Search Results (93)

Background/Objectives: Chronic urate nephropathy (CUN), also referred to as gouty nephropathy, represents a severe renal disease primarily precipitated by long-term hyperuricemia (HUA) and gout. However, the precise molecular mechanisms underlying its pathogenesis remain poorly understood. The present study was designed to explore these mechanisms from the perspective of targeted metabolomics. Methods: The HUA mice constructed by urate oxidase (Uox) gene knockout (KO) and their corresponding wild-type controls were employed for the present study. Serum clinical biochemical parameters were determined, and renal histopathological changes were evaluated using hematoxylin-eosin (HE) staining and Masson’s trichrome staining. A targeted metabolomic strategy based on multiple reaction monitoring (MRM) was utilized to profile the renal metabolic landscape of Uox-KO mice, and potential metabolic biomarkers for CUN were identified via multivariate data analysis. Results: Clinical biochemical analysis revealed a significant elevation in serum uric acid, creatinine, and urea nitrogen levels in Uox-KO mice compared with control mice. Histopathological observations confirmed a typical CUN phenotype in Uox-KO mice, characterized by renal tubular vacuolar degeneration and dilatation, desquamation of tubular epithelial cells into the lumen, neutrophil infiltration, glomerular crowding, and renal interstitial fibrosis. Metabolomic analysis identified a total of 291 differentially regulated metabolites in Uox-KO mice relative to control animals. These perturbed metabolites were involved in multiple key biochemical pathways, including amino acid biosynthesis, ABC transporter signaling pathway, purine metabolism, aminoacyl-tRNA biosynthesis, protein digestion and absorption, glycerophospholipid metabolism, and serotonergic synaptic transmission. Notably, pathological parameters, including biochemical measurements and histological observations, were significantly correlated with key differential metabolites associated with CUN progression. Furthermore, eleven differential metabolites (pyroglutamic acid, fructose, riboflavin, dimethyl-L-arginine, glucaric acid, indoxyl sulfate, palmitoylethanolamide, trimethylamine N-oxide, 3-hydroxyanthranilic acid, spermidine, and hippuric acid) were identified as potential metabolic biomarkers for the diagnosis and prognosis of CUN. Conclusions: These findings illustrate that targeted tissue metabolomic analysis constitutes a powerful tool for deciphering the molecular mechanisms of diseases, thus offering novel insights into the pathogenesis of CUN. Full article

The genus Bacillus is widely recognized for its metabolic versatility, enabling it to colonize extreme environments, including sites contaminated with metals. In this study, we report the genome of B. velezensis strain HM1, isolated from sulfur-rich mine tailings from silver mining activities in southwestern Mexico. Isolation was performed by heat treatment followed by selective cultivation in a medium enriched with mine tailings extract (metals and sulfates), resulting in a single dominant morphotype corresponding to strain HM1. Whole-genome sequencing was carried out using the Illumina NovaSeq platform (2 × 250 bp). The assembled genome of strain HM1 has a size of 4,044,128 bp, distributed across 20 contigs, with an N50 of 700,388 bp and an L50 of 3, and an average coverage of 66.8×. The GC content was 46.31%, with an estimated completeness of 99.81% and contamination of 0.01%. Genome analyses indicate that the assembly corresponds to a single chromosome, with no evidence of plasmid replicons. Genome annotation identified 3950 coding sequences (CDSs), 83 tRNAs, 11 rRNAs, 26 ncRNAs, and 4 sORFs. Phylogenomic analysis, together with genomic similarity metrics (ANI > 98.6%, AAI > 98.8%, dDDH > 87%), confirms its classification as Bacillus velezensis. Functionally, the genome encodes multiple genes involved in resistance to metals and metalloids (including ABC transporters, efflux pumps, and biotransformation enzymes), as well as a complete pathway for sulfate assimilation. Collectively, these genomic features reveal a broad repertoire of adaptive strategies employed by strain HM1 to thrive in metal-contaminated environments. Full article

