Search Results (2,610)

Rheumatoid arthritis (RA) is the most common inflammatory polyarthritis. In addition, 60–80% of patients express anti-citrullinated protein antibodies (ACPAs), which serve as a diagnostic marker for RA. The effector functions of these autoantibodies can be heavily affected by the N-glycosylation of their Fc region. Here we present a comparison of the Fc N-glycosylation of ACPA IgG to that of non-ACPA IgG from the same patients, and of healthy controls, in an IgG isoform-specific manner. We isolated ACPA and normal serum IgG, digested by trypsin, and separated the resulting peptide mixture by a reversed-phase nanoLC coupled to a Bruker Maxis II Q-TOF, and determined the relative abundance of glycoforms. The paired analysis of galactosylation and sialylation of the IgG subclasses of ACPA and non-ACPA IgG has shown a significant, moderate negative correlation with the inflammatory markers, the level of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), as well as with rheuma-factor (RF), but not with the disease activity score (DAS) or cyclic citrullinated peptide specific antibodies (anti-CCP). However, we detected a significant negative correlation between glycosylation and DAS in the non-ACPA IgG fractions. Furthermore, the isoform-specific analysis revealed additional insight into the changes of the glycosylation features of IgG in RA: changes in the frequencies of the bisecting GlcNAc unit between sample groups could be explained by only the IgG1 isoform; while invariance in fucosylation is the result of the superposition of two isoforms with opposite changes. These results highlight the importance of analyzing immunoglobulin glycosylation in an isoform-specific manner. Full article

This study employed molecular dynamics simulations to investigate the impact of N-linked glycosylation (GlcNAc₂) at the K20N position on the structural dynamics and stability of the bacterial immunity protein Im7. Simulations were conducted in both aqueous and 2 M urea denaturing environments. The simulation results in aqueous solution indicate that glycosylation has only a minor effect on the protein, consistent with expectations. In contrast, simulations in urea reveal that K20N glycosylation significantly destabilizes Im7. Analyses of RMSD, native contacts, SASA, RMSF, correlation matrix, PCA, helical content and hydrophobic centroid distance consistently demonstrate that K20N glycosylation increases the flexibility of Helix I and Helix II and weakens the concerted motion among helical domains (particularly between Helix I and Helix II/IV). The destabilizing effect of K20N glycosylation on Im7 originates in Helix I (where glycan attaches) and propagates to Helix II and the loop region connecting Helix I and Helix II. The instability of Helix II is closely associated with the disruption of hydrophobic interactions within the hydrophobic core. These findings provide new insights into the relationship between site-specific glycosylation and protein stability. Full article

The reaction of 4,4′-bipyridine (C₁₀H₈N₂) with the alkali metal pentacyanocyclopentadienides [Na{C₅(CN)₅}(MeOH)] and [KC₅(CN)₅] gives the coordination polymers [Na{C₅(CN)₅}(EtOH)(H₂O)(C₁₀H₈N₂)] (1) and [K{C₅(CN)₅}(H₂O)₂] • 2 (C₁₀H₈N₂) (2) after recrystallization from EtOH. Both compounds show octahedral coordination around the metal ion with a NaN₄O₂ and KN₂O₄ environment. The [C₅(CN)₅] acts as a 1,1-bridging ligand in 1 and a 1,2-bridging ligand in 2. The 4,4′-bipyridine acts as a N,N′-bridging ligand between dimeric [Na₂(EtOH)₂(H₂O)₂(µ-{C₅(CN)₅}₂] units, while it acts only as a guest molecule in the voids between polymeric [K(µ-H₂O)_4/2{µ-C₅(CN)₅}_2/2]_∞ chains. Both compounds employ multiple hydrogen bonds and π stacking to stabilize the crystalline structures. Full article

