Search Results (992)

Passion fruit (Passiflora edulis) quality is defined by integrated sensory and nutritional traits, including sugar–acid balance, volatile organic compounds (VOCs), pigment-related attributes, and bioactive compounds such as ascorbic acid and phenolics. These traits emerge from coordinated regulation of carbon allocation, mineral nutrition, ripening metabolism, and stress- and defense-related signaling pathways, which are strongly modulated by environmental conditions. Sustainable biological inputs are increasingly explored as tools to influence these regulatory networks; however, evidence linking such interventions to reproducible fruit quality outcomes in Passiflora remains fragmented. This review first synthesizes current knowledge on the physiological, biochemical, and molecular mechanisms underlying passion fruit quality formation and maintenance, and then discusses how biofertilizers; microbial inoculants (including plant growth-promoting rhizobacteria—PGPR and arbuscular mycorrhizal fungi—AMF); fungal-derived elicitors such as chitosan and chitooligosaccharides; and complementary postharvest biological strategies may modulate these processes. Emphasis is placed on traits beyond yield, including sugar–acid balance, aroma and VOC profiles, color, nutritional quality, texture, and shelf life. By integrating genomics, transcriptomics, metabolomics, proteomics, and microbiome-based evidence, we examine how environmental modulation and key signaling pathways intersect with metabolic networks underlying fruit quality. Available studies indicate that responses to biological inputs are context-dependent and often non-linear. Key knowledge gaps and priorities for mechanism-informed sustainable management of passion fruit quality are identified. Full article

Background/Objectives: DNA methylation is a key epigenetic modification involved in regulating many cellular processes, including gene expression and the maintenance of genome stability. Ultraviolet (UV) radiation induces DNA damage in the form of pyrimidine-pyrimidone (6-4) photoproducts [(6-4)PPs] and cyclobutane pyrimidine dimers (CPDs), which can lead to mutations if not efficiently repaired. While cytosine methylation has been implicated in influencing UV-induced DNA damage formation, the effect of DNA methylation modulators such as S-adenosyl-L-methionine (SAM) and RG108 on UV damage formation and repair remains unclear. Methods: Here, using immunoslot blot assays, we investigated the effects of SAM and RG108 on UV-induced DNA damage formation and repair in human lymphoblastoid cells. Results: We found that SAM, but not RG108, rapidly suppresses the formation of both (6-4)PP and CPD, with detectable effects within minutes of exposure. Although SAM pretreatment was associated with modestly accelerated early (6-4)PP repair, this effect was accompanied by substantially lower initial damage levels. When cells were treated with SAM or RG108 immediately after UV irradiation to ensure equivalent initial damage burden, no significant differences in repair were observed for either lesion type, demonstrating that the accelerated early (6-4)PP repair reflects reduced lesion burden rather than increased intrinsic nucleotide excision repair (NER). Global 5-methylcytosine (5mC) levels remained stable following SAM or RG108 treatment and during UV damage repair, suggesting that these effects occur independently of global alterations in DNA methylation. Conclusions: Together, our findings reveal that SAM modulates UV damage susceptibility at the level of lesion formation without altering repair, highlighting a previously unrecognized role for DNA methylation modulators in regulating genome stability. Full article

