Search Results (1,095)

Background/Objectives: Neurodegenerative diseases (NDs) such as Alzheimer’s (AD), Parkinson’s (PD), Huntington’s (HD), and Amyotrophic Lateral Sclerosis (ALS) are clinically distinct but share overlapping molecular mechanisms. Methods: To identify conserved systemic signatures, we analyzed blood RNA-Seq datasets using Weighted Gene Co-Expression Network Analysis (WGCNA), differential expression, pathway enrichment, and miRNA–mRNA network mapping. Results: Two modules, the red and turquoise, showed strong preservation across diseases. The red module was enriched for cytoskeletal and metabolic regulation, while the turquoise module involved immune, stress-response, and proteostatic pathways. Discussion: Key hub genes, such as HMGCR, ACTR2, MYD88, PTEN, EP300, and regulatory miRNAs like miR-29, miR-132, and miR-146a, formed interconnected networks reflecting shared molecular vulnerabilities. The absence of classical heat shock proteins in preserved blood modules highlights tissue-specific expression differences between blood and neural systems. Several hub genes overlap with known pharmacological targets, suggesting potential in translational relevance. Conclusions: Together, these findings reveal conserved blood-based transcriptional modules that suggest parallel central neurodegenerative processes and may support future biomarker development and possible therapeutic exploration. Full article

Photodynamic therapy (PDT) has evolved considerably over the past decades, progressing from first-generation porphyrins to second- and third-generation photosensitizers, including nanocarrier-based systems with improved selectivity and bioavailability. In parallel, matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) has become a gold standard for the characterisation of complex biomolecules, enabling precise determination of molecular mass, purity and stability. This narrative review explores the intersection of these two fields, focusing on how MALDI-TOF MS supports the development, characterisation and clinical application of photosensitizers used in PDT. Literature searches were performed across PubMed, Web of Science, Scopus and Base-search, followed by targeted retrieval of studies on MALDI and PDT applications. Findings indicate that MALDI-TOF MS plays a crucial role at multiple stages: confirming the synthesis and chemical integrity of novel photosensitizers, monitoring their metabolic stability in biological systems and characterising photodegradation products after PDT. Moreover, MALDI imaging mass spectrometry (MALDI-IMS) enables spatial mapping of photosensitizer distribution in tissues, while rapid pathogen identification by MALDI-TOF supports antimicrobial PDT applications. Collectively, the evidence highlights that MALDI-MS is not only a tool for molecular characterisation but also a versatile analytical platform with a direct translational impact on PDT. Its integration with other omics and multimodal imaging approaches is expected to enhance the personalization and clinical effectiveness of photodynamic therapy. Full article

Vitamin B6 is an essential coenzyme involved in various metabolic processes critical for plant growth and development. However, its biosynthesis and regulatory mechanisms remain poorly understood in the ancient gymnosperm Ginkgo biloba. In this study, we identified two members of the PDX2 gene family (Gb_34755 and Gb_34990) through genome-wide analysis and characterized their molecular and functional properties. Bioinformatic analysis revealed distinct physicochemical traits and subcellular localizations, with Gb_34755 predicted in the cytoplasm and Gb_34990 in both chloroplasts and cytoplasm. Both proteins contain the glutaminase-related PLN02832 domain, indicating involvement in VB6 biosynthesis. Chromosomal mapping placed the genes in transcriptionally active regions on chromosomes 6 and 9. Phylogenetic analysis showed close evolutionary relationships between Ginkgo PDX2 genes and those in ferns and gymnosperms, distinct from angiosperms. Promoter analysis revealed differential enrichment of cis-elements: Gb_34990 harbored low-temperature and salicylic acid-responsive elements, while Gb_34755 showed motifs related to development. Gene expression profiling indicated significant upregulation (p < 0.05) of both genes during the late developmental stages of Ginkgo kernels, coinciding with peak VB6 content. Functional validation via transient overexpression in Nicotiana benthamiana confirmed a positive regulatory role, with VB6 levels increasing from 3.38 μg/g to 12.17 μg/g (p < 0.05). This study provides the first comprehensive functional analysis of the PDX2 gene family in Ginkgo and confirms their critical role in VB6 biosynthesis. These findings enhance our understanding of vitamin metabolism in gymnosperms and present promising targets for metabolic engineering in plants. Full article