This study investigates the challenges of promoting accessibility for deaf teachers and students in higher education, focusing on the development of inclusive teaching materials. A qualitative case study was conducted in ten teacher training programmes at the Federal University of Alagoas (Brazil), including nine distance learning courses and one face-to-face LIBRAS programme. Analysis of the Virtual Learning Environment revealed a predominance of text-based content, with limited use of Libras videos, visual resources, or assistive technologies. The integration of Brazilian Sign Language into teaching practices was minimal, and digital translation tools were rarely used or contextually appropriate. Educators reported limited training, technical support, and institutional guidance for the creation of accessible materials. Time constraints and resource scarcity further hampered inclusive practices. The results highlight the urgent need for institutional policies, continuous teacher training, multidisciplinary support teams, and the strategic use of digital technologies and Artificial Intelligence (AI). Compared with previous studies, significant progress has been made. The present study highlights the establishment of an Accessibility Centre (NAC) and an Accessibility Laboratory (LAB) at the university. These facilities are designed to support the development of policies for the inclusion of people with disabilities, including deaf students, and to assist teachers in designing educational resources, which is essential for enhancing accessibility and learning outcomes. Artificial intelligence tools—such as sign language translators including Hand Talk, VLibras, SignSpeak, Glove-Based Systems, the LIBRAS Online Dictionary, and the Spreadthesign Dictionary—can serve as valuable resources in the teaching and learning process. Full article

Background/Objectives: Alfalfa is a widely cultivated high-quality forage crop, and salinity tolerance is one of the most important breeding goals. Glycine max SALT INDUCED NAC 1 (GmSIN1) was found to enhance salinity tolerance in soybean plants. The phylogenetic analysis showed there were two homologs of GmSIN1 in Medicago truncatula, MtSIN1a and MtSIN1b. This raised questions regarding the roles of MtSIN1s in alfalfa under salinity stress. Methods: From a Tnt1 mutant collection, we identified the mutants of MtSIN1a. We recorded the survival rate and plant height of mtsin1a-1 and mtsin1a-2 after 100 mM NaCl treatment. Subsequently, we generated 35S:MtSIN1a-GFP transgenic alfalfa lines via genetic transformation. Two lines with relatively high MtSIN1a expression, 35S:MtSIN1a-GFP#3 and 35S:MtSIN1a-GFP#4, were selected for gradient NaCl treatments. In addition, DAB and NBT staining were performed, and the H₂O₂ content and catalase (CAT) activity were determined. Then, we used RNA-seq analysis and RT-qPCR to study the mechanism of its tolerance. Results: This study found that after salt treatment, the survival rate and plant height of mtsin1a-1 and mtsin1a-2 were significantly lower than those of the WT. The mutants of MtSIN1a were sensitive to salinity stress. The transgenic alfalfa plants exhibited higher plant height, weaker DAB staining, stronger NBT staining, less H₂O₂ content, and enhanced CAT activity. The transgenic alfalfa constructed by transforming MtSIN1a showed enhanced salinity tolerance with elevated ROS scavenging. We identified MsSOD1 showing elevated expression levels in transcriptomic analysis. Conclusions: MtSIN1a is a positive regulator for enhancing salinity tolerance in alfalfa with activated ROS scavenging. Full article

Polyamines are polycationic compounds present in all living cells that exert functions at different levels in the metabolism. They bind to DNA and RNA and modulate DNA replication and gene expression. Some of these regulatory effects are exerted by promoting condensation of nucleosomes, a mechanism closely connected with epigenetic modification by histone methylation and acetylation. The polyamines 1,3-diaminopropane and spermidine induce expression of the global regulator LaeA and increase by several folds the formation of the α-NAC transcriptional co-activator, a subunit of the nascent polypeptide-associated complex. The global regulator LaeA controls the switch from primary growth to secondary metabolite production and differentiation when an essential nutrient in the growth medium becomes limiting. α-NAC exerts significant control over the biosynthesis of secondary metabolites and fungal pathogenicity on plants. When purified α-NAC protein is added to a tomato host plant, it induces plant resistance to fungal infections and triggers the development of system-acquired resistance in other plants. Spermidine extends the life of yeast cells and prolongs the half-life of penicillin gene transcripts in Penicillium chrysogenum. This article discusses advances in the basis of understanding the mechanism of plant–fungi interaction and the effect of small fungal metabolites and epigenetic modifiers in this interaction. Full article

