Search Results (6,248)

The interaction between Angiostrongylus vasorum and the vascular endothelium of the host plays a key role in the pathogenesis of canine angiostrongylosis. The adult stage of A. vasorum resides in right ventricles and pulmonary arteries of dogs and foxes and maintains close contact with the endothelium, whose activation may contribute to the hemostatic and hemorrhagic disorders observed in infected animals. However, the molecular mechanisms underlying this endothelial dysfunction remain poorly understood. To investigate this interaction, an in vitro model of vascular endothelial cells was stimulated with the adult A. vasorum homogenate. Quantitative proteomic analysis, combined with bioinformatic tools, identified 691 and 6011 protein groups in the cell supernatants and the cell lysates, respectively. Of these, 213 proteins in the cell supernatants (193 up-regulated and 20 down-regulated) and 564 in the cell lysates (358 up-regulated and 206 down-regulated) showed differential expression compared to control cells. Up-regulated proteins included TFPI, CD59, VWF, ANGPT2, MMRN1, and FLT1, which are involved in endothelial activation, angio-genesis, and coagulation regulation. Conversely, C3, SERPINE1, SERPINB2, PLAU, PLAUR, and ICAM1 were down-regulated, suggesting modulation of fibrinolysis, inflammation, and cell adhesion pathways. These findings indicate that adult A. vasorum homogenate induces a multifactorial endothelial activation characterized by dysregulation of coagulation, complement, and vascular remodelling pathways. Future studies focusing on the temporal and molecular characterization of endothelial responses to excretory/secretory antigens in both definitive and accidental hosts will further clarify the mechanisms of vascular pathology and parasite tolerance. Full article

BASIC PENTACYSTEINE (BPC) transcription factors are plant-specific and play crucial roles in regulating plant development and responses to abiotic stresses. However, the genomic characteristics of the BPC gene family in Brassica juncea and its regulatory mechanisms in response to light and salicylic acid remain poorly understood. In this study, we identified 25 BjuBPC genes in the B. juncea genome using bioinformatic approaches. All BjuBPC proteins were predicted to localize exclusively to the nucleus, with their distribution scattered across 14 chromosomes of B. juncea. Phylogenetic analysis classified these BjuBPC genes into three subfamilies (A, B, and C). The 25 BjuBPC genes showed strong collinearity with BPC orthologs from Arabidopsis thaliana, Brassica rapa, and Brassica nigra, and members of the same subfamily shared highly conserved exon–intron architectures and motif compositions, and a highly conserved canonical GAGA DNA-binding domain. Expression profiling across tissues revealed both tissue-specific and constitutive expression patterns among BjuBPC members. Subsequent expression analyses under four light qualities and exogenous salicylic acid treatment demonstrated that BjuBPC1, BjuBPC9, and BjuBPC24 were specifically responsive to both light and salicylic acid signals, with markedly strong induction by blue light. These findings provide valuable insights for future functional characterization of BjuBPC genes and enhance our understanding of their biological roles in B. juncea. Full article

Accumulating studies have identified the pivotal role of long non-coding RNAs (lncRNAs) in participating in host–virus interactions during virus infections. However, the regulatory roles of lncRNAs in influenza A virus (IAV) infection are still not fully elucidated. In this study, using high-throughput sequencing, we comprehensively compared the expression profiles of lncRNAs and mRNAs in mouse lungs infected either with the nonpathogenic parental (SDL124) H7N9 virus or its moderately pathogenic mouse-adapted (S8) variant. A total of 7636 significantly differentially expressed (SDE) lncRNAs were obtained in the S8-infected group compared to the mock group. As for the SDL124 group, 1042 SDE lncRNAs were identified. Subsequently, the mRNAs co-expressed with SDE lncRNAs were subjected to functional annotation and pathway enrichment analysis. The results indicated that the target mRNAs regulated by the S8 virus were mainly enriched in various immunological processes and exhibited a strong correlation with inflammatory-related signaling pathways. Moreover, 12 lncRNAs and 10 mRNAs co-expressed with SDE lncRNAs were selected and successfully verified by RT-qPCR. Among these lncRNAs, NONMMUG032982.2 and NONMMUG032328.2 exhibited strong antiviral activity against IAV. Additionally, these two lncRNAs were chosen for further in-depth bioinformatics analysis, including transcription factor prediction, coding capacity assessment, genomic location, construction of secondary structure, and prediction of potential interacting proteins. Taken together, these findings provide a cluster of lncRNAs probably associated with the virulence of IAV in mice and shed light on the anti-IAV effects of two functional lncRNAs, establishing a molecular foundation for further exploring the regulatory mechanisms of lncRNAs in IAV infection. Full article

