Search Results (5,545)

Magnetopolymeric nanocomposites represent promising platforms for advanced nanomedicine due to their ability to combine magnetic responsiveness with polymer-mediated biological functionality. In this study, a hybrid nanocomposite system based on maghemite (Mh), poly(ethyl cyanoacrylate) (PECA), and chitosan (Cs) was developed and systematically characterized for biomedical applications. Mh nanoparticles (NPs) were incorporated as magnetic cores, while PECA acted as a biodegradable polymeric matrix, and chitosan provided surface functionalization and enhanced biocompatibility. The nanocomposites were prepared following anionic polymerization and coacervation methods and characterized in terms of structure particle size, electrokinetics and magnetic responsiveness. The results demonstrated the formation of a nanoscale (core/shell)/shell system with superparamagnetic properties. Importantly, the nanocomposites were evaluated as magnetic resonance imaging (MRI) contrast agents, exhibiting significant transverse relaxivity. In vitro cytotoxicity assays demonstrated the absence of significant toxic effects, while ex vivo hemocompatibility studies confirmed their compatibility with blood components. Furthermore, their potential as hyperthermia agents was demonstrated in vitro under the influence of an alternating magnetic field (AMF). Overall, the (core@shell)@shell nanocomposites combined superparamagnetic functionalities with favorable biological properties, supporting their potential use as multifunctional platforms for theranostic applications, including MRI contrast enhancement and magnetically induced hyperthermia. Full article

Background/Objectives: Synthetic compounds, particularly thiadiazine derivatives with antibacterial properties, have emerged as promising candidates in addressing the growing challenge of bacterial multidrug resistance. Thiadiazine derivatives are six-membered heterocyclic compounds containing two nitrogen atoms and one sulfur atom, exhibiting diverse medical and pharmacological activities. This study aimed to evaluate the potentiating activity of thiadiazine derivatives against multidrug-resistant bacteria. Methods: ADMET (absorption, distribution, metabolism, excretion, and toxicity) assays were performed to assess similarity with more than 370,000 three-dimensional structures of bioactive compounds. The multidrug-resistant bacterial strains Staphylococcus aureus 10 and Pseudomonas aeruginosa 24 were used to investigate both the direct antibacterial activity and the antibiotic-modifying activity of thiadiazine derivatives. Results: The thiadiazine analogs did not exhibit direct antibacterial activity, presenting a minimum inhibitory concentration of 1024 μg/mL. However, they demonstrated a significant antibiotic-modifying effect, potentiating the activity of conventional antibiotics, particularly norfloxacin, against the tested strains. In silico analyses indicated that the analogs predominantly exhibited affinity for G protein-coupled receptors and possessed physicochemical characteristics compatible with potential drug candidates. Conclusions: Although the evaluated thiadiazine derivatives lacked direct antibacterial activity, they significantly enhanced the efficacy of antibiotics against multidrug-resistant bacteria. Combined with their favourable in silico pharmacokinetic and physicochemical profiles, these findings suggest that thiadiazine derivatives may represent promising antibiotic adjuvants for combating multidrug-resistant bacterial infections. Full article

Background/objectives: Multidrug-resistant and extensively drug-resistant Gram-negative pathogens are a major cause of severe ocular infections, yet treatment options are increasingly compromised by escalating antibiotic resistance. Membrane-active peptides (colistin and Mel4) offer the potential to restore antibiotic susceptibility. This study investigated the efficacy of peptide- and colistin-based adjuvant strategies in enhancing the activity of conventional antibiotics. Methods: Antibacterial activity was assessed using MIC/MBC testing, checkerboard assays, time–kill kinetics, and biofilm disruption studies, supported by confocal microscopy. Toxicity was assessed using L929 fibroblasts and red blood cells. A mechanistic study was performed with a membrane permeability assay. Results: Clinical isolates of Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae showed high resistance to six antibiotic classes (up to MICs > 2048 mg/L), while polymyxin B and colistin remained active (MIC ≤ 2 mg/L). Mel4 displayed variable activity (MIC 7.8–500 mg/L). A total of 102 antibiotic–antibiotic, antibiotic–Mel4, and antibiotic–colistin combination tests were performed, of which 45 showed synergistic interactions. Combining traditional antimicrobials with either colistin or Mel4 restored antibiotic susceptibility, reducing MICs up to 2048-fold. Aminoglycoside–colistin combinations significantly lowered MICs, especially against K. pneumoniae. Time–kill assays confirmed rapid bactericidal effects (>3 log10 reduction in 3 h). The ciprofloxacin–Mel4 combination effectively disrupted biofilms (62–92%) with low toxicity and high cell viability. Membrane permeability assays showed that ciprofloxacin has limited activity, whereas both Mel4 and the ciprofloxacin–Mel4 combination showed enhanced activity across concentration gradients and over time. Conclusions: Membrane-active antimicrobials, colistin and Mel4, enhance conventional antibiotics against multidrug- and extensively drug-resistant ocular Gram-negative pathogens by restoring susceptibility, accelerating bactericidal effects, and disrupting biofilms. With low toxicity, these combinations represent promising therapeutic strategies for severe multidrug-resistant ocular infections. Full article

