Highest Fold Change Research Articles

Gene expression profiling in PBMCs for acute rejection in lung transplant recipients reveals myeloid responses

The acute rejection (AR) diagnosis depends on transbronchial biopsy, which is semi-invasive and not easily performed. Our study used the Nanostring gene expression technology on PBMCs obtained from lung transplant recipients (LTRs) to search for biomarkers. We identified distinct differential gene profiles between patients with stable status (STA) and AR. Subsequently, we independently evaluated monocyte compositions in PBMCs using flow cytometry and assessed the levels of 7 chemokines in serum using Luminex. The 48 top differentially expressed genes (DEGs) were identified, utilizing a criterion of at least a 1.5-fold change between two groups, with a false discovery rate (FDR) p-Adj < 0.05. Of these 48 genes, the top 10 genes with the highest fold changes and significant p-values were selected for qPCR validation. CD68, ANXA1, ITGB, and IFI30 can be confirmed among the validated genes. A significantly lower percentage of CD14 + CD16- classical monocytes was observed in AR than in STA patients, which aligns with downregulated DEGs. Many of the DEGs were related to monocytes-macrophages and chemokines. Although these results still need to be confirmed in larger cohorts, they suggest that gene profiling of PBMC can help to identify markers related to AR in LTRs.

Transcriptionally distinct B cell profiles in systemic immune tissues and peritoneal cavity of Atlantic salmon (Salmo salar) infected with salmonid alphavirus subtype 3.

Teleost B cells producing neutralizing antibodies contribute to protection against salmonid alphavirus (SAV) infection, the etiological agent of pancreas disease, thereby reducing mortality and disease severity. Our previous studies show differences in B cell responses between the systemic immune tissues (head kidney (HK) and spleen) and the peritoneal cavity (PerC) after intraperitoneal SAV3 infection in Atlantic salmon (Salmo salar) where the response in PerC dominates at the late time points. By employing the same infection model, we aimed to further characterize these B cells. Immunophenotyping of teleost B cells is challenging due to limited availability of markers; however, RNA-seq opens an opportunity to explore differences in transcriptomic responses of these cells. Our analysis identified 334, 259 and 613 differentially expressed genes (DEGs) in Atlantic salmon IgM+IgD+ B cells from HK, spleen, and PerC, respectively, at 6 weeks post SAV3 infection. Of these, only 34 were common to all the three immune sites. Additionally, out of the top 100 genes with the highest fold change in expression, only four genes were common across B cells from the three sites. Functional enrichment analyses of DEGs using KEGG and GO databases demonstrated differences in enriched innate immune signaling and the cytokine-cytokine interaction pathways in B cells across the sites, with varying numbers of genes involved. Overall, these findings show the presence of transcriptionally distinct B cell subsets with innate immune functions in HK, spleen and PerC of SAV3-infected Atlantic salmon. Further, our data provide new insights into the immunoregulatory role of fish B cells through the differential expression of various cytokine ligands and receptors and will be a useful resource for further studies into B cell immune compartments.

Proteomics reveals that nanoplastics with different sizes induce hepatocyte apoptosis in mice through distinct mechanisms involving mitophagy dysregulation and cell cycle arrest.

Nanoplastics (NPs) can penetrate the intestinal barrier of organisms and accumulate in the liver, thereby inducing hepatocyte apoptosis. However, the underlying mechanisms remain incompletely elucidated. This study examined the effects of PS-NPs exposure on hepatocyte apoptosis and revealed the role of cell cycle arrest and mitophagy. The C57BL/6 mice were administered a diet containing 100nm and 500nm PS-NPs at a concentration of 0.1g/kg for 180days, respectively. TUNEL staining confirmed that 100nm PS-NPs induced more pronounced apoptosis compared to 500nm PS-NPs in mouse liver. Mechanistically, proteomic analysis revealed that Pdcd2l, associated with the S phase of cell cycle and apoptosis, exhibited the highest fold changes among all detected proteins in 100nm and 500nm PS-NPs exposure groups. Notably, the expression of Tbc1d17, Bcl2l13, and Pgam5 involved in mitophagosome formation in mouse liver was upregulated by 100nm PS-NPs but not by 500nm PS-NPs; moreover, mitophagosomes were observed in HepG2 cells exposed to 100nm PS-NPs. Additionally, 100nm PS-NPs internalized by HepG2 cells could penetrate lysosomes. The protein levels of Igf2r and Rab7a were altered, and p62 mRNA expression was increased in mouse liver, suggesting 100nm PS-NPs, but not 500nm PS-NPs, impaired lysosomal function and subsequently inhibited mitophagy degradation. Collectively, 500nm PS-NPs induced Pdcd2l-mediated cell cycle arrest, thereby exacerbating hepatocyte apoptosis; while 100nm PS-NPs not only triggered similar levels of cell cycle arrest as 500nm PS-NPs, but also disrupted mitophagy, which was also associated with hepatocyte apoptosis.

