Search Results (21,655)

Background/Objectives: Fibroblast activation protein (FAP) has emerged as a promising target for oncologic molecular imaging due to its high expression in cancer-associated fibroblasts and low presence in healthy tissues. Among available FAP ligands, [⁶⁸Ga]Ga-FAPi-46 has shown rapid tumor accumulation, low background uptake, and broad tumor applicability. This study reports the successful translation of [⁶⁸Ga]Ga-FAPi-46 from preclinical development to routine clinical radiopharmacy practice, detailing automated synthesis, quality control performance, radiochemical stability, and the first clinical imaging results. Methods: Automated radiolabeling of FAPi-46 with gallium-68 was performed using a synthesis module. Quality control included radiochemical purity assessments by iTLC, SPE, and RP-HPLC (pH, appearance, endotoxin levels, and membrane integrity testing). Radiochemical stability was evaluated in saline (up to 6 h) and human serum (up to 90 min). In vitro characterization included the partition coefficient and serum protein binding determination. A clinical evaluation was conducted in a woman with newly diagnosed lung adenocarcinoma who underwent both [¹⁸F]FDG PET/CT and [⁶⁸Ga]Ga-FAPi-46 PET/CT. Results: Automated synthesis of [⁶⁸Ga]Ga-FAPi-46 achieved a high radiochemical yield (87.9 ± 1.3%) and radiochemical purity greater than 98%. All batches met release specifications for sterility, apyrogenicity, and physicochemical parameters. The radiotracer demonstrated high stability in saline and human serum, with radiochemical purity consistently above 95% at all evaluated time points. The compound showed a hydrophilic profile (LogP = −3.32 ± 0.14) and 40–60% serum protein binding. Clinically, [⁶⁸Ga]Ga-FAPi-46 PET/CT provided superior lesion delineation compared to [¹⁸F]FDG, revealing additional mediastinal, supraclavicular, and brain metastases. Conclusions: [⁶⁸Ga]Ga-FAPi-46 can be reliably synthesized using automated procedures under routine radiopharmacy conditions, meeting regulatory quality standards and demonstrating excellent stability. Its enhanced lesion detectability compared with [¹⁸F]FDG in the first patient case supports its potential value for oncological staging and clinical implementation. Full article

The desert ecosystem harbors a resilient microbial community that sustains plant life under extreme stress. Understanding the endophytic microbiota of desert flora provides key insights into how these microorganisms enable plant survival and maintain ecological balance in arid landscapes. To date, the endophytic bacterial communities of dominant desert plants in the Arabian Peninsula have not been comprehensively characterized. Here, we investigated the endophytic microbiota of five co-adapted desert species, namely, Schweinfurthia papilionacea, Sesuvium verrucosum, Ochtocloa compressa, Helianthemum nummularium, and Convolvulus arvensis. These plants coexist in hyper-arid habitats and exhibit exceptional tolerance to drought, salinity, and nutrient scarcity. We hypothesized that, despite their phylogenetic divergence, these plants host functionally convergent microbial communities shaped by desert selection pressures. Using 16S rRNA gene amplicon sequencing, we obtained 3.4 million high-quality reads from 25 samples. Clustering at 97% similarity revealed 35 phyla and 17 dominant genera, highlighting notable microbial richness and ecological complexity. Alpha-diversity indices showed comparable species richness across hosts, while beta-diversity indicated community differentiation driven by environmental filtering. The dominant phyla included Pseudomonadota, Actinomycetota, Cyanobacteriota, and Bacillota, reflecting microbial adaptation to extreme desert conditions. Functional pathway prediction revealed enrichment of genes associated with DNA repair and protein turnover, suggesting metabolic flexibility and enhanced survival under stress. Overall, this study provides a comparative metagenomic insight into the endophytic bacterial communities of five desert plant species, uncovering a consistent pattern of functional convergence across diverse hosts. The findings suggest the presence of shared functional traits among the endophytic microbiota examined here, offering preliminary evidence for microbial contributions to plant resilience in arid environments. Full article

