Search Results (191)

Background: The candidate therapeutic peptide TnP demonstrates broad, system-level regulatory capacity, revealed through integrated network analysis from transcriptomic data in zebrafish. Our study primarily identifies TnP as a multifaceted modulator of drug metabolism, wound healing, proteolytic activity, and pigmentation pathways. Results: Transcriptomic profiling of TnP-treated larvae following tail fin amputation revealed 558 differentially expressed genes (DEGs), categorized into four functional networks: (1) drug-metabolizing enzymes (cyp3a65, cyp1a) and transporters (SLC/ABC families), where TnP alters xenobiotic processing through Phase I/II modulation; (2) cellular trafficking and immune regulation, with upregulated myosin genes (myhb/mylz3) enhancing wound repair and tlr5-cdc42 signaling fine-tuning inflammation; (3) proteolytic cascades (c6ast4, prss1) coupled to autophagy (ulk1a, atg2a) and metabolic rewiring (g6pca.1-tg axis); and (4) melanogenesis-circadian networks (pmela/dct-fbxl3l) linked to ubiquitin-mediated protein turnover. Key findings highlight TnP’s unique coordination of rapid (protease activation) and sustained (metabolic adaptation) responses, enabled by short network path lengths (1.6–2.1 edges). Hub genes, such as nr1i2 (pxr), ppara, and bcl6aa/b, mediate crosstalk between these systems, while potential risks—including muscle hypercontractility (myhb overexpression) or cardiovascular effects (ace2-ppp3ccb)—underscore the need for targeted delivery. The zebrafish model validated TnP-conserved mechanisms with human relevance, particularly in drug metabolism and tissue repair. TnP’s ability to synchronize extracellular matrix remodeling, immune resolution, and metabolic homeostasis supports its development for the treatment of fibrosis, metabolic disorders, and inflammatory conditions. Conclusions: Future work should focus on optimizing tissue-specific delivery and assessing genetic variability to advance clinical translation. This system-level analysis positions TnP as a model example for next-generation multi-pathway therapeutics. Full article

Madagascar harbors a rich marine biodiversity, yet detailed knowledge of its fish species remains limited. Of the 1689 species listed in 2018, only 22% had accessible cytochrome oxidase I (COI) sequences in public databases. In response to growing pressure on fishery resources, this study aims to strengthen biodiversity monitoring tools. Its objectives were to enrich the COI database for Malagasy marine fishes, create the first 12S reference library, and evaluate the taxonomic resolution of different 12S metabarcodes for eDNA analysis, namely MiFish, Teleo1, AcMDB, Ac12S, and 12SF1/R1. An integrated approach combining morphological, molecular, and phylogenetic analyses was applied for specimen identification of fish captured using various types of fishing gear in Toliara and Ranobe Bays from 2018 to 2023. The Malagasy COI database now includes 2146 sequences grouped into 502 Barcode Index Numbers (BINs) from 82 families, with 14 BINs newly added to BOLD (The Barcode of Life Data Systems), and 133 cryptic species. The 12S library comprises 524 sequences representing 446 species from 78 families. Together, the genetic datasets cover 514 species from 84 families, with the most diverse being Labridae, Apogonidae, Gobiidae, Pomacentridae, and Carangidae. However, the two markers show variable taxonomic resolution: 67 species belonging to 35 families were represented solely in the COI dataset, while 10 species from nine families were identified exclusively in the 12S dataset. For 319 species with complete 12S gene sequences associated with COI BINs (Barcode Index Numbers), 12S primer sets were used to evaluate the taxonomic resolution of five 12S metabarcodes. The MiFish marker proved to be the most effective, with an optimal similarity threshold of 98.5%. This study represents a major step forward in documenting and monitoring Madagascar’s marine biodiversity and provides a valuable genetic reference for future environmental DNA (eDNA) applications. Full article