The inhibition effect of psoralen on prostate cancer PC3 cells via down-regulation of long non-coding RNA ENST00000510619.

New medications are needed to improve outcomes of castration-resistant prostate cancer (CRPC). Psoralen has been reported to have anti-cancer properties for various tumors, but there are limited reports about psoralen treatment in prostate cancer (PCa). This study aimed to investigate the effect of psoralen on PC3 cells and to investigate potential underlying mechanisms of action. The effect of psoralen on the proliferation and cell cycle progression of PC3 cells was determined using Cell Counting Kit-8 (CCK-8) test and flow cytometry, respectively. The differential gene profiles in PC3 cells treated with psoralen were determined with microarray analyses. The effect of psoralen on long non-coding RNA (lncRNA) ENST00000510619 expression in PC3 cells was detected by real-time quantitative polymerase chain reaction (RT-qPCR). The effect of psoralen and transfection of small interfering lnc-RNA (si-lncRNA) ENST00000510619 on cell viability, invasion ability, and migratory activity of PC3 cells were evaluated using the CCK-8 test, transwell assay, and wound healing, respectively. Psoralen significantly inhibited PC3 cells in a concentration- and time-dependent manner and caused G1 phase and G2/M phase cycle arrests. When screened with a fold change (FC) of ≥2 and a P value of <0.05, 1,716 lncRNAs and 1,160 messenger RNAs (mRNAs) were significantly up-regulated, whereas 3,269 lncRNAs and 3,263 mRNAs were significantly down-regulated in PC3 cells after psoralen treatment. Among the differentially down-regulated lncRNAs in which the signal of the probe showed significant differences compared to the background, lncRNA ENST00000510619 had the highest FC. The expression of lncRNA ENST00000510619 was shown to be down-regulated by psoralen in a concentration-dependent manner. CCK-8 assay, wound healing, and transwell assay showed that both psoralen and si-lncRNA ENST00000510619 transfection significantly inhibited the activity, invasion, and migration of PC3 cells (P<0.01 for all). Psoralen was confirmed to inhibit proliferation and block the cell cycle in PC3 cells in this in vitro study. The molecular mechanism involves multiple differentially expressed lncRNAs and mRNAs and is related to the down-regulation of lncRNA ENST000000510619 expression. This study provides the experimental basis for the development of psoralen as a novel anti-CRPC drug and for the consideration of lncRNA ENST00000510619 as a potential clinical target for CRPC.

Evaluation of Biocides Susceptibility and Expression of Qace-Δ1 And Suge1 Genes of Pseudomonas Aeruginosa in Exposure to Biocides and Meropenem