Sucrose phosphate synthase (SPS) is a key rate-limiting enzyme that regulates carbon partitioning and stress tolerance in plants. In this study, we systematically characterized the SPS gene family in maize (Zea mays L.) and identified key members and their interaction networks involved in drought responses. A total of seven ZmSPS genes were identified through genome-wide bioinformatics analyses. Motif composition, gene structure, phylogenetic relationships, and synteny analyses indicated that the ZmSPS gene family is highly conserved among monocot species. Promoter analysis revealed that the upstream regions of ZmSPS genes are enriched with multiple stress responsive cis-acting elements. Drought stress treatments combined with quantitative real-time PCR (RT-qPCR) analyses showed that the expression of ZmSPS3 was significantly upregulated with increasing stress duration. Furthermore, yeast two-hybrid assays demonstrated that ZmSPS3 physically interacts with protein kinases and F-box proteins. These interactions suggest a potential involvement of ZmSPS3 in post-translational modification and protein stability regulation during osmotic stress. As a potential candidate gene responsive to drought, ZmSPS3 provides a preliminary basis for understanding the complex drought-response networks in maize. Full article

Background and Aims: The rising global incidence of cholangiocarcinoma (CCA) coincides with epidemics of type 2 diabetes (T2D) and chronic hepatitis B virus (HBV) infection. Although both are established independent risk factors, the shared molecular mechanisms by which they contribute to cholangiocarcinogenesis remain poorly understood. We hypothesized that T2D and HBV converge on a state of chronic metabolic inflammation (“metaflammation”) that drives CCA progression through a conserved transcriptomic network. Methods: We performed an integrative bioinformatics analysis of transcriptomic data from public repositories, including samples of CCA (TCGA-CHOL, n = 45; GSE107943, n = 163), T2D-affected liver (GSE23343, n = 20), and HBV-infected liver (GSE58208, n = 102). Acknowledging that the T2D and HBV datasets were derived from whole-liver tissue, whereas CCA originates in the biliary epithelium, we identified differentially expressed genes (DEGs) across conditions and defined a core gene set shared among them. Subsequent analyses included functional enrichment, construction of protein–protein interaction (PPI) networks, survival analysis, and protein validation. Results: We identified a core metaflammation signature comprising 156 genes that were consistently dysregulated across T2D, HBV, and CCA. Pathway analysis revealed significant enrichment in PPAR signaling, cytokine–cytokine receptor interaction, PI3K-Akt, and TNF signaling pathways. Protein–protein interaction (PPI) network analysis identified IL6, TNF, AKT1, STAT3, and PPARG as the top hub genes. These hubs were functionally modularized into clusters associated with inflammatory signaling, metabolic regulation, and cell growth and survival. In the TCGA CCA cohort, high expression of IL6, TNF, AKT1, and STAT3 and low expression of PPARG correlated with advanced tumor stage and poorer overall survival (e.g., IL6: ρ = 0.42, p = 0.01). A metaflammation score derived from these hubs (weighted combination of the five genes) emerged as an independent prognostic factor (HR = 2.8, p < 0.001). Protein-level dysregulation of these hubs was confirmed via immunohistochemistry. Conclusions: This study defines a conserved metaflammation network that links T2D and HBV to CCA, identifying key hub genes and pathways. This signature provides a mechanistic explanation for epidemiological risks, serves as a novel prognostic tool, and offers a rationale for targeting metaflammation in prevention and therapy for high-risk populations. Full article

Cuticular proteins (CPs)—key components of the insect exoskeleton—not only regulate development but also serve as structural barriers that enhance resistance against environmental stressors. This study identified CP gene families in Apis mellifera and analyzed their expression patterns during the worker capped brood development stages from mature larva to pre-eclosion. Using a comprehensive genome-wide bioinformatic approach, we identified 85 CP genes in A. mellifera which comprise six families: CPR (n = 43), CPAPs (n = 27), CPF (n = 2), Tweedle (n = 2), CPLCP (n = 8) and Apidermin (n = 3). Analysis of CP gene evolutionary relationship revealed that each CP family forms a distinct, relatively independent clade. Domain and motif analyses confirmed that all CPR members harbor a conserved Chitin_Bind_4 domain, consistent with CPR family structures in other taxa. Additionally, CPAP members possess one or three Chitin-binding Peritrophin-A domain (CBM_14), CPF members possess a conserved Pupal cuticle protein C1 domain (Cuticle_3), and Tweedle members contain a conserved domain of unknown function (DUF243). In addition, the analysis found no conserved domain within the CPLCP and Apidermin families. RNA-seq data revealed dynamic expression patterns of AmCPs during pupal development, with each gene family displaying a relatively characteristic temporal profile. Quantitative PCR validation of eight highly expressed CPR genes at 9 days post-capping confirmed the RNA-seq results. This work provides a comprehensive bioinformatic characterization and transcriptional analysis of CP genes in A. mellifera, offering a foundation for future functional studies on cuticle formation and identifying candidate genes potentially involved in cuticle development in honeybees. This work relies on transcriptomic data and in silico analyses. All proposed biological roles are hypothetical and require experimental validation. Full article