Background: Antimicrobial resistance is a One Health problem driven by the intricate interactions across human, animal, and environmental interfaces that enable microbial exchange and movement of mobile genetic elements encoding resistance and virulence. This study investigated the genomic epidemiology of ESBL and non-ESBL Escherichia coli across One Health interfaces in Oman. Methods: This prospective cross-sectional study analyzed 295 non-duplicate Escherichia coli isolates derived from 104 clinical, 173 animal [diseased (123) and healthy (50)], 14 sewage and four water sources. Antimicrobial susceptibility testing was performed phenotypically, and a representative subset of 50 ESBL and non-ESBL Escherichia coli from the three interfaces underwent whole genome sequencing to determine MLST, phylogroups, resistance genes, virulence determinants and plasmid replicons. Results: ESBL prevalence was highest in human isolates (73%), followed by sewage (28.6%) and animals (16.3% diseased; 8% healthy). blaCTX-M-15 predominated in humans, whereas blaCTX-M-55 dominated in animals and sewage, suggesting ecological partitioning with partial overlap. Quinolone resistance was lowest in the animal interface. Sewage isolates harbored the most complex resistome, including rmtB and plasmid-mediated quinolone resistance genes. MLST analysis revealed high diversity in human isolates, including globally recognized ExPEC lineages (ST10, ST38, ST73, ST127, ST131), while ST224 dominated in animals with evidence of possible spillover to humans. ST167 was confined to sewage, consistent with environmental maintenance of high-risk clones. Phylogroup structuring showed predominance of A, B2 and D among human isolates and A, B1, and E among animal and sewage isolates. Virulence profiling demonstrated broader virulome diversity in humans, but shared core determinants (fimH, sitA, traT) across all domains. IncFIB(AP001918) was the dominant plasmid replicon, particularly among ESBL isolates, underscoring its role in horizontal gene dissemination. Alarmingly, mutation in pmrB (V161G) was identified in a healthy animal isolate, pointing to a need for greater colistin restriction in animal husbandry. Conclusions: This study highlights plasmid-mediated resistance and shared virulence determinants linking reservoirs; although AMR profile was quite distinct across the three interfaces, human isolates demonstrated greater resistance than animal isolates, suggesting healthcare-driven AMR in Oman. Continued integrated genomic surveillance is essential to monitor gene flow and inform coordinated antimicrobial stewardship strategies. Full article

Telomerase reverse transcriptase subunit (TERT) is a key factor involved in telomere maintenance and genome stability, and the decline in its expression is closely related to cellular senescence. In this study, we established TERT monoallelic knockout (TERT+/−) and TERT overexpression (TERT-Over) cell lines in porcine iliac artery endothelial cells (PIEC) using CRISPR/Cas9 and PiggyBac systems to compare the effects of TERT monoallelic knockout versus overexpression on cellular biology. TERT expression and telomere length were assessed via qPCR and Western blot analysis. Cellular proliferation and senescence were evaluated using CCK-8 assays, cell cycle analysis, and SA-β-gal staining. Furthermore, the expression of key genes involved in cell proliferation, metabolism, and related signaling pathways was quantified using q-PCR. The results showed that the TERT mRNA level and telomere length decreased in TERT+/− cells. Meanwhile, we also observed that TERT+/− cells exhibited G1 phase arrest in the cell cycle, with suppressed proliferation and increased SA-β-gal-positive cells. This was accompanied by downregulation of cell cycle and proliferation-related genes, including c-Myc, the E2F family, and Ki-67, as well as downregulation of cell metabolism-related genes, including HIF1α, HK2, GLUT1, the SMAD family, FOXO1, and ATF4. In addition, cytochrome C was downregulated, suggesting activation of mitochondrial apoptotic signaling. Together, these findings indicate impaired proliferative and metabolic activity and are consistent with cellular senescence associated with telomere shortening. In TERT-overexpressing cells, the TERT gene expression and telomere length increase, cell proliferation accelerates, and the survival rate significantly increases under H₂O₂ treatment. This indicated that the overexpression of TERT can enhance resistance to oxidative stress, thus showing a kind of anti-aging phenotype. In conclusion, TERT monoallelic knockout induces cellular senescence-associated phenotypes in porcine endothelial cells, whereas TERT overexpression enhances proliferation and resistance to oxidative stress under the experimental conditions used in this study. The two porcine cell models established here may provide useful experimental materials for studying aging-related mechanisms and evaluating anti-aging interventions in large animals. Further studies are needed to directly determine their effects on cellular replicative lifespan. Full article