Pseudomonas aeruginosa is a species of medical significance that plays a role in nosocomial infections, particularly those resulting from burns and wounds. Bacterial antibiotic resistance may have developed as a result of the abuse of biocides in hospitals. This study aimed to determine the minimum inhibitory concentrations (MICs) of carbapenem-resistant P. aeruginosa isolates in relation to ethylenediaminetetraacetic acid (EDTA), chlorohexidine (CHX), and resazurin dye using a microtiter plate assay. Additionally, it evaluated the expression of the efflux pump genes (qacE-Δ1 and sugE1) at sub-inhibitory concentrations of the biocides using RT-qPCR (delta delta Ct method) to improve their efflux pump system. The MICs of 24 P. aeruginosa isolates (14 isolates were resist to carbapenems and 10 isolates sensitive to carbapenems) against Chloroxylenol (Dettol) revealed that the range of MICs were (0. 125-2%). The results of MICs of Chlorohexidine (CHX) revealed that the range of inhibitory activity was (0.8-102.4 µg/ml), also the findings of MICs of EDTA demonstrated that the range of inhibitory activity was (125-2000 µg/ml). The genes involved in efflux pump (qacE -Δ1 and sugE1) were found to be significantly up-regulated in the local isolates, according to our findings.. The four isolates' sugE1 gene expression folds ranged from 1.81 to 5.39; this result was more than the fold of the control (the fold change is 1), with the meropenem isolate having the highest fold value (5.39) and sub-MIC value (8 µg/ml). Furthermore, the four isolates' qacE-Δ1 gene expression folds ranged from 2.11 to 5.01, which was higher than the fold of the control, where the highest fold value was recorded for the EDTA (5.01) with the sub-MIC value (125-500 µg/ml). Also, a high value of upregulation of the gene qacE –Δ1, during the treatment with dettol with sub-MIC (0.25-0.5%), and the fold change was 4.19. In conclusion, the present findings indicated to the significant relationship between the treatments with meropenem and the high values of gene expression of the gene sugE1 in comparison with the control and other agents, Furthermore, compared to the antibiotic and control, there was a strong correlation found between the high fold changes of the gene qacE -Δ1 with the presence of dettol and EDTA.

Identifying High Recurrence Risk in Breast Carcinoma Patients Through Spatial Transcriptomic Analysis.

Comparing gene expression profiles according to recurrence risk using spatially resolved transcriptomic analysis has not been reported. This study aimed to identify distinct genetic features of breast carcinoma associated with a high Oncotype DX Recurrence Score (ORS). Patients were categorized into two groups, ORS-high (ORS-H; two patients) and ORS-non-high (ORS-NH; five patients). We performed digital spatial profiling and bioinformatic analyses to investigate the spatial transcriptomic profiles. Lysozyme (LYZ), complement C1q C chain (C1QC), and complement C1q B chain (C1QB) exhibited the highest fold changes in the stromal compartment of the ORS-H group. Gene ontology enrichment analysis of the ORS-H group revealed significant up-regulation of genes associated with immune response in the stromal compartment, including lymphocyte-mediated immunity, adaptive immune response related to the immunoglobulin superfamily, and leukocyte-mediated immunity. Gene set enrichment analysis showed significant positive enrichment of gene sets associated with interferon (IFN) response and complement pathways in the stromal compartment. This study highlights significant differences in gene expression profiles and spatially resolved transcriptional activities between ORS-H and ORS-NH breast carcinomas. The significant up-regulation of genes and pathways associated with cell-mediated immunity, IFN response, and complement C1q in the stromal compartment of the ORS-H group warrants further evaluation with larger population cohorts.

Cellulase gene expression in the thermophilic Thermomyces lanuginosus isolated from compost

Thermophilic fungi are superlative microorganisms for enzyme production, especially cellulase, and their using in biotechnological applications is due to their stability at utmost temperatures. In the current investigation, we isolated six genera encompassing six fungal species and one species variety from 30 samples of compost at 45 °C and 55 °C. Thermomyces lanuginosus was the most rampant species. The colony diameter of T. lanuginosus ranged from 2.8 to 4.3 cm at 45 °C on yeast-starch agar (YpSs) medium with white or greyish-brown mycelia. Fifteen isolates of T. lanuginosus were cellulase producers with variable competencies with a C/Z range of 1.09–1.38 cm. Fascinatingly, the clear zone diameter was much bigger when using Iodine than those obtained using Congo red. T. lanuginosus isolate no. 33 produced substantial amounts of cellulase on the four used media: Corncob (CC), Corncob treated with NaOH (C-NA), Yeast Peptone Dextrose (YPD), and CarboxyMethyl Cellulose (CMC) with the highest activity on CC; 143.9 μg/min, also cellulase gene expression levels of cel6Aq, cel7Aq, and bgl3Aq genes exhibited higher fold changes in the CC condition (7.26-fold, 11.51-fold, and 3.39-fold, respectively). X-ray fluorescence (XRF) analysis revealed the presence of 11 minerals with higher concentrations in CC than in C-NA. Supplementation of corncob medium with rosemary essential oil (CR) completely inhibited cellulase production. It adversely affected the growth, and changes in conidia, which were depicted using a scanning electron microscope (SEM). Interestingly, the conidia appeared much bigger than other media, and the large conidia diameter was 10.2–12.1 μm.