Background/Objectives: Essential oils (EOs) are complex mixtures extracted from plants. The aim of this study was to evaluate the chemical composition, antioxidant and antimicrobial properties, as well as in vivo toxicity against Drosophila melanogaster of the EOs extracted from Achillea millefolium L. (AM), Mentha longifolia L. (ML), and Thymus serpyllum L. (TS) from the mountains in Sibiu County, Romania. Methods: EOs were extracted by hydrodistillation. Their phytocompounds were determined by Gas Chromatography–Mass Spectrometry. Antioxidant potential was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azinobis [3-ethylbenzothiazoline-6-sulfonic acid]-diammonium salt (ABTS), and ferric-reducing antioxidant power (FRAP) assays. Antibacterial action was measured against eight pathogenic bacteria. An in vivo D. melanogaster diet-dependent viability assay was conducted to assess the toxicity of the EOs. Results: Chamazulene (49.72%), pulegone (36.20%), and thymol (42.11%) were the most abundant constituents of the AM, ML, and TS EOs, respectively. All tested EOs exerted antioxidant activity, with TS EO being the most efficient in the DPPH (98.19% inhibition) and ABTS (1.82 mmol Trolox equivalent (TE)/mL EO) scavenging assays, while AM EO performed best in the FRAP assay (66.70 μmol TE/mL EO). Against TS EO, Bacillus subtilis was the most sensitive, with an inhibition zone of 37 mm. A dose-dependent decrease in the viability of D. melanogaster L. was observed when their diet was supplemented with AM, ML, and TS EOs. Conclusions: The analyzed EOs demonstrated antioxidant and antimicrobial effects, suggesting their potential applications in various fields. However, due to their toxicity, an in-depth analysis is required before introducing such products in therapy. Full article

Acanthamoeba keratitis is a severe, sight-threatening corneal infection caused by free-living amoebae widely distributed in soil, natural waters, and domestic or recreational water systems. Following entry into the corneal microenvironment, disease develops within a redox conflict in which host-derived reactive oxygen species (ROS) and reactive nitrogen species (RNS) may contribute to parasite control while simultaneously promoting inflammation and tissue injury. Acanthamoeba responds through an adaptable defense network involving superoxide dismutases, catalase, thioredoxin- and glutathione-dependent systems, peroxiredoxins, and mitochondrial mechanisms. However, most mechanistic evidence derives from in vitro trophozoite studies, whereas the contribution of individual redox pathways to mature cyst survival and persistence in the infected cornea remains poorly defined. This review critically integrates evidence on host oxidative and nitrosative responses, parasite antioxidant adaptation, bidirectional redox crosstalk, and redox-modulating therapeutic strategies. Current data support neither indiscriminate suppression nor uncontrolled amplification of reactive species. Instead, future interventions should achieve spatially, temporally, and stage-specifically controlled redox modulation that weakens parasite defenses while preserving corneal integrity and essential innate immune functions. Progress will require causal validation of redox targets, separate assessment of trophozoites and mature cysts, long-term excystation and regrowth assays, evaluation across clinical isolates and genotypes, and parallel assessment of host-cell toxicity in clinically relevant corneal models. Full article

