bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mmu-miR-25-3p promotes macrophage autophagy by targeting DUSP10 to reduce mycobacteria survival
Authors: Yuan Wenqi , Zhan Xuehua , Liu Wei , Ma Rong , Zhou Yueyong , Xu Guangxian , Ge Zhaohui 
Published: May 2023

BackgroundThe present study aimed to investigate the regulation of miR-25-3p on macrophage autophagy and its effect on macrophage clearance of intracellular Mycobacterium bovis Bacillus Calmette-Guerin (BCG) retention based on the previous findings on the differential expression of exosomal miRNA in macrophages infected with BCG.MethodsThrough enrichment analysis and Hub gene analysis, key differentially expressed miRNA and its target genes were selected. The targeted binding ability of the screened mmu-miR-25-3p and its predicted target gene DUSP10 was determined through the TargetScan database, and this was further verified by dual luciferase reporter gene assay. mmu-miR-25-3p mimics, mmu-miR-25-3p inhibitor, si-DUSP10, miR-NC,si-NC and PD98059 (ERK Inhibitor) were used to intervene macrophages Raw264.7. Rt-qPCR was used to detect the expression levels of mmu-miR-25-3p and DUSP10 mRNA. Western blot was used to detect the expression levels of DUSP10, LC3-II, p-ERK1/2, beclin1, Atg5 and Atg7. The autophagy flux of macrophage Raw264.7 in each group was observed by confocal laser microscopy, and the expression distribution of DUSP10 and the structure of autophagosomes were observed by transmission electron microscopy. Finally, the intracellular BCG load of macrophage Raw264.7 was evaluated by colony-forming unit (CFU) assay.ResultsBioinformatics analysis filtered and identified the differentially expressed exosomal miRNAs. As a result, mmu-miR-25-3p expression was significantly increased, and dual specificity phosphatase 10 (DUSP10) was predicted as its target gene that was predominantly involved in autophagy regulation. The dual luciferase reporter gene activity assay showed that mmu-miR-25-3p was targeted to the 3’-untranslated region (UTR) of DUSP10. The infection of BCG induced the upregulation of mmu-miR-25-3p and downregulation of DUSP10 in RAW264.7 cells, which further increased the expression of LC3-II and promoted autophagy. Upregulated mmu-miR-25-3p expression decreased the level of DUSP10 and enhanced the phosphorylation of ERK1/2, which in turn upregulated the expression of LC3-II, Atg5, Atg7, and Beclin1. Immuno-electron microscopy, transmission electron microscopy, and autophagic flux analysis further confirmed that the upregulation of mmu-miR-25-3p promotes the autophagy of macrophages after BCG infection. The CFU number indicated that upregulated mmu-miR-25-3p expression decreased the mycobacterial load and accelerated residual mycobacteria clearance.Conclusionmmu-miR-25-3p promotes the phosphorylation of ERK1/2 by inhibiting the expression of DUSP10, thus enhancing the BCG-induced autophagy of macrophages. These phenomena reduce the bacterial load of intracellular Mycobacterium and facilitate the clearance of residual mycobacteria. mmu-miR-25-3p has great potential as a target for anti-tuberculosis immunotherapy and can be the optimal miRNA loaded into exosomal drug delivery system in future studies.
Comparative effectiveness of different probiotics supplements for triple helicobacter pylori eradication: a network meta-analysis
Authors: Wang Yue , Wang Xue , Cao Xue-Yan , Zhu Han-Long , Miao Lin 
Published: May 2023

