Search Results (2,632)

Climate-change-induced thermal stress poses a significant threat to cold-adapted aquatic species, particularly fish endemic to high-altitude ecosystems such as Gymnocypris eckloni, which is native to the Qinghai-Tibetan Plateau. To elucidate the molecular and metabolic mechanisms underlying their response to elevated temperatures, we integrated RNA-seq, miRNA-seq, and LC-MS-based metabolomic analyses of liver tissue from fish exposed to chronic thermal stress (HT) versus control (CT) conditions. Although no significant differences were observed in growth parameters, histopathological examination revealed structural damage under heat stress. Transcriptomic analysis identified widespread dysregulation of genes involved in energy metabolism, with significant downregulation of pathways related to amino acid, fatty acid, glucose, and oxidative phosphorylation. In contrast, upregulated DEGs were enriched in N-glycan biosynthesis, protein processing in the endoplasmic reticulum, and phagosome. Concomitant miRNA profiling revealed differentially expressed miRNAs, including miR-196a-5p, miR-132-3p, and miR-181b-5p, which were predicted to regulate key metabolic genes such as ugt1a1, pepck, and calr. Metabolomic analysis further demonstrated significant alterations in metabolic profiles, with glutathione metabolism, tryptophan metabolism, steroid hormone biosynthesis, and pyruvate metabolism emerging as central pathways in the heat stress response. Integrated multi-omics analysis confirmed coordinated regulation of these pathways, highlighting the critical role of glutathione and tryptophan, as well as disruptions in purine and energy metabolism. The DEMiR-DEG-DEM networks involving miR-196a-5p-pepck-PEP, miR-133a-3p-gne-UDP-GlcNAc, and miR-132-3p-ugt1a1-Bilirubin may play an important role in thermal stress. This study provided a new perspective on the molecular, regulatory, and metabolic adaptations of Gymnocypris eckloni to thermal stress, identifying potential biomarkers and regulatory networks that may inform conservation strategies for cold-water fish under global warming. Full article

Understanding the molecular crosstalk between drought and iron (Fe) homeostasis is crucial for developing drought-tolerant wheat cultivars with enhanced nutrient quality. In this study, transcriptomic data mining identified 23,271 and 5933 differentially expressed genes (DEGs) under drought and Fe deficiency, respectively, with 2479 DEGs in response to both stresses. Notably, this overlapping set included significant numbers of genes encoding transcription factors (TFs) (149 genes), Fe homeostasis components (274 genes), and those involved in phytohormones pathways (245 genes), particularly the abscisic acid (ABA) pathway. Gene Ontology (GO) analysis revealed specific and commonly affected biological processes, such as response to abiotic stimulus and heme binding. Furthermore, co-expression network analysis revealed modules highly enriched with genes involved in transcriptional regulation and Fe uptake, enabling the identification of key hub regulatory genes, belonging to the MYB, NAC, BHLH, and AP2/ERF families, involved in the shared stress response. Finaly, the expression of a set of candidate TF-encoding genes was validated using qRT-PCR in durum wheat under drought and Fe starvation, providing a detailed overview of the possible shared regulatory mechanisms linking drought and Fe deficiency responses. Full article