Crinum amoenum Roxb. ex Ker Gawl. (C. amoenum) is traditionally used in Nepal, but its antidiabetic potential remains insufficiently validated. This study characterized the 80% (v/v) ethanol bulb extract of C. amoenum and evaluated its antioxidant, α-amylase inhibitory, hypoglycemic, molecular docking, molecular dynamics (MD) simulation, and ADMET profiles. The ethanolic bulb extract was evaluated through phytochemical screening, thin-layer chromatography, total phenolic content (TPC), total flavonoid content (TFC) estimation, LC-MS analysis, antioxidant assays, α-amylase inhibition assays, acute toxicity testing, and hypoglycemic/oral glucose tolerance test (OGTT) studies in Wistar rats. Lycorine, pratorinine, and palmatine were docked against α-amylase (PDB ID: 5U3A) and GLP-1R (PDB ID: 6GB1), followed by 200 ns MD simulations and ADMET prediction. Qualitative analysis of the extract was positive for flavonoids, phenolic compounds, tannins, saponins, alkaloids, and carbohydrates, and a positive Salkowski reaction indicated the presence of constituents occurring in glycosidic form. The TPC was 173.38 ± 1.22 mg GAE/g, and the TFC was 314.58 ± 0.09 mg QE/g. LC-MS tentatively annotated lycorine, pratorinine, and palmatine based on retention time, m/z values in positive-mode electrospray ionization, and comparison with previously reported spectral information. The extract showed DPPH scavenging activity (IC₅₀: 90.98 μg/mL) and strong α-amylase inhibition (IC₅₀: 49.31 μg/mL) compared with acarbose (IC₅₀: 51.51 μg/mL). No deaths were observed following oral administration at 5000 mg/kg to rats. The 500 mg/kg dose produced the greatest hypoglycemic response, reducing blood glucose by 35.78% at 120 min in non-diabetic Wistar rats and by 19.21% at 60 min in glucose-loaded rats. Among all the compounds tested, pratorinine demonstrated the highest docking affinity with α-amylase (−8.2 kcal/mol; ASP300) and GLP-1R (−7.0 kcal/mol; GLY132). MD simulation supported greater stability of the α-amylase complex, and ADMET prediction identified pratorinine as a comparatively favorable predicted lead candidate (LD₅₀: 1000 mg/kg; Class 4 toxicity category). Pratorinine was identified as the most promising in silico antidiabetic candidate from the C. amoenum extract, primarily due to stable α-amylase interactions and favorable ADMET properties. Full article

Background/Objectives: Cancer remains one of the leading causes of death worldwide. Although chemotherapy is widely used, it is associated with severe side effects, including myelosuppression and systemic toxicity. Nanoparticles have emerged as promising candidates for modulating drug activity. In this study, we investigated whether platinum nanoparticles (PtNPs) of various sizes interact with idarubicin (IDA), an anthracycline anticancer drug used primarily to treat acute leukaemia. Methods: Interactions between PtNPs and IDA were analysed using dynamic light scattering (DLS), atomic force microscopy (AFM), fluorescence spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, and near-infrared (NIR) spectroscopy. Thermodynamic and thermal properties were assessed using isothermal titration calorimetry (ITC) and differential scanning calorimetry (DSC). Biological effects were evaluated using the Ames mutagenicity assay on the Salmonella enterica serovar Typhimurium TA98 strain and cytotoxicity assays on SK-BR-3 and MCF-7 cell lines. Results: DLS demonstrated changes in the hydrodynamic diameter of PtNPs following IDA addition, which were further supported by AFM imaging. PtNPs significantly quenched IDA fluorescence, indicating close molecular interactions, which were further supported by FTIR and NIR. ITC revealed that the interactions were endothermic, with enthalpy values ranging from 1.2 to 3.6 kcal/mol, and DSC demonstrated that the PtNP-IDA combination altered the melting temperature of IDA. Biological assays revealed that all examined PtNP sizes influenced IDA mutagenicity in the Salmonella enterica serovar Typhimurium TA98 strain. Furthermore, PtNPs modulated the cytotoxicity of IDA in SK-BR-3 and MCF-7 cell lines in a dose-dependent manner. Conclusions: These findings demonstrate that PtNPs interact with IDA and modulate its biological activity. However, in this study no non-cancerous cell lines were examined; therefore, the observed interactions and biological effects support further investigation of the PtNP-IDA combination in the context of nanoparticle-assisted anticancer therapy on a broader range of in vitro cell lines. Full article