Fine-grained energy management in smart-campus buildings requires accurate load forecasting together with reliable and interpretable anomaly diagnosis. This study presents an integrated forecasting–diagnosis framework for building energy systems. Hourly energy demand is modeled using a Transformer-based sequence-to-sequence architecture, in which a domain-aware attention mechanism is introduced to separately represent historical consumption dynamics, environmental influences, and temporal regularities commonly observed in building energy use. Anomaly diagnosis is conducted through a dual-scale strategy that supports both the timely detection of abrupt abnormal events and the identification of gradual performance degradation. Short-term anomalies are detected from forecasting residuals using adaptive thresholds, while long-term anomalies are identified by comparing current residual patterns with same-season historical baselines and validating multi-window trends over a 48 h horizon. The two detection streams are jointly used to distinguish point, pattern, and composite anomalies. To support practical operation and maintenance, SHAP-based explanations are provided to interpret both energy predictions and detected anomalies. Case studies on two educational buildings from the Building Data Genome Project 2 demonstrate that the proposed framework achieves the best overall forecasting performance against both conventional baselines and stronger recent Transformer-based models, with mean absolute percentage errors of approximately 3%. The results indicate that the proposed framework provides a practical solution for data-driven energy monitoring and decision support in smart buildings. Full article

Robust genetic tools are a prerequisite for causal, perturbation-based tests of redox physiology in acetogens. Here we establish practical genetic entry points for Sporomusa sphaeroides DSM 2875 under strictly anaerobic handling. We first attempted genome editing via double-crossover allelic exchange targeting pyrF using a non-replicative pUC19-based knockout construct and 5-fluoroorotic acid counterselection. Diagnostic PCR identified ΔpyrF candidates with the expected size shifts, demonstrating that homologous recombination is technically feasible in DSM 2875; however, the ΔpyrF genotype exhibited severe growth defects and could not be stably maintained over repeated passages, indicating a key limitation of a pyrF-based workflow under our current conditions. We then evaluated multiple E. coli–anaerobe shuttle plasmids for introduction and maintenance. Among the tested vectors, pJIR751 reproducibly yielded erythromycin-resistant transformants after prolonged incubation and supported serial passaging on selective media. Plasmid retention was confirmed by diagnostic PCR from liquid cultures in all tested isolates. Importantly, this maintainable plasmid platform enables genetically grounded perturbation-and-rescue experiments under electrode- or Fe⁰-assisted conditions, allowing mechanistic hypotheses in bioelectrochemical acetogenesis to be tested causally rather than inferred from phenotypes alone. Together, these results define current practical boundaries for S. sphaeroides genetics and establish pJIR751 as a practical foundation for downstream genetic manipulation in bioelectrochemical studies. Full article

G-quadruplexes (G4s) are noncanonical nucleic acid structures involved in gene regulation and genome stability. Among them, the telomeric repeat-containing RNA (TERRA) forms biologically relevant RNA G4s (rG4s) that participate in telomere maintenance and genome stability. Although many ligands targeting DNA G4s have been reported, the recognition and modulation of RNA G4 topologies remain less explored. In this work, we investigated the interaction between TERRA and the spermine-functionalized Zn(II) porphyrin, ZnTCPPSpm4, using UV–vis absorption, fluorescence, resonance light scattering (RLS), and circular dichroism (CD) spectroscopy. In K⁺, where TERRA adopts a parallel G4 conformation, ZnTCPPSpm4 binds through a stepwise mechanism involving external end-stacking, forming discrete supramolecular complexes without altering the native topology. In contrast, under Na⁺ conditions, ZnTCPPSpm4 induces a gradual conformational rearrangement of TERRA from the antiparallel to a parallel-like G4 topology. A CD melting study showed that ZnTCPPSpm4 stabilizes the parallel RNA G4, while slightly destabilizing the antiparallel topology. Overall, our results demonstrate that ZnTCPPSpm4 is not a simple G4 binder, but a topology-selective ligand capable of remodeling TERRA G4 structures, highlighting the potential of metalloporphyrins as RNA G4-targeting scaffolds. Full article