Exploring the Wilderness within: An Integrative Metabolomics and Transcriptomics Study on Near-Wild and Colonized Aedes aegypti.

This study examines the phenotypic differences between wild-derived F2 Central Valley mosquitoes and the insecticide-susceptible Rockefeller (Rock) lab strain of Ae. aegypti. Given the rarity of wild pyrethroid-susceptible populations, the focus of this work is to develop an understanding of the resistance physiology in this invasive mosquito population and explore the potential of metabolites as diagnostic biomarkers for metabolic resistance. This study utilizes metabolomic, gene expression, and lifespan data for a comparison between strains. The findings indicate that wild-derived mosquitoes with greater metabolic resistance have a lifespan sensitivity to restricted larval nutrition. In terms of metabolism and gene expression, Central Valley mosquitoes show increased activity in oxidoreductase, glutathione metabolism, and the pentose phosphate pathway. Conversely, Rock mosquitoes display signs of metabolic inefficiency and mitochondrial dysregulation, likely tolerated due to the consistency and nutritional abundance of a controlled lab environment. The study also examines Ae. aegypti P450 and GSTE profiles in relation to other insecticide-resistant groups. While metabolomic data can differentiate our study groups, the challenges in biomarker development arise from few detected markers meeting high fold change thresholds.

Diagnostic performance of plasma pTau217, pTau181, Aβ1-42 and Aβ1-40 in the LUMIPULSE automated platform for the detection of Alzheimer disease

BackgroundRecently developed blood markers for Alzheimer's disease (AD) detection have high accuracy but usually require ultra-sensitive analytic tools not commonly available in clinical laboratories, and their performance in clinical practice is unknown.MethodsWe analyzed plasma samples from 290 consecutive participants that underwent lumbar puncture in routine clinical practice in a specialized memory clinic (66 cognitively unimpaired, 130 participants with mild cognitive impairment, and 94 with dementia). Participants were classified as amyloid positive (A +) or negative (A-) according to CSF Aβ1–42/Aβ1–40 ratio. Plasma pTau217, pTau181, Aβ1–42 and Aβ1–40 were measured in the fully-automated LUMIPULSE platform. We used linear regression to compare plasma biomarkers concentrations between A + and A- groups, evaluated Spearman’s correlation between plasma and CSF and performed ROC analyses to assess their diagnostic accuracy to detect brain amyloidosis as determined by CSF Aβ1–42/Aβ1–40 ratio. We analyzed the concordance of pTau217 with CSF amyloidosis.ResultsPlasma pTau217 and pTau181 concentration were higher in A + than A- while the plasma Aβ1–42/Aβ1–40 ratio was lower in A + compared to A-. pTau181 and the Aβ1–42/Aβ1–40 ratio showed moderate correlation between plasma and CSF (Rho = 0.66 and 0.69, respectively). The areas under the ROC curve to discriminate A + from A- participants were 0.94 (95% CI 0.92–0.97) for pTau217, and 0.88 (95% CI 0.84–0.92) for both pTau181 and Aβ1–42/Aβ1–40. Chronic kidney disease (CKD) was related to increased plasma biomarker concentrations, but ratios were less affected. Plasma pTau217 had the highest fold change (× 3.2) and showed high predictive capability in discriminating A + from A-, having 4–7% misclassification rate. The global accuracy of plasma pTau217 using a two-threshold approach was robust in symptomatic groups, exceeding 90%.ConclusionThe evaluation of blood biomarkers on an automated platform exhibited high diagnostic accuracy for AD pathophysiology, and pTau217 showed excellent diagnostic accuracy to identify participants with AD in a consecutive sample representing the routine clinical practice in a specialized memory unit.

Systemic inflammatory cytokine profiles in patients with gout during flare, intercritical and treat-to-target phases: TNFSF14 as new biomarker

IntroductionUntreated gout is characterised by monosodium urate (MSU) crystal accumulation responsible for recurrent flares that are commonly separated by asymptomatic phases. Both phases are inflammatory conditions of variable intensity. Gout...

