Search Results (77)

Despite growing interest in South African medicinal plants, advanced metabolomic workflows that integrate positive (ESI+) and negative (ESI−) ionization modes in UPLC-MS/MS remain sparsely applied to South African flora, and especially to Acorus calamus and Lippia javanica species. Herein, application of a dual-polarity (positive (ESI+) and negative (ESI−) ionization modes) using an untargeted UPLC–MS/MS workflow, integrated with HEK293T cytotoxicity screening, to map their metabolomes, and rank potential signature metabolites for targeted antiviral follow-up. SwissADME supported in silico drug-likeness. Neither plant extract was cytotoxic across the concentration range, with absorbance-based cell viability of 73.82% for L. javanica and 77.23% for A. calamus at 250 µg/mL, and fluorescence-based cell viability ≥59.87% and ≥55.89%, respectively. Dual-polarity expanded coverage with ESI− yielded 312 features, compared with 225 with ESI+, consistent with the predominance of acidic phenolics in plant species. Unsupervised and supervised models segregated the plant species (PCA PC1/PC2 variance: ESI+ 89.4%/3.0%; ESI− 93.5%/1.8%; R²X(cum) = 0.799). Differential analysis identified 118 significant features in ESI+ with 80 up-regulated, 38 down-regulated, and 139 in ESI− with 96 up-regulated, 43 down-regulated. The ESI− showed the wider dynamic range. Chemotypes enriched among significant metabolites include flavonols of 3-O-methylkaempferol, apigenin, and conjugates of Pollenin A, iridoid glycosides of oleoside, forsythoside B, and jasmonate-pathway oxylipins of 7-epi-12-hydroxyjasmonic acid and its glucoside. These also include caryoptosidic acid and catechin-7-glucoside, which are ionized in both modes, pinning the increase in biomarker robustness. In conclusion, a dual-mode UPLC–MS/MS approach, integrated with cytotoxicity exploration, delivers a complementary metabolome coverage and a safety awareness for shortlisting of potential signature metabolites from L. javanica and A. calamus. Moreover, in vitro inhibition of SARS-CoV-2 papain-like protease (PL^pro) by these plants links chemical signatures to antiviral relevance. Shortlisted significant metabolites that demonstrated favorable drug-likeness include flavonol scaffolds of 3-O-methylkaempferol, Pollenin A, and jasmonate-pathway derivatives of 7-epi-12-hydroxyjasmonic acid. Moreover, the dual ionization mode may eliminate ionization bias, broaden metabolome coverage, and yield a mechanism-ready shortlist of metabolites from South African medicinal plants for downstream antiviral investigation. Full article

This study investigates the modulation effects of varying infill densities and phase angles on the radiation attenuation properties of three 3D-printed polymers: acrylonitrile butadiene styrene (ABS), polylactic acid (PLA), and thermoplastic polyurethane (TPU). Using the EpiXS software for radiation attenuation calculations, the study assessed the linear attenuation coefficients (LACs) of the materials under different infill densities (30%, 50%, 70%, 90%, and 100%) and phase angles (0°, 30°, 45°, 60°, and 90°) for radiation in the 1–100 keV energy range, which corresponds to the X-ray spectrum. TPU demonstrated the highest attenuation values, with a baseline coefficient of 20.199 cm⁻¹ at 30% infill density, followed by PLA at 18.835 cm⁻¹, and ABS at 13.073 cm⁻¹. Statistical analysis via the Kruskal–Wallis test confirmed that infill density significantly impacts attenuation, while phase angle exhibited no significant effect, with p-values exceeding 0.05 across all materials. TPU showed the highest sensitivity to infill density, with a slope of 1.1194, compared to 0.7257 for ABS and 0.9251 for PLA, making TPU the most suitable candidate for radiation protection applications, particularly in applications where flexibility and high attenuation are required. The findings support the potential of 3D printing to produce customized, cost-effective radiation protection gear for medical and industrial applications. Future work can further optimize material designs by exploring more complex infill geometries and testing under broader radiation spectra. Full article