Two fluorescent ureido-dihomooxacalix[4]arene derivatives containing naphthyl residues at the lower rim (1 and 2) were studied for the detection of nitroaromatic compounds (NACs) in solution and in vapour phases. Their affinity in solution was determined by UV-Vis absorption, fluorescence and NMR spectroscopy. For NAC vapour sensing, calixarenes were dispersed in a polytetrafluoroethylene (PTFE) matrix. Four new solvated crystals of dihomooxacalix[4]arene 2 were obtained and the solvent’s influence on its structural characteristics was investigated. The solvent-dependent structural variations observed in the crystal structures highlight the intrinsic flexibility of the calixarene framework. Such conformational adaptability, evident in the disruption and reorganization of hydrogen bonding and π–π interactions, is directly relevant to nitroaromatic sensing, where a rapid and reversible host response is crucial for effective detection. Theoretical calculations were also performed to provide further insights on the binding process. The corrected Stern–Volmer constants (K_SV) obtained showed that both receptors present selectivity for TNP and follow the same quenching order (TNP > NT > NB > DNT > TNT > DNB). Factors other than electron density distribution should dominate the quenching extent and therefore the values of the SV constants, which will be greatly overestimated if no correction to the inner filter effect is applied. Detection of NB and NT and vapours by both calixarenes produced a complete, very fast (2 to 5 s), and reversible quenching, indicating the potential use of this porous PTFE–calixarene matrix for the sensing of volatile NACs. Full article

Sialyl-Tn (sTn) is a tumor-associated carbohydrate antigen (TACA) abundantly expressed by various types of carcinomas. While conventional antibody-based platforms have traditionally been used for the detection and targeting of sTn, alternative binding scaffolds may offer distinct advantages. Variable lymphocyte receptor B (VLRB), the immunoglobulin-like molecule of jawless vertebrates, offers a promising alternative for glycan recognition. In this study, a phage-displayed VLRB library was utilized to identify sTn-specific binders. Two candidates, designated as ccombodies A8 and B11, were isolated after four rounds of biopanning. Both were expressed and purified using Ni-affinity and FPLC, yielding proteins with apparent molecular weights of ~27 kDa in SDS-PAGE. Sequence analysis revealed a preference for glycan-binding residues in randomized hypervariable regions, with A8 exhibiting an increased aliphatic content. ELISA confirmed selective binding to sTn and other O-glycans containing the core α-GalNAc, with EC₅₀ values of 18.2 and 14.2 nM for A8 and B11, respectively. Vicia villosa lectin inhibited ccombody binding to sTn, indicating shared epitope recognition. Additionally, both ccombodies bound to sTn-positive glycoproteins and carcinoma cell lines HeLa and LS174T. These findings demonstrate that phage display of VLRBs enables the identification of high-affinity, glycan-specific binders, offering a compelling alternative to immunoglobulin-based platforms for future diagnostic and therapeutic applications targeting tumor-associated glycans. Full article

N-acetylglucosamine (GlcNAc) is an important functional monosaccharide that serves as a key component in macromolecules such as cell walls and chitin. It has a wide range of applications in medicine, health supplements, and the chemical industry, leading to a growing market demand. This study evaluated the potential genotoxicity of GlcNAc produced by Bacillus subtilis BNZR 2-7 through a comprehensive assessment in vitro and in vivo assays. GlcNAc was non-mutagenic in the Ames test using Salmonella typhimurium and Escherichia coli. Meanwhile, GlcNAc was non-genotoxic in the in vitro micronucleus assay using Chinese hamster ovary cells. In the in vivo assays, GlcNAc was non-genotoxic in the in vivo mammalian erythrocyte micronucleus test and spermatocyte chromosome aberration test in mice. These studies provide additional evidence that GlcNAc produced by Bacillus subtilis BNZR 2-7 is not genotoxic at the doses tested, supporting its safety for use in foods. Full article

Lycoris longituba produces a single flower bearing six tepals. The double-petaled phenotype of L. longituba has gained significant interest in China due to its ornamental and commercial value in tourism industries. This double-petal phenotype, characterized by stamen petalization, shows improved esthetic characteristics compared with conventional single-petal form. However, the molecular mechanisms underlying this floral trait remain largely undefined. In this study, RNA-based comparative transcriptomic analysis was performed between single- and double-petaled flowers of L. longituba at the fully opened flower stage. Approximately 13,848 differentially expressed genes (DEGs) were identified (6528 upregulated and 7320 downregulated genes). Functional annotation through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed several DEGs potentially involved in double-petal development. Six candidate genes, including the hub genes LlbHLH49, LlNAC1, LlSEP, LlTIFY, and LlAGL11, were identified based on DEG functional annotation and weighted gene co-expression network analysis (WGCNA). Transcription factors responsive to phytohormonal signaling were found to play a pivotal role in modulating double-petal development. Specifically, 123 DEGs were involved in phytohormone biosynthesis and signal transduction pathways, including those associated with auxin, cytokinin, gibberellin, ethylene, brassinosteroid, and jasmonic acid. Moreover, 521 transcription factors (TFs) were identified, including members of the MYB, WRKY, AP2/ERF, and MADS-box families. These results improve the current understanding of the genetic regulation of the double tepal trait in L. longituba and offer a base for future molecular breeding strategies to enhance ornamental characteristics. Full article