Impact of heat waves on semen quality: A retrospective study in Argentina between 2005 and 2023

Heat waves, defined as periods with daily temperatures surpassing the historical average for a specific region, have become more frequent worldwide in recent years. Previous studies have reported a negative association between temperature and semen quality, but the focus has mainly been on Asian and European populations.The study included 54,926 men (18–60 years) undergoing routine semen analysis between 2005 and 2023 at CEUSA-LAEH andrology unit, in Buenos Aires, Argentina. Hourly temperature readings were provided by the Servicio Meteorológico Nacional. R programming (R Studio v2022.07.2) was used to define heat waves, calculate key characteristics, visualize results, and perform statistical tests at the IBYME laboratory.During the period studied, a total of 124 days had heat waves (defined after at least 3 consecutive days with 32.3 °C and 22 °C). Men exposed to heat waves during spermatogenesis exhibited lower sperm number (concentration and count; P < 0.0001) and decreased normal morphology (percentage of normal sperm and normal motile count; P < 0.05) compared to those not exposed. These differences were most pronounced between semen samples from years with several heat waves (2013, 2023) and none (2005, 2007, 2016), displaying 4–5 times higher fold changes (P < 0.05).Further analysis employing multiple regression revealed a significantly negative association between semen quality and heat wave length, suggesting that a prolonged exposure may be more detrimental than an acute exposure. Subsequent analysis focusing on prolonged exposure (≥6-days heat wave) during spermatogenesis revealed a negative (P < 0.05) association between early exposure (spermatocytogenesis: 64–90 days prior semen collection) and semen quality.This study underscores the negative association between early exposure to heat waves during sperm development and semen quality, raising concerns about its possible association with the worldwide declining male fertility. A comprehensive collaborative approach is crucial, involving global governmental policies, sustainable practices, and coordinated efforts across scientific, healthcare, and policy domains.

Transcriptomic investigations of polymyxins and colistin/sulbactam combination against carbapenem-resistant Acinetobacter baumannii

Carbapenem-resistant Acinetobacter baumannii (CRAB) is a Priority 1 (Critical) pathogen urgently requiring new antibiotics. Polymyxins are a last-line option against CRAB-associated infections. This transcriptomic study utilized a CRAB strain to investigate mechanisms of bacterial killing with polymyxin B, colistin, colistin B, and colistin/sulbactam combination therapy. After 4 h of 2 mg/L polymyxin monotherapy, all polymyxins exhibited common transcriptomic responses which primarily involved disruption to amino acid and fatty acid metabolism. Of the three monotherapies, polymyxin B induced the greatest number of differentially expressed genes (DEGs), including for genes involved with fatty acid metabolism. Gene disturbances with colistin and colistin B were highly similar (89 % common genes for colistin B), though effects on gene expression were generally lower (0–1.5-fold in most cases) with colistin B. Colistin alone (2 mg/L) or combined with sulbactam (64 mg/L) resulted in rapid membrane disruption as early as 1 h. Transcriptomic analysis of this combination revealed that the effects were driven by colistin, which included disturbances in fatty acid synthesis and catabolism, and inhibition of nutrient uptake. Combination therapy produced substantially higher fold changes in 72 % of DEGs shared with monotherapy, leading to substantially greater reductions in fatty acid biosynthesis and increases in biofilm, cell wall, and phospholipid synthesis. This indicates synergistic bacterial killing with the colistin/sulbactam combination results from a systematic increase in perturbation of many genes associated with bacterial metabolism. These mechanistic insights enhance our understanding of bacterial responses to polymyxin mono- and combination therapy and will assist to optimize polymyxin use in patients.