Metastatic breast carcinoma (BC) cells are prone to spreading in the bone microenvironment, leading to a vicious cycle between local osteoclast-mediated osteolysis and tumor progression. Therefore, the targeted pharmacological down-modulation of BC cell proliferation as well as osteoclast differentiation and hyperactivity might represent a promising treatment option. We developed a multifunctional peptide nanocarrier combining bioactive EPI-X4 peptides and the Rho-inhibiting C3bot enzyme from Clostridium botulinum. C3bot is preferentially internalized into the cytosol of monocytic cells, including osteoclasts, where it inhibits Rho-mediated signal transduction. However, Rho-mediated cellular processes like migration and cell division can also be inhibited in non-monocytic cells if C3bot is delivered into their cytosol by a nanocarrier. To accomplish this, we designed a supramolecular transporter where one molecule of biotinylated C3bot and three biotinylated entities of the human EPI-X4 peptide-derived CXCR4 antagonist JM173 are assembled on avidin as a central platform. This modular transport system (JM173)₃-Avi-C3 down-modulated osteoclast formation and hyperactivity and delivered the therapeutic cargo C3bot successfully into the cytosol of breast cancer cells, where it inhibited Rho. Full article

Background: Medulloblastoma is an aggressive pediatric brain tumor characterized by marked molecular heterogeneity, which significantly impacts prognosis. The low frequency of genomic mutations in medulloblastoma suggests that alternative mechanisms, such as epigenetic regulation, may play a critical role in its pathogenesis. Methods: Using the EpiFactors database, we investigated the expression of epigenetic regulators in two independent RNA sequencing cohorts [Pediatric Brain Tumor Atlas (PBTA) and Williamson], stratified by molecular subgroups and clinical outcomes. We further analyzed expression heterogeneity at the single-cell level in malignant medulloblastoma cells using single-cell RNA sequencing. Results: Members of the SWI/SNF superfamily were dysregulated across all four molecular subtypes of medulloblastoma. Subtype-specific alterations were also observed: the acetyltransferase complex was shared between Group 3 (with SMARCD3 as a potential marker) and Group 4 (with RBM24 as a potential marker); SWR1, β-catenin/TCF, and protein–DNA complexes were specifically enriched in SHH-MB (with EYA1 and SATB2 as SHH markers); and RSC-type, PRC1, DNA polymerase complexes, and X-chromosome-related factors were enriched in WNT-MB (with FOXA1 and PIWIL4 as WNT markers). An epigenetic score (epi-score), linked to RNA metabolism and S-adenosyl-L-methionine pathways, was developed and identified as an independent adverse prognostic factor. High epi-scores were associated with proliferative, stem-like SHH malignant cells (characterized by G2/M phase, low pseudotime, and high entropy), exhibiting alterations in RNA splicing, DNA recombination, and nuclear division. Conclusions: Expression heterogeneity of epigenetic regulators is closely associated with molecular subgroups and clinical outcomes in medulloblastoma. These findings highlight the role of epigenetic dysregulation in RNA metabolism and tumor progression, particularly in SHH-driven proliferative cells. Full article

Accurately understanding and modulating thermal and thermoelectric transport in penta-XP₂ (X = Pd, Pt) monolayers is crucial for their applications in nanoelectronics and energy conversion. We systematically investigate the thermal conductivity and thermoelectric properties of penta-XP₂ monolayers through first-principles calculations, incorporating four-phonon (4ph) scattering and electron–phonon interaction (EPI) effects. The 4ph scattering, particularly Umklapp and redistribution processes, markedly suppresses lattice thermal conductivity by generating substantial thermal resistance and disrupting phonon population distributions. At 300 K, the lattice thermal conductivity is reduced to 0.87 W/mK (80% reduction) for penta-PdP₂ and 1.64 W/mK (79% reduction) for penta-PtP₂ compared to three-phonon-only scattering. Combining this with EPI-optimized electronic transport yields enhanced thermoelectric figures of merit (ZT), increasing from 0.21 to 0.86 for penta-PdP₂ and from 0.11 to 0.34 for penta-PtP₂, alongside a broadened optimal carrier concentration range. These findings highlight momentum-conserving 4ph scattering as a key mechanism for phonon transport modulation and thermoelectric efficiency improvement in penta-XP₂ materials, providing theoretical guidance for designing high-performance nanoscale thermal management and energy conversion devices. Full article

