01-0.65, P=0.0197). Furthermore, after adjusted age, sex, DM duration, HbA1c, hypertension, intraoperative retinal photocoagulation, vitreous hemorrhage, macular detachment, fibrovascular membrane, intraocular lens implantation and microincision vitrectomy surgery, the results were consistent (OR=0.66, 95% CI: 0.05-9.49, P=0.7621; OR=0.06, 95% CI: 0.00-0.81, P=0.0342). The same trend was observed in these adjusted models as well (p for trend was 0.0254, 0.0141, and 0.0311, respectively).ConclusionIn conclusion, our results of the secondary analysis should be interpreted as a significant association between insulin treatment and reduced risks of postoperative DME in Japanese PDR patients with PPV surgery, compared with oral medications. Well glycemic control with longstanding insulin therapy may be beneficial to reduce the risks of postoperative DME in PDR patients. Our investigation calls for large-scale and long-term prospective clinical studies for a full evaluation of the exact role of insulin in the progression of postoperative DME.
Reduced leukocyte mitochondrial copy number in metabolic syndrome and metabolically healthy obesity
Authors: Agius Rachel , Pace Nikolai Paul , Fava Stephen 
Published: July 2022

ObjectiveThis study aimed to investigate the associations between peripheral blood leukocyte mitochondrial copy number, metabolic syndrome, and adiposity-related body composition phenotypes in a high prevalence population.MethodsA single center cross-sectional study was conducted, consisting of 521 middle-aged subjects of Maltese-Caucasian ethnicity. Participants were stratified according to the presence of metabolic syndrome and different metabolic health definitions based on NCEP-ATP III criteria. Relative leukocyte mitochondrial DNA copy number was determined by quantitative polymerase chain reaction and corrected for leukocyte and platelet count. The associations between mitochondrial copy number and metabolic syndrome components was evaluated and adjusted for age and gender.ResultsSignificant negative correlations between mtDNA copy number and BMI, waist circumference, triglyceride levels, fasting plasma glucose, HbA1c, HOMA-IR and hsCRP were observed, along with a positive correlation with HDL-C levels. Mitochondrial copy number was lower in individuals with metabolic syndrome. When compared to metabolically healthy normal weight subjects, a reduction in mtDNA copy number was observed in both the metabolically healthy and unhealthy obese categories.ConclusionOur data supports the association between reduced leukocyte mtDNA copy number, obesity, and metabolic syndrome. This investigation expands on the spectrum of associations between mtDNA copy number and metabolic phenotypes in different populations and underpins the role of mitochondrial dysfunction in the development and progression of metabolic syndrome and its components.
Discovery of Novel Variants on the CHD7 Gene: A Case Series of CHARGE Syndrome
Authors: Wu Xiangtao , Chen Liang , Lu Weihong , He Shaoru , Li Xiaowen , Sun Lingling , Zhang Longjiang , Wang Dejuan , Zhang Ruigui , Liu Yumei , Sun Yunxia , Feng Zhichun , Wei Zhang Victor 
Published: July 2022

Background: CHARGE syndrome (CS) is a single-gene genetic disorder with multiple organ malformations caused by a variant of the chromodomain helicase DNA-binding protein 7 (CHD7) gene on chromosome 8q12.1. In this study, we aimed to investigate new variants that have emerged in these cases compared with typical CS and the relationship between the genes and phenotypes.Methods: Patients with suspected genetic diseases were subjected to Whole Exome Sequencing (WES) at a genetics laboratory in Guangzhou. The average sequencing coverage depth was &gt;200 ×, and 96% was &gt;20 ×. The variant interpretation was manipulated according to the American College of Medical Genetics (ACMG) guidelines. Molecular data on databases for ClinVar and CHD7 were also collected and collated. We reviewed the currently described CHD7 variants and analyzed the genetic variation and phenotypic heterogeneity.Results: Data of 12 patients with CS from four hospitals in China were collected. According to gestational age, most of them (8/12) were near-term babies with a lower birth weight than their peers, averaging 2.62 kg. In this study, the most common phenotypes were respiratory tract malformations (11/12), heart malformations (10/12), and central nervous system malformations (9/12). Two fetuses were confirmed to have brain or heart abnormalities during prenatal testing, while 10/12 were found to have abnormalities during prenatal testing. The maximum Acute Physiology and Chronic Health Evaluation (APACHE II) score at admission was 19, and the average was 11.58. Five variants in the CHD7 gene c.7012C &gt; T (p.Q2338*), c.7868delC (p.P2623Rfs*16), c.5405-3C &gt; G, c.6936 + 2T &gt; C, and c.8077-2A &gt; G) were novel and were located in exons 33, 36, and introns 25, 32, and 37, respectively. There may be a positive correlation between exon location and phenotype.Conclusion: Five novel variants were discovered. These expanded the mutational spectrum of the CHD7 gene and the phenotype of CS. There may be a correlation between the new mutation sites and the phenotype, which has some reference value for the evaluation of mutation sites.
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

BackgroundMultiple 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.MethodRNA-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.ResultA 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.ConclusionIn 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

ObjectiveTo 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.MethdsA 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&lt;0.001), cholesterol (CHOL) (r=0.314, P=0.003) and low-density lipoprotein (LDL) (r=0.362, P=0.001) levels.ConclusionsOur 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

BackgroundThe 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.ObjectThis 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.ResultsRSV 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.ConclusionThese 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

BackgroundColorectal 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.MethodsThe 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.ResultsWe 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.ConclusionAn 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

RationaleThe 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.MethodsWe 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.ResultsWe 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.ConclusionTargeting 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.
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

ObjectiveQuantitative 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.MethodsA 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.ResultsThe 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 &gt;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.ConclusionQuantitative HBsAg and HBV DNA are valuable, but their capabilities are divergent in delimiting the natural history phases.