Background: Sulfate transporters (SULTRs) are integral membrane proteins responsible for sulfate uptake, translocation, and plant adaptation to abiotic stresses. However, knowledge regarding the SULTR gene family in the economically important crop, Brassica rapa (Chinese cabbage), limited. The aim of this study is to conduct a genome-wide identification and functional characterization of BrSULTR genes and to explore their potential functions under abiotic stress. Methods: We identified 19 BrSULTR genes in the B. rapa genome by performing homology searches with Arabidopsis thaliana SULTR sequences as queries. Subsequent bioinformatics analysis included phylogenetic classification, chromosomal localization, gene structure, conserved motif dissection, cis-regulatory element prediction, and protein–protein interaction (PPI) network analysis. Tissue-specific expression profiles of BrSULTRs were assessed using publicly available transcriptome data. Furthermore, their expression dynamics under salt (150 mM NaCl) and low-temperature (4 °C) stress were investigated by integrating transcriptomic, proteomic, and qRT-PCR data. Results: The 19 identified BrSULTR members were phylogenetically categorized into four subfamilies and were mapped unevenly across seven chromosomes. Promoter analysis identified an array of cis-regulatory elements associated with development, hormone response, and stress response. Expression profiles revealed distinct tissue-specific patterns in roots, stems, leaves, flowers, and siliques. Under salt stress, BrSULTR13 was significantly upregulated, while BrSULTR9 and BrSULTR11 were significantly suppressed under low-temperature stress. PPI network projection indicated that the Arabidopsis homologs of BrSULTR5 may physically interact with stress-regulating enzymes such as APS and APR. Conclusions: Our work presents a comprehensive genomic and functional overview of the BrSULTR gene family in B. rapa. The results underscore the potential functions of BrSULTRs, highlighting their involvement in sulfate transport and abiotic stress responses. These insights establish valuable insights and a foundation for further research aiming at improving stress tolerance in B. rapa through the manipulation of sulfur metabolism pathways. Full article

Background/Objectives: Dietary fibers play key roles in shaping gut microbiome and intestinal homeostasis. While purified diets offer experimental precision and reproducibility in rodent models, they omit the complex mixture of fermentable and non-fermentable fibers found in grain-based chow diets. We hypothesized that excluding fermentable fiber impairs intestinal homeostasis by reducing microbial metabolites and altering the colonic epithelial transcriptome, thereby increasing susceptibility to inflammation. Methods: Wildtype male C57BL/6 mice were maintained on either a standard grain-based chow diet or a purified low-fat diet (LFD) containing 5% non-fermentable cellulose for ten weeks. Fecal microbiomes, short-chain fatty acid (SCFA) profiles, and colonic epithelial transcriptomes were analyzed. A separate group was challenged with dextran sodium sulfate (DSS) following a five-week dietary intervention to compare colitis severity between the two diet groups. Results: Relative to mice fed the grain-based chow, those consuming the purified LFD (containing only non-fermentable cellulose) showed decreased gut microbial diversity and significantly lower SCFA levels. These changes were accompanied by marked differences in colonic epithelial cell transcriptomes. In LFD-fed mice, the top upregulated gene networks included ribosomal pathways and MHC complex protein binding, suggesting increased growth and gut inflammation. The most downregulated pathways included mineral absorption, actin and tubulin binding, and membrane organelle assembly, indicating major alterations in cellular structure and transport. LFD-fed mice also exhibited increased colonic expression of S100a9, a gut inflammation biomarker, and more severe disease symptoms when challenged with DSS compared to chow-fed mice. Conclusions: Fermentable fibers are one of the factors contributing to intestinal homeostasis and mitigating the severity of ulcerative colitis. Full article

Multiple myeloma (MM) is a clonal plasma cell neoplasm characterized by autonomous immunoglobulin overproduction. Despite associations between serum metabolites and MM, causal mechanisms remain unclear. Here, we employed bidirectional Mendelian randomization (MR) using 452 serum metabolites to elucidate causal associations with MM risk. The inverse variance-weighted (IVW) method was prioritized, complemented by MR-Egger and weighted median (WM) analyses to address horizontal pleiotropy. Sensitivity analyses—including Cochran’s Q test, MR-Egger intercept evaluation, and leave-one-out (LOO) robustness checks—confirmed result stability. Pathway enrichment was performed using MetaboAnalyst 6.0. RNA-seq data were integrated to identify transcriptional regulators and signaling pathways mediating serum metabolite-driven MM. Among 21 metabolites significantly associated with MM, 8 exhibited protective inverse correlations, while 13 showed risk-enhancing effects. Sensitivity analyses further confirmed the validity of the observed relationships, while bidirectional MR confirmed no reverse causality. Pathway enrichment highlighted valine/leucine/isoleucine biosynthesis and biotin metabolism as pivotal pathways. Integrating transcriptomic data revealed 11 overlapping genes enriched in metal ion transmembrane transporter activity and glycosaminoglycan biosynthesis—chondroitin sulfate/dermatan sulfate. This study established a causal relationship between specific serum metabolites and MM and revealed that key genes may affect the development of MM through metabolic-epigenetic crosstalk, providing preliminary insights into potential therapeutic targets. Full article