Background/Objectives: Cystic fibrosis (CF) is a rare autosomal recessive genetic disease that has a progressive and multisystemic course. The spectrum and frequency of mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) vary both in European countries and in other geographical regions. The aim of our retrospective study was to present the genetic variants identified in a group of 48 CF patients from the Moldova region (Romania), as well as to establish genotype–phenotype correlations. Methods: Genetic testing was initially performed for 38 CFTR mutations, and in heterozygous patients or those in whom no mutation was detected, CFTR gene sequencing (NGS) was performed. Results: The compound heterozygous genotype was identified in 26 (54.16%) of the patients (with one of the alleles being F508del), while 22 (45.83%) patients had the homozygous F508del genotype. The F508del variant was the most frequent (69.79%), followed by G542X (6.25%, 6/96). Several new variants were also identified that had not been reported in other studies from Romania (R1158X, K598*, R347H, c.2589_2599del, R496H, and CFTRdele2). Phenotypic manifestations in patients with CFTR class I, II, III and VII variants (homozygous and compound heterozygous) were more severe compared to those in patients with CFTR class IV, V and VI mutations, with the data obtained being consistent with those in the literature. Respiratory tract involvement was present in 77.08% of the patients, being more frequent in patients with the compound heterozygous genotype compared to the homozygous F508del genotype. Most patients had exocrine pancreatic insufficiency (EPI) (85.41%). Gastrointestinal manifestations included hepatocytolysis (66.66%) and biliary cirrhosis (0.41%). Meconium ileus was detected in 18.75% of patients, all with a compound heterozygous genotype. Conclusions: We compared the results obtained with data from the literature and correlated the detected CFTR variant (genotype) with the phenotypic manifestations, highlighting certain particularities present in some patients. Genetic testing allows for early diagnosis and adapted management, including personalized treatment for each patient. Identification of novel unclassified CFTR variants still remains a challenge for clinicians. NGS-based screening of heterozygous healthy carriers is important for both genetic counseling and prenatal diagnosis. Full article

Rheum tataricum L.fil., known for its high tolerance to drought, salinity, and nutritional deficiency, is the least studied species of wild rhubarb. Extract of roots and rhizomes of R. tataricum has been traditionally used for the treatment of different diseases such as liver, kidney, womb, and bladder diseases and also relapsing fever. An ethanol extract of the roots of R. tataricum was prepared and further successively fractionated by extraction with tert-butyl methyl ether (TBME) and ethyl acetate (EtOAc). The obtained extract fractions were subjected to a series of chromatographic separations on silica gel for the isolation of its individual compounds. A total of 12 individual compounds, 2-O-β-D-glucopyranoside of R-(4-hydroxyphenyl)-2-butanol (rhododendrin) 1, gallic acid 2, 2-O-β-D-glucopyranoside of S-4-(4-hydroxyphenyl)-2-butanol (epi-rhododendrin) 3, their aglycones (-)-(2R)-rhododendrol 4 and (+)-(2S)-rhododendrol 5, gallotannin β-glucogallin 6, chlorogenic acids (3,5-di-O-caffeoylquinic acid 7 and 5-O-caffeoyl-3-O-(p-coumaroyl) quinic acid 8), 4-(4-hydroxyphenyl)-2-butanon (raspberry ketone) 9 and three stilbenes (rhaponticin 10, desoxyrhaponticin 11 and resveratroloside 12), were isolated and characterized. The structure of desoxyrhaponticin 11 was confirmed by X-ray diffraction analyses. The results of in vitro biological assays (the MTT test) showed that ethanol extract Rheum tataricum was non-toxic against the normal epithelial VERO cells. The isolated compounds 1, 4, 11 and 12 exhibited cytotoxicity against a cervical cancer cell line (CaSki), breast adenocarcinoma (MCF7) and glioblastoma cell line (SNB-19) at low micromolar concentrations. Polyhydroxystilbenes 11 and 12 showed the best potency against adenocarcinoma cells (GI₅₀ = 7–8 μM). The inhibition activity towards cancer cells was comparable to those of the standard drug doxorubicin. The available from R. tataricum secondary metabolites may serve as new leads for the discovery of anticancer drugs. Full article