Background: Hilar cholangiocarcinoma (HC) is a highly aggressive malignancy with a poor prognosis, highlighting the urgent need to elucidate its molecular drivers. This study aimed to systematically identify and functionally validate key genes and pathways driving HC pathogenesis. Methods: RNA sequencing (RNA-seq) was performed on paired primary HC tumors and matched adjacent non-tumorous tissues to identify differentially expressed genes (DEGs). Subsequent bioinformatic analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein–protein interaction (PPI) network construction, were conducted to characterize the functional landscape and identify hub genes. Transwell assays and orthotopic metastatic models were used to investigate the functions of Contactin-1 (CNTN1) in HC invasion in vitro and metastasis in vivo. Results: RNA-seq analysis identified 35 DEGs in HC, mainly involved in cell adhesion, cytoskeletal regulation, and axon development. PPI network analysis identified six hub genes, including CNTN1, NCAM1, PLP1, GPM6B, SLC1A3, and PMP2. Furthermore, we demonstrated that CNTN1, a neuronal membrane glycoprotein, was markedly up-regulated in HC at both mRNA and protein levels, and its elevated expression correlated with poor prognosis. Gain- and loss-of-function studies demonstrated that CNTN1 promotes HC cell invasion in vitro and metastasis in vivo. Mechanistically, CNTN1 exerts its pro-invasive effects by activating the PI3K-AKT signaling pathway and inducing epithelial–mesenchymal transition (EMT). Conclusions: Our integrated analysis identifies CNTN1 as a critical oncogenic driver in HC, promoting metastasis through PI3K-AKT-mediated EMT. These findings nominate CNTN1 as a potential prognostic biomarker and therapeutic target in HC. Full article

Endometrial cancer (EC) is the leading gynecological malignancy worldwide. Obesity is reported to be associated with 50% of EC cases. Significant gaps remain in investigating specific molecular mechanisms behind the obesity-driven EC. Women diagnosed with EC undergoing total hysterectomy were recruited. Patients were divided into two groups: EC-obese with BMI > 29.9 kg/m² (n = 10) and EC-Non-obese with BMI ≤ 29.9 kg/m² (n = 10). Tumor tissues were subjected to label-free quantitative proteomic analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Differentially expressed proteins were identified and subjected to pathway enrichment and network analyses to characterize obesity-associated alterations. Proteomic profiling showed a significant dysregulation of 456 proteins: 171 upregulated and 285 downregulated. Proteins involved in endoplasmic reticulum quality control particularly endoplasmic reticulum lectin 1 (ERLEC1), were reduced. Conversely, EC-obese demonstrated upregulation of hepatocyte growth factor (HGF), integrin-linked kinase (ILK), CTTNBP2 N-terminal-like protein (CTTNBP2NL), and lysyl oxidase homolog 1 (LOXL1), implicating activation of inflammatory pathways. Bioinformatic analysis showed downregulation of immune-related pathways, including neutrophil degranulation, complement activation in the EC-obese group. ROC analysis identified apolipoprotein(a), phospholipase B-like 1, CTTNBP2NL, and ILK as significant proteins that can differentiate between the obese and non-obese states. Our findings provide insights into obesity-associated proteomic changes in EC and highlight candidate proteins that can be used for molecular stratification after further validation. Full article