Iron deficiency anemia remains a global nutritional challenge due to the low bioavailability and side effects of conventional inorganic iron supplements. A novel organic iron supplement, oyster peptide ferrous chelate (OP-Fe), was prepared using oyster peptides as ligands. Its preparation process was optimized via single-factor experiments and statistical methods with the optimal conditions identified as 1% peptide concentration, 35 °C chelation temperature, 3.91:1 peptide-to-iron ratio, 1.49% ascorbic acid concentration and pH 6.05. Under these conditions, the chelate’s iron content reached 15.44 ± 0.18 g/kg. Multi-dimensional characterization confirmed that Fe²⁺ formed stable complexes with oyster peptides through carboxyl, amino, and imidazole groups. In vitro Caco-2 cell experiments showed OP-Fe achieved a maximum iron absorption rate of 76.07%, significantly higher than ferrous sulfate (52.39%). In vivo pharmacokinetic studies in mice demonstrated higher iron accumulation in serum and small intestine for OP-Fe. Key iron transport-related genes (PEPT1, TFR1, DMT1) were upregulated, contributing to enhanced absorption. OP-Fe exhibits favorable structural stability and bioavailability, holding potential as an efficient iron supplement. Full article

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with unclear pathogenic mechanisms. Dysregulated zinc metabolism contributes to AD pathology. This study aimed to identify zinc metabolism-related hub genes to provide potential biomarkers and therapeutic targets for AD. Methods: We performed an integrative analysis of multiple transcriptomic datasets from AD patients and normal controls. Differentially expressed genes and weighted gene co-expression network analysis (WGCNA) were combined to identify hub genes. We then conducted Gene Set Enrichment Analysis (GSEA), immune cell infiltration analysis (CIBERSORT), and receiver operating characteristic (ROC) curve analysis to assess the hub gene’s biological function, immune context, and diagnostic performance. Drug-gene interactions were predicted using the DrugBank database. Results: We identified a single key zinc transporter–related hub gene, SLC30A3, which was significantly downregulated in AD and demonstrated potential diagnostic value (AUC 0.70–0.80). Lower SLC30A3 expression was strongly associated with impaired synaptic plasticity (long-term potentiation, long-term depression, calcium signaling pathway, and axon guidance), mitochondrial dysfunction (the citrate cycle and oxidative phosphorylation), and pathways common to major neurodegenerative diseases (Parkinson’s disease, AD, Huntington’s disease, and amyotrophic lateral sclerosis). Furthermore, SLC30A3 expression correlated with specific immune infiltrates, particularly the microglia-related chemokine CX3CL1. Zinc chloride and zinc sulfate were identified as potential pharmacological modulators. Conclusions: Our study systematically identifies SLC30A3 as a novel biomarker in AD, linking zinc dyshomeostasis to synaptic failure, metabolic impairment, and neuroimmune dysregulation. These findings offer a new basis for developing targeted diagnostic and therapeutic strategies for AD. Full article

Sulfur metabolism plays an important role in plant growth and environmental adaptation. Sulfate transporters (SULTRs) are essential players that mediate sulfur acquisition and distribution in many plants, thereby influencing the cellular redox homeostasis under abiotic stress. In this study, we identified 16 putative HvSULTRs genes in barley at the genome-wide level. The conservation and divergence of the SULTR gene family were assessed through a phylogenetic tree and gene structure analysis, revealing that these genes are closely distributed along the chromosomes. Furthermore, the expression pattern of SULTRs in multiple tissues, including flower, root, leaf, stem, seeds, female, male, root meristem, and apical meristem, were analyzed among ten land plants using a public database. Interestingly, the expression of HvSULTR2, HvSULTR4, and HvSULTR5 was upregulated after four days of heat treatment, suggesting their importance in barley’s adaptive response to heat stress. In addition, HvSULTR11 was confirmed to be localized at the plasma membrane and display functional interactions with Hv14-3-3A/Hv14-3-3D. In addition, haplotypes of the HvSULTR11 based on SNP (Single Nucleotide Polymorphism) were divided into ten types across 123 barley varieties. Together, these results provide a new clue to clarify the molecular mechanism of SULTRs in stress response and a new candidate gene resource to enhance the stress (e.g., heat and drought) tolerance in barley. Full article