Agnostic identification of plasma biomarkers for postpartum hemorrhage risk

Postpartum hemorrhage is difficult to predict, is associated with significant maternal morbidity, and is the leading cause of maternal mortality worldwide. The identification of maternal biomarkers that can predict increased postpartum hemorrhage risk would enhance clinical care and may uncover mechanisms that lead to postpartum hemorrhage. This retrospective case-control study employed agnostic proteomic profiling of maternal plasma samples to identify differentially abundant proteins in controls and postpartum hemorrhage cases. Maternal plasma samples were procured from a cohort of >60,000 participants in a single institution's perinatal repository. Postpartum hemorrhage was defined as a decrease in hematocrit of ≥10% or receipt of transfusion within 24 hours after delivery. Postpartum hemorrhage cases (n=30) were matched by maternal age and delivery mode (vaginal or cesarean) with controls (n=56). Mass spectrometry was used to identify differentially abundant proteins using integrated peptide peak areas. Statistically significant differences between groups were defined as P<.05 after controlling for multiple comparisons. By study design, cases and controls did not differ in race, ethnicity, gestational age at delivery, blood type, or predelivery platelet count. Cases had slightly but significantly lower predelivery and postdelivery hematocrit and hemoglobin. Mass spectrometry detected 1140 proteins, including 77 proteins for which relative abundance differed significantly between cases and controls (fold change >1.15, P<.05). Of these differentially abundant plasma proteins, most had likely liver or placental origins. Gene ontology term analysis mapped to protein clusters involved in responses to wound healing, stress response, and host immune defense. Significantly differentially abundant proteins with the highest fold change (prostaglandin D2 synthase, periostin, and several serine protease inhibitors) did not correlate with predelivery hematocrit or hemoglobin but identified postpartum hemorrhage cases with logistic regression modeling revealing good-to-excellent area under the operator receiver characteristic curves (0.802-0.874). Incorporating predelivery hemoglobin with these candidate proteins further improved the identification of postpartum hemorrhage cases. Agnostic analysis of maternal plasma samples identified differentially abundant proteins in controls and postpartum hemorrhage cases. Several of these proteins are known to participate in biologically plausible pathways for postpartum hemorrhage risk and have potential value for predicting postpartum hemorrhage. These findings identify candidate protein biomarkers for future validation and mechanistic studies.

Cardiometabolic Differences in People Living with HIV Receiving Integrase Strand Transfer Inhibitors Compared to Non-nucleoside Reverse Transcriptase Inhibitors: Implications for Current ART Strategies.

In people living with HIV (PLHIV), integrase strand transfer inhibitors (INSTIs) are part of the first-line combination antiretroviral therapy (cART), while non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens are alternatives. Distinct cART regimens may variably influence the risk for non-AIDS comorbidities. We aimed to compare the metabolome and lipidome of INSTI and NNRTI-based regimens. The 2000HIV study includes asymptomatic PLHIV (n = 1646) on long-term cART, separated into a discovery cohort with 730 INSTI and 617 NNRTI users, and a validation cohort encompassing 209 INSTI and 90 NNRTI users. Baseline plasma samples from INSTI and NNRTI users were compared using mass spectrometry-based untargeted metabolomic (n = 500) analysis. Perturbed metabolic pathways were identified using MetaboAnalyst software. Subsequently, nuclear magnetic resonance spectroscopy was used for targeted lipoprotein and lipid (n = 141) analysis. Metabolome homogeneity was observed between the different types of INSTI and NNRTI. In contrast, higher and lower levels of 59 and 45 metabolites, respectively, were found in the INSTI group compared to NNRTI users, of which 77.9% (81/104) had consistent directionality in the validation cohort. Annotated metabolites belonged mainly to 'lipid and lipid-like molecules', 'organic acids and derivatives' and 'organoheterocyclic compounds'. In pathway analysis, perturbed 'vitamin B1 (thiamin) metabolism', 'de novo fatty acid biosynthesis', 'bile acid biosynthesis' and 'pentose phosphate pathway' were detected, among others. Lipoprotein and lipid levels in NNRTIs were heterogeneous and could not be compared as a group. INSTIs compared to individual NNRTI types showed that HDL cholesterol was lower in INSTIs compared to nevirapine but higher in INSTIs compared to doravirine. In addition, LDL size was lower in INSTIs and nevirapine compared to doravirine. NNRTIs show more heterogeneous cardiometabolic effects than INSTIs, which hampers the comparison between these two classes of drugs. Targeted lipoproteomic and lipid NMR spectroscopy showed that INSTI use was associated with a more unfavorable lipid profile compared to nevirapine, which was shifted to a more favorable profile for INSTI when substituting nevirapine for doravirine, with evidently higher fold changes. The cardiovascular disease risk profile seems more favorable in INSTIs compared to NNRTIs in untargeted metabolomic analysis using mass-spectrometry.