Wheat Fusarium crown rot (FCR), predominantly caused by Fusarium species, is a devastating fungal disease that severely threatens global wheat production. In this study, we combined phytopathological assays, molecular techniques, and bioinformatic analyses to systematically identify the causal agents of FCR in Xinjiang and to screen for potential biocontrol bacteria. A total of 296 fungal isolates were obtained from 195 FCR samples, collected from Yumin County and Xinhe County. Morphological and phylogenetic analyses revealed that Fusarium culmorum was the predominant pathogen, accounting for 73.6% of the total isolates. To evaluate the resistance of local wheat cultivars, F. culmorum XN22-1, a highly virulent strain from Xinhe County, was inoculated to 30 wheat varieties. The results demonstrated that most cultivars lacked resistance to FCR, with the exception of three varieties—Xinchun 19, Xinchun 50, and Youpi 23, which showed a mid-resistance. Given the scarcity of resistant cultivars, we focused on biological control. To control FCR, Pseudomonas aeruginosa J-7, exhibiting broad-spectrum antagonistic activity, was successfully isolated from rhizosphere soil based on the analysis of healthy rhizosphere soil microbial diversity. Subsequently, pot experiments showed that P. aeruginosa J-7 could significantly reduce the disease incidence and lower the disease index of wheat FCR. Furthermore, whole-genome sequencing, in-plate metabolite analysis, and observation on inhibition of spores and mycelium revealed that P. aeruginosa J-7 mediates its biocontrol activity primarily through the production of phenazine and siderophores, which collectively inhibit conidial germination and cause structural damage to the mycelium. This study not only clarifies the composition of FCR pathogens in Xinjiang but also provides a promising biocontrol agent and new strategic insights for the management of wheat crown rot. Full article

Heavy metal-associated isoprenylated plant protein (HIPP) family genes are known to be involved in plant development and stress responses. Even though the HIPPs have been identified and characterized in some plants, the roles of these genes in plant abiotic stress tolerance remain unclear in G. soja (Glycine soja), especially in response to alkaline stress. In the present study, a total of 79 potential HIPP family genes were obtained in G. soja using the Hidden Markov Model. Bioinformatics analysis was used to explore their physicochemical properties, gene structure, phylogenetic relationships, cis-acting elements, chromosomal location and collinearity. Expression profiling showed that 18 HIPP family genes were displayed significantly different transcript levels under alkaline stress, among which GsHIPP79 was selected for functional characterization. The results showed that GsHIPP79 exhibited enhanced alkaline stress tolerance in transgenic Arabidopsis plants, as evidenced by it exhibiting higher chlorophyll contents, strengthening the antioxidant defense system, and regulating the expression of stress-responsive marker genes. Moreover, overexpression of GsHIPP79 in transgenic soybean hairy roots conferred enhanced alkaline stress tolerance. In conclusion, this study provided valuable information on HIPP family genes in G. soja and identified the positive roles of GsHIPP79 in response to alkaline stress tolerance. Full article

The TIFY family, known as a novel group of transcription factors unique to the plant, plays a number of roles and has been functionally characterized in numerous plant species. However, TIFY proteins remain unexplored in litchi. Here, we identified 14 TIFY genes in litchi, which were unevenly located on 8 of 15 chromosomes. All of the LcTIFY proteins were predicted to be nuclear-localized and were phylogenetically categorized into four subfamilies (TIFY, PPD, ZML, and JAZ). Duplication analysis detected no tandem duplications but identified one segmental duplication event with LcTIFY genes, suggesting that segmental duplication served as the primary driving force for the expansion of LcTIFY genes. Comparative collinear analysis revealed 12, 5, and 27 collinear gene pairs between litchi and Arabidopsis, rice, and apple, respectively, providing valuable clues for understanding the evolution of the LcTIFY genes. RNA-Seq and qRT-PCR analyses indicated tissue-preferential expression patterns among LcTIFY genes. Notably, LcPPD1 and LcJAZ5 expressions were negatively correlated with anthocyanin accumulation in the ‘Feizixiao’ variety, except that LcJAZ5 displayed a positive correlation under CPPU treatment. In contrast, LcJAZ7 expression showed a positive correlation across all treatments, implicating these genes in the regulation of pericarp pigmentation. Collectively, these findings lay the groundwork for future investigations into the functional roles of TIFY genes in litchi and offer valuable genetic resources for elucidating the mechanisms underlying litchi pigmentation, thereby providing fresh perspectives for subsequent research into the molecular mechanisms of color formation in plants. Full article