Broussonetia papyrifera has strong adaptability and exhibits a strong ability to accumulate selenium. Its leaves are rich in crude protein, amino acids, and minerals, making them high-quality feed materials. To improve the selenium-enriched ability of B. papyrifera and promote the development of selenium-enriched agricultural products, we screened and identified the sulfate transporters associated with selenium absorption in B. papyrifera. By treating the leaves of B. papyrifera with different concentrations of sodium selenate and analyzing the correlation between gene expression and selenium content, we identified BpSULTR3;1 and BpSULTR3;4, which may be involved in selenium absorption and transport in B. papyrifera. We further validated the functions of BpSULTR3;1 and BpSULTR3;4 through transgenic experiments in Arabidopsis thaliana. The results showed that overexpressing BpSULTR3;1 significantly increased the total selenium content in A. thaliana, up to 2.31 times, and also increased the contents of three forms of organic selenium (SeCys₂, MeSeCys and SeMet) in transgenic A. thaliana. These findings provide solid theoretical support for improving B. papyrifera’s selenium enrichment ability through genetic improvement. Full article

Sulfate availability critically influences plant growth, yet the role of small RNAs, particularly microRNAs (miRNAs), in regulating responses to sulfate deficiency remains poorly understood. Here, we conducted a temporal analysis of sulfate deficiency-responsive miRNAs in the roots and leaves of Solanum lycopersicum (tomato), using an updated miRNA annotation in the SL4.0 genome. We found 40 differentially expressed miRNAs, including 2 novel, tomato-specific miRNAs. Tomato miRNAs showed an important time- and organ-specific regulation, similar to the described response of the mRNA transcriptome. Integration with transcriptomic data and Degradome-seq analysis highlighted both canonical and non-canonical targets for sulfate-responsive miRNAs. miR395, the most extensively studied miRNA, was found to control not only its conserved targets involved in sulfate transport and assimilation, but also genes involved in redox homeostasis, photosynthesis and chloride transport. Notably, most targets were repressed in leaves, suggesting miRNA-mediated downregulation of energy-intensive processes, while root targets were predominantly upregulated, including genes related to protein remodeling and antioxidant defense. Comparative analysis with Arabidopsis thaliana revealed a broader functional repertoire in tomato, suggesting species-specific adaptations to sulfate deficiency. Overall, our results underscore the critical role of miRNAs in fine-tuning organ-specific metabolic reprogramming during nutrient stress, expanding the current understanding of the regulatory landscape underlying sulfate deficiency in plants. Full article

Zn is a trace element necessary for the functioning of about 300 enzymes. It plays a biochemical, structural, and regulatory role. It participates in the immune response, proper functioning of the endocrine system, and regulation of gene expression. Its deficiencies are most often caused by the mismatch between dietary intake and the body’s needs. Bioavailability of zinc depends on interactions with other food components. Phytates negatively affect this element’s absorption, whereas proteins, peptides, and amino acids increase its bioavailability. It has been proven that organic forms of zinc are better absorbed than inorganic compounds, like zinc oxide and sulfate. Amino acid combinations with zinc can use amino acid transporters in the absorption process. Estimation of Zn bioavailability and bioaccessibility are based on in vivo and in vitro studies, each having their advantages and disadvantages. The current review aims to gather and summarize recent research on the dietary role of Zn, especially data on bioavailability from food substances promoting/inhibiting absorption, and the latest methods for determining the level of bioavailability of this nutrient. Full article

Sulfate transporters (SULTRs) are key players that regulate sulfur acquisition and distribution within plants, thereby influencing cellular redox hemostasis under pathogen attacks, such as Alternaria brassicicola (Ab). In this study, a total of 23 BolSULTR (Brassica oleracea SULTR) genes were identified from the Brassica genome. These BolSULTRs are distributed across nine chromosomes, with all collinear BolSULTR gene pairs undergoing purifying selections. Phylogenetic analysis reveals that the SULTR family is evolutionarily conserved among plant kingdoms. qRT-PCR analysis demonstrated that the expression of BolSULTRs varies across different plant organs and is modulated by hormonal signals. Furthermore, transcriptome analysis identified several BolSULTRs whose expression levels were depressed in Ab-challenged leaves in broccoli. Among them, the BolSULTR2;1 gene emerged as a key player in the plant’s response to Ab. Virus-induced gene silencing (VIGS) of BolSULTR2;1s resulted in elevated glutathione (GSH) levels and enhanced tolerance to Ab. Taken together, these findings underscore the role of BolSULTR2;1 in maintaining redox homeostasis and enhancing plant disease resistance, suggesting its potential as a target for genome editing to develop broccoli varieties with improved pathogen tolerance. Full article