Mild behavioral impairment (MBI) is a clinical syndrome characterized by the late-life onset and persistence of neuropsychiatric symptoms (NPSs), representing a change from longstanding behavior or personality and considered a potential prodrome of neurodegenerative disease. MBI is classified into five domains: decreased motivation, affective dysregulation, impulse dyscontrol, social inappropriateness, and psychotic symptoms. In this narrative review, we synthesize clinical, neuroanatomical, and molecular evidence linking MBI to the spectrum of tauopathies, including Alzheimer’s disease (AD), frontotemporal spectrum disorders (FTSDs), and primary four-repeat tauopathies such as progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Emerging evidence suggests that early behavioral symptoms associated with MBI may reflect the selective vulnerability of frontolimbic, salience, default mode, and frontostriatal networks to tau-mediated neurodegeneration. Mechanistically, converging findings support roles for tau-related synaptic dysfunction, including synaptotoxic soluble tau species, cytoskeletal and axonal transport disruption, monoaminergic neurotransmitter imbalance in brainstem systems, and neuroinflammatory and glial pathways. We also highlight genotype-related behavioral profiles in genetic frontotemporal lobar degeneration and discuss how scalable blood-based biomarkers, including neurofilament light chain, glial fibrillary acidic protein, and plasma phospho-tau species, may complement MBI-based phenotyping for differential diagnosis and prognostic stratification in clinical research. Full article

Alpha-mangostin (AM), a xanthone from Garcinia mangostana, has shown promising nephroprotective properties, but its mechanisms in acute kidney injury (AKI) remain incompletely defined. In this study, we applied an integrative network pharmacology pipeline combined with molecular docking to clarify AM’s multi-target mechanisms in AKI. We identified 128 predicted AM targets and intersected them with AKI-related genes, yielding 122 shared targets. Protein–protein interaction analysis identified ten hub genes—TNF, AKT1, IL6, SRC, CTNNB1, HSP90AA1, NFKB1, HIF1A, PPARG, and PTGS2—implicating inflammatory, hypoxia, and cell-survival pathways. KEGG enrichment highlighted HIF-1 signaling, PI3K–Akt signaling, chemokine signaling, AGE–RAGE signaling, and pathways related to cellular senescence and oxidative stress, while GO terms emphasized responses to chemical/oxygen-containing compounds, kinase activity, signal transduction, and apoptosis. Molecular docking against the ten hub proteins showed favorable binding energies across multiple targets. The strongest predicted affinities were observed for PTGS2 (−11.13 kcal/mol), TNF (−9.74 kcal/mol), and AKT1 (−9.48 kcal/mol). Docking positioned AM within the COX-2 catalytic pocket, engaging key catalytic and hydrophobic residues similar to known inhibitors. MD simulation interaction analysis confirmed that AM maintained stable contacts with key human PTGS2 residues, characterized by dominant hydrogen bonds and water-bridge interactions with SER353, TYR355, ARG513, and SER530, along with consistent hydrophobic contacts, and persistent interactions sustained throughout the 200 ns trajectory. Collectively, these results suggest that AM modulates interconnected inflammatory, hypoxic, and survival pathways relevant to AKI, acting as a multi-target ligand with notable interaction involving COX-2, TNF, and AKT1. Further experimental validation and formulation strategies to improve bioavailability are recommended for the advancement of AM toward therapeutic evaluation in AKI. Full article

Aim: Using real-world data from an obesity clinic, we aimed primarily to define the body composition phenotype associated with increasing obesity severity and to quantify follow-up retention and clinically meaningful weight loss. As a secondary exploratory objective, we also examined how diabetes mellitus (DM) relates to these patterns beyond BMI. Methods: Among 5350 screened adults in the Obesity Clinic database, 2879 eligible individuals were included in the baseline cross-sectional analyses, including a non-obese comparison subgroup with BMI < 30 kg/m². The longitudinal cohort comprised 730 patients with obesity who returned for regular follow-up and had repeat BIA measurements at least 6 months after baseline. Patients were classified according to BMI and glycemic status. Results: Increasing BMI was associated with higher glucose, HbA1c, uric acid, triglyceride, C-reactive protein, and leukocyte levels and with lower HDL cholesterol. Body composition deterioration was driven predominantly by disproportionate increases in visceral fat score, fat mass, and total fat-to-muscle ratio rather than by parallel gains in muscle compartments. As obesity severity increased, the proportion of patients with diabetes also increased. Only 29.3% of the baseline obesity cohort achieved regular 6-month follow-up, and 79.0% of those followed lost less than 5% of baseline body weight. In age- and sex-adjusted analyses, the most pronounced DM-related body composition differences were observed in the BMI 30–39.9 kg/m² group, particularly through higher waist-to-height ratio and total fat-to-muscle ratio. Conclusions: This study shows that increasing obesity severity is accompanied by a more adverse metabolic profile and a body composition pattern characterized by greater adiposity. Within this framework, diabetes-related body composition differences were not homogeneous across BMI categories and appeared to be most evident in the BMI 30–39.9 kg/m² group. The weaker association observed in the BMI ≥ 40 kg/m² group may be related to the reduced discriminative value of waist-based measures in severe obesity, where fat accumulation may extend across multiple compartments. Given the low continuity of follow-up and the limited rates of clinically meaningful weight loss, these findings support a more refined phenotyping approach in obesity management that incorporates body composition and fat distribution in addition to BMI. Full article