Wine pomace is the residue of pressed grapes from wine production. This research focuses on expanding the use of winery by-products by evaluating the bioactivity and safety of Portugieser wine pomace. Moreover, the study discussed that the valorisation of winery by-products can support circular economy principles and improve resource efficiency in agro-industrial management systems. Here, the phenolic profile and bioactivity of Portugieser wine pomace extract (WPE) were investigated. The (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) (MTT) assay was carried out on malignant human neuroblastoma (SH-SY5Y) and normal human fibroblast cells (MRC-5). The MIC assay and growth dynamics were evaluated in probiotic and pathogenic Escherichia coli strains. WPE antioxidant activity and in vivo toxicity in Artemia salina were evaluated. Predominant WPE compounds included trans-cinnamic acid, gallic acid, catechin, and naringenin. Moderate cytotoxicity to SH-SY5Y cells has been detected (up to 41.7%). The growth capacity of probiotic E. coli has been enhanced. WPE showed notable antioxidant activity and good safety, as indicated by the Artemia survival rate (LD₅₀: 2.27 mg/mL, 24 h). The results justify further rigorous testing of WPE to unambiguously confirm its potential as a functional ingredient and its application in the development of value-added products. Moreover, the study highlights the need for organisational strategies to foster the sustainable valorisation of by-products, such as wine pomace. Full article

Background: The emergence of antifungal resistance and the limited number of clinically available antifungal drug classes necessitate the development of new agents with improved efficacy and safety. We investigated how linker architecture influences the antifungal activity and lead properties of hybrid triazole-thiazolidine derivatives. Methods: A focused library of triazole-thiazolidine hybrids incorporating alkylamine, amide, cyclic amine, 2-hydroxypropyl, and thiazepane linkers was synthesized and characterized. Antifungal activity was evaluated against reference strains and clinical isolates of Candida spp., Aspergillus fumigatus, dermatophytes, and Cryptococcus neoformans. Structure–activity relationships were analyzed by molecular docking. Selected compounds were further assessed by SCRAPPY profiling, fluorescence microscopy, mammalian-cell cytotoxicity assays, acute oral toxicity studies, and evaluation of microsomal stability and interactions with human CYP450 isoforms. Results: Linker architecture strongly influenced antifungal potency. Amide- and cyclic amine-containing hybrids were generally the most active, whereas simple alkylamide derivatives showed narrower activity profiles. Compound 28 emerged as the most promising lead, exhibiting sub-microgram MIC values against several Candida isolates, particularly C. parapsilosis, and retaining measurable activity against an azole-resistant C. albicans strain. Docking generated putative CYP51-binding models, while SCRAPPY profiling and fluorescence microscopy revealed an azole-like cellular response consistent with perturbation of sterol-associated homeostasis. Compound 28 was tolerated at 300 mg/kg in an acute oral study but showed concentration- and time-dependent cytotoxicity and rapid CYP3A4-mediated microsomal metabolism. Conclusions: Systematic variation of linker architecture identified compound 28 as a promising exploratory antifungal lead. Further optimization should focus on improving metabolic stability and cytotoxicity, together with direct target validation, pharmacokinetic characterization, and in vivo efficacy studies. Full article

