Search Results (85)

Sparse-scan ptychography accelerates data acquisition but compromises the overlap-induced redundancy essential for stable blind reconstruction. In low-overlap cases, object errors are often transferred to the probe update, causing crosstalk and artifacts. In this work, we propose a sparse-scan ptychography method termed hybrid-scan ptychography, which combines a hybrid-overlap scanning strategy with a reference-guided ePIE reconstruction algorithm. In this method, a localized high-overlap scan is used to establish a reliable probe estimate for reconstructing a wide field of view scanned on a low-overlap grid. As a stabilizing prior, this probe estimate is integrated into the ePIE probe update for the low-overlap region through an additional quadratic regularization term, thereby ensuring accurate probe reconstruction for sparse-scan region. This method effectively suppresses sparse-scan artifacts and ensures robust, high-fidelity reconstruction, as demonstrated by numerical simulations and soft X-ray ptychography experiments. With the new method, the acquisition efficiency of ptychography can be increased by at least 2 times without significant resolution reduction. Full article

Sparse-view computed tomography (CT) reconstruction aims to recover high-quality CT volumes from a limited number of X-ray projection images, thereby reducing radiation exposure during image acquisition. However, this problem is inherently ill-posed because each projection provides only indirect line-integral supervision, and different attenuation distributions can explain similar sparse measurements. Existing analytic and iterative methods often suffer from streak artifacts and unstable solutions, while supervised learning-based methods require paired training data and may generalize poorly across anatomical regions or acquisition settings. Neural Radiance Field (NeRF)-based methods have recently shown promise by representing the attenuation field as a continuous coordinate-based function optimized directly from projection images. Nevertheless, these methods mainly enforce projection consistency and do not explicitly use volume-domain uncertainty to guide subsequent reconstruction. In this work, we propose EpiC-NeRF, a CT-specific closed-loop framework that actively feeds estimated epistemic uncertainty back into sparse-view reconstruction. EpiC-NeRF adapts evidential uncertainty estimation and aggregation to the X-ray CT line-integral formulation and maintains the resulting spatial uncertainty in a persistent three-dimensional Epistemic Grid Map. The accumulated uncertainty is used by Epistemic-Adaptive Layer Normalization to modulate intermediate features and by dual active sampling to guide ray- and point-level sample allocation. The newly estimated uncertainty then updates the grid map and guides subsequent optimization iterations, forming a unified feedback loop between uncertainty estimation and CT reconstruction. Experiments on four CT volume datasets demonstrate that EpiC-NeRF achieves improved reconstruction fidelity over existing analytic, iterative, and neural implicit reconstruction methods. Full article

Thirteen new decaline polyketides, namely, zosteropenillines T–W (1–4), 8-hydroxypallidopenilline A (5), 13-epi-zosteropenilline P (6), 11-epi-zosteropenilline N (7), 15-hydroxyzosteropenilline M (8), 8-hydroxyzosteropenilline M (9), 11-epi-zosteropenilline M (10), and zosteropenillines X–Z (11–13), along with 17 known related compounds (14–30) were isolated from the ethyl acetate extract of the marine-derived fungus Penicillium yezoense KMM 4679 cultivated on MgCl₂-containing nutrient medium. The structures of the isolated compounds were established based on spectroscopic methods. The absolute configurations of zosteropenillines T (1) and V (3) were determined using time-dependent density functional theory (TD-DFT) calculations of the ECD spectra. X-ray diffraction analysis data were obtained for the known zosteropenilline S (28). A biogenetic pathway for 1–13 was proposed. The effects of the compounds on Staphylococcus aureus and Candida albicans growth and biofilm formation were observed. Zosteropenillines U (2), Y (12) and Z (13) with higher activity against C. albicans biofilms were nontoxic for normal cardiomyocyte H9c2 cells, making them promising anti-candidal agents. Moreover, zosteropenillines U and Y demonstrated cardioprotective effects in acute ischemia/reperfusion and CoCl₂-mimicking hypoxia in vitro models. Full article