Background/Objectives: Potassium (K⁺) channels are essential transmembrane proteins that regulate ion flow, playing a critical role in regulating action potentials and neuronal transmission. Although K⁺ channel openers (agonists, K⁺ Ag) are widely used in treating neurological and psychiatric disorders, their precise mechanisms of action remain unclear. Our study explored how K⁺ channel openers might influence the expression of voltage-gated K⁺ channels (Kv) in rat brain. Methods: Briefly, eight rats per group received intraperitoneal injections of diazoxide (Dia), chlorzoxazone (Chl), or flupirtine (Flu). Two hours post-injection, the prefrontal cortex (PFC), nucleus accumbens (NAc), dorsal striatum (dSTR), dorsal hippocampus (dHIP), and ventral hippocampus (vHIP) were collected for mRNA expression analysis of various Kv. Results: Dia administration altered expression of Kcna6 in the NAc, dSTR, and vHIP, and Kcnq2 in the PFC, dSTR, and dHIP. The mRNA levels of Kcna2 and Kcna3 changed in the NAc, dHIP, and vHIP, while Kcna6 expression increased in the PFC, dHIP, and vHIP of rats treated with Chl. Injection of Flu resulted in altered expression for Kcna1 in the NAc, dSTR, and dHIP; Kcna3 in the PFC, NAc, dHIP, and vHIP; Kcna6 in the dSTR, dHIP, and vHIP; and Kcnq2 and Kcnq3 in the PFC, dHIP, and vHIP. We also found dose-dependent changes. Conclusions: To our knowledge, this is the first study to identify the effects of potassium channel openers on gene expression within the mesocorticolimbic and nigrostriatal dopaminergic systems. These findings reveal a novel molecular mechanism underlying the action of these drugs in the brain. Importantly, our results have broader implications for translational neuroscience, particularly in the context of repurposing FDA-approved drugs, such as diazoxide and chlorzoxazone, for the treatment of neurological disorders. Full article

Obesity and metabolic syndrome (MetS), growing global health concerns, are closely linked to the development of insulin resistance, type 2 diabetes, steatotic liver disease, and cardiovascular diseases (CVDs). An increase in visceral adipose tissue, the main symptom of MetS, contributes to systemic metabolic dysfunction, resulting in disturbances in glucose and lipid metabolism, mitochondrial dysfunction, and redox imbalance, which creates a vicious cycle of inflammation and oxidative stress, accelerating comorbidities. N-acetylcysteine (NAC), a precursor to glutathione, with antioxidant and anti-inflammatory properties, is described as a potent metabolic modulator that restores metabolic homeostasis. NAC’s ability to modulate oxidative stress and inflammation may be particularly valuable in preventing or mitigating cardiovascular complications of MetS. The aim of this narrative review is to summarize current evidence from cellular, animal, and human studies on NAC’s impact on metabolic health. MetS affects nearly one-third of the global population; therefore, there is a pressing need for accessible therapeutic strategies. NAC appears to offer potential benefits as an adjunctive agent for individuals with metabolic disturbances, but further research is needed to confirm its efficacy and establish its role in clinical practice. Full article