Cancer remains one of the leading causes of morbidity and mortality worldwide, highlighting the need for safe and effective therapeutic strategies targeting multiple oncogenic pathways. Cinnamon (Cinnamomum spp.) contains several bioactive phytochemicals with reported antioxidant and anticancer properties; however, their potential interactions with key cancer-associated signaling proteins have not been comprehensively investigated. In this study, an integrated computational and preliminary experimental approach was employed to evaluate four major cinnamon phytochemicals, namely e-cinnamaldehyde, eugenol, p-cymene, and cinnamic acid. Consensus molecular docking was performed using AutoDock Vina (v1.2.7), Smina (v2020.12.10), and GNINA (v1.3.3) against phosphoinositide 3-kinase (PI3K), nuclear factor kappa B (NF-κB), and mammalian target of rapamycin (mTOR). Docking analyses were complemented by protein-ligand interaction profiling, pharmacokinetic and toxicity prediction (ADMET), and a 100 ns molecular dynamics simulation with MM/GBSA binding free-energy analysis of the selected mTOR-p-cymene complex. In addition, the antioxidant activity and cytotoxic effects of a crude methanolic cinnamon bark extract were evaluated using in vitro antioxidant assays and MTT assays against HCT-116 and HT-29 colorectal cancer cell lines. Consensus docking predicted that all four phytochemicals were capable of interacting with the selected protein targets, although the predicted binding profiles varied among the compounds. Eugenol showed comparatively more favorable predicted interactions with PI3K, p-cymene produced the lowest predicted docking score for NF-κB, and cinnamic acid displayed a comparatively consistent predicted multitarget binding profile across PI3K, NF-κB, and mTOR. ADMET analysis suggested that all compounds satisfied major drug-likeness criteria and exhibited predicted oral bioavailability, although potential cytochrome P450 interactions and hepatotoxicity were predicted for some compounds. Molecular dynamics simulation indicated that the selected mTOR-p-cymene complex maintained a stable binding pose throughout the simulation, while MM/GBSA analysis yielded a modest binding free-energy estimate (ΔG_bind = −4.70 ± 8.20 kcal/mol), which should be interpreted cautiously because of the observed energetic variability. The crude methanolic cinnamon bark extract exhibited antioxidant activity and reduced the viability of HCT-116 and HT-29 colorectal cancer cells in a concentration-dependent manner. Collectively, these findings provide computational predictions of potential interactions between selected cinnamon-derived phytochemicals and cancer-associated signaling proteins and are consistent with the preliminary observation that the crude cinnamon extract exhibits antioxidant activity and cytotoxic effects in colorectal cancer cell lines. However, the computational analyses do not establish direct inhibition of the PI3K/NF-κB/mTOR signaling pathway, and the biological assays were performed using a crude extract rather than isolated phytochemicals. Therefore, further studies using purified compounds, biochemical target validation, pathway-specific cellular analyses, and in vivo models are required to determine whether the predicted protein-ligand interactions contribute to the observed biological activity. Full article

Background/Objectives: The development of multifunctional small molecules capable of simultaneously addressing cancer progression and antimicrobial resistance represents an important challenge in medicinal chemistry. This study aimed to design, synthesize, and biologically evaluate a series of novel morpholine-based nitrogen-rich heterocyclic hybrids as potential anticancer and antibacterial agents, supported by computational investigations. Methods: Twelve morpholine-derived nitrogen-enriched heterocyclic hybrids incorporating pyran, triazine, pyrimidinone, and sulfur-containing scaffolds were synthesized and fully characterized using IR, ¹H NMR, ¹³C NMR, mass spectrometry, and elemental analysis. Their antiproliferative activities were evaluated against MCF-7 and HCT-116 cancer cell lines. The most active compounds were further investigated through kinase inhibition assays, cell cycle analysis, apoptosis, mitochondrial membrane potential, intracellular ROS determination, and apoptosis-related gene expression. Antibacterial, antibiofilm, antioxidant, and computational studies, including molecular docking, molecular dynamics simulations, MM-GBSA/MM-PBSA binding free-energy calculations, DFT calculations, and ADMET prediction, were also performed. Results: Compounds 3, 10, and 12 exhibited the highest antiproliferative activity, with compound 10 emerging as the lead candidate. It potently inhibited EGFR, PI3K, and mTOR, with IC₅₀ values of 0.086 ± 0.003, 0.107 ± 0.005, and 0.223 ± 0.008 μM, respectively. Mechanistic investigations revealed G₂/M arrest in MCF-7 cells and G₀/G₁ arrest in HCT-116 cells, accompanied by apoptosis rates of 32.66% and 37.12%; mitochondrial membrane depolarization; a 3.55-fold increase in intracellular ROS; upregulation of caspase-3, caspase-9, and Bax; and downregulation of Bcl-2, supporting activation of the intrinsic apoptotic pathway. Compound 10 also displayed the broadest antibacterial spectrum, surpassed ciprofloxacin against several tested isolates, exhibited MIC values of 5–20 μg/mL, achieved 42.80% inhibition of Pseudomonas aeruginosa biofilm formation, and showed the strongest antioxidant activity in DPPH and ABTS assays. Computational analyses supported the experimental findings by predicting stable interactions with EGFR and Staphylococcus aureus DNA gyrase, together with favorable MM-GBSA/MM-PBSA binding free energies of −23.44 and −24.99 ± 2.71 kcal/mol, respectively. Conclusions: The present findings identify compound 10 as a promising multifunctional lead with potent anticancer, antibacterial, antibiofilm, antioxidant, and multitarget kinase inhibitory activities. The combined biochemical, cellular, and computational findings support the proposed involvement of the EGFR/PI3K/mTOR signaling pathway in its antiproliferative activity and identify DNA gyrase as a potential antibacterial target. Nevertheless, the present study is limited to in vitro biological evaluation and computational investigations. Therefore, further in vivo efficacy studies, pharmacokinetic profiling, toxicity assessment, and experimental validation of the proposed molecular targets are warranted before considering preclinical development. Full article