Background: Konjac (Amorphophallus spp.) is an economically important crop valued for the glucomannan content in its corms. Currently, the konjac industry faces germplasm degeneration due to long-term asexual propagation. Developing tissue culture and genetic transformation techniques is essential for its genetic improvement. The WUSCHEL-related homeobox (WOX) transcription factors are critical regulators of somatic embryogenesis and stem cell maintenance in plants. Methods: In this study, we performed genome-wide identification and characterization of WOX genes in the A. konjac reference genome. Furthermore, comparative transcriptomic analyses and functional verification were conducted in A. bulbifer. Results: A total of 12 AkWOX genes were identified in A. konjac, and their structural features were documented. Comparative transcriptomic analysis of A. bulbifer revealed that AbWOX genes were differentially expressed between embryogenic calli (EC) and non-embryogenic calli (nEC). Notably, AbWOX2 was significantly upregulated in EC. Overexpression of AbWOX2 significantly promoted callus proliferation and shoot regeneration in A. bulbifer. Furthermore, AbWOX2-overexpressing lines exhibited a 5.3-fold increase in genetic transformation efficiency (from 5.12% to 27.31%) compared to the control. Conclusions: We characterized the diverse expression patterns of the WOX gene family in Amorphophallus. Crucially, we identified specific individual members—most notably the markedly upregulated AbWOX2—that function as pivotal drivers of somatic embryogenesis and serve as promising candidates for enhancing regeneration and genetic engineering efficiency in Amorphophallus species. Full article

NANOG overexpression has been reported to reverse aging-associated decline in mesenchymal stem/stromal cell (MSC) function, but the molecular machinery engaged by NANOG in MSCs remains incompletely defined. Here, we applied APEX proximity labeling coupled with quantitative mass spectrometry to define the NANOG proximity interactome (proxeome) in human MSCs. Of 1040 quantified proteins, 828 were significantly enriched in the APEX-NANOG (H₂O₂ labeling) samples, consistent with a broad NANOG-centered neighborhood rather than a single stoichiometric complex. Enriched proteins encompass RNA-processing pathways (including splicing/RNP factors and selected m6A-related proteins), transcriptional coactivation and elongation control (Mediator and 7SK/P-TEFb regulators), chromatin repression/poising modules (Polycomb and HDAC/NuRD/CoREST/SIN3), ATP-dependent chromatin remodeling (BAF/SWI-SNF), three-dimensional genome organization and replication-coupled chromatin maintenance (CTCF/cohesin, CHAF1A, RIF1, UHRF1), and regulators of MSC identity and signal integration (Hippo/mechanotransduction and TGFβ-linked transcriptional circuits). Together, these data provide a spatial proteomic map of NANOG-associated nuclear neighborhoods in MSCs and a foundation for mechanistic hypotheses for how NANOG may stabilize stem-like programs. Full article

Background: Hepatocellular carcinoma (HCC) remains a major cause of cancer mortality worldwide, yet reliable molecular biomarkers for early diagnosis and prognosis are limited. The cytochrome P450 (CYP) enzyme superfamily plays central roles in hepatic metabolism and tumor biology, but its global dysregulation in HCC has not been comprehensively defined. Methods: Here, we systematically analyzed 57 CYP genes across multi-cohort transcriptomic datasets (GepLiver, TCGA-LIHC, HCCDB2.0) to delineate their diagnostic, prognostic, and functional significance. Results: CYP2R1 emerged as a consistently upregulated and clinically relevant member, showing excellent diagnostic accuracy (AUC = 0.95, 95% CI: 0.94–0.98, p < 0.001) and strong overexpression validated across independent cohorts and spatial transcriptomics. Prognostic modeling identified CYP2C9 (favorable) and CYP26B1 (unfavorable) as independent survival markers. Functional enrichment analyses revealed that high CYP2R1 expression was associated with activation of DNA repair and replication pathways (NES = 1.31, adjusted p = 1.05 × 10⁻⁵) and with co-expression of core repair genes such as POLA2, LIG1, and PCNA. Moreover, CYP2R1 correlated with myeloid-derived suppressor cell infiltration, suggesting an immunosuppressive phenotype. Conclusions: These findings establish CYP2R1 as a novel metabolic and immunogenomic biomarker in HCC, linking hepatic metabolism, genomic maintenance, and tumor immune modulation. Full article