BackgroundProbiotics has been reported as an effective supplement for Helicobacter pylori eradication. However, knowledge of their comparative efficacy is still lacking.AimIn this study, we used network meta-analysis of current probiotics supplement used in standard triple therapy to assess and rank their comparative effectiveness.MethodsAll randomized controlled trials from three main databases (PubMed, Embase and Cochrane Library) up to April 2022 were collected and filtered to meet our criterion. We used Bayesian network meta-analysis to evaluate the eligible randomized controlled trials and gave a rank for the efficiency and incidence of side effects of each probiotics supplement. The ranking probability for each therapy was assessed by means of surfaces under cumulative ranking values. Subgroup analysis was conducted to evaluate other possible influencing factors.Results34 eligible randomized controlled trials entered the following meta-analysis, including 9,004 patients randomized to 10 kinds of therapies. Result showed that most probiotics added therapies had better outcomes than triple therapy, among which Bifidobacterium-Lactobacillus and Bifidobacterium-Lactobacillus-Saccharomyces adjuvant therapy could obtain comprehensive benefit with high eradication rate (78.3% and 88.2% respectively), and cause few side effects. Combination of different probiotics, adding probiotics before or after triple therapy and longer duration of probiotics can improve therapeutic effect in H.pylori infected individuals.ConclusionFor triple therapy of H.pylori infection, adding probiotics can increase eradication rate and bring protective effect. Considering the overall influence, Bifidobacterium-Lactobacillus or Bifidobacterium-Lactobacillus-Saccharomyces therapy can be a better choice in improving H.pylori eradication process.
An efficient method for the preparation of magnetic Co3O4 nanoparticles and the study of their catalytic application
Authors: Ardeshirfard Hakimeh , Elhamifar Dawood 
Published: May 2023

In this study, magnetic cobalt oxide (Co3O4) nanoparticles (NPs) were synthesized through a new and green method using cobalt chloride hexahydrate (CoCl2.6H2O), pluronic P123 as a stabilizer, and sodium borohydride (NaBH4). The CO3O4 nanoparticles were characterized by diffuse reflectance infrared Fourier transform spectroscopy, powder X-ray diffraction, X-ray photoelectron spectroscopy, energy-dispersive X-ray spectroscopy, scanning electron microscopy, and vibrating sample magnetometer.The magnetic Co3O4 NPs were used as a catalyst with high activity and stability in the synthesis of tetrahydrobenzo[b]pyran derivatives. This reaction was carried out in water, as it is an environmentally friendly solvent, using a low loading of Co3O4 NPs at room temperature. Various derivatives of aldehydes were used as substrates to obtain a high yield of the corresponding tetrahydrobenzo[b]pyrans in short times. In addition, the catalyst was recovered and reused several times with no notable decrease in its activity.
Sutureless vs. rapid-deployment valve: a systemic review and meta-analysis for a direct comparison of intraoperative performance and clinical outcomes
Authors: Wang Chenhao , Xie Yi , Zhang Hongwei , Yang Peng , Zhang Yu , Lu Chen , Liu Yu , Wang Haiyue , Xu Zhenyuan , Hu Jia 
Published: May 2023

BackgroundSutureless and rapid-deployment valves are bioprostheses anchoring within the aortic annulus with few sutures, and they act as a hybrid of conventional surgical and transcatheter valves under aortic valve replacement. Considering that the 3F Enable valve is now off-market, the only two sutureless and rapid-deployment valves available on the world marketplace are the Perceval and Intuity valves. However, a direct comparison of the function of these two valves eludes researchers.PurposeAgainst this background, we performed this systematic review and meta-analysis comparing the intraoperative performance and early clinical outcomes between the Perceval valve and the Intuity valve under sutureless and rapid-deployment aortic valve replacement.MethodsWe systematically searched electronic databases through PubMed/MEDLINE, OvidWeb, Web of Science, and Cochrane Central Register of Controlled Trials (from the establishment of the database to November 17, 2022, without language restriction) for studies comparing the sutureless valve (the Perceval) and the rapid-deployment valve (the Intuity) under aortic valve replacement. Our primary outcomes were early mortality and postoperative transvalvular pressure gradients. The secondary outcomes were defined to include aortic cross-clamp and cardiopulmonary bypass time, paravalvular leak (any paravalvular leak, moderate-to-severe paravalvular leak) after aortic valve replacement, need for pacemaker implantation, postoperative neurological events (stroke), and intensive care unit stay.ResultsThis meta-analysis included ten non-randomized trials with 3,526 patients enrolled (sutureless group = 1,772 and rapid-deployment group = 1,754). Quality assessments were performed, with the mean scores of the studies reading 6.90 (SD = 0.99) out of 9 according to the Newcastle–Ottawa Scale. Compared with rapid-deployment aortic valve replacement, sutureless aortic valve replacement was associated with higher mean and peak transvalvular pressure gradients postoperatively. In contrast, aortic cross-clamp and cardiopulmonary time were needed less in sutureless aortic valve replacement vs. rapid-deployment aortic valve replacement. There was no evidence of significant publication bias observed by the funnel plot and Egger's test.ConclusionsFor postoperative hemodynamics, sutureless aortic valve replacement was associated with increased mean and peak transvalvular pressure gradients compared with rapid-deployment aortic valve replacement. In sharp contrast, sutureless aortic valve replacement significantly reduced the amount of time needed for fixing the aortic cross-clamp and the cardiopulmonary bypass procedure.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022343884.
Metabolic drivers of dysglycemia in pregnancy: ethnic-specific GWAS of 146 metabolites and 1-sample Mendelian randomization analyses in a UK multi-ethnic birth cohort
Authors: Fuller Harriett , Iles Mark M. , Moore J. Bernadette , Zulyniak Michael A. 
Published: May 2023