This study presents a hybrid computational investigation into the radiation shielding behavior of Fe-enriched Al-based alloys (Al-Fe-Mo-Si-Zr) for potential use in nuclear applications. Four alloy compositions with varying Fe contents (7.21, 6.35, 5.47, and 4.58 wt%) were analyzed using a combination of Monte Carlo simulations, machine learning (ML) predictions based on multilayer perceptrons (MLPs), EpiXS, and SRIM-based charged particle transport modeling. Key photon interaction parameters—including mass attenuation coefficient (MAC), half-value layer (HVL), buildup factors, and effective atomic number (Z_eff)—were calculated across a wide energy range (0.015–15 MeV). Results showed that the 7.21Fe alloy exhibited a maximum MAC of 12 cm²/g at low energies and an HVL of 0.19 cm at 0.02 MeV, indicating improved gamma attenuation with increasing Fe content. The ML model accurately predicted MAC values in agreement with Monte Carlo and XCOM data, validating the applicability of AI-assisted modeling in material evaluation. SRIM calculations demonstrated enhanced charged particle shielding: the projected range of 10 MeV protons decreased from ~55 µm (low Fe) to ~50 µm (high Fe), while alpha particle penetration reduced accordingly. In terms of fast neutron attenuation, the 7.21Fe alloy reached a maximum removal cross-section (Σ_R) of 0.08164 cm⁻¹, showing performance comparable to conventional materials like concrete. Overall, the results confirm that Fe-rich Al-based alloys offer a desirable balance of lightweight design, structural stability, and dual-function radiation shielding, making them strong candidates for next-generation protective systems in high-radiation environments. Full article

Polyetheretherketone (PEEK) is a high-performance, biocompatible polymer with remarkable mechanical properties, making it a promising candidate for medical implants. However, its intrinsic radiolucency poses a challenge for post-operative imaging. This study investigates the photon shielding capabilities and X-ray imaging qualities of pure PEEK and its composites with barium sulfate (BaSO₄), tantalum (Ta), bismuth oxide (Bi₂O₃), and hydroxyapatite (HA). The Monte Carlo-based Geant4 toolkit and the EpiXS application were used to evaluate key photon interaction parameters, including mass attenuation coefficients, effective atomic number (Z_eff), and effective electron density (N_eff), as well as the imaging performance metrics such as energy deposition and signal-to-noise ratio (SNR). Results indicate that high atomic number composites significantly enhance PEEK’s photon attenuation and imaging contrast. PEEK-Bi₂O₃ exhibited the highest attenuation coefficients and energy deposition, making it the most effective X-ray shielding material. PEEK-Ta provided a balanced performance with enhanced shielding and lower secondary radiation effects, making it suitable for applications requiring both radiopacity and imaging stability. PEEK-BaSO₄ moderately improved attenuation while maintaining a lower density, offering a trade-off between radiopacity and mechanical properties. Conversely, PEEK-HA demonstrated minimal enhancement in photon attenuation, limiting its effectiveness for radiographic applications. The findings suggest that incorporating high atomic number elements into PEEK significantly enhances its suitability for radiopaque medical implants, allowing for improved post-operative monitoring. Full article

Grain protein content (GPC) is gaining attention due to increasing consumer demand for nutritious foods. The present study carried out at ICAR-IIRR, Hyderabad, focused on the identification of quantitative trait loci (QTLs) linked with GPC and other quality traits. We utilized a population of 188 F₂ individuals developed from BPT 5204 (low GPC) X JAK 686 (high GPC) for QTL analysis. QTL analysis yielded four significant QTLs for GPC, three for amylose content, and multiple QTLs for other quality traits. qPC1.2, a major QTL in milled rice, was located in the marker interval RM562-RM11307 on chromosome 1 with an LOD value of 4.4. qPC1.2 explained 15.71% of the phenotypic variance (PVE). Additionally, the Interval Mapping for Epistatic QTLs (IM-EPI) method detected 332 pairs of di-genic epistatic QTLs. Fifteen QTLs exhibited a positive additive effect, indicating that the contributing allele(s) was from JAK 686. Five F₂ plants, viz., F₂-140, F₂-12, F₂-7, F₂-147, and F₂-41, exhibited a high GPC of 14.67%, 14.36%, 14.32%, 13.60%, and 13.36%, respectively. Additionally, these plants also exhibited high per-plant grain yield (~17.0–29.0 g) with desirable agronomic traits. The QTLs identified are valuable resources for developing high-grain-protein varieties with high grain yield and desirable quality traits. Full article