Well established long ago for bacterial and fungal detection, Matrix-Assisted Laser Desorption/Ionization–Time of Flight (MALDI-TOF) technique is not so well established in the virology field, and taking care of its advantages (speed, precision and low cost), this can be a powerful method for viral identification. To explore the feasibility and potential of MALDI-TOF for viral detection, this study shows the development of an in-house spectral library including several uninfected cell cultures and cultures infected with different clinically relevant viruses, such as SARS-CoV-2. This library was applied to the identification of viral infections directly on cell cultures, assessing the ability of the technique to discriminate between infected and non-infected profiles. Additionally, bioinformatic analyses were conducted to evaluate the structure, specificity, and reproducibility of the in-house library, and to understand its strengths and limitations. Sensitivity and specificity of the method were estimated by testing multiple culture batches from selected viruses included in the library. Together, these results provide a deeper understanding of the performance and applicability of MALDI-TOF in the virological context, highlighting its potential as a valuable research platform and a prospective tool for clinical viral detection. Full article

Background: There is an abundance of the neuroactive β-N-oxalyl-L-α,β-diaminopropionic acid (β-ODAP) in grass pea (Lathyrus sativus), pea (Pisum sativum), and several Chinese traditional herbs such as Panax notoginseng. It is well known for its dose- and context-dependent effects on its toxicological characteristics (inducing neurodegenerative neurolathyrism upon excessive consumption) or for its pharmacological effects (including neuroprotection and wound healing). Therefore, reducing β-ODAP levels improves the safety profile of β-ODAP-containing species for utilization, whereas increasing them facilitates their isolation and purification. LsBAHD3 acyltransferase, named after the first letter of BEAT benzylalcohol O-acetyltransferase (BEAT), anthocyanin O-hydroxycinnamoyltransferase (AHCT), anthranilate N-hydroxycinnamoyl/benzoyltransferase (HCBT), and deacetylvindoline 4-Oacetyltransferase (DAT), was proven to be β-ODAP synthetase. Methods: In this report, the interaction of miR172f with LsBAHD3 was investigated through bioinformatic analysis and transient co-expression assays in Nicotiana benthamiana. Functions of miR172f in β-ODAP biosynthesis were also investigated through knockdown in the hairy roots of L. sativus and via transcriptomic analysis. Results: The results suggest that the knockdown of miR172f in hairy roots of L. sativus increased β-ODAP content via targets to LsBAHD3. In this process, protein ubiquitination, cysteine and methionine metabolism, enzyme regulator activity, and so on were associated with β-ODAP biosynthesis. Conclusions: These results identify miR172f as a novel regulator of β-ODAP biosynthesis through targeting of LsBAHD3, offering new insight into the gene expression of β-ODAP synthetase and the genetic network governing β-ODAP biosynthesis in L. sativus. Full article

Studying epigenetic changes in cancer development can reveal the role of tumor suppressor genes and their regulation by DNA methylation. CpG islands, found in promoter regions, are of particular interest, as their hypermethylation can silence tumor suppressor gene expression. Here, we present a practical analysis pipeline for wet-lab biologists with the aim of identify novel epigenetically regulated tumor suppressors using freely available online tools. Bioinformatic platforms such as the R2 Genomics Analysis and Visualization Platform enable analysis of genomic organization, CpG islands, and regulatory elements. Differential methylation and gene expression analyses are based on datasets including TCGA, using tools such as MethSurv, TCGA Wanderer, and GEPIA2 to correlate DNA methylation with gene expression. This bioinformatic step is the basis for the tumor suppressor verification in the wet-lab. Using this pipeline, we identified CLDN10 and GJB2 as potential tumor suppressors in melanoma. Experimentally, our approach includes DNA methylation analysis based on DNA bisulfite conversion, combined bisulfite restriction analysis (CoBRA), pyrosequencing for specific CpG methylation quantification, and RT-PCR for RNA expression quantification. We verify these results in primary tumors, metastases, and cell line models. This approach supports efficient identification of novel epigenetically regulated tumor suppressors, providing practical research guidelines. Full article

Nenestatins (NENs) belong to benzo[b]fluorene-containing atypical angucyclines, a structurally diverse class of microbial natural products. Bioinformatic analysis of the NEN biosynthetic gene cluster (nes BGC) from the deep-sea sediment-derived Micromonospora echinospora SCSIO 04089 implicated Nes5 as an α/β hydrolase. The targeted inactivation of the nes5 gene led to the accumulation of five new analogs, NENs E–I (1–5), together with the known monomer homo-dehydrorabelomycin E (6). Their structures were elucidated by comprehensive spectroscopic analysis and electronic circular dichroism calculations. Notably, both NEN A and NEN B were absent in the Δnes5 mutant, indicating that Nes5 is essential for their biosynthesis; however, the exact function of Nes5 requires further exploration. Full article