Among accumulating knowledge of invertebrate immune-like responses, antiviral mechanisms in mollusks remain poorly understood. Pinctada birnavirus (PiBV) infects the mantle epithelial cells of the pearl oyster (Pinctada fucata), causing mass mortality of juveniles during high-temperature periods. Here, we examined immune memory-like responses of pearl oysters to PiBV reinfection. At a high temperature (24–25 °C), experimental infection caused ~80% mortality, whereas mortality remained <30% and did not differ significantly from uninfected controls at a lower temperature (18–20 °C). Juveniles that survived infection at the low temperature and were subsequently reinfected at the higher temperature showed 10% mortality, which was significantly lower than the ~50% observed in naïve oysters infected under the same conditions. At 28 days post-infection at the lower temperature, oysters exhibited gene expression profiles distinct from those of naïve oysters. Ex vivo infection demonstrated significantly reduced PiBV replication in mantle explants from previously infected oysters compared with those from naïve individuals. These findings indicate that P. fucata acquires resistance to PiBV reinfection, and at least part of this resistance is mediated within the mantle, independently of other tissues. Culture supernatants of mantle explants from previously infected oysters were positive for viral genomic RNA even without viral inoculation, suggesting that persistent infection may contribute to the maintenance of immune-like responses. Full article

Ultraviolet (UV) radiation from the sun causes adverse skin changes such as premature aging. UV-induced mitochondrial DNA (mtDNA) alterations, including deletions, contribute to photoaging and cellular dysfunction. While the most frequent mtDNA rearrangement is the common deletion (CD), characterized by the loss of nearly one-third of the genome (4977 bp), detailed knowledge of mechanisms governing UV-mediated initiation of the CD and mitigation strategies are lacking. Here, we investigated how increasing UV exposure increases CD levels in human skin fibroblasts via cellular reactive oxygen species (ROS) formation and mtDNA oxidation and demonstrated that antioxidant preconditioning of cells prevents UVA-induced CD accumulation. Conversely, UVB exposure induced cyclobutane pyrimidine dimers (CPDs) without affecting ROS, suggesting an ROS-independent pathway. Using a 3D full-thickness human skin model, we confirmed UVA-dependent CD formation in both the epidermis and dermis. RNA-Seq analysis of UVA-exposed fibroblasts revealed upregulation of mitochondrial DNA replication genes and downregulation of mtDNA repair genes. These findings provide insight into how UVA and UVB differ in detrimental effects on mtDNA, with UVA impacting mtDNA maintenance and transcription via a ROS-dependent mechanism, and provide a physiologically relevant platform to evaluate potential interventions. Full article

HIV latency, driven by a complex interplay of host factors, remains a key barrier to viral clearance. Current latency-reversing agents (LRAs) demonstrate limited efficacy and specificity, and none have been approved for clinical use. Although natural products have shown promise as LRAs, the therapeutic potential of fungal metabolites remains underexplored. Candida albicans, a prevalent human commensal and opportunistic pathogen, produces diverse secondary metabolites that can influence host pathways, affecting latency dynamics. This study aimed to investigate the latency-modulating potential of secondary metabolites of C. albicans using an integrative network pharmacology and computational pipeline. C. albicans secondary metabolites were retrieved from the literature, screened for drug-likeness, and mapped to human targets and biological pathways annotated in HIV latency. Key metabolites, hub genes, and pathways were systematically characterized through network and computational analyses. Six drug-like candidates, identified from 185 absorption, distribution, metabolism, excretion, and toxicity (ADMET)-screened metabolites, collectively mapped to 369 human genes with a 6.5% overlap in HIV latency (176 shared and 20 hub genes). These overlapping genes were significantly enriched for signal transduction, membrane localization, and adaptive responses to chemical stimuli. Kyoto encyclopedia of genes and genomes (KEGG) enrichment revealed oncogenic diseases (non-small cell lung, pancreatic, and prostate cancers) and latency-associated cascades, including PD-L1/PD-1, HIF-1, Ras, PI3K-Akt, calcium, and cAMP signaling. Six hub targets (MAPK1, PIK3CA, MAPK3, EGFR, MTOR, and AKT1) were consistently annotated within the top 30 KEGG pathways and displayed strong binding affinities for MET 15 and MET 119. Molecular dynamics (MD) simulations confirmed favorable binding free energies (BFEs) and stable conformational dynamics for the top-ranked metabolite MET 15. C. albicans secondary metabolites preferentially target oncogenic signaling networks central to HIV latency maintenance, notably PI3K/AKT/MTOR and MAPK/ERK, which regulate cell survival, metabolic homeostasis, and viral transcriptional repression. MET 15 is a top-ranked candidate metabolite for HIV latency-reversing therapeutics and warrants experimental validation in established latency models. Full article