Background. Dystroglycanopathies (DGPs) constitute a set of recessive, neuromuscular congenital dystrophies that result from impaired glycosylation of dystroglycan (DG). These disorders typically course with CNS alterations, which, alongside gradual muscular dystrophy, may include brain malformations, intellectual disability and a panoply of ocular defects. In this process, the protein products of 22 genes, collectively dubbed DGP-associated genes, directly or indirectly participate sequentially along a complex, branched biosynthetic pathway. POMGNT2 and POMGNT1 are two enzymes whose catalytic activity consists of transferring the same substrate, a molecule of N-acetylglucosamine (GlcNAc) to a common substrate, the O-mannosylated α subunit of DG. Despite their presumptive role in retinal homeostasis, there are currently no reports describing their expression pattern or function in this tissue. Purpose. This work focuses on POMGNT2 and POMGNT1 expression in the mammalian retina, and on the characterization of their distribution across retinal layers, and in the 661W photoreceptor cell line. Methods. The expression of POMGNT2 protein in different mammalian species’ retinas, including those of mice, rats, cows and monkeys, was assessed by immunoblotting. Additionally, POMGNT2 and POMGNT1 distribution profiles were analyzed using immunofluorescence confocal microscopy in retinal sections of monkeys and mice, and in 661W cultured cells. Results. Expression of POMGNT2 was detected in the neural retina of all species studied, being present in both cytoplasmic and nuclear fractions of the monkey and mouse, and in 661W cells. In the cytoplasm, POMGNT2 was concentrated in the endoplasmic reticulum (ER) and/or Golgi complex, depending on the species and cell type, whereas POMGNT1 accumulated only in the Golgi complex in both monkey and mouse retinas. Additionally, both proteins were present in the nucleus of the 661W cells, concentrating in the euchromatin and heterochromatin, as well as in nuclear PML and Cajal bodies, and nuclear speckles. Conclusions. Our results are indicative that POMGNT2 and POMGNT1 participate in the synthesis of O-mannosyl glycans added to α-dystroglycan in the ER and/or Golgi complex in the cytoplasm of mammalian retinal cells. Also, they could play a role in the modulation of gene expression at the mRNA level, which remains to be established, in a number of nuclear compartments in transformed retinal neurons. Full article

Low-temperature stress severely restricts the growth, development, and yield of bitter gourd (Momordica charantia L.), a warm-loving crop with inherent low cold tolerance. NAC transcription factors (TFs) serve as crucial regulators in plant responses to abiotic stresses like cold, while their roles in coping with cold stress in bitter gourd remain unclear. This study identified cold-responsive genes in bitter gourd and characterized the candidate NAC TF McNAC087 through transcriptome analysis. Transcriptome sequencing of cold-tolerant (R) and cold-sensitive (S) bitter gourd inbred lines under 5 °C stress (0 h, 6 h, 12 h, 24 h) revealed 1157 co-expressed differentially expressed genes (DEGs), enriched via Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis in cold tolerance-related pathways (signal transduction, carbohydrate/amino acid metabolism). RT-qPCR showed higher McNAC087 expression in R than S under cold stress, and subcellular localization confirmed it as a nucleus-localized protein. McNAC087 overexpression in Arabidopsis enhanced cold tolerance after sequential stress (−14 °C for 1.5 h, 4 °C for 16 h, and 22 °C recovery for 2 days), with less damage compared to wildtype (WT). Physiologically, overexpressing lines had higher proline, elevated superoxide dismutase/peroxidase/catalase (SOD/POD/CAT) activities, lower malondialdehyde/hydrogen peroxide/superoxide anion (MDA/H₂O₂/O₂⁻) accumulation under cold stress, and upregulated ICE-CBF-COR pathway marker genes (CBF1, DREB2A, RD29A, COR47). In conclusion, McNAC087 enhances Arabidopsis cold tolerance by regulating physiology and activating cold-responsive genes, providing insights for bitter gourd cold tolerance mechanisms and crop breeding. Full article