The Difference in Shoot Metabolite Profiles of a Wild and a Cultivated Barley Genotype in Response to Four Nitrogen Forms

Plants can utilize different N forms, including organic and inorganic N resources, and show great differences in the utilization efficiency of each N form among species and genotypes within a species. Previously, we found that the Tibetan wild barley genotype (XZ16) was better in the utilization of organic nitrogen in comparison with the cultivated barley genotype (Hua30). In this study, the metabolite profiles of the two barley genotypes were comprehensively compared in their response to four N forms, including nitrate (NO3−), ammonium (NH4+), urea, and glycine. The macro and micro nutrient concentrations in shoots were mostly found to be higher in the nitrate and urea treatments than in ammonium and glycine in both the genotypes. XZ16 had higher concentrations of nutrient ions in the glycine treatment, but Hua30 accumulated more nutrients in the ammonium treatment. Among a total of 163 differentially regulated metabolites, the highest up-regulation and highest down-regulation values were found in XZ16 in the glycine and urea treatments, respectively. Some important metabolites, such as proline, glutamine, serine, asparagine, L-homoserine, aspartic acid, putrescine, ornithine, and 4-aminobutyrate, were up-regulated in the glycine treatment in both the genotypes with a higher fold change in XZ16 than that in Hua30. Similarly, fructose-6-PO4, aconitic acid, and isocitrate were only up-regulated in XZ16 in the glycine treatment. Here, we concluded that the genotype XZ16 exhibited a better response to the glycine treatment, while Hua30 showed a better response to the NH4+ treatment, which is attributed to the better utilization of glycine-N and NH4+-N, respectively.

Humoral immune response to tumor-associated antigen Ubiquilin 1 (UBQLN1) and its tumor-promoting potential in lung cancer

BackgroundThis study aims to investigate the expression of UBQLN1 in lung cancer (LC) tissue and the diagnostic capability of autoantibody to UBQLN1 (anti-UBQLN1) in the detection of LC and the discrimination of pulmonary nodules (PNs).MethodsSera from 798 participants were used to discover and validate the level of autoantibodies via HuProt microarray and Enzyme-linked immunosorbent assay (ELISA). Logistic regression analysis was applied to establish model. Receiver operating characteristic curve (ROC) analysis was performed to evaluate the diagnostic potential. Immunohistochemistry was performed to detect UBQLN1 expression in 88 LC tissues and 88 para-tumor tissues. qRT-PCR and western blotting were performed to detect the expression of UBQLN1 at the mRNA and protein levels, respectively. Trans-well assay and cell counting kit-8 (CCK-8) was used to investigate the function of UBQLN1.ResultsAnti-UBQLN1 was identified with the highest fold change by protein microarray. The level of anti-UBQLN1 in LC patients was obviously higher than that in NC or patients with benign lung disease of validation cohort 1 (P<0.05). The area under the curve (AUC) of anti-UBQLN1 was 0.610 (95%CI: 0.508-0.713) while reached at 0.822 (95%CI: 0.784-0.897) when combining anti-UBQLN1 with CEA, CYFRA21-1, CA125 and three CT indicators (vascular notch sign, lobulation sign and mediastinal lymph node enlargement) in the discrimination of PNs. UBQLN1 protein was overexpressed in lung adenocarcinoma (LUAD) tissues compared to para-tumor tissues. UBQLN1 knockdown remarkably inhibited the migration, invasion and proliferation of LUAD cell lines.ConclusionsAnti-UBQLN1 might be a potential biomarker for the diagnosis of LC and the discrimination of PNs.

Integrative Analysis of Cytokine and Lipidomics Datasets Following Mild Traumatic Brain Injury in Rats.