Bacterial resistance on farms can be driven by antimicrobial use. Less is known about inter-farm transfer of resistance genes and their persistence under low antimicrobial pressure. Over two years and nine visits, we examined the shedding of resistant indicator bacteria (Escherichia coli) on one lower- and one higher-antimicrobial-usage pig farm. There was a unidirectional transfer of some less healthy pigs from the former to the latter. Faecal pools (180) were cultured on Chromagar ECC, with and without added cefotaxime or ciprofloxacin. Presumptive E. coli were phenotyped, and many ciprofloxacin-resistant isolates were whole-genome sequenced. Comparing farms, there was more (p < 0.0001) phenotypic resistance to the antimicrobial panel from the higher-usage unit, and markedly more (about ten-fold) multi-resistance. Significantly elevated individual drug resistances on this unit correlated with recently used antimicrobials. Ciprofloxacin and/or cefotaxime-resistant isolates were often present, although in low proportions. Neither of these antimicrobial classes had been administered recently, except for one fluoroquinolone course late in the study. AMR genes were more diverse from the higher-usage farm, but some resistant and multi-resistant isolates were closely related between farms. Thus, we demonstrated the maintenance of resistance genes in strains present on farms, even where selective pressure was low. Full article

The unique ecological gradients of Xinjiang have fostered a rich reservoir of genetic resources in local sheep populations. However, the population genetic structure, adaptive mechanisms to extreme environments, and the genetic basis underlying key economic traits of these breeds remain poorly understood. To address this gap, we performed whole-genome resequencing of 140 individuals from seven indigenous sheep populations—Altay, Bayinbuluke, Kazakh, Kirgiz, Bashibai, Turpan Black, and Yemule White—identifying 18,700,507 high-quality SNPs. Genetic diversity analyses revealed that all populations exhibited comparable levels of genetic diversity, with modest variation across breeds, with Turpan Black sheep exhibiting the highest observed heterozygosity (Ho = 0.3110) and proportion of polymorphic sites, whereas Kirgiz sheep showed comparatively lower values. Population structure analyses consistently indicated that geographic isolation is the primary driver of genetic differentiation, with Kirgiz sheep from the Pamir Plateau in southern Xinjiang displaying the greatest genetic distance relative to northern Xinjiang populations. By integrating multiple selection signature detection methods—including F_ST, π ratio, and XP-CLR—we found that genes under selection in Kirgiz sheep were significantly enriched in biological pathways related to stem cell pluripotency regulation (e.g., BMPR1B), DNA repair (e.g., DDB2), and neural development, thereby elucidating their unique genetic adaptations to high-altitude environments. In contrast, Turpan Black sheep appear to cope with heat stress through mechanisms involving basal transcriptional regulation (e.g., GTF2I), maintenance of protein homeostasis (e.g., DNAJB14), and melanin biosynthesis (e.g., MC1R). Furthermore, comparative analysis of body size identified a suite of candidate genes associated with growth and development (e.g., CUX1, KIT), which are primarily involved in transcriptional regulation, protein kinase activity, and the ubiquitin-mediated proteolytic system, thereby revealing a multi-layered genetic regulatory network governing body conformation. Collectively, this study provides a comprehensive genomic framework for understanding the genetic structure, adaptive evolution, and molecular basis of economically important traits in indigenous sheep breeds from Xinjiang, offering valuable candidate targets for future functional validation and precision breeding programs. Full article