Cyanobacteria are prolific producers of secondary metabolites, some of which are potent cyanotoxins that threaten ecosystem integrity and human health. Although blooms have been extensively studied in temperate regions, Southeast Asia’s (SEA’s) tropical marine and estuarine ecosystems remain comparatively underexplored despite their ecological richness and socio-economic importance. This review consolidates current knowledge on marine cyanobacteria and cyanotoxins in SEA, drawing on ecological surveys, ecotoxicological studies, and cyanobacterial bloom case reports. Diverse taxa including Trichodesmium, Lyngbya, Oscillatoria, Neolyngbya, and Aliinostoc, have been documented in SEA’s marine waters, many producing cyanotoxins with various toxic effects. Ecotoxicological risks are intensified by monsoonal variability, nutrient enrichment, and climate-driven shifts that collectively amplifies cyanoblooms and toxin production. Detection methods such as PCR-based assays, LC-MS/MS, and biosensor technologies are increasingly applied to identify toxin biosynthesis genes, cryptic species, and novel metabolites. Environmental challenges including eutrophication from wastewater discharge, trophic transfer of toxins, and climate induced shifts in species distribution, further complicates bloom dynamics and management. Mitigating this requires a multi-pronged approach: advancing biosensors for rapid detection, embedding monitoring within predictive climate frameworks, and expanding molecular surveillance to capture cryptic diversity and gene transfer events. Such strategies are essential for environmental management of cyanobacterial blooms in SEA. Full article

Abiotic stresses—drought, salinity, extreme temperature, flooding, and heavy-metal toxicity—constrain rice (Oryza sativa L.) yield worldwide, and the cellular programmes underlying them are unevenly distributed across cell types that bulk-tissue assays average together. This review examines, from a methodological standpoint, what single-cell and spatial omics technologies can and cannot establish about rice abiotic stress biology. We first define the modality space: single-cell omics measures RNA, chromatin accessibility, DNA methylation, protein, or metabolite features at the resolution of individual cells or nuclei, whereas spatial omics measures such features while retaining tissue coordinates; the two are complementary rather than interchangeable. We then treat each platform class—droplet-based scRNA-seq, combinatorial-indexing approaches including SPLiT-seq, nuclei-based snRNA-seq and multiome, sequencing-based and imaging-based spatial transcriptomics—under a common template covering measurement principle, the questions each can answer, applicability to rice tissues, dominant biases, and the inferences each cannot support. To make evidence strength comparable across a heterogeneous literature, we apply a four-tier scheme throughout: Tier A, direct rice cell-resolved or spatial evidence with functional or field validation; Tier B, robust rice functional and localization evidence without single-cell data; Tier C, cell-resolved evidence without causal validation; and Tier D, cross-species analogy or reasoned proposal. Applying this scheme shows that the genes with genuine breeding traction in rice—SUB1A, OsHKT1;5, OsHMA3, OsNRAMP5, DRO1—rest on Tier B evidence from classical genetics and field testing, whereas the most cell-resolved rice evidence concentrates in root outer layers and barrier formation at Tier C, and heat and cold stress, despite dominating yield loss, lack rice cell-resolved data almost entirely. We extend the discussion beyond transcriptomics to single-cell DNA methylome profiling, spatial proteomics and metabolomics, and three-dimensional analysis of thick plant tissues, in each case distinguishing demonstrated plant capability from mammalian-only capability, and we assess the expanding role of artificial intelligence in annotation, segmentation, batch correction, integration, and perturbation prediction alongside its documented failure modes. Rice, maize, and wheat are compared to identify transferable methodology. Cell-resolved omics has to date improved biological interpretation and candidate prioritization; demonstrating an incremental breeding advantage from it remains an unmet requirement. Full article

Breast cancer remains one of the most common malignancies worldwide. Highly invasive HER2-positive breast cancer carries a high risk of metastasis and poses a significant therapeutic challenge. Boron neutron capture therapy (BNCT) may be an option for patients with this severe diagnosis. Here we evaluated the effectiveness of BNCT with elemental boron nanoparticles obtained by laser fragmentation and coated Silane-PEG-COOH and conjugated with the Affibody _ZHER2:342 guide protein (BPs) against the HER2-positive breast cancer. The MTT assay after BNCT with BPs revealed an almost twofold reduction in surviving BT-474 tumor cells compared to the control group. The results of the clonogenic test showed totally death of BT-474 cells after BNCT with BPs at a concentration of 40 μg/mL in the culture medium. The same results was found for in vivo. In female SCID mice bearing BT-474 breast tumor xenografts, BNCT with intratumoral injection of BPs at a dose of 60 mg/kg led to a significant slowdown in xenograft growth beginning on the 17th day compared with control animals and the 39th day compared with irradiated females. A single intratumoral administration of BPs at a dose of 60 mg/kg did not show toxic effects. Histological examinations did not reveal systemic accumulation of the studied BPs in major organs; instead BPs was selectively retained within the xenografts and surrounding tissues. Thus, laser fragmented functionalized with Silane-PEG-COOH and the Affibody _ZHER2:342 (BPs B-PEG-AFF) represent a promising platform for boron delivery in targeted BNCT applications. Full article

Background: Metabolic reprogramming enables cancer cells to adapt to energetic stress and sustain proliferation. Simultaneous inhibition of glycolysis and mitochondrial respiration has emerged as a promising strategy to overcome metabolic plasticity. This study evaluated the antiproliferative effects of the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) alone and in combination with metformin in human cancer cell lines. Methods: Human cervical carcinoma (HeLa), lung adenocarcinoma (A549), colorectal adenocarcinoma (HT-29), and normal lung fibroblasts (MRC-5) were treated with 2-DG or metformin individually, or with metformin in the presence of a fixed concentration of 2-DG (1 mM). Cell viability was assessed using the sulforhodamine B assay after 24 and 48 h. IC₅₀ values were calculated by nonlinear regression, Dose Reduction Index (DRI) analysis evaluated sensitization to metformin, and molecular docking was performed to investigate interactions with selected metabolic targets. Results: Both 2-DG and metformin inhibited cell proliferation in a concentration- and time-dependent manner. HeLa cells were the most sensitive to glycolytic inhibition, while A549 and HT-29 cells showed moderate susceptibility. Co-treatment with 2-DG significantly enhanced metformin activity, reducing its IC₅₀ in HeLa cells from 6.04 to 2.00 mM after 24 h and from 2.28 to 1.56 mM after 48 h. DRI analysis demonstrated increased sensitivity to metformin in all cancer cell lines, particularly HT-29 and A549, whereas normal MRC-5 fibroblasts remained comparatively less affected. Molecular docking revealed favorable binding of both 2-DG and metformin to proteins involved in cellular energy metabolism. Conclusions: Combined inhibition of glycolysis and mitochondrial respiration potentiates the antiproliferative effects of metformin, increases metabolic vulnerability in cancer cells, and is supported by molecular docking evidence of interactions with metabolic targets, while showing limited toxicity toward normal fibroblasts. These findings support dual metabolic targeting as a promising therapeutic strategy and warrant further mechanistic and in vivo studies. Full article