CD19 and CXCR4 are pivotal regulators of B-cell activation and migration, respectively. Specifically, CXCR4 signaling critically influences the dissemination of various malignant B cells through constitutive activation and aberrant expression. This study explores the interaction between CD19 and CXCR4 signaling in the context of B-cell lymphomas, particularly focusing on diffuse large B-cell lymphoma (DLBCL) and Waldenström Macroglobulinemia (WM). We assessed the roles of CD19 in survival and CXCL12-induced migration by using knockout (KO) cells of DLBCL and WM origin alongside evaluating the impact of CD19 monoclonal antibodies (mAbs) on antibody-dependent cell-mediated cytotoxicity (ADCC). Our results highlight that CD19 is important for survival and CXCL12-induced migration, and mAbs variably increase CXCL12-induced migration and enhance ADCC. Additionally, we demonstrate that the endogenous peptide inhibitor of the CXCR4 (EPI-X4) derivative JM#21 effectively inhibits CD19-mediated migration enhancement and promotes ADCC, thereby augmenting the therapeutic efficacy of CD19 mAb-based immunotherapy in lymphoma models. Our study underscores the potential of targeting both CD19 and CXCR4 to refine therapeutic strategies for treating B-cell malignancies, suggesting a synergistic approach could improve clinical outcomes in WM treatment. Full article

Five novel 2-methyl-4-(1-glycerol)furan (MGF) dimers, namely nocardifuran A (1), 13-acetyl-nocardifuran A (2), 15-epi-nocardifuran A (3), nocardifuran B (4), and nocardifuran C (5), were isolated from the Gause liquid fermentation of the marine-derived Nocardiopsis sp. ZSN1. Their structures were elucidated through HRESIMS, 1D and 2D NMR spectroscopic data analysis, and ECD calculations. Compounds 1–4 were identified as derivatives of MGF with its rearrangement of furan or pyran derivatives, while compound 5 was identified as the derivative of MGF with an indole derivative. These MGF dimers, representing a new structural class, were isolated from a marine microorganism for the first time, thereby enhancing chemical diversity. Screening for farnesoid X receptor (FXR) agonistic activity revealed that MGF dimers could activate FXR. Furthermore, bioactivity evaluations demonstrated that these types of compounds exhibited lipid-lowering activity with lower cytotoxicity in vitro. Consequently, our findings not only contribute to the chemical diversity of marine-derived MGF-type natural products but also offer potential insights into the development of MGF dimers as lead compounds for FXR agonists in the dysregulation of hepatic lipid metabolism. Full article

Background/Objectives: Pteridine reductase 1 (PTR1) has been one of the prime targets for discovering novel antileishmanial therapeutics in the fight against Leishmaniasis. This enzyme catalyzes the NADPH-dependent reduction of pterins to their tetrahydro forms. While chemotherapy remains the primary treatment, its effectiveness is constrained by drug resistance, unfavorable side effects, and substantial associated costs. Methods: This study addresses the urgent need for novel, cost-effective drugs by employing in silico techniques to identify potential lead compounds targeting the PTR1 enzyme. A library of 1463 natural compounds from AfroDb and NANPDB, prefiltered based on Lipinski’s rules, was used to screen against the LmPTR1 target. The X-ray structure of LmPTR1 complexed with NADP and dihydrobiopterin (Protein Data Bank ID: 1E92) was identified to contain the critical residues Arg17, Leu18, Ser111, Phe113, Pro224, Gly225, Ser227, Leu229, and Val230 including the triad of residues Asp181-Tyr194-Lys198, which are critical for the catalytic process involving the reduction of dihydrofolate to tetrahydrofolate. Results: The docking yielded 155 compounds meeting the stringent criteria of −8.9 kcal/mol instead of the widely used −7.0 kcal/mol. These compounds demonstrated binding affinities comparable to the known inhibitors; methotrexate (−9.5 kcal/mol), jatrorrhizine (−9.0 kcal/mol), pyrimethamine (−7.3 kcal/mol), hardwickiic acid (−8.1 kcal/mol), and columbamine (−8.6 kcal/mol). Protein–ligand interactions and molecular dynamics (MD) simulation revealed favorable hydrophobic and hydrogen bonding with critical residues, such as Lys198, Arg17, Ser111, Tyr194, Asp181, and Gly225. Crucial to the drug development, the compounds were physiochemically and pharmacologically profiled, narrowing the selection to eight compounds, excluding those with potential toxicities. The five selected compounds ZINC000095486253, ZINC000095486221, ZINC000095486249, 8alpha-hydroxy-13-epi-pimar-16-en-6,18-olide, and pachycladin D were predicted to be antiprotozoal (Leishmania) with Pa values of 0.642, 0.297, 0.543, 0.431, and 0.350, respectively. Conclusions: This study identified five lead compounds that showed substantial binding affinity against LmPTR1 as well as critical residue interactions. A 100 ns MD combined with molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) calculations confirmed the robust binding interactions and provided insights into the dynamics and stability of the protein–ligand complexes. Full article