Accurate quantification of campus vegetation carbon stocks is essential for advancing carbon neutrality goals and refining urban carbon management strategies. This study pioneers the integration of drone and backpack LiDAR data to overcome limitations in conventional carbon estimation approaches. The Comparative Shortest-Path (CSP) algorithm was originally developed to segment tree crowns from point cloud data, with its design informed by metabolic ecology theory—specifically, that vascular plants tend to minimize the transport distance to their roots. In this study, we deployed the Comparative Shortest-Path (CSP) algorithm for individual tree recognition across 897 campus trees, achieving 88.52% recall, 72.45% precision, and 79.68% F-score—with 100% accuracy for eight dominant species. Diameter at breast height (DBH) was extracted via least-squares circle fitting, attaining >95% accuracy for key species such as Magnolia grandiflora and Triadica sebifera. Carbon storage was calculated through species-specific allometric models integrated with field inventory data, revealing a total stock of 163,601 kg (mean 182.4 kg/tree). Four dominant species—Cinnamomum camphora, Liriodendron chinense, Salix babylonica, and Metasequoia glyptostroboides—collectively contributed 84.3% of total storage. As the first integrated application of multi-platform LiDAR for campus-scale carbon mapping, this work establishes a replicable framework for precision urban carbon sink assessment, supporting data-driven campus greening strategies and climate action planning. Full article

Background: Very preterm infants (VPIs) are born with an undeveloped immune system and are more susceptible to infection. Acquired immune responses must develop in a complex nutritional and metabolic environment as these babies transition from parenteral to enteral nutrition. We explored the feasibility of a multi-omics approach to investigate the changes in metabolic and molecular profiles between day 3 and day 10 of life. Methods: Blood and plasma samples were collected at day 3 and day 10 of life from eight infants born <29 weeks’ gestation and used to perform microarray transcriptomics and ¹H NMR metabolomics. All data were analysed using univariate statistics and mapped to biological pathways and molecular functions using an assortment of databases. Results: We found 1185 genes differentially expressed. The expression patterns found mapped to different immune function, maturation, and development pathways as well as providing mechanistic insights into metabolic changes, notably the downregulation of the metallothionein pathways. We found five metabolites that presented significant differential abundance. These linked to sugar and fat metabolic pathways, known to be altered in the preterm infants. Conclusions: We show that a multi-omics approach is feasible in VPIs and can identify simultaneous changes in the complex metabolic processes and immune adaptation that occur in the first ten days of life. Full article

Background: Colorectal cancer (CRC) is significantly associated with multiple metabolic diseases, with plasma metabolites potentially mediating this relationship. This large-scale metabolomics study aims to (1) quantify the genetic correlations and causal effects between 10 metabolic disease-related phenotypes and CRC risk; (2) identify the plasma metabolites mediating these effects; and (3) explore downstream regulatory genes and druggable targets. Methods: Using linkage disequilibrium score regression and two-sample Mendelian randomization, we assessed the causal relationships between each metabolic trait and CRC. A total of 1091 plasma metabolites and 309 metabolite ratios were identified and analyzed for mediating effects by a two-step MR approach. Colocalization analyses evaluated shared genetic loci. The findings were validated in the UK Biobank for metabolite-trait associations. The expression of candidate genes was explored using data from TCGA, GTEx, and GEO. A FADS1-centered protein–protein interaction (PPI) network was constructed via STRING. Results: BMI, waist circumference, basal metabolic rate, insulin resistance and metabolic syndrome exhibited both genetic correlation and causal effects on CRC. Five plasma metabolites—mannonate, the glucose/mannose ratio, plasma free asparagine, 1-linolenoyl-2-linolenoyl-GPC (18:2/18:3), and the mannose/trans-4-hydroxyproline ratio—were identified as shared central mediators. A colocalization analysis showed rs174546 linked CRC and 1-linolenoyl-2-linoleoyl-GPC. Validation in the UK Biobank confirmed the associations between phosphatidylcholine (the lipid class of this metabolite), adiposity measures, and CRC risk. An integrative analysis of TCGA, GTEx, and GEO revealed consistent upregulation of FADS1/2/3 and FEN1 in CRC, with high FADS1 expression predicting a poorer prognosis and showing the distinct cell-type expression in adipose and colon tissue. The PPI network mapping uncovered nine FADS1 interacting proteins targeted by supplements such as α-linolenic acid and eicosapentaenoic acid. Conclusions: This study systematically reveals, for the first time, the shared intermediary plasma metabolites and their regulatory genes in the causal pathway from metabolic diseases to CRC. These findings provide candidate targets for subsequent functional validation and biomarker development. Full article