Jasmonate ZIM-domain (JAZ) proteins play a pivotal role in mediating plant growth, development, and responses to both biotic and abiotic stresses. However, our knowledge about the JAZ family genes in Areca catechu remains limited. This study conducted a genome-wide screening and analysis of JAZ genes in A. catechu to investigate their biochemical characteristics, gene structure features, phylogenetic relationships, and expression profiles in different organs. A total of 14 JAZ genes (AcJAZs) were detected in the A. catechu genome, all containing an N-terminal TIFY domain and a C-terminal Jas domain. Phylogenetic analysis categorized these AcJAZs into five subfamilies according to their similarities in protein sequences. Quantitative real-time reverse transcription PCR (qRT-PCR) experiments demonstrated the ample expression specificity of these AcJAZ genes across different organs and flower development stages. More importantly, most AcJAZ genes are expressed significantly higher in blooming male flowers than female flowers, suggesting that they may participate in regulating the difference between male and female flowers of A. catechu. This study elucidates the genomic features and functions of JAZ genes in A. catechu, providing new insights into the mechanisms underlying the development and differentiation of unisexual flowers in A. catechu. Full article

Abscisic acid (ABA), a pivotal phytohormone regulating plant growth and stress adaptation, orchestrates abiotic stress responses through the ABA-responsive element-binding factors ABF/AREB/ABI5. Nevertheless, the functional characterization of ABF/AREB/ABI5 homologs in Z. jujuba cv. Dongzao remains unexplored. In this study, we identified seven ZjABF genes distributed across five chromosomes. Domain analyses revealed high structural conservation, particularly within the basic leucine zipper (bZIP) DNA-binding domain. Subcellular localization confirmed nuclear targeting of all seven ZjABF proteins. Phylogenetic classification resolved these factors into three clades (A–C). Cis-regulatory element profiling implicated the involvement of the ZjABFs in hormone signaling, abiotic stress transduction, and photoregulatory pathways. Synteny analyses identified three segmental duplication events within the gene family. Tissue-specific expression patterns indicated critical roles for ZjABF2 and ZjABF3 in fruit maturation, and most of the ABF/AREB/ABI5 genes were highly expressed in the root. Under drought stress, four ZjABF genes exhibited differential expression, with ZjABF2 demonstrating pronounced sensitivity. These findings establish a molecular framework for understanding ZjABF-mediated abiotic stress responses in non-model woody perennials. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, remains a major global health threat. The virus enters host cells by binding to the angiotensin-converting enzyme 2 (ACE2) receptor. Several small-molecule antiviral drugs, including molnupiravir, favipiravir, remdesivir, and nirmatrelvir have been shown to inhibit SARS-CoV-2 replication and are approved for treating SARS-CoV-2 infections. Nirmatrelvir inhibits the viral main protease (M^pro), a key enzyme for processing polyproteins in viral replication. In contrast, molnupiravir, favipiravir, and remdesivir are prodrugs that target RNA-dependent RNA polymerase (RdRp), which is crucial for genome replication and subgenomic RNA production. However, undergoing extensive metabolism profoundly impacts their therapeutic effects. Carboxylesterases (CES) are a family of enzymes that play an essential role in the metabolism of many drugs, especially prodrugs that require activation through hydrolysis. Molnupiravir is activated by carboxylesterase-2 (CES2), while remdesivir is hydrolytically activated by CES1 but inhibits CES2. Nirmatrelvir and remdesivir are oxidized by the same cytochrome P450 (CYP) enzyme. Additionally, various transporters are involved in the uptake or efflux of these drugs and/or their metabolites. It is well established that drug-metabolizing enzymes and transporters are differentially expressed depending on the cell type, and these genes exhibit significant polymorphisms. In this review, we examine how CES-related cellular and genetic factors influence the therapeutic activities of these widely used COVID-19 medications. This article highlights implications for improving product design, targeted inhibition, and personalized medicine by exploring genetic variations and their impact on drug metabolism and efficacy. Full article

Drought can limit plant growth. The ABRE binding factor (ABF) gene family is extensively involved in multifarious bioregulatory processes in plants. However, kiwifruit has not yet been systematically analyzed. This study analyzed the response of kiwifruit AcABF genes to drought stress. Eleven AcABF genes were distributed on nine chromosomes and clustered into three subfamilies with Arabidopsis AtABF genes, AcABF2, AcABF3, AcABF8, AcABF9, and AcABF10, which have drought resistance functions, and AtABF1, AtABF2, AtABF3, and AtABF4 were clustered in Group I. The structural domains of the nine ABF genes in Group I were highly conserved, and the protein structures were highly similar. In the analysis of the five AcABF genes in Group I, all of their cis-acting elements were related to ABA, the content of ABA-like hormones was significantly increased after drought stress, and most of the GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment results were related to hormonal processes. A total of six AcABF genes were upregulated under drought stress. qRT-PCR was performed to validate the AcABF genes of Group I. The correlation coefficients of the results with the transcriptome data were all above 0.70, and the expression level of ABA increased under drought treatment. These results indicated that the five AcABF genes were positively correlated with ABA under drought stress and that, by synthesizing ABA and facilitating the expression of ABF gene family members, the tolerance of kiwifruit increased. These results provide a solid foundation for further research on improving drought tolerance in kiwifruit. Full article