Background/Objectives: Osteonecrosis of the femoral head (ONFH) is a progressive condition characterized by bone necrosis, impaired vascularization, and immune dysregulation, often resulting in femoral head collapse. Effective strategies to halt disease progression are limited. Extracellular vesicles (EVs), including exosomes and microvesicles, mediate intercellular communication and influence osteogenesis, angiogenesis, and immune responses. This review summarizes current evidence on EVs in ONFH and their translational potential. Methods: A structured narrative review of PubMed, Scopus, Web of Science, and Cochrane Central databases was conducted, including in vitro, preclinical, and clinical studies on EVs in ONFH. Data on EV sources, molecular cargo, signaling pathways, functional effects, and translational implications were qualitatively synthesized. No pooled statistical analysis was performed because the extracted data were heterogeneous. Bioinformatic analyses such as Gene Ontology, KEGG enrichment, and protein–protein interaction networks were also summarized. Results: In vitro, EVs from bone marrow mesenchymal stem cells, endothelial cells, and M2 macrophages modulate osteogenic differentiation, angiogenesis, and inflammation. Preclinical studies demonstrate that EV administration reduces femoral head necrosis, improves trabecular structure, and enhances neovascularization. Clinical studies have identified EV-associated molecules (SAA1, C4A, RPS8) linked to disease stage and the risk of femoral head collapse. Bioinformatic analyses connect EV cargo to pathways regulating bone formation, vascularization, immunity, and metabolism. Conclusions: EVs appear to play key roles in ONFH pathogenesis and may represent promising candidates for diagnostic and therapeutic applications. However, current clinical evidence remains limited and requires validation in larger studies. Nonetheless, heterogeneity and limited clinical data require standardized, longitudinal studies to validate their translational relevance. Full article

Epstein–Barr virus (EBV) establishes lifelong infection in most humans, yet its biology in immunocompetent hosts is commonly framed as a binary alternation between latency and productive lytic replication. Accumulating molecular and single-cell evidence challenges this view, indicating that EBV frequently enters abortive forms of lytic reactivation that do not culminate in virion production. Here, we propose a conceptual framework in which EBV persistence is governed by feedback-regulated interactions and permissive conditions for reactivation rather than a strictly sequential life cycle. Immediate-early and early gene expression can be repeatedly induced by inflammatory signaling, cellular stress, and epigenetic changes. However, progression to viral DNA replication represents a highly functional barrier that likely requires the coordinated convergence of multiple viral and host conditions. Failure to reach this threshold arrests reactivation before late gene expression, generating a stable partial lytic state characterized by sustained immunomodulatory viral protein expression without the production of infectious particles. Immune surveillance reinforces this bottleneck by eliminating cells undergoing full lytic replication while sparing those stalled in early phases. We argue that EBV persistence reflects a dynamic equilibrium shaped by regulatory interactions between viral gene expression and host immunity, with implications for biomarker interpretation and therapeutic strategies in chronic inflammatory and autoimmune disease. Full article

DREB (Dehydration-Responsive Element-Binding Protein) transcription factors are a subfamily of the AP2/ERF transcription factor family and play a crucial role in the regulation of plant responses to abiotic stress. In this study, we successfully cloned the IbDREB1d gene from the leafy sweet potato cultivar Fucaishu18. The open reading frame (ORF) of the IbDREB1d gene comprises 792 base pairs and encodes a protein consisting of 263 amino acids. Protein sequence analysis indicates that IbDREB1d is characterized by acidic, hydrophilic, and unstable properties, with its closest phylogenetic relationships to Ipomoea trifida and Ipomoea triloba. Quantitative real-time PCR (RT-qPCR) analysis revealed that IbDREB1d is expressed in the roots, stems, and leaves of sweet potato, with increased expression under low temperature, hydrogen peroxide (H₂O₂), and drought conditions. Overexpression of IbDREB1d in sweet potato resulted in transgenic plants exhibiting dwarfism, shortened internode lengths, smaller leaf size, and microscopic evidence of impaired vascular tissue development. Hormonal analysis indicated significant reductions in the levels of indole-3-acetic acid, indole-3-butyric acid, salicylic acid, and zeatin in these transgenic plants. These decreases may explain the observed phenotypic changes, such as inhibited growth and reduced leaf size. This study provides novel theoretical insights into the role of IbDREB1d in stress-responsive expression and modulating plant growth in sweet potato. Full article