IntroductionGestational diabetes mellitus (GDM) is the most common pregnancy complication worldwide and is associated with short- and long-term health implications for both mother and child. Prevalence of GDM varies between ethnicities, with South Asians (SAs) experiencing up to three times the risk compared to white Europeans (WEs). Recent evidence suggests that underlying metabolic difference contribute to this disparity, but an investigation of causality is required.MethodsTo address this, we paired metabolite and genomic data to evaluate the causal effect of 146 distinct metabolic characteristics on gestational dysglycemia in SAs and WEs. First, we performed 292 GWASs to identify ethnic-specific genetic variants associated with each metabolite (P ≤ 1 x 10-5) in the Born and Bradford cohort (3688 SA and 3354 WE women). Following this, a one-sample Mendelian Randomisation (MR) approach was applied for each metabolite against fasting glucose and 2-hr post glucose at 26-28 weeks gestation. Additional GWAS and MR on 22 composite measures of metabolite classes were also conducted.ResultsThis study identified 15 novel genome-wide significant (GWS) SNPs associated with tyrosine in the FOXN and SLC13A2 genes and 1 novel GWS SNP (currently in no known gene) associated with acetate in SAs. Using MR approach, 14 metabolites were found to be associated with postprandial glucose in WEs, while in SAs a distinct panel of 11 metabolites were identified. Interestingly, in WEs, cholesterols were the dominant metabolite class driving with dysglycemia, while in SAs saturated fatty acids and total fatty acids were most commonly associated with dysglycemia.DiscussionIn summary, we confirm and demonstrate the presence of ethnic-specific causal relationships between metabolites and dysglycemia in mid-pregnancy in a UK population of SA and WE pregnant women. Future work will aim to investigate their biological mechanisms on dysglycemia and translating this work towards ethnically tailored GDM prevention strategies.
Omicron (B.1.1.529) BA.1 or BA.2-related effects on immune responses in previously naïve versus imprinted individuals: immune imprinting as an advantage in the humoral immune response against novel variants
Authors: Sonnleitner Sissy Therese , Walder Samira , Knabl Ludwig , Poernbacher Roswitha , Tschurtschenthaler Thomas , Hinterbichler Eva , Sonnleitner Stefanie , Muehlmann Viktoria , Posch Wilfried , Walder Gernot 
Published: May 2023

BackgroundImmune imprinting is a phenomenon in which a person's immune system develops a specific immunological memory of the pathogen or vaccine due to a previous exposure. This memory basically leads to a faster and stronger immune response in a subsequent contact to the same pathogen or vaccine. However, what happens if the pathogen has changed considerably in the meantime due to mutations in the main target region of antibodies, as in the evolution of SARS-CoV-2 from the ancestral strain to B.1.1.529 (Omicron)? In this case, does immune imprinting also confer an advantage in repeated contact and does it lead to a stronger immune response?MethodsTo clarify these questions, we investigated the effects of immune imprinting in the context of SARS-CoV-2 by comparing a group of previously infection-naïve versus imprinted study participants and determined differences in humoral and cellular immune responses during and after infection with strain SARS-CoV-2 B.1.1.529 BA.1 and BA.2, respectively. We used a commercial CLIA, immunoblots, IFN-γ ELISpots and a plaque-reduction neutralization test to generate a clear and comparable picture of the humoral and cellular immune response in the two study groups.ResultsImprinted participants developed significantly higher antibody titers and showed significantly stronger neutralization capacity against the ancestral strain, BA.1 and BA.5. The immune response of naïve study participants was narrower and related mainly to the receptor-binding domain, which resulted in a lower neutralization capacity against other strains including BA.5. Naïve study participants showed a significantly higher cellular immune response than the imprinted study group, indicating a higher antigenic challenge. The cellular immune response was directed against general structures of SARS-CoV-2 and not specifically against the receptor-binding domain.ConclusionViral variant infection elicits variant-specific antibodies and prior mRNA vaccination or infection with a previous SARS-CoV-2 variant imprints serological responses toward the ancestral strain rather than variant antigens. On the other hand, our study shows that the initially higher specific antibody titers due to former imprinting via vaccination or prior infection significantly increased the humoral immune response, and therefore outperformed the humoral immune response of naïve study participants.
Indeterminate results of interferon gamma release assays in the screening of latent tuberculosis infection: a systematic review and meta-analysis
Authors: Zhou Guozhong , Luo Qingyi , Luo Shiqi , Chen Hongbo , Cai Shunli , Guo Xin , He Jian , Xia Yuan , Li Hanse , Zhou Yingchen , Zhang Yazhou , Song Chao 
Published: May 2023