Yield components are the most important breeding objectives, directly determining maize high-yield breeding. It is well known that these traits are controlled by a large number of quantitative trait loci (QTL). Therefore, deeply understanding the genetic basis of yield components and identifying key regulatory candidate genes can lay the foundation for maize marker-assisted selection (MAS) breeding. In this study, our aim was to identify the key genomic regions that regulate maize yield component formation through bioinformatic methods. Herein, 554 original QTLs related to 11 yield components, including ear length (EL), hundred-kernel weight (HKW), ear weight (EW), cob weight (CW), ear diameter (ED), cob diameter (CD), kernel row number (KRN), kernel number per row (KNR), kernel length (KL), grain weight per plant (GW), and kernel width (KW) in maize, were collected from the MaizeGDB, national center for biotechnology information (NCBI), and China national knowledge infrastructure (CNKI) databases. The consensus map was then constructed with a total length of 7154.30 cM. Approximately 80.32% of original QTLs were successfully projected on the consensus map, and they were unevenly distributed on the 10 chromosomes (Chr.). Moreover, 44 meta-QTLs (MQTLs) were identified by the meta-analysis. Among them, 39 MQTLs controlled two or more yield components, except for the MQTL4 in Chr. 1, which was associated with HKW; MQTL11 in Chr. 2, which was responsible for EL; MQTL19 in Chr. 3, which was related to KRN; MQTL26 in Chr. 5, which was involved in HKW; and MQTL36 in Chr. 7, which regulated EL. These findings were consistent with the Pearson correlation results, indicating that these traits exhibited co-linked heredity phenomena. Meanwhile, 159 candidate genes were found in all of the above MQTLs intervals, of which, 29 genes encoded E3 ubiquitin protein ligase, which was related with kernel size and weight. Other genes were involved in multiple metabolic processes, including plant hormones signaling transduction, plant growth and development, sucrose–starch synthesis and metabolism, and reproductive growth. Overall, the results will provide reliable genetic resources for high-yield molecular breeding in maize. Full article