Background/Objectives: Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by sustained inflammation, leading to diabetic kidney disease (DKD). This study investigated urinary tubular injury biomarkers and metabolomic profiles in relation to albuminuria and renal function across varying durations of T1D. Methods: A cross-sectional analysis was conducted in 247 youth-onset T1D patients categorized by disease duration: short ≤ 5 years (T1D-S, n = 62), medium 6–10 years (T1D-M, n = 67), and long > 10 years (T1D-L, n = 118). Urinary cytokines (MCP-1, KIM-1, NGAL) were measured by ELISA. Metabolomic profiling was performed using ¹H-NMR spectroscopy. Results: Urinary MCP-1/Cr, KIM-1/Cr, and NGAL/Cr levels were significantly elevated in T1D patients compared with non-diabetic controls, but did not correlate with disease duration. Metabolomic profiling identified distinct urinary signatures across T1D duration. Specifically, N-acetylcysteine (NAC) and N-delta-acetylornithine (NAO) increased progressively, while N-acetylaspartate (NAA) and pyruvic acid decreased with longer disease duration. These four metabolites remained statistically significant after both based on Mann–Whitney tests with false discovery rate (FDR) correction (q < 0.05) and application of a conservative alpha threshold (p < 0.01), suggesting potential disruptions in amino acid and carbohydrate metabolism. Conclusions: Urinary biomarkers (MCP-1/Cr, NGAL/Cr, and KIM-1/Cr) are sensitive indicators of subclinical kidney dysfunction in T1D patients, often preceding albuminuria. Alterations in amino acid-related metabolites (NAC, NAA, and NAO) and pyruvate highlight possible metabolic disturbances associated with T1D duration and oxidative stress. However, given the cross-sectional design, longitudinal studies are needed to confirm causality and clarify their predictive value in DKD progression. Full article

Aggregates of misfolded α-synuclein proteins are key markers of Parkinson’s disease. The protein α-synuclein (aSyn) is an intrinsically disordered protein (IDP) and therefore lacks a single stable 3D structure, instead sampling multiple conformations in solution. It is primarily located in presynaptic terminals and is thought to help regulate synaptic vesicle trafficking and neurotransmitter release. ASyn proteins have three domains: an N-terminal domain, a hydrophobic non-amyloid-β component (NAC) core implicated in aggregation, and a proline-rich C-terminal domain. Asyn proteins with truncated C-terminal domains are known to be prone to aggregation and suggest that understanding domain–domain interactions in aSyn monomers could help elucidate the role of the flanking domains in modulating protein structure. To this end, we used Gaussian accelerated molecular dynamics (GAMD) to simulate wild-type (WT), N-terminal truncated (ΔN), C-terminal truncated (ΔC), and isolated NAC domain (isoNAC) aSyn protein variants. Using clustering and contact analysis, we found that removal of the N-terminal domain led to increased contacts between NAC and C-terminal domains and the formation of inter-domain β-sheets. Removal of either flanking domain also resulted in increased compactness of every domain. We also found that the contacts between flanking domains in the WT protein result in an electrostatic potential (ESP) that may lead to favorable interactions with anionic lipid membranes. Removal of the C-terminal domain disrupts the ESP in a way that could result in over-stabilized protein–membrane interactions. These results suggest that cooperation between the flanking domains may modulate the protein’s structure in a way that helps maintain elongation and creates an ESP that may aid favorable interactions with the membrane. Full article

[Background] Marigold (Tagetes erecta L.) is the main source of the natural pigment lutein. [Methods] In this study, Marigold served as the experimental material for systematic observation of floral organ development. Based on floral morphology and lutein content, the full-flowering stage was identified as the optimal harvesting period. [Results] Under different light intensity gradients (30–1500 μmol·m⁻²·s⁻¹), the highest lutein content in petals occurred at ≈500 μmol·m⁻²·s⁻¹. Increased light intensities promoted flowering and enlarged flower diameter while significantly shortening the growth cycle. Transcriptome analysis revealed that light intensity variation markedly influenced the expression of genes related to metabolic pathways, plant hormone signal transduction, and carotenoid biosynthesis, and enriched transcription factor families including bHLH, MYB, NAC, and WRKY. Metabolomic profiling identified lutein esters, such as lutein dimyristate and lutein dipalmitate, as the dominant accumulated forms, with their contents positively correlated with light intensity; under high light, intermediate metabolites, including α-cryptoxanthin and zeaxanthin, were significantly up-regulated. [Conclusions] This study clarifies the molecular mechanism by which light intensity precisely regulates lutein accumulation through coordinated synthesis, esterification, and degradation pathways, offering a theoretical foundation for light-regulated cultivation of T. erecta L. and efficient lutein production. Full article