ObjectivesWe aimed to evaluate the indeterminate rate of interferon gamma release assays (IGRAs) in the detection of latent tuberculosis infection (LTBI).MethodsOn 15 November 2022, we searched the PubMed® (National Library of Medicine, Bethesda, MD, USA), Embase® (Elsevier, Amsterdam, the Netherlands), and Cochrane Library databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two investigators independently extracted the study data and assessed their quality using a modified quality assessment of diagnostic accuracy studies (i.e., QUADAS-2) tool. A random-effects model was used to calculate pooled results.ResultsWe included 403 studies involving 486,886 individuals and found that the pooled indeterminate rate was 3.9% (95% CI 3.5%–4.2%). The pooled indeterminate rate for QuantiFERON®-TB (QFT) was similar to that for T-SPOT®.TB (T-SPOT) [odds ratio (OR) = 0.88, 95% CI 0.59–1.32]; however, the indeterminate rate for a new generation of QFT (QFT-plus) was lower than that of T-SPOT (OR = 0.24, 95% CI 0.16–0.35). The indeterminate rate in the immunocompromised population was significantly higher than that in healthy controls (OR = 3.51, 95% CI 2.11–5.82), and it increased with the reduction of CD4+ cell count in HIV-positive patients. Children’s pooled indeterminate rates (OR = 2.56, 95% CI 1.79–3.57) were significantly higher than those of adults, and the rates increased as the children’s age decreased.ConclusionOn average, 1 in 26 tests yields indeterminate IGRA results in LTBI screening. The use of advanced versions of the QuantiFERON-TB assay (QFT-plus), may potentially reduce the occurrence of an indeterminate result. Our study emphasizes the high risk of immunosuppression and young age in relation to indeterminate IGRA, which should receive more attention in the management of LTBI.Systematic review registrationPROSPERO https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020211363, CRD42020211363.
Human cytomegalovirus and Epstein–Barr virus infections occurring early after transplantation are risk factors for antibody-mediated rejection in heart transplant recipients
Authors: Saldan Alda , Mengoli Carlo , Sgarabotto Dino , Fedrigo Marny , Angelini Annalisa , Feltrin Giuseppe , Gambino Antonio , Gerosa Gino , Barzon Luisa , Abate Davide 
Published: May 2023

BackgroundAntibody-mediated rejection (AMR) is a serious complication affecting the survival of patients receiving transplantation. Human cytomegalovirus (CMV) and Epstein–Barr virus (EBV) are common viral infections that occur after transplantation, frequently emerging as viral reactivation in donor grafts or transplant recipients. The present study aimed to investigate the association between CMV and EBV infections and early-onset AMR.Materials and methodsThis study was conducted at the Heart Transplantation Center of Padova General Hospital and included a cohort of 47 heart transplant recipients (HTxs), including 24 HTxs diagnosed with AMR and 23 control HTxs with no episodes of AMR. Only early cases of CMV and/or EBV infections (1–90 days after transplantation) were considered. Fisher’s exact test and logistic regression analysis were used to statistically analyze the correlation and association between AMR and CMV or EBV infection.ResultsWe observed a positive statistical association between CMV and EBV infections (two-sided Fisher’s exact test, p = 0.0136) and between EBV infection and AMR (two-sided Fisher’s exact test, p = 0.0034). Logistic regression analysis revealed a direct statistical association between CMV and EBV infections and AMR risk (p = 0.037 and 0.006 and odds ratio = 1.72 and 2.19, respectively). AMR occurrence was associated with increased viral loads of both CMV and EBV early after transplantation.DiscussionThese findings suggest the role of CMV and EBV infections as relevant risk factors for AMR in HTxs for the first time.
ATM and ATR, two central players of the DNA damage response, are involved in the induction of systemic acquired resistance by extracellular DNA, but not the plant wound response
Authors: Vega-Muñoz Isaac , Herrera-Estrella Alfredo , Martínez-de la Vega Octavio , Heil Martin 
Published: May 2023