The lung is increasingly recognized as an organ with dual endocrine and respiratory roles, participating in a complex bidirectional crosstalk with systemic hormones and local/paracrine activity. Endocrine and paracrine pathways regulate lung development, ventilation, immunity, and repair, while pulmonary cells express hormone receptors and secrete mediators with both local and systemic effects, defining the concept of the “endocrine lung”. This narrative review summarizes current evidence on the endocrine–pulmonary axis. Thyroid hormones, glucocorticoids, sex steroids, and metabolic hormones (e.g., insulin, leptin, adiponectin) critically influence alveologenesis, surfactant production, ventilatory drive, airway mechanics, and immune responses. Conversely, the lung produces mediators such as serotonin, calcitonin gene-related peptide, endothelin-1, leptin, and keratinocyte growth factor, which regulate vascular tone, alveolar homeostasis, and immune modulation. We also describe the respiratory manifestations of major endocrine diseases, including obstructive sleep apnea and lung volume alterations in acromegaly, immunosuppression and myopathy in Cushing’s syndrome, hypoventilation in hypothyroidism, restrictive “diabetic lung”, and obesity-related phenotypes. In parallel, chronic pulmonary diseases such as chronic obstructive pulmonary disease, interstitial lung disease, and sleep apnea profoundly affect endocrine axes, promoting insulin resistance, hypogonadism, GH/IGF-1 suppression, and bone metabolism alterations. Pulmonary neuroendocrine tumors further highlight the interface, frequently presenting with paraneoplastic endocrine syndromes. Finally, therapeutic interactions are discussed, including the risks of hypothalamic–pituitary–adrenal axis suppression with inhaled corticosteroids, immunotherapy-induced endocrinopathies, and inhaled insulin. Future perspectives emphasize mapping pulmonary hormone networks, endocrine phenotyping of chronic respiratory diseases, and developing hormone-based interventions. Full article

Background: Gemcitabine (GEM) remains a cornerstone in the treatment of pancreatic cancer. Upon exposure to GEM, pancreatic cancer cells (PCCs) tend to adapt quickly to outcompete drug-induced cytotoxicity, thereby contributing to treatment failure. Thus, understanding GEM-induced molecular changes in PCCs is important. Methods: Three primary PCC lines (PCC-1, PCC-2, PCC-7) and Mia PaCa-2 cultured for 40 passages (p) in the absence (control) or presence of GEM (GemR) were assessed for phenotypic changes. Proteome profiles for all PCCs at p10, p20, p25, p30, p35, and p40 were obtained using mass spectrometry (MS). Protein expression was determined using immunoblotting. Differentially abundant proteins (DAPs) were evaluated for enrichment of functional and biological attributes and protein–protein interactions. Results: GEM sensitivity and growth were both reduced in GemR versus paired controls for all four PCC lines. MS mapped > 7000 proteins in each PCC line, and the abundance of 70–83% of these was found to be significantly altered when comparing all sample groups. Proteomic changes in GemR versus paired controls differed remarkably among the PCCs and were affected by passaging and treatment duration. DAPs at p40 were mostly related to metabolic pathways, including nucleotide metabolism and diverse cell growth processes. Several closely related DAPs and multiple hub proteins in each PCC line were identified. Conclusions: Overall, this study revealed cell-line-specific, heterogeneous changes in proteome profiles of PCCs following their long-term exposure to GEM, and these were likely affected by treatment duration, dosage, and passaging. Full article

Background: Primary hepatocellular carcinoma (HCC) and liver metastases differ in origin, progression, and therapeutic response, yet a direct high-resolution spatial comparison of their tumor microenvironments (TMEs) within the liver has not previously been performed. Methods: We applied high-definition spatial transcriptomics to fresh-frozen specimens of one HCC and one liver metastasis (>16,000 genes per sample, >97% mapping rates) as a proof-of-principle two-specimen study, cross-validated in human proteomics and patients’ survival datasets. Transcriptional clustering revealed spatially distinct compartments, rare cell states, and pathway alterations, which were further compared against an independent systemic dataset. Results: HCC displayed an ordered lineage architecture, with transformed hepatocyte-like tumor cells broadly dispersed across the tissue and more differentiated hepatocyte-derived cells restricted to localized zones. By contrast, liver metastases showed two sharply compartmentalized domains: an invasion zone, where proliferative stem-like tumor cells occupied TAM-rich boundaries adjacent to hypoxia-adapted tumor-core cells, and a plasticity zone, which formed a heterogeneous niche of cancer–testis antigen–positive germline-like cells. Across both tumor types, we detected a conserved metabolic program of “porphyrin overdrive,” defined by reduced cytochrome P450 expression, enhanced oxidative phosphorylation gene expression, and upregulation of FLVCR1 and ALOX5, reflecting coordinated rewiring of heme and lipid metabolism. Conclusions: In this pilot study, HCC and liver metastases demonstrated fundamentally different spatial architectures, with metastases uniquely harboring a germline/neural-like plasticity hub. Despite these organizational contrasts, both tumor types converged on a shared program of metabolic rewiring, highlighting potential therapeutic targets that link local tumor niches to systemic host–tumor interactions. Full article