Pain remains a major clinical challenge due to its complex physiopathology and limited treatment options. In this context, several supplements based on palmitoylethanolamide (PEA) and alpha-lipoic acid (ALA) are known for their neuroprotective properties. ALA-based supplements have shown potential, but concerns about adverse effects persist. This study examines the formulations of two commercial products based on ALA and PEA, IperALA^® and IperALA^® Forte, in which ALA and vitamin D3 are replaced with Coriandrum sativum extract (C. sativum e.s.), N-acetylcysteine (NAC) and glutathione (GSH), assessing improvement of neuroprotective, anti-inflammatory and analgesic properties of the new formulation. Intestinal, blood–brain barrier (BBB), and central nervous system (CNS) models were sequentially stimulated with the test compounds. Both formulations were assessed for cytotoxicity, barrier integrity, permeability, oxidative stress, inflammation, and neuroprotection-related biomarkers. IperALA^® Forte demonstrated superior performance compared to IperALA^® and individual agents. It enhanced cell viability, preserved intestinal and BBB integrity, and improved compound permeability. Notably, it reduced ROS and pro-inflammatory cytokines (TNFα, IL-1), while increasing analgesic markers (CB2R, GABA) in the central system. The replacement of ALA and vitamin D3 with C. sativum, NAC, and GSH in IperALA^® Forte significantly improved the neuroprotective, antioxidant, and anti-inflammatory profile of the supplement. These results indicate a possible connection between the observed neuroprotective properties and the pathways involved in nociception and pain regulation, stating the hypothetical potential relevance of this approach for the treatment of pain-related conditions. Full article

Cisplatin (CIS) is a widely used chemotherapeutic agent known for its efficacy; however, it induces several adverse effects, most notably cachexia, which is characterized by progressive loss of skeletal muscle mass, weakness, and reduced body weight. N-acetylcysteine (NAC) a compound with antioxidants properties, has been shown to mitigate CIS-induced neurotoxicity in experimental models. This study aimed to investigate the myoprotective effects of NAC during CIS treatment and explore the redox and molecular mechanisms involved in this response. For this, female Wistar rats were divided into four experimental groups: Control, NAC (300 mg/day/8 days), CIS (3 mg/kg i.p for 5 days), and NAC + CIS (NAC for 8 days, with CIS administered from day 4 onward). After treatment, muscle strength, redox status, mitochondrial biogenesis, expression of myogenic microRNAs and morphological changes were evaluated. CIS treatment caused muscle atrophy, decreased GSH/GSSG ratio, impaired cellular function, increased lipid peroxidation and altered antioxidant enzymes activity. These effects were mitigated by NAC coadministration. CIS also reduced the mtDNA/nDNA ratio; however, NAC treatment tended to increase TFAM and PGC-1α expression levels. Furthermore, CIS suppressed the expression of muscular miR-1-3p, miR-133a-3p and miR-206-3p, while NAC restored their levels when co-administered with CIS. These findings suggest that NAC may serve as a promising adjuvant therapeutic strategy to counteract CIS-induced myotoxicity through redox regulation and modulation of molecular pathways related to muscle integrity and regeneration. Full article

Sugar transporters of the SWEET family play a crucial role in sugar partitioning and fruit quality, yet their functions remain uncharacterized in Chinese bayberry (Morella rubra). In this study, we present the first genome-wide identification and characterization of the SWEET gene family in species, revealing 15 MrSWEET genes distributed across eight chromosomes. Phylogenetic analysis classified these genes into four conserved clades with distinct tissue-specific expression patterns. During fruit ripening, transcripts of MrSWEET1, 2b, 4, and 15 accumulated progressively, with MrSWEET15 showing the strongest increase. Weighted gene co-expression network analysis (WGCNA) identified a “lightcyan” module that correlates strongly with fruit sugar content (r > 0.8) and contains MrSWEET15, three additional MrSWEET genes, and 47 transcription factors (Dof, MYB, NAC, ERF, MADS, WRKY). Promoter analysis of MrSWEET15 revealed the presence of light- and hormone-responsive cis-elements (MYB, MYC, HY5, bZIP, and Dof), and MYB1, HY5, and Dof1.5 expression profiles are synchronized with MrSWEET15, suggesting potential regulatory relationships. These findings establish MrSWEET15 as a priority candidate for sugar transport in Chinese bayberry and our understanding of the molecular basis of sugar transport and fruit quality formation. Full article