The energy band alignment of a stacked Si/GaN heterostructure was investigated using X-ray photoelectron spectroscopy (XPS) depth profiling, highlighting the influence of the amorphous interface region on the electronic properties. The crystalline Si/GaN pn heterostructure was formed by stacking a Si nanomembrane onto a GaN epi-substrate. The amorphous layer formed at the stacked Si/GaN interface altered the energy band of the stacked heterostructure and affected the injection of charge carriers across the junction interface region. This study revealed the interfacial upward energy band bending of the stacked Si/GaN heterostructure with surface potentials of 0.99 eV for GaN and 1.14 eV for Si, attributed to the formation of the amorphous interface. These findings challenge the conventional electron affinity model by accounting for interfacial bonding effects. Electrical measurements of the stacked Si/GaN pn heterostructure diode exhibited a rectifying behavior, consistent with the XPS-determined energy band alignment. The diode outperformed early design with a low leakage current density of 5 × 10⁻⁵ A/cm² and a small ideality factor of 1.22. This work underscores the critical role of the amorphous interface in determining energy band alignment and provides a robust methodology for optimizing the electronic performance of stacked heterostructures. The XPS-based approach can be extended to analyze and develop multi-layered bipolar devices. Full article

AlGaN is attractive for fabricating deep ultraviolet (DUV) optoelectronic and electronic devices of light-emitting diodes (LEDs), photodetectors, high-electron-mobility field-effect transistors (HEMTs), etc. We investigated the quality and optical properties of Al_xGa_1−xN films with high Al fractions (60–87%) grown on sapphire substrates, including AlN nucleation and buffer layers, by metal–organic chemical vapor deposition (MOCVD). They were initially investigated by high-resolution X-ray diffraction (HR-XRD) and Raman scattering (RS). A set of formulas was deduced to precisely determine x(Al) from HR-XRD data. Screw dislocation densities in AlGaN and AlN layers were deduced. DUV (266 nm) excitation RS clearly exhibits AlGaN Raman features far superior to visible RS. The simulation on the AlGaN longitudinal optical (LO) phonon modes determined the carrier concentrations in the AlGaN layers. The spatial correlation model (SCM) analyses on E₂(high) modes examined the AlGaN and AlN layer properties. These high-x(Al) Al_xGa_1−xN films possess large energy gaps E_g in the range of 5.0–5.6 eV and are excited by a DUV 213 nm (5.8 eV) laser for room temperature (RT) photoluminescence (PL) and temperature-dependent photoluminescence (TDPL) studies. The obtained RTPL bands were deconvoluted with two Gaussian bands, indicating cross-bandgap emission, phonon replicas, and variation with x(Al). TDPL spectra at 20–300 K of Al_0.87Ga_0.13N exhibit the T-dependences of the band-edge luminescence near 5.6 eV and the phonon replicas. According to the Arrhenius fitting diagram of the TDPL spectra, the activation energy (19.6 meV) associated with the luminescence process is acquired. In addition, the combined PL and time-resolved photoluminescence (TRPL) spectroscopic system with DUV 213 nm pulse excitation was applied to measure a typical AlGaN multiple-quantum well (MQW). The RT TRPL decay spectra were obtained at four wavelengths and fitted by two exponentials with fast and slow decay times of ~0.2 ns and 1–2 ns, respectively. Comprehensive studies on these Al-rich AlGaN epi-films and a typical AlGaN MQW are achieved with unique and significant results, which are useful to researchers in the field. Full article