Here, we present a unique case of the combination of two rare hereditary diseases—a familial form of dilated cardiomyopathy (DCM) and arterial calcification (AC)—in a 10-month-old boy. DCM was caused by a novel pathogenic nucleotide variant (NV) c.542G>T in the MYH7 gene, and AC was caused by biallelic nucleotide variants c.3421C>T and c.4015C>T in the ABCC6 gene. NVs were identified by the next-generation sequencing (NGS) of a broad panel of 404 genes potentially involved in cardiovascular disorders and subsequently validated by Sanger sequencing in the proband and his parents. Cardiologic examinations confirmed the familial nature of cardiomyopathy and the pathogenicity of variant c.542G>T in MYH7 gene. This case highlights the clinical utility of NGS in identifying complex co-existing hereditary conditions and emphasizes the need for the comprehensive genetic testing of patients with atypical clinical presentations. Full article

Background: Cashmere is one of the important economic products of goats, and the KRTAP gene family, as an important family of regulatory genes in the growth process of cashmere fiber, largely affects the quality of cashmere. Methods: In this study, the KRTAP6-3 gene was identified and located on goat chromosome 1 using a goat genome homology search combined with a phylogenetic tree approach. The Longdong cashmere goat KRTAP6-3 gene variation and its effect on cashmere quality were explored by using the polymerase chain reaction single-stranded conformation polymorphism (PCR-SSCP) technique, in situ hybridization, and the allele presence/absence model. Results: The results identified a total of six SNPs in KRTAP6-3, three of which were located in the coding region and two of which were synonymous mutations, in addition to 45- bp deletion sequences detected in alleles C and F. Moreover, the KRTAP6-3 mRNA showed a strong expression signal in the cortical layer of the primary and secondary follicles in the inner root sheaths, as well as in the cells of the hair papillae and the matrices during the anagen phase, and signaling at the sites described above is attenuated during the telogen phase. The presence of allele C was associated with increased MFD (mean fiber diameter) (p < 0.01). The MFD of goats with allele C genotype (genotype AC) was significantly higher (p < 0.05) than that of goats without allele C genotype (genotypes AA and AB). Conclusions: This indicates that genetic variation in the KRTAP6-3 gene in goats is significantly associated with cashmere traits and can serve as a candidate gene for molecular markers of cashmere traits. Full article

Drought stress limits plant survival and yield in arid regions. Uncovering the molecular mechanisms of drought tolerance is key to developing resilient crops. This study used Arabidopsis thaliana as a model to perform an in silico analysis of miRNA–mRNA interactions linked to post-transcriptional drought response. Using the MirTarget program, 274 miRNAs and 48,143 gene transcripts were analyzed to predict high-confidence miRNA–mRNA interactions based on binding free energies (−79 to −129 kJ/mole). Predicted binding sites were located in the CDS, 5′UTR, and 3′UTR regions of target mRNAs. Key regulatory interactions included ath-miR398a-c and ath-miR829-5p targeting ROS detoxification genes (CSD1, FSD1); ath-miR393a/b-5p and ath-miR167a-c-5p targeting hormonal signaling genes (TIR1, ARF6); and the miR169 family, ath-miR414, and ath-miR838 targeting drought-related transcription factors (NF-YA5, DREB1A, WRKY40). Notably, ath-miR414, ath-miR838, and the miR854 family showed broad regulatory potential, targeting thousands of genes. These findings suggest the presence of conserved regulatory modules with potential roles in abiotic stress tolerance. While no direct experimental validation was performed, the results from Arabidopsis thaliana provide a useful genomic framework for hypothesis generation and future functional studies in non-model plant species. This work provides a molecular foundation for improving drought and salt stress tolerance through bioinformatics-assisted breeding and genetic research. Full article