Non-small cell lung cancers (NSCLCs), most notably adenocarcinoma and large cell carcinoma, have been the most frequently diagnosed lung cancer and continue to represent a leading cause of cancer-related mortality worldwide, largely due to its aggressive growth and limited therapeutic responsiveness. Natural products derived from traditional medicinal plants remain a valuable source for the discovery of novel anti-cancer agents. In this study, the anti-cancer potential of Angiopteris evecta (G. Forst.) Hoffm., a medicinal fern widely used in Thai traditional medicine, was investigated in human NSCLC, A549 and H1299 cells. Subsequential solvent extraction yielded hexane, ethyl acetate, and ethanol fractions, among which the ethyl acetate extract (AE-EA) exhibited the strongest growth inhibitory activity. Bioactivity-guided fractionation of AE-EA by thin-layer chromatography generated an (-)-epi-osmundalactone-rich fraction (OLRF), which contained three closely related lactone/furanone derivatives, with (-)-epi-osmundalactone as the predominant constituent, as determined by NMR analysis. AE-EA and OLRF significantly suppressed NSCLC cell viability and clonogenic survival and induced G0/G1 cell cycle arrest, accompanied by downregulation of cyclin D1, cyclin E1, CDK-2, and CDK-4 (p < 0.05). Both treatments also triggered intrinsic apoptosis, as evidenced by mitochondrial membrane depolarization, reduced expression of Bcl-2, and Bcl-xL, and survivin, and activation of cleaved caspase-9 and caspase-3. Mechanistically, AE-EA and OLRF significantly suppressed mitogen-activated protein kinase (MAPK) signaling through inhibition of ERK1/2, JNK1/2, and p38 phosphorylation in both NSCLC cells (p < 0.05). Collectively, these findings demonstrate that AE-EA and OLRF exert pronounced anti-cancer effects in both NSCLC cells through coordinated inhibition of MAPK signaling, induction of cell-cycle arrest, and activation of intrinsic apoptosis, supporting their potential for further development as plant-derived anti-cancer agents. Full article

Veterinary metabolomics has redefined bile acids (BAs) from simple digestive surfactants to systemic endocrine signals within a microbial–host metabolic axis. This review aims to evaluate how BA dysmetabolism acts as a central pathogenic factor in canine and feline disease. We analyze the BA pool’s integrity, which depends on a specialized functional guild, primarily Peptacetobacter hiranonis, responsible for 7α-dehydroxylation. We delineate two principal pathological profiles: (1) microbial collapse, characterized by secondary bile acid (SBA) depletion and compromised farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5) signaling, which exacerbates inflammation in chronic enteropathy (CE), protein-losing enteropathy (PLE), and exocrine pancreatic insufficiency (EPI); and (2) hepato-biliary spillover, wherein host-induced dysfunction results in primary bile acid (PBA) excess. Recent data have linked these disruptions to skeletal health, feline renal fibrosis, cardiac remodeling in myxomatous mitral valve disease (MMVD), and neuroinflammation in epilepsy and hepatic encephalopathy. The discovery of microbially conjugated bile acids (MCBAs) and microbial extracellular vesicles (MEVs) reveals highly specific, vesicle-mediated communication pathways impacting systemic health. Diagnostic protocols should prioritize functional profiling, including the dysbiosis index (DI), serum conjugated BA analysis, and SBA/PBA ratios. Clinical management is moving beyond empirical fecal microbiota transplantation (FMT), towards precision synthetic microbial consortia (SynComs), neuroprotective BAs like tauroursodeoxycholic acid (TUDCA), and molecular postbiotics to restore the collaborative metabolome. Full article

Incorporating protein feed ingredients that exhibit strong attractiveness to the target fish species is an effective and sustainable feeding strategy to improve feed intake and enhance growth performance. An 8-week feeding experiment was performed to elucidate the manipulation impact of graded levels of jack mackerel meal (JMM) in diets replacing 10% fish meal (FM) with corn protein concentrate (CPC) on the growth, feed utilization, and blood chemistry of rockfish (Sebastes schlegeli), as well as to perform an economic analysis. A total of 450 fish were randomly assigned to 15 plastic tanks (30 juveniles/tank). Five experimental diets were formulated to be isoproteic (50.0% crude protein) and isolipidic (15.5% crude lipid). The control (Con) diet contained 55% FM. In the Con diet, 10% of the FM was substituted with CPC, and graded levels of JMM at 0%, 20%, 40%, and 60% were subsequently incorporated instead of the FM, