Search Results (12,020)

This work investigates the physicochemical characteristics of waste tire pyrolysis char (WTP-char) produced at 500 °C in an industrial-scale auger reactor. The study uniquely combines material profiling with environmental safety assessment, specifically targeting organic contaminants and polymer stabilizers, evaluating WTP-char’s potential for circular economy applications. The samples underwent comprehensive analysis, including GC-MS, TGA, SEM-EDS, TXRF, and BET surface area measurements. The results revealed a high volatile matter content (13 wt.%), attributed to the thermal inertia typical of industrial-scale units. The organic fraction was dominated by n-alkanes (48.3%) and a significant concentration (6.97%) of the stabilizer Tris(2,4-di-tert-butylphenyl) phosphate (bDtBPP), posing potential environmental risks due to its cytotoxicity. Polycyclic aromatic hydrocarbon (PAH) analysis showed a prevalence of high-molecular-weight (HMW) compounds (79.7%), indicating high chemical stability. Although the specific surface area was low (28.9 m²/g), suggesting the need for activation, the material exhibits potential as a low-cost semi-reinforcing filler or solid fuel. By moving beyond laboratory-scale experiments to real industrial production, this study establishes a practical framework for evaluating both the performance and environmental safety of waste tire pyrolysis char. Full article

Objectives: Multidrug-resistant (MDR) Pseudomonas aeruginosa represents a major clinical challenge, driven in part by resistance–nodulation–division (RND) efflux pumps that reduce intracellular antibiotic concentrations and limit the efficacy of many antibacterial agents, including fluoroquinolones. The aim of this study was to identify and characterize TXA11114 as a small-molecule efflux pump inhibitor (EPI) capable of restoring the activity of the fluoroquinolone levofloxacin against MDR P. aeruginosa. Methods: The antibacterial activity of the TXA11114–levofloxacin combination was evaluated using minimum inhibitory concentration (MIC) assays against panels of clinical isolates. Mechanistic studies included levofloxacin accumulation assays, ethidium bromide accumulation assays, outer-membrane permeability measurements, and whole-genome sequencing of mutants with altered potentiation phenotypes. In vivo efficacy was evaluated in murine thigh and lung infection models, while preliminary safety and drug-like properties were assessed using cytotoxicity assays and in vitro ADME profiling. Results: The TXA11114–levofloxacin combination produced > 1 log₁₀ CFU reductions in bacterial burden in murine thigh and lung infection models, exceeding the activity of levofloxacin monotherapy. TXA11114 markedly potentiated levofloxacin activity, producing substantial reductions in levofloxacin MIC values across multiple MDR clinical isolates, and also enhanced the activity of several additional efflux pump substrates, including β-lactams, tetracyclines, chloramphenicol, and trimethoprim–sulfamethoxazole. Mechanistic experiments demonstrated increased intracellular accumulation of efflux substrates without evidence of nonspecific membrane disruption, and mutations in ompH were associated with altered potentiation phenotypes. Conclusions: The TXA11114–levofloxacin combination produced significantly greater bacterial reductions than levofloxacin monotherapy in murine infection models. Levofloxacin was selected because fluoroquinolone resistance in P. aeruginosa is frequently driven by efflux-mediated mechanisms. While this study focused on levofloxacin potentiation, future work will evaluate additional efflux pump substrates and further define the molecular target of TXA11114. Full article

Controlled environment agriculture (CEA) relies on hydroponic systems to achieve high yields, yet optimizing plant performance remains a challenge. Beneficial endophytic bacteria offer a sustainable solution by promoting growth and nutrient uptake. Here, we investigated the mechanistic basis of growth enhancement in lettuce (Lactuca sativa) inoculated with Pseudomonas psychrotolerans IALR632 in a nutrient film technique (NFT) system. Growth measurements showed significant increases in shoot and root biomass and leaf greenness. RNA-seq profiling at 4, 10, and 15 days after transplanting revealed dynamic transcriptional reprogramming, with 38, 796, and 7642 differentially expressed genes, respectively. MapMan and GO analyses indicated up-regulation of pathways related to cell wall remodeling, lipid metabolism, nitrogen assimilation, and stress adaptation, alongside modulation of ethylene signaling. Root bacterial microbiome through 16S metabarcoding sequencing demonstrated distinct community shifts, confirmed by analysis of similarity (ANOSIM) (R = 1, p = 0.028), with enrichment of genera linked to nutrient cycling and plant growth promotion. These findings provide integrated molecular and ecological evidence that IALR632 enhances lettuce growth by coordinating host gene expression and rhizobiome restructuring, offering a mechanistic framework for microbial inoculant strategies in hydroponic horticulture. Full article

Background/Objectives: Salidroside, a bioactive phenylethanol glycoside primarily derived from Rhodiola rosea, and its major in vivo metabolite tyrosol exhibit diverse pharmacological activities. However, their direct molecular targets remain poorly defined. Methods: In the present study, an integrated strategy combining transcriptomic profiling, Connectivity Map (CMap) analysis, and multi-level experimental validation was employed. Transcriptomic signatures derived from A549 cells treated with salidroside or tyrosol were queried against the CMap database. Molecular docking, surface plasmon resonance (SPR), and cellular thermal shift assays (CETSA) were performed to predict and validate binding interactions. Functional validation was performed in SH-SY5Y cells. The phosphorylation level of extracellular signal-regulated kinase (ERK), a downstream signaling event of dopamine D2 receptor (DRD2), was detected after salidroside and tyrosol treatment. DRD2 antagonist sulpiride pre-intervention and small interfering RNA (siRNA)-mediated DRD2 knockdown were conducted to verify the receptor dependence of the compounds’ effects. Results: CMap analysis revealed that the transcriptomic signatures of salidroside and tyrosol showed significant similarity to known DRD2 modulators. Molecular docking predicted potential binding interactions between the two compounds and DRD2, which was confirmed by SPR and CETSA to be direct physical binding. Functional studies showed that both compounds rapidly induced DRD2 downstream ERK phosphorylation in SH-SY5Y cells; this effect was abrogated by sulpiride or DRD2 knockdown, indicating DRD2-dependent signaling activation. Conclusions: These findings identify DRD2 as a direct molecular target of salidroside and tyrosol and provide mechanistic insight into their dopaminergic regulatory effects. This study highlights the utility of CMap-guided target discovery combined with rigorous experimental validation for elucidating the molecular mechanisms of natural products. Full article

Chemoresistance is a major challenge in lung adenocarcinoma (LUAD) treatment and is associated with mitochondrial metabolism. Using publicly available LUAD transcriptome data, we established a five-gene prognostic signature (YWHAZ, HSPD1, NOTCH3, PGK1, and PPARG) for LUAD through differential gene expression profiling, univariate Cox analysis, and machine learning–based feature selection. Patients with LUAD were classified into a high-risk group (HRG) and a low-risk group (LRG) based on their risk scores. Enrichment analysis revealed significant differences between the HRG and LRG in multiple pathways related to metabolism and immunity. The immune microenvironment also differed significantly between the two groups, and the prognostic genes were correlated with infiltrating immune cells. A total of 110 compounds exhibited differential sensitivity across the groups. Molecular docking demonstrated a favorable binding affinity between the prognostic genes and the predicted drugs. Furthermore, YWHAZ knockdown significantly suppressed cancer cell proliferation in cell and animal models. In addition, YWHAZ knockdown markedly reduced cisplatin resistance by downregulating key regulators of the DNA replication and repair pathway, including POLA1 and MCM4. These results provide insight into the molecular mechanisms underlying chemoresistance and identify putative therapeutic targets for LUAD treatment. Full article

Alzheimer’s disease (AD) remains a significant global health challenge, highlighting the need for novel dual inhibitors targeting acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). This study investigated the trunk bark of Terminalia triptera Stapf. as a potential source of bioactive secondary metabolites for AD management. Bioassay-guided isolation led to the identification of two flavan-3-ol derivatives, epicatechin-(4β→8)-ent-catechin (1) and (−)-catechin (2), reported here for the first time from this species. In vitro assays demonstrated that the dimeric compound 1 exhibited stronger dual inhibitory activity against AChE and BChE, with IC₅₀ values of 4.41 × 10⁻⁴ and 4.75 × 10⁻⁴ mol/L, respectively, surpassing the reference compound berberine chloride. Molecular docking analysis revealed that compound 1 formed extensive interactions within both catalytic and peripheral anionic sites of the enzymes. Density Functional Theory (DFT) calculations indicated high kinetic stability, reflected by large HOMO–LUMO energy gaps (6.66–6.97 eV), while global reactivity descriptors suggested lower electrophilicity (ω = 2.19–2.34 eV), supporting a potentially favorable safety profile. Furthermore, 100 ns molecular dynamics simulations confirmed stable ligand–protein complexes stabilized by hydrogen-bond networks and deep binding within catalytic pockets. Overall, these findings highlight T. triptera and its dimeric proanthocyanidins as promising multi-target candidates for anti-Alzheimer drug development. Full article

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy characterized by profound molecular heterogeneity and high relapse rates, posing significant clinical challenges. Programmed cell death (PCD), encompassing diverse regulated modalities such as apoptosis, necroptosis, and ferroptosis, plays a key role in leukemogenesis and therapeutic response; however, a comprehensive prognostic framework integrating multi-modal PCD pathways in AML remains elusive. In this study, we performed a systematic transcriptomic analysis of 1624 genes associated with 13 distinct PCD forms. A novel computational pipeline combining a variational autoencoder (VAE) for dimensionality reduction and a multilayer perceptron (MLP) for classification was employed to identify robust PCD-related biomarkers, interpreted via SHapley Additive exPlanations (SHAP) analysis. This approach identified 48 candidate genes with discriminative potential between AML and normal bone marrow. Unsupervised consensus clustering based on these genes delineated two molecular subtypes exhibiting divergent clinical outcomes and immune microenvironment profiles. The subtype demonstrated an immunosuppressive phenotype, characterized by enriched regulatory T cells, M2 macrophages, and elevated expression of inhibitory immune checkpoints, correlating with inferior survival. We developed an 8-gene prognostic signature (SORL1, PIK3R5, RIPK3, ELANE, GPX1, VNN1, CD74, and IL3RA) that effectively categorized patients into high- and low-risk groups with notable survival differences, validated across independent cohorts. A prognostic nomogram combining the risk score, age, and cytogenetic risk enhanced the prediction accuracy for overall survival. Our study presents an integrative model that connects multi-modal PCD pathways to AML prognosis, offering a new molecular subtyping system and a clinically applicable risk assessment tool for improved prognostication and personalized treatment strategies. Full article

Drought stress severely limits plant growth and productivity, yet the molecular basis of drought tolerance and post-drought recovery remains incompletely understood in many forage legumes. Medicago ruthenica is a perennial legume native to arid and cold regions and exhibits strong drought resilience. Results: We integrated key physiological traits related to stomatal regulation, photosynthesis, osmotic adjustment and antioxidant defense with RNA-seq across four stages (well-watered control, CK; drought for 9 days, D9; drought for 12 days, D12; and rewatering for 4 days, RW). Drought triggered stage-dependent physiological shifts, and transcriptome profiling identified >3000 drought- and rewatering-responsive genes enriched in primary metabolism, redox homeostasis and hormone signaling. WGCNA highlighted two drought-associated modules (MEcyan and MEcoral1) and prioritized three hub transcription factors for functional validation: 861 (AP2/ERF), 22 (WRKY) and 89 (bZIP). Overexpression of each gene in tobacco improved drought tolerance, as indicated by enhanced growth/root traits, increased osmolyte accumulation and antioxidant enzyme activities, and reduced membrane damage. Conclusions: Together, these results provide an integrated view of drought stress response and recovery in M. ruthenica and identify 861, 22 and 89 as candidate regulatory genes for engineering drought resilience in legumes. Full article

Excessive macrophage activation is thought to be the primary cause of the cytokine storm that results in severe coronavirus disease 2019 (COVID-19) complications. The underlying mechanisms remain elusive, and more research is needed to find disease-critical genes and develop effective therapies. In this study, we used publicly accessible microarray datasets of cytokine storm in cultured human monocyte-derived macrophages challenged with cytokines, and employed bioinformatics, such as weighted gene co-expression network analysis (WGCNA) and differential expression analysis, to dissect gene expression profiles and identify putative disease-related molecules. Initially, three co-expression modules and related key genes were discovered, which highly correlated to macrophages challenged with cytokines. Then, a preliminary gene expression signature consisting of 203 upregulated and 24 downregulated genes was identified. Next, protein–protein interaction analysis and hub gene identification were used to identify 11 crucial hub genes, namely tripartite motif-containing 21 (TRIM21), interferon regulatory factor 1 (IRF1), guanylate binding protein 1 (GBP1), transporter associated with antigen processing 1 (TAP1), nuclear myosin I (NMI), interleukin 15 receptor subunit alpha (IL15RA), apolipoprotein L1 (APOL1), intercellular adhesion molecule 1 (ICAM-1), protein tyrosine phosphatase non-receptor type 1 (PTPN1), E74-like ETS transcription factor 4 (ELF4) and guanylate binding protein 2 (GBP2). Then, the LINCS L1000 characteristic direction signatures search engine (L1000CDS2) was employed for drug repurposing studies. Dasatinib was predicted to be the leading therapeutic compound to perturb the gene signature of cytokine storm in human macrophages. Connectivity Map results suggested that dasatinib may normalize ICAM-1 expression. In addition, the results of molecular docking studies and molecular dynamics simulation revealed that dasatinib may spontaneously interact with ICAM-1 via several key residues and form a relatively stable protein–ligand complex. Overall, this work, based on an analysis of co-expression correlation networks, gene expression signatures and pivotal genes in human macrophages challenged with cytokines, combined with drug repurposing studies, demonstrated that dasatinib may interact with ICAM-1 and could be a potential candidate for cytokine storm. However, due to the limitations of computational approaches, further experimental validation is necessary. Full article