Background/Objectives: To evaluate changes in background parenchymal enhancement (BPE) in the contralateral breast on MRI before and after neoadjuvant chemotherapy (NAC), stratified by molecular subtype in patients with unilateral breast cancer. Methods: This study retrospectively analyzed 116 individuals diagnosed with unilateral breast cancer by biopsy, all of whom underwent breast MRI examinations before and after neoadjuvant chemotherapy. Contralateral breast BPE was graded into four levels (BPEC: 1 = minimal, 2 = mild, 3 = moderate, 4 = marked) by two readers in consensus. Histopathological features and BPE reduction were compared according to molecular subtype. Results: BPE showed a reduction across all molecular subtypes after NAC. In ER-positive cancers, BPEC shifted from 26/16/28/30% to 68/28/4/0%; in HER2-positive cancers, from 37.8/26.7/22.2/13.3% to 73.3/20.0/6.7/0%; and in triple-negative breast cancers, from 47.6/14.3/23.8/14.3% to 76.2/14.3/9.5/0%. Compared to the ER-positive cancer, the reduction in BPE over time was significantly greater in the HER2-positive cancer group (Estimate = 0.48, p = 0.0168) and TNBC (Estimate = 0.55, p = 0.0321), suggesting that the extent of BPE decrease varied by subtype. Conclusions: The extent of BPE reduction on breast MRI following NAC varies significantly across different molecular subtypes of breast cancer. Full article

Soil alkalinity severely restricts the cultivation of Lupinus angustifolius, a valuable legume. Wild soybean (Glycine soja) is a leguminous plant with extremely strong alkaline resistance (pH 8.5). Transferring the alkali-tolerant genes from wild soybeans into lupinus can effectively enhance the alkali tolerance. In this study, we combined transcriptome profiling and genetic transformation to elucidate the molecular basis of alkaline stress response in lupinus. RNA-seq analysis of root tips under acid (HCl, pH 4.0) and alkali (NaHCO₃, pH 8.5) stress revealed 104,353 annotated unigenes, with differential expression patterns highlighting enrichment in cellular component, binding, and catalytic activity categories. KEGG pathway analysis indicated that early responses involved ribosome-related pathways, while later stages activated plant hormone signaling and MAPK pathways. Notably, no homeodomain-leucine zipper (HD-Zip) family genes were identified in the lupinus genome. Therefore, we transferred GsHZ4, an alkali-resistant HD-Zip transcription factor from wild soybean into lupinus hairy roots via Agrobacterium rhizogenes-mediated transformation. Overexpression of GsHZ4 significantly enhanced antioxidant enzyme activities (CAT, POD, and SOD) and reduced malondialdehyde content under NaHCO₃ stress. Furthermore, the promoter of GsHZ4 expression was strongly induced by indole-3-acetic acid (IAA). Key alkali-responsive genes (LaKIN, LaMYB34, LaDnaJ1, LaDnaJ20, LaNAC22, and LaNAC35) were upregulated in transgenic lines, suggesting that GsHZ4 integrates into the endogenous stress-regulation network. Our findings demonstrate that heterologous expression of GsHZ4 can enhance alkaline tolerance of lupinus, providing a novel strategy for breeding stress-resistant varieties and expanding lupinus cultivation in saline–alkali soils. Full article