Traumatic brain injury (TBI) is a significant source of disability in the United States and around the world and may lead to long-lasting cognitive deficits and a decreased quality of life for patients across injury severities. Following the primary injury phase, TBI is characterized by complex secondary cascades that involve altered homeostasis and metabolism, faulty signaling, neuroinflammation, and lipid dysfunction. The objectives of the present study were to (1) assess potential correlations between lipidome and cytokine changes after closed-head mild TBI (mTBI), and (2) examine the reproducibility of our acute lipidomic profiles following TBI. Cortices from 54 Sprague Dawley male and female rats were analyzed by ultra-high-performance liquid chromatography mass spectrometry (LC-MS) in both positive and negative ionization modes and multiplex cytokine analysis after single (smTBI) or repetitive (rmTBI) closed-head impacts, or sham conditions. Tissue age was a variable, given that two cohorts (n = 26 and n = 28) were initially run a year-and-a-half apart, creating inter-batch variations. We annotated the lipidome datasets using an in-house data dictionary based on exact masses of precursor and fragment ions and removed features with statistically significant differences between sham control batches. Our results indicate that lipids with high-fold change between injury groups moderately correlate with the cytokines eotaxin, IP-10, and TNF-α. Additionally, we show a significant decrease in the pro-inflammatory markers IL-1β and IP-10, TNF-α, and RANTES in the rmTBI samples relative to the sham control. We discuss the major challenges in correlating high dimensional lipidomic data with functional cytokine profiles and the implications for understanding the biological significance of two related but disparate analysis modes in the study of TBI, an inherently heterogeneous neurological disorder.

Transcriptome profiling of equine ovarian cortex during foetal and adult stages

AbstractThe equine foetal ovary has some unique characteristics that differ from other animals, such as ovary hyperplasia and high oestrogen secretion, and inverted location of cortex and medulla present in adult mare. The ovarian cortex supports the process of folliculogenesis and development, the synthetics and expression of oestrogen; however, the character‐related molecular mechanisms and specific biological functions in equine foetal ovarian cortex are still poorly understood. To explore the associated regulatory networks and molecular events of equine foetal ovary during the hyperplasia stage, we analysed the transcriptomic differences between the equine second‐trimester foetal ovarian cortex and adult ovarian cortex by RNA‐seq. There were 6334 differentially expressed genes (DEGs) present in foetal vs. adult, of which 3234 and 3100 DEGs were upregulated and downregulated, respectively. GO and KEGG were used for functional and pathway enrichment analysis of the DEGs. In particular, we found that some DEGs with high fold changes were related to steroid production and metabolism, such as CYP11A1, CYP17A1, LDLR, STAR and SCARB1, which were in line with the efficient oestrogen production in the equine foetal ovary. The transcriptome profile revealed the functional and developmental characteristics and gene expression patten of the ovarian cortex in the foetal and adult stages of the mare. Our study provides new insights into the molecular mechanism of equine second‐trimester foetal ovarian development through transcriptome analysis and provides insights for improving care or treatment for the pregnant mare and the foetus.

Evaluation of Acute and Convalescent Antibody Concentration Against Pneumococcal Capsular Polysaccharides for the Diagnosis of Pneumococcal Infection in Children with Community-Acquired Pneumonia.

We evaluated whether the quantification of IgG to pneumococcal capsular polysaccharides is an accurate diagnostic test for pneumococcal infection in children with pneumonia in Nepal. Children with pneumococcal pneumonia did not have higher convalescent, or higher fold change, IgG to pneumococcal polysaccharides than children with other causes of pneumonia. Caution is needed in interpreting antibody responses in pneumococcal infections.

Genome-Wide Characterization and Expression Analysis of Annexin Genes under High-Temperature Stress in Sorghum bicolor L.

The annexin family is found in animals and plants and responds to a wide range of environmental stressors. In this study, 19 annexin proteins were identified based on their putative annexin repeats in Sorghum bicolor and further grouped on a phylogenic tree. These genes were randomly distributed across seven chromosomes. The amino acid length of sorghum annexins (SbAnn) varied from 241 (SbAnn3) to 370 (SbAnn2). Additionally, selective pressure analysis suggests the role of purification selection in conserving the annexin gene family in sorghum. Most SbAnns were located in the nucleus, cytoplasm, chloroplast, and mitochondrion. Also, higher syntenic relationships were observed between S. bicolor and monocots (S. italica, Z. mays, and O. sativa) than in A. thaliana. Cis-acting elements in the SbAnns gene promoters were grouped into response to light, hormone and environmental stress, and development-related elements. A number of miRNAs related to abiotic stress response targeted eleven SbAnns. Furthermore, five (SbAnn 4, 5, 14, 15, and 18) of the seven SbAnn genes utilized had relatively higher fold change under high-temperature treatment. This research provides insights into the characterization and functions of annexins under high temperatures.