Global warming has become a significant public health concern, with intensive livestock farming as a major contributor. To mitigate greenhouse gas emissions, strategies such as manipulating the ruminal environment with dietary additives are essential. This study evaluated Moringa oleifera, a globally widespread tree with antioxidant, multivitamin, protein-rich, and anti-inflammatory properties, as a feed additive. Rumen fluid was collected from three Pelibuey sheep, homogenized, and subjected to an in vitro fermentation study for 48 h with three alfalfa/moringa ratio treatments: T0 Control (100:0), T1 Low (85:15), and T2 High (70:30). Total RNA was extracted, followed by high-definition sequencing of the metatranscriptome. The sequencing yielded approximately 456 million sequences. A total of 117 phyla were identified and approximately 1300 genera were mapped. Predominant phylum differed by treatment: T0, Firmicutes; T1, Proteobacteria; and T2 with Synergistetes, at least one sample per treatment. Archaea were nearly absent in T1, which explains a statistically significant decrease in methane production. In the Gene Set Enrichment Analysis (GSEA), it was observed that one of the metabolic pathways with a statistically significant difference (p-value < 0.05) was that of methane, specifically in the low moringa treatment (T1) compared to the control (T0). From the functional analysis, differentially expressed enzymes were identified, some of which are involved in the methane metabolic pathway, such as formate dehydrogenase (EC 1.17.1.9) and glycine hydroxymethyltransferase (EC 2.1.2.1), which are intermediates in methane formation. These results suggest that 15% Moringa oleifera supplementation alters ruminal microbiota, reduces archaeal activity, and suppresses methane-related pathways. These findings provide molecular evidence supporting the potential of M. oleifera as a methane mitigation strategy in ruminant nutrition. Full article

Background: Differentiated thyroid cancer (DTC) is commonly treated with radioactive iodine (RAI), but resistance to RAI remains a significant clinical challenge. The molecular mechanisms driving dedifferentiation and RAI refractoriness, particularly in BRAF^V600E-mutated tumors, are not fully understood. Methods: RNA sequencing was conducted on BRAF^V600E-mutated DTC and RAIR-DTC tissue samples to identify differentially expressed genes. Gadd45B was identified as significantly downregulated in RAIR-DTC. Functional studies including overexpression and knockdown experiments were performed in thyroid cancer cell lines and xenograft models. Downstream targets, including MAP3K4 and MYCBP, were evaluated through co-immunoprecipitation, luciferase assays, and Western blot. The therapeutic efficacy of recombinant Gadd45B protein in combination with BRAF^V600E and TERT inhibitors was assessed in patient-derived xenograft (PDX) models. Results: Gadd45B overexpression suppressed MAPK pathway activity by interacting with MAP3K4 and downregulated c-MYC stability through competition with MYCBP. These interactions enhanced the expression of iodine-metabolism genes (NIS, TPO, Tg), increased RAI uptake, and reversed tumor dedifferentiation. In vivo, Gadd45B restoration reduced tumor burden and improved RAI uptake. Combined treatment with Gadd45B protein, PLX4720, and BIBR1532 produced synergistic therapeutic effects in PDX models. Conclusions: Gadd45B plays a pivotal role in regulating the differentiation status and RAI sensitivity of BRAF^V600E-mutated thyroid cancer. These findings identify Gadd45B as a promising therapeutic target for restoring RAI responsiveness in RAIR-DTC patients. Full article