Lenticel spots (fruit dots) on pear peel strongly influence consumer preference and market price, yet the regulatory networks underlying their lignin/cellulose deposition remain elusive. Here, we integrated electron microscopy, metabolomics, and RNA-seq across three developmental stages (30, 40, and 60 d after full bloom, DAFB) in the pear cultivar ‘Dangshansuli’ (SL) and its bud-sport ‘Dangshanxisu’ (XS). XS exhibited fewer lenticel spots and lower lignin, cellulose, and hemicellulose contents than SL, with the critical onset of lignin and cellulose accumulation detected between 40 and 60 DAFB. Metabolome-wide analysis detected five differentially accumulated lignin monomers, while transcriptome profiling revealed 79 differentially expressed genes (padj ≤ 0.05, |log₂FC| ≥ 1) enriched in phenylpropanoid and cellulose-synthase pathways. Weighted gene co-expression network analysis (WGCNA) uncovered two modules (|r| > 0.8, p < 0.05) positively correlated with lignin and cellulose content, harboring 11 structural genes (4CL, F5H, CCR, COMT, PRX/POD and CESA isoforms) and five transcription-factor families (MYB, NAC, AP2/ERF, WRKY, bHLH). RT-qPCR validated the coordinated down-regulation of these genes in XS relative to SL. Our results decipher the gene–metabolite circuitry driving lenticel lignification in pear, providing molecular targets for breeding peel-perfect cultivars and for cultural practices that minimize superficial blemishes. Full article

Salinity is one of the key threats to food security and sustainability. To make saline soils productive again, we need to develop salt-tolerant crop varieties. Developing salt-tolerant wheat requires a detailed understanding of the molecular mechanisms underlying salt stress responses. In this study, we analyzed the Chinese Spring genome and identified 559 putative NAC transcription factors (TFs), which are recognized as key regulators of both abiotic and biotic stress. Protein family analysis revealed four distinct domain architectures, with more than 95% of the proteins containing a single NAC domain, consistent with their conserved regulatory role. Through in silico analyses, four salt stress-responsive TFs, NAC_1D, NAC_2D, NAC_4A, and NAC_5A, were highlighted, sharing nine of 13 DNA-binding residues. Promoter analysis of their putative target genes identified seven candidates, which, together with the NAC TFs, were subjected to RT-qPCR expression analysis in BARI Gom-25 plants exposed to 100 mM NaCl. The expression data revealed contrasting regulatory patterns between NAC TFs and their target genes. For example, Hsp70 was strongly upregulated in both shoots and roots, despite opposite patterns of NAC_1D expression between tissues. Similarly, bZIP expression mirrored the downregulation of NAC_2D, whereas HKT8 expression remained stable under salt stress. NAC_4A showed a root-specific pattern suggestive of positive regulation of a Non-specific serine/threonine protein kinase, while NAC_5A upregulation corresponded with downregulation of Plant cadmium resistance 2. Collectively, these results provide functional insights into four NAC TFs and identify potential molecular targets for improving wheat salt tolerance. By targeting key tolerance genes at the DNA level offers greater precision and can significantly reduce breeding time. Full article

Viruses account for the most abundant biological entities in the biosphere and can be either symbiotic or pathogenic. While pathogenic viruses have developed strategies to evade immunity, the host immune system has evolved overlapping and redundant defenses to sense and fight viral infections. Nutrition and metabolic needs sculpt viral–host interactions and determine the course and outcomes of the infection. In this review, we focus on the hexosamine biosynthesis pathway (HBP), a nutrient-sensing pathway that controls immune responses and host–viral interactions. The HBP converges on O-GlcNAcylation, a dynamic post-translational modification of cellular proteins, that emerged as a critical effector of immune cell development, differentiation, and effector functions. We present a broad overview of uncovered O-GlcNAc substrates identified in the context of viral infections and with a functional impact on antiviral immunity and viral restriction, or conversely on exacerbating viral-induced pathologic inflammation or viral oncogenesis. We discuss the clinical implications of these findings, current limitations, and future perspectives to harness this pathway for therapeutic purposes. Full article