The intestinal mucosal barrier is a layered structure comprising fundamental components that play important roles in regulating paracellular permeability. Disruption of intestinal barrier homeostasis predisposes to infections, mucosal damage, and metabolic and allergic diseases. To provide protection against potential damage to the intestinal mucosa, agents such as prebiotics and probiotics are recommended due to their ability to secrete components and metabolites (e.g., bacteriocins, organic acids, enzymes) that can exert beneficial biological effects. The aim of this study is to comprehensively investigate the effects of a postbiotic derived from Pediococcus acidilactici on healthy rat intestinal tissue. A total of 78 Wistar Albino rats were used in this study. Following compositional analysis of the postbiotic, the animals were administered the postbiotic orally via gavage for different durations (7, 14, 21, 28 days) and at different doses (250 mg/Kg, 500 mg/Kg, 1000 mg/Kg). Characterization of the produced postbiotic revealed a diverse spectrum of biologically active compounds, including organic acids, phenolics, and volatile compounds. Histopathological examination of intestinal sections (duodenum, jejunum, ileum, cecum, colon, and rectum) showed no pathological lesions in any of the experimental groups. Conversely, immunohistochemical analysis revealed that the postbiotic increased the expression of CLDN3, OCLN, ZO1, AQP4, and AQP8, proteins involved in intestinal permeability and fluid transport, in a dose-dependent manner. These results highlight the potential of Pediococcus acidilactici as a supportive agent in a range of intestinal pathologies, including major intestinal diseases such as Crohn’s disease, ulcerative colitis, and inflammatory bowel disease (IBD). Full article

House dust mite allergens Der p 1, Der p 2, and Der p 23 are recognized as major clinically relevant allergens worldwide; however, it is difficult to obtain these proteins in purified form from a natural source, which limits their use in molecular targeted immunotherapy and in vivo diagnosis. In this study, we developed and validated robust methodologies for the large-scale purification and individual characterization of native nDer p 1, nDer p 2, and nDer p 23 allergens from the natural sensitization source, Dermatophagoides pteronyssinus. Each allergen was isolated through an independent downstream process based on successive chromatographic steps, achieving high purity and preserving the structural integrity. Molecular standardization was performed in vivo in 27 mite-allergic patients by skin prick testing (SPT), enabling the separate determination of histamine equivalent potency (HEP) values: 7.43 µg/mL for nDer p 1, 8.11 µg/mL for nDer p 2, and 1.55 µg/mL for nDer p 23. These data establish a direct relationship between the protein concentration and biological activity for each major allergen. In conclusion, the successful production and biological standardization of native nDer p 1, nDer p 2, and nDer p 23 proteins provide well-defined reagents for in vivo molecular diagnosis and enable more precise and reproducible standardization compared with complex allergen extracts. Full article

Background/Objectives: Curcumin derivatives have attracted interest due to their redox-modulating properties and potential applications in aquatic organisms, yet their molecular interactions and environmental safety remain insufficiently characterized. This study aimed to evaluate the redox-related molecular behavior and ecotoxicological profile of curcumin derivatives, with emphasis on their interaction with glutathione S-transferase from L. vannamei. Methods: Molecular docking and molecular dynamics simulations were performed to assess binding stability and interaction patterns between the derivatives and LvGSTmu. In parallel, computational predictions were used to estimate environmental persistence, bioaccumulation (BCF/BAF), and acute and chronic aquatic toxicity across multiple trophic levels. Results: Docking and dynamics analyses indicated stable ligand–protein interactions, particularly for CURNO, which showed favorable binding behavior without destabilizing the protein structure. Ecotoxicological predictions suggested low bioaccumulation potential and limited persistence for most derivatives, with CURH and CURNO showing higher sediment persistence. Toxicity responses varied by organism and exposure time but did not differ significantly among derivatives relative to curcumin. Conclusions: The derivatives retained redox-related molecular features while presenting an overall acceptable predicted environmental profile. CURNO emerged as a promising candidate, although its environmental behavior supports the need for further monitoring and experimental validation. Full article