Background: Cytology from cerebrospinal fluid (CSF) is standard-of-care to detect central nervous system (CNS) cancers but suffers from low-sensitivity and lacks associated molecular information, often requiring brain biopsy or resection to obtain. Belay Diagnostics offers analytically and clinically validated CSF-based tests to support the diagnosis and management of primary and secondary CNS cancers. However, the clinical utility (CU) of these assays has not been previously evaluated. Methods: This retrospective study presents a real-world, single institution experience of using the Belay Summit liquid biopsy test for all orders received (n = 123) between October 2024 and September 2025. Clinical information was reviewed for demographics, provisional diagnosis, oncology history, CSF cytology results, and tumor genomic profiling results. The primary endpoint of this study was to evaluate the impact of Belay CSF-based assays on physician diagnosis and treatment decisions. Secondary endpoints included evaluating the clinical performance of the Belay Summit test verses cytology in CNS malignancy detection (sensitivity, specificity, and accuracy). Results: The cohort included 120 patients with suspected or previously diagnosed primary (n = 40) or metastatic (n = 80) CNS tumors; three patients completed longitudinal testing for a total of 123 specimens and test orders. Summit showed higher sensitivity for CNS malignancy (90%) over CSF cytology (12%). The Belay CSF liquid biopsy test demonstrated strong clinical utility and was essential to clinical course pursued in 93% (114/123) of specimens, informing treatment and management decisions. Conclusions: The Belay Summit test provides clinically meaningful information to support physician decision-making for the diagnosis and management of primary and secondary CNS tumors, especially in cases where tissue sampling is infeasible. Full article

Recently, oral decitabine/cedazuridine has been approved for the treatment of AML patients who are not eligible for intensive chemotherapy. Although efficacy data on phenotypic features and the prognostic impact of molecular aberrations at diagnosis were reported in the registration study, serial determinations of the mutational landscape during therapy were not reported. In this study, we present data on a subset of five patients in whom molecular markers were monitored during treatment with oral decitabine/cedazuridine within the registration study. The following observations were made in individual patients. Regarding the changes in the molecular landscape during therapy in four/five patients, there was no major (>50%) reduction in mutated AML clones. There was only one patient with CRi and more than 50% reduction in the VAF of clones with molecular aberrations, including RAS pathway mutations. We observed a marked drop of blast cells (>50%) in two other patients without changes in the molecular profile. The overall survival was significantly longer in patients with CRi and PR, respectively, as compared to patients with no response. Finally, four/five (80%) of patients had druggable molecular aberrations at diagnosis, including mutations in IDH2 (2/5), NPM1 (2/5), and FLT3 (1/5). Our results show that in the majority of patients, changes in the genetic profiles are not seen despite decreases in blast cells in some patients. Disease-modifying activity with decreases in mutated clones is rare. Although the exact mechanism behind our findings remains undetermined, they are in line with the proposed effects of HMA on epigenetics in leukemia cells. Full article

Colored potato cultivars are rich in phenolic compounds that confer high antioxidant capacity; however, these beneficial metabolites could be susceptible to oxidation by polyphenol oxidases (PPOs), leading to enzymatic browning and the loss of antioxidant potential. Despite the agronomic relevance of this trade-off, the dynamics of the PPO gene family (StPPOs) gene expression in pigmented potatoes remains poorly characterized. Here, we present an integrated biochemical and molecular analysis of two purple-fleshed Peruvian landraces (Siriñacha and Angashungo), a partially pigmented landrace (Sapa), and non-pigmented cultivars, including the commercial cultivar Desirée. We quantified the total phenolic content, antioxidant capacity, and enzymatic browning index (EBI) using colorimetric and spectrophotometric methods. We also generated gene expression profiles of ten StPPO genes using semi-quantitative and digital PCR. Purple-fleshed cultivars exhibited significantly higher phenolic content and antioxidant capacity but also displayed accelerated browning kinetics compared to non- or partially pigmented genotypes. Expression analysis revealed cultivar-specific StPPO patterns, with StPPO2 and StPPO8 being markedly upregulated in pigmented materials, particularly StPPO8. These findings provide the first integrated biochemical and transcriptional evidence linking specific StPPO isoforms to enzymatic browning in colored potatoes, and highlight their potential for biotechnological applications. Full article