Peptidoglycan recognition proteins (PGRPs) are essential for innate immune recognition and regulation from insects to mammals. However, the specific role of PGRPs in responding to Bacillus thuringiensis (Bt) infection and maintaining midgut microbial homeostasis in Plutella xylostella remains poorly understood. In this study, we identified and characterized a PGRP gene from P. xylostella, designated PxPGRP4. The spatiotemporal expression analysis revealed that PxPGRP4 is predominantly expressed in the midgut of naïve larvae and at adult stages. A homozygous mutant strain featuring a four-base pair nucleotide deletion was successfully generated through CRISPR/Cas9-mediated knockout of PxPGRP4. The bioassay results indicated that the susceptibility of P. xylostella larvae to Cry1Ac protoxin was significantly increased by the loss of PxPGRP4 expression. Furthermore, 16S rRNA sequencing and qPCR analysis revealed that the PxPGRP4 mutants exhibited a significantly reduced total bacterial load and altered microbiota composition in the midgut compared to the wild-type strain, with a shift in the dominant bacterial family from Enterobacteriaceae to Enterococcaceae. Additionally, the knockout of PxPGRP4 resulted in significant alterations in the expression of midgut immune-related genes. These findings highlight the crucial role of PxPGRP4 as a modulator of midgut microbiota and immune responses and provide valuable insights into Bt resistance management. Full article

Understanding how hybrids integrate lineage-specific regulatory variants at the haplotype level is crucial for elucidating the genetic basis of heterosis in livestock. In this study, we established three crossbred pig families derived from distant genetic lineages and systematically identified variants from different lineages, including single nucleotide polymorphisms (SNPs) and structural variations (SVs). At the phase level, we quantitatively analyzed gene expression, four histone modifications (H3K4me3, H3K27ac, H3K4me1, and H3K27me3), and the binding strength of transcription factor (CTCF) in backfat (BF) and longissimus dorsi (LD) muscle. By colocalization analysis of phased genetic variants with phased gene expression levels and with phased epigenetic modifications, we identified 18,670 expression quantitative trait loci (eQTL) (FDR < 0.05) and 8,652 epigenetic modification quantitative trait loci (epiQTL) (FDR < 0.05). The integration of eQTL and epiQTL allowed us to explore the potential regulatory mechanisms by which lineage-specific genetic variants simultaneously influence gene expression and epigenetic modifications. For example, we identified a Large White lineage-specific duplication (DUP) encompassing the KIT gene that was significantly associated with its promoter activity (FDR = 7.83 × 10⁻⁴) and expression levels (FDR = 9.03 × 10⁻⁴). Additionally, we found that a Duroc lineage-specific SNP located upstream of AMIGO2 was significantly associated with a Duroc-specific H3K27ac peak (FDR = 0.035) and also showed a significant association with AMIGO2 expression levels (FDR = 5.12 × 10⁻⁴). These findings underscore the importance of phased regulatory variants in shaping lineage-specific transcriptional programs and highlight how the haplotype-resolved integration of eQTL and epigenetic signals can reveal the mechanistic underpinnings of hybrid regulatory architecture. Our results offer insights for molecular marker development in precision pig breeding. Full article

Tea plants (Camellia sinensis) are among the world’s most significant economic tree species. Tissue culture serves as a crucial method in commercial breeding by facilitating the rapid propagation of valuable genotypes and the generation of disease-free clones. However, callus browning represents a prevalent challenge in tea plant tissue culture, and may adversely affect explant growth and development. Our research demonstrates that although anti-browning agents can effectively suppress browning, they induce distinct color changes in the callus. These color variations could significantly influence callus induction and subsequent growth patterns. In this study, callus tissues from C. sinensis var. Assamica cv. Mengku were employed as experimental materials and treated with three commonly used anti-browning agents: ascorbic acid (VC), activated carbon (AC), and polyvinylpyrrolidone (PVP). The results demonstrated that while these three reagents effectively inhibited browning, they also induced distinct color changes in the explants, which appeared red, green, and white, respectively. Furthermore, this study investigated the molecular mechanisms underlying callus color changes using transcriptomic and metabolomic approaches. Based on transcriptome analysis, it was revealed that photosynthesis and flavonoid biosynthesis pathways were significantly enriched. Metabolome analysis identified 14 phenolic acids, which exhibited significant variation in accumulation across calluses of different colors. The differential expression of genes involved in flavonoid biosynthesis pathways, coupled with the distinct accumulation patterns of metabolites, can effectively alleviate photooxidative damage and enhance the resistance of callus to browning. AC activates the photosynthesis of callus by regulating carbon source allocation and upregulating the expression of key genes in the psa, psb, and pet families within the photosynthetic system. This process promotes chlorophyll biosynthesis, thereby enabling the callus to grow green, while VC activates the expression of key genes such as CHS, F3H, C4H, CYP75B1, and ANR in the flavonoid pathway, which are involved in the regulation of pigment synthesis in red callus. This study elucidated the molecular mechanisms underlying the effects of anti-browning agents on color variations in C. sinensis callus, thereby providing a robust theoretical foundation for optimization, the establishment of tea plant tissue culture systems, and enhancing cultivar quality. Full article