Background/Objectives: Infection from Streptococcus pneumoniae can lead to serious complications, such as meningitis and pneumonia, in children under 2 years of age, older adults, and immunocompromised populations. Conjugate vaccines against the pathogen have been licensed for the prevention of invasive pneumococcal disease. Conjugate vaccine development is an involved process demanding extensive characterization of both the polysaccharide (PS) and protein (Pr) moieties in complex structures. One powerful tool in our analytical tool kit that can shed light on various analytical attributes of conjugate vaccines, such as molecular weight and composition and conjugation efficiency, is the size-exclusion chromatography-multi-angle light scattering detector (SEC-MALS) technique. Herein, we demonstrate the applicability of the SEC-MALS approach for pneumococcal conjugate vaccine product characterization. Methods: Capsular polysaccharides for serotypes (STs) 1, 3, 5, 10 A, 18 C, 24 F, and 33 F conjugated to rCRM197 carrier protein were chosen for this study. Results: The technique was very straightforward, with a high degree of accuracy (>90% based on standards) and repeatability (<2% RSD) for conjugate molar mass measurements. In addition, leveraging the capability of SEC-MALS for compositional analysis, we were able to get detailed information on the molecular assembly and conformation of the conjugates and further tweak the conjugation process to yield conjugates of a desired molar mass. Conclusions: Thus, this study highlights the usefulness of the SEC-MALS technique for in-depth conjugate vaccine biophysical characterization, which is critical for achieving optimal product attributes, driving manufacturing consistency and vaccine potency. Full article

Selective protein terminal labeling has become essential for system-wide studies of proteolytic mechanisms in disease. These methods enable precise tracking of cleavage dynamics, protease interactions, and cellular networks, offering transformative potential for proteolytic event analysis. This review explores recent advances in N-/C-terminal modification strategies, specifically for the applications in terminomics—the field focused on protein termini characterization. While protein termini provide valuable insights into functional proteome states, their low abundance in complex samples demands highly selective labeling approaches. We evaluate modern chemical and chemoenzymatic methods that leverage engineered chemical reactivity thresholds or enzymatic precision for site-specific modifications. Emerging strategies show enhanced substrate adaptability, reaction efficiency, and workflow compatibility, enabling broader applications in terminome studies. Full article

Bone formation requires a substantial energy supply to sustain extracellular matrix production and mineralization, yet the temporal contribution of lipid metabolism during osteoblast maturation remains incompletely characterized. This study investigated the molecular and transcriptional remodeling of lipid metabolism. Intracellular lipid distribution was analyzed by confocal microscopy using Nile Red staining. Transcriptional modulation of lipid synthesis, storage, lipolysis, genes associated with mitochondrial fatty acid oxidation, and osteogenic markers were assessed by quantitative real-time PCR, and the biochemical composition was evaluated by Raman spectroscopy. Early stages of spheroid development showed higher expression of genes involved in lipid synthesis and storage (FASN, DGAT2, and PLIN2) together with intracellular lipid accumulation, whereas later stages displayed increased expression of lipolytic and β-oxidation markers (PNPLA2/ATGL, CPT1A, and HADHA), accompanied by the redistribution of lipid droplets. The Raman analysis revealed a time-dependent variation of lipid-associated CH₂/CH₃ bands and modulation of protein-related Amide I–III signals, consistent with biochemical remodeling during maturation. Overall, the data indicate a coordinated transcriptional shift from lipid accumulation-associated pathways toward lipid mobilization during osteogenic progression in a 3D culture. This model provides a controlled experimental platform for investigating metabolic regulation during bone formation and for studying metabolic alterations associated with skeletal disorders. Full article

Background: Elaeagnus oxycarpa Schltdl. (Elaeagnaceae) is a vital sand-fixing tree species in the arid, semi-arid, and desert regions of China, holding significant ecological and economic value. However, its chloroplast (cp) genome has not been previously characterized. Results: In this study, we sequenced the complete cp genome of Elaeagnus oxycarpa using Illumina high-throughput sequencing technology. We performed de novo assembly, annotation, and comparative genomic and phylogenetic analyses with six other Elaeagnaceae species. The results revealed a typical quadripartite structure for the E. oxycarpa cp genome, with a total length of 150,567 bp and a GC content of 36.90%. Annotation identified 132 genes, comprising 86 protein-coding genes (PCGs), 38 tRNA genes, and 8 rRNA genes. Codon usage bias analysis indicated a preference for A/U endings, with leucine codons being the most frequent (9.5%). Additionally, 77 simple sequence repeat (SSR) loci were detected, predominantly mononucleotide repeats (71.4%). Comparative genomic analysis demonstrated high sequence conservation among the seven Elaeagnus species, with nucleotide variations primarily concentrated in non-coding regions and intergenic spacers of genes such as rps16, ycf1, and trnC-GCA. These variable regions and SSR loci represent valuable molecular markers for future population genetics and species identification studies on Elaeagnus. Phylogenetic analysis strongly supported the notion that E. oxycarpa and Elaeagnus angustifolia form a sister clade, indicating their close genetic relationship. Conclusions: Our findings provide crucial genomic resources and a theoretical foundation for the species identification and elucidation of the evolutionary history of Elaeagnaceae. Full article