The Candida tropicalis (C. tropicalis) named YB-3 was isolated by the Atmospheric and room temperature plasma mutagenesis from 6.5 g/L furfural tolerance. The comprehensive transcriptomic analysis of YB-3 was performed. During the stress of furfural treatment, C. tropicalis YB-3 protected cells from oxidative stress damage by increasing the accumulation of the glutathione reductase gene and the expression of antioxidant enzymes, with the enhancement of the inositol phosphate synthase to maintain the structural integrity and transport function of the inner membrane system, thereby affecting the cells’ tolerance. Through the gene knockout and exogenous verification, it was further confirmed that the pathways involved in the three genes of sulfate adenosine transferase gene, glutathione reductase gene, and inositol phosphate synthase gene had significant effects on improving the tolerance of the strain to furfural. The deep excavation of furfural-tolerant gene components and directional modification of C. tropicalis to enhance tolerance are key steps for improving the utilization rate of biomass. Full article

Alternaria panax, the primary pathogen that causes ginseng Alternaria leaf blight disease, can lead to a 20–30% reduction in ginseng yield. WD40 repeat-containing proteins are evolutionarily conserved proteins with diverse functions between different organisms. In this study, we characterized the roles of a WD40 repeat-containing protein in A. panax. The deletion of ApWD40a impaired the mycelial growth, reduced the sporulation, and significantly decreased the efficiency in utilizing various carbon sources. The ΔApwd40a mutant showed increased sensitivity to osmotic stress and metal ion stress induced by sorbitol, NaCl, and KCl, but decreased the sensitivity to a cell wall stress factor (SDS) and oxidative stress factors (paraquat and H₂O₂). Pathogenicity assays performed on detached ginseng leaves and roots revealed that the disruption of ApWD40a significantly decreased the fungal virulence through attenuating melanin and mycotoxin production by A. panax. A comparative transcriptome analysis revealed that ApWD40a was involved in many metabolic and biosynthetic processes, including amino acid metabolism, carbon metabolism, sulfate metabolic pathways, and secondary metabolite pathways. In particular, a significantly upregulated gene that encoded a sulfate permease 2 protein in ΔApwd40a, named ApSulP2, was deleted in the wild-type strain of A. panax. The deletion of ApSulP2 resulted in reduced biomass under sulfate-free conditions, demonstrating that the sulfate transport was impaired. Taken together, our findings highlight that ApWD40a played crucial roles in different biological processes and the pathogenicity of A. panax through modulating the expressions of genes involved in various primary and secondary metabolic processes. Full article

Some marine and extremophilic microorganisms are capable of synthesizing sulfated polysaccharides with a unique structure. A number of studies indicate significant biological properties of individual sulfated polysaccharides, such as antiproliferative activity, which makes them a promising area for further research. In this study, the capsular polysaccharide (CPS) was obtained from the bacterium Cobetia marina KMM 1449, isolated from a marine sediment sample collected along the shore of the Sea of Japan. The CPS was isolated by saline solution, purified by a series of chromatographic procedures, and studied by chemical methods along with 1D and 2D ¹H and ¹³C NMR spectroscopy. The following new structure of the CPS from C. marina KMM 1449 was established and consisted of sulfated and simultaneously phosphorylated disaccharide repeating units: →4)-α-L-Rhap2S-(1→3)-β-D-Manp6PGro-(1→. To elucidate the genetic basis of the CPS biosynthesis, the whole genomic sequence of C. marina KMM 1449 was obtained. The CPS biosynthetic gene cluster (BGC) of about 70 genes composes four regions encoding nucleotide sugar biosynthesis (dTDP-Rha and GDP-Man), assembly (GTs genes), translocation (ABC transporter genes), sulfation (PAPS biosynthesis and sulfotransferase genes) and lipid carrier biosynthesis (wcb operon). Comparative analysis of the CPS BGCs from available Cobetia genomes showed the presence of KMM 1449-like CPS BGC among strains of all three Cobetia species. The study of new natural sulfated polysaccharides, as well as the elucidation of the pathways of their biosynthesis, provides the basis for the development of potential anticancer drugs. Full article