Drought stress is a major abiotic factor limiting maize yield and stability. Although Jumonji C (JMJ) histone demethylases are known to regulate plant growth, development, and stress responses, their systematic characterization in maize has remained limited. Here, 27 ZmJMJ genes were identified in the maize genome through BLAST and conserved-domain analyses and classified into five subfamilies: JMJD6, KDM3/JHDM2, KDM4/JHDM3, KDM5/JARID1, and JmjC domain-only. Members within the same subfamily showed similar physicochemical properties, domain composition, and motif distribution, whereas clear divergence was observed among subfamilies. Chromosomal mapping revealed that ZmJMJ genes were unevenly distributed across nine chromosomes, with two interchromosomal homologous gene pairs, suggesting roles for segmental and/or whole-genome duplication in family expansion. Promoter analysis indicated widespread enrichment of elements related to light responsiveness, growth and development, and hormone and stress responses. Expression profiling showed that most ZmJMJ genes were highly expressed in leaves, while several displayed tissue specificity. Under drought stress, ZmJMJ17a, ZmJMJ17b, ZmJMJ28, and ZmJMJ32 were significantly induced, highlighting them as promising candidates for functional studies and molecular breeding for drought tolerance in maize. This study provides a foundation for elucidating the evolution and functions of the ZmJMJ family and identifies candidate genes for drought-related functional validation and molecular breeding. Full article

The rapid expansion of cardiac imaging has substantially increased patient and occupational exposure to low-dose ionizing radiation. Evidence suggests that cumulative exposures below 100 mSv may contribute to long-term risks of cancer and non-cancer diseases, including cardiovascular disease. However, establishing causality at these dose levels is challenging, as epidemiological studies are limited by heterogeneous endpoints, uncertainties in dose reconstruction, and incomplete control of confounding factors. Molecular biomarkers offer a promising strategy to bridge the gap between radiation exposure and clinically manifest disease, enabling more precise individualized risk assessment and targeted preventive strategies. This review summarizes current evidence on genetic and epigenetic biomarkers for evaluating the biological effects of radiation in cardiac imaging and interventional cardiology and examines their potential role in risk stratification and occupational surveillance. Genetic markers—including γ-H2AX foci, micronucleus assays, and telomere length alterations—alongside epigenetic modifications such as DNA methylation changes and microRNA expression profiles provide sensitive indicators of radiation-induced cellular damage. Integrating biomarker profiling with individualized dosimetry and longitudinal follow-up may improve risk prediction, enhance occupational protection, and support safer, more sustainable imaging practices in contemporary cardiovascular care. Full article

Escherichia coli, Streptococcus equi subsp. zooepidemicus, Klebsiella oxytoca, and Enterococcus durans are microorganisms capable of causing severe infections, particularly in patients with underlying comorbidities or immune dysfunction. We report a rare clinical case of a 65-year-old man with advanced cardiac and hepatic disease who developed severe diarrheal syndrome followed by septic shock, rapid clinical deterioration, and death. Microbiological examination of autopsy specimens from the intestinal wall and spleen identified Escherichia coli O128 with an enterotoxigenic profile (lt+, st+, eae−), together with Streptococcus equi subsp. zooepidemicus, Klebsiella oxytoca, and Enterococcus durans. Histopathological analysis demonstrated catarrhal enteritis with fibrinous deposits, mucosal edema, vascular congestion, and inflammatory infiltration. Although the microbiological findings were partly derived from autopsy material and postmortem bacterial translocation cannot be completely excluded, the concordance between clinical presentation, laboratory findings, and morphological changes supports the presence of a clinically significant infectious process. To our knowledge, this is the first reported human case of fatal polymicrobial infection involving these four pathogens. The case highlights the potential severity of polymicrobial infections in patients with cirrhosis-associated immune dysfunction and underscores the importance of integrated microbiological and molecular diagnostics for accurate etiological assessment. Full article