Ethylene plays a crucial role in plant growth, development, and stress responses, with 1-aminocyclopropane-1-carboxylate synthase (ACS) being a key enzyme in its biosynthetic pathway. However, the ACS gene family of Myrica rubra has not yet been systematically identified and characterized. In this study, we identified and characterized seven ACS genes (MrACS) in Myrica rubra through genome-wide analysis. Phylogenetic analysis revealed that these genes belong to three major subfamilies, with certain members clustering closely with ACS genes from Rosaceae species, suggesting a conserved evolutionary relationship. Gene structure and the conserved motif analyses confirmed functional conservation, while chromosomal localization indicated an uneven distribution across the genome. Collinearity analysis revealed strong homologous relationships between Myrica rubra and other plant species, particularly Solanum lycopersicum, Vitis vinifera, and Prunus persica. Furthermore, the transcriptome data demonstrated distinct temporal and tissue-specific expression patterns, with MrACS5 showing fruit-specific expression, suggesting its potential role in fruit ripening. These findings provide comprehensive insights into the ACS gene family in Myrica rubra, offering a valuable foundation for further functional studies on ethylene biosynthesis and its regulatory mechanisms in fruit development. Full article

N6-methyladenosine (m⁶A) methylation functions as a vital post-transcriptional and epigenetic modification in higher plants regulated by α-ketoglutarate-dependent dioxygenases (ALKBH). However, the role of ALKBH genes in oriental melon (Cucumis melo L.) fruit ripening has not been explored. Therefore, we treated oriental melon with an exogenous m⁶A demethylase inhibitor (mechlorfenamic acid) then analyzed endogenous ethylene production and ripening-related indicators to explore the effects of m⁶A methylation on ripening. Bioinformatics and real-time quantitative PCR analyses were used to determine the impact of ALKBH genes on key ethylene synthesis gene expression. Treatment effectively inhibited endogenous ethylene production, firmness changes, and soluble solid contents, thereby extending fruit ripening. Eight ALKBH gene family members belonging to five major groups were identified in the melon genome. All members were expressed in ripening fruits, with different expression patterns during ripening. CmALKBH6, CmALKBH7, and CmALKBH8 expression was inhibited by an ethylene inhibitor (1-methylcyclopropene). The transient overexpression (OE) of CmALKBH8 in oriental melon led to the increased expression of the ethylene synthesis genes CmACS1, CmACS2, and CmACO1. In summary, the ethylene-regulated gene CmALKBH8 may participate in oriental melon fruit ripening regulation by modulating the methylation levels of ethylene synthesis-related genes. These findings help us better understand how m⁶A methylation regulates melon ripening. Full article

High-salinity stress induces severe oxidative damage in plants, leading to growth inhibition through cellular redox imbalance. Chalcone synthase (CHS), a pivotal enzyme in the flavonoid biosynthesis pathway, plays critical roles in plant stress adaptation. However, the molecular mechanisms underlying CHS-mediated salt tolerance remain uncharacterized in Areca catechu L., a tropical crop of high economic and ecological significance. Here, we systematically identified the CHS gene family in A. catechu and revealed tissue-specific and salt-stress-responsive expression patterns, with AcCHS5 exhibiting the most pronounced induction under salinity. Transgenic Arabidopsis overexpressing AcCHS5 displayed enhanced salt tolerance compared to wild-type plants, characterized by elevated activities of antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD), increased flavonoid accumulation, and reduced reactive oxygen species (ROS) accumulation. Furthermore, we identified the transcription factor AcMYB176 as a direct activator of AcCHS5 through binding to its promoter. Our findings demonstrate that the AcMYB176-AcCHS5 regulatory module enhances salt tolerance by orchestrating flavonoid biosynthesis and ROS scavenging. This study provides functional evidence of CHS-mediated salt adaptation in A. catechu and highlights its potential for improving stress resilience in tropical crops. Full article