BackgroundThe plant immune response to DNA is highly self/nonself-specific. Self-DNA triggered stronger responses by early immune signals such as H2O2 formation than nonself-DNA from closely related plant species. Plants lack known DNA receptors. Therefore, we aimed to investigate whether a differential sensing of self-versus nonself DNA fragments as damage- versus pathogen-associated molecular patterns (DAMPs/PAMPs) or an activation of the DNA-damage response (DDR) represents the more promising framework to understand this phenomenon.ResultsWe treated Arabidopsis thaliana Col-0 plants with sonicated self-DNA from other individuals of the same ecotype, nonself-DNA from another A. thaliana ecotype, or nonself-DNA from broccoli. We observed a highly self/nonself-DNA-specific induction of H2O2 formation and of jasmonic acid (JA, the hormone controlling the wound response to chewing herbivores) and salicylic acid (SA, the hormone controlling systemic acquired resistance, SAR, to biotrophic pathogens). Mutant lines lacking Ataxia Telangiectasia Mutated (ATM) or ATM AND RAD3-RELATED (ATR) – the two DDR master kinases – retained the differential induction of JA in response to DNA treatments but completely failed to induce H2O2 or SA. Moreover, we observed H2O2 formation in response to in situ-damaged self-DNA from plants that had been treated with bleomycin or SA or infected with virulent bacteria Pseudomonas syringae pv. tomato DC3000 or pv. glycinea carrying effector avrRpt2, but not to DNA from H2O2-treated plants or challenged with non-virulent P. syringae pv. glycinea lacking avrRpt2.ConclusionWe conclude that both ATM and ATR are required for the complete activation of the plant immune response to extracellular DNA whereas an as-yet unknown mechanism allows for the self/nonself-differential activation of the JA-dependent wound response.
Mast cell marker gene signature: prognosis and immunotherapy response prediction in lung adenocarcinoma through integrated scRNA-seq and bulk RNA-seq
Authors: Zhang Pengpeng , Liu Jianlan , Pei Shengbin , Wu Dan , Xie Jiaheng , Liu Jinhui , Li Jun 
Published: May 2023

BackgroundMast cells, comprising a crucial component of the tumor immune milieu, modulate neoplastic progression by secreting an array of pro- and antitumorigenic factors. Numerous extant studies have produced conflicting conclusions regarding the impact of mast cells on the prognosis of patients afflicted with lung adenocarcinoma (LUAD).MethodsEmploying single-cell RNA sequencing (scRNA-seq) analysis, mast cell-specific marker genes in LUAD were ascertained. Subsequently, a mast cell-related genes (MRGs) signature was devised to stratify LUAD patients into high- and low-risk cohorts based on the median risk value. Further investigations were conducted to assess the influence of distinct risk categories on the tumor microenvironment. The prognostic import and capacity to prognosticate immunotherapy benefits of the MRGs signature were corroborated using four external cohorts. Ultimately, the functional roles of SYAP1 were validated through in vitro experimentation.ResultsAfter scRNA-seq and bulk RNA-seq data analysis, we established a prognostic signature consisting of nine MRGs. This profile effectively distinguished favorable survival outcomes in both the training and validation cohorts. In addition, we identified the low-risk group as a population more effective for immunotherapy. In cellular experiments, we found that silencing SYAP1 significantly reduced the proliferation, invasion and migratory capacity of LUAD cells while increasing apoptosis.ConclusionOur MRGs signature offers valuable insights into the involvement of mast cells in determining the prognosis of LUAD and may prove instrumental as a navigational aid for immunotherapy selection, as well as a predictor of immunotherapy response in LUAD patients.