Background/Objectives: Prepulse inhibition (PPI) is a robust, reproducible phenotype associated with schizophrenia and other psychiatric disorders. This study was carried out to identify gene(s) influencing PPI. Methods: We performed Quantitative Trait Locus (QTL) analysis of PPI in 59 strains from the BXD recombinant inbred (BXD RI) mouse family and used a 2-LOD region for candidate gene identification. Genes significantly correlated with the candidate gene were identified based on genetic, partial, and literature correlation, and were further studied through gene enrichment and protein–protein interaction analyses. Phenome-wide association study (PheWAS) and differential expression analyses of the candidate gene were performed using human data. Results: We identified one significant (GN Trait 11428) and two suggestive male-specific QTLs (GN Traits 11426 and 11427) on Chromosome 19 between 27 and 36 Mb with peak LRS values of 19.2 (−logP = 4.2), 14.4 (−logP = 3.1), and 13.3 (−logP = 2.9), respectively. Atad1, ATPase family, AAA domain containing 1 was identified as the strongest candidate for the male-specific PPI loci. Atad1 expression in BXDs is strongly cis-modulated in the nucleus accumbens (NAc, LRS = 26.5 (−logP = 5.7). Many of the Atad1-correlated genes in the NAc were enriched in neurotransmission-related categories. Protein–protein interaction analysis suggested that ATAD1 functions through its direct partners, GRIA2 and ASNA1. PheWAS revealed significant associations between Atad1 and psychiatric traits, including schizophrenia. Analysis of a human RNA-seq dataset revealed differential expression of Atad1 between schizophrenia patients and the control group. Conclusions: Collectively, our analyses support Atad1 as a potential candidate gene for PPI and suggest that this gene should be further investigated for its involvement in psychiatric disorders. Full article

Nucleus accumbens-associated protein 1 (NAC1), a cancer-related transcriptional regulator, is overexpressed in several malignancies, including ovarian cancer. However, its role in ovarian carcinogenesis remains unclear. We aimed to investigate whether NAC1 contributes to metabolic adaptation in endometriosis-related ovarian neoplasms (ERONs) and elucidate its regulatory mechanisms. The clinical relationship between NAC1 and its potential downstream target, phosphoenolpyruvate carboxykinase isoform 2 (PCK2), was examined using immunohistochemical analysis of ovarian cancer specimens. A cell viability assay was performed to clarify the impact of PCK2 on ovarian cancer cell viability. Reporter and chromatin immunoprecipitation (ChIP) assays were conducted to evaluate transcriptional regulation by NAC1. Metabolomic profiling was performed to assess the functional impact of the NAC1–PCK2 axis. A positive correlation between NAC1 and PCK2 expression was observed, and co-expression was associated with poor long-term survival. Knockdown of PCK2 led to a significant reduction in cell viability, indicating that PCK2 is required for maintaining cell survival. Reporter and ChIP assays confirmed that NAC1 directly binds to the PCK2 promoter via the CATG motif. The metabolomic analysis demonstrated that NAC1 promotes truncated gluconeogenesis and de novo serine synthesis through PCK2 upregulation. These findings suggest that NAC1 contributes to ovarian cancer progression by promoting metabolic adaptation, highlighting the NAC1–PCK2 axis as a potential therapeutic target for ERONs. Full article

Abiotic stressors such as drought, salinity, waterlogging, and high and low temperatures significantly reduce the growth and productivity of rice (Oryza sativa) and soybean (Glycine max), which are vital for global food and nutritional security. These stressors disrupt physiological, biochemical, and molecular processes, resulting in decreased yield and quality. Biostimulants represent promising sustainable solutions to alleviate stress-induced damage and improve crop performance under stressful conditions. This review provides a comprehensive analysis of the role of biostimulants in enhancing rice and soybean resilience under abiotic stress. Both microbial and non-microbial biostimulants including phytohormones such as salicylic acid; melatonin; humic and fulvic substances; seaweed extracts; nanoparticles; and beneficial microbes have been discussed. Biostimulants enhance antioxidant defenses, improve photosynthesis and nutrient uptake, regulate hormones, and activate stress-responsive genes, thereby supporting growth and yield. Moreover, biostimulants regulate molecular pathways such as ABA- and ROS-mediated signaling and activate key transcription factors (e.g., WRKY, DREB, NAC), linking molecular responses with physiological and phenotypic resilience. The effectiveness of biostimulants depends on crop species, growth stage, stress severity and application method. This review summarizes recent findings on the role of biostimulants in enhancing the mechanisms underlying growth, yield, and stress tolerance of rice and soybean under abiotic stress. Additionally, the incorporation of biostimulants into sustainable farming practices to increase productivity in the context of climate-related challenges has been discussed. Furthermore, the necessity for additional research to elucidate the underlying mechanisms, refine application methods, and verify their effectiveness in field conditions has been highlighted. Full article