Background/Objectives: The basic helix–loop–helix (bHLH) transcription factor family regulates plant development, metabolism, and stress responses. Yet, its genome-wide composition remains unexplored in Lilium bakerianum var. rubrum (LBVR), an ornamental lily valued for its floral traits. This study aimed to identify, classify, and profile the bHLH family in LBVR using full-length transcriptomic resources. Methods: PacBio HiFi full-length transcriptome sequencing was combined with Illumina RNA-seq for accurate structural annotation and expression quantification. Candidate bHLHs were identified by iTAK and HMMER-Pfam, and their physicochemical properties, secondary structures, motifs, and phylogenetic positions were examined. Expression patterns were analyzed across four floral stages (bud, initial bloom, full bloom, and late bloom). Results: A total of 113 high-confidence bHLH genes were identified, with ~90% successfully annotated. The proteins displayed variation in molecular weight, isoelectric point, structural features, and motif composition. Phylogenetic analysis placed them into 13 clades consistent with Arabidopsis subfamilies, revealing lineage-specific expansions and contractions. Expression profiling showed that 95 genes were active in at least one stage, with two transcriptional waves: a strong bud-to-initial-bloom activation and a secondary wave spanning anthesis. Seventeen genes were expressed exclusively at the bud stage, suggesting roles in early floral-organ initiation and pigmentation. Conclusions: This work provides the first genome-wide characterization of bHLHs in LBVR. The integrated sequencing approach generated a robust catalogue and developmental expression map, offering candidates for functional studies and resources for breeding in lilies. Full article

Transketolase-like protein 1 (TKTL-1) has been implicated in altered cancer metabolism, yet its structure and molecular function remain poorly understood. In this study, we established a homology model of TKTL-1 using multiple templates and validated it through sequence alignment and structural comparison with the canonical transketolase (TKT). Binding-site identification was performed using CASTp, receptor cavity mapping, and blind docking, all of which consistently pointed to a conserved region involving interactive residues shared between TKT and TKTL-1. Comparative docking revealed the reduced affinity of TKTL-1 for TDP, supporting functional divergence between TKTL-1 and TKT. We further analyzed conserved residues and receptor surfaces, which enabled us to propose predictive scaffolds as potential modulators of TKTL-1. While these scaffolds remain theoretical, they provide a computational framework to guide future pharmacophore modeling, molecular dynamics simulations, and experimental validation. Together, our study highlights the structural features of TKTL-1, establishes its key differences from TKT, and lays the groundwork for future drug discovery efforts targeting cancer metabolism. Full article

Lesion mimic mutants (LMMs) represent valuable biological tools for investigating plant defense mechanisms and cell death. Although multiple genes triggering lesion mimic formation have been identified, the connection between the lesion mimic phenotype and primary nutrient biosynthesis remains poorly understood. In our study, we characterized a novel rice LMM, lmm9, which exhibited persistent reddish-brown necrotic lesions from seedling stage to maturity, coupled with compromised agronomic traits and increased mortality rates. Map-based cloning and whole-genome sequencing identified a causal insertion in the promoter of Os03g03450/OsPAT1, the sole homolog of Arabidopsis PAT1 in rice, resulting in reduced gene expression. Genetic complementation and RNAi assays confirmed that downregulation of OsPAT1 led to lesion mimic formation in lmm9. OsPAT1 could translate into two variants—the predominant OsPAT1.1 and the C-terminal variant OsPAT1.2. Structural modeling demonstrated high conservation between OsPAT1 and yeast TRP4, and OsPAT1.1 combining the plastid signal sequence of Arabidopsis PAT1 successfully complemented the trp4 mutant in yeast. Notably, OsPAT1.1 and OsPAT1.2 showed different localization patterns, with OsPAT1.1 targeted to mitochondria and OsPAT1.2 localized to chloroplasts. Transcription analysis showed significant upregulation of tryptophan biosynthesis pathway genes in lmm9, consequently increasing the relative abundance of tryptophan and associated metabolites. Our findings provided further evidence that mutations in tryptophan biosynthetic genes can induce lesion mimic phenotypes in rice and would enhance the understanding of metabolic homeostasis in plant stress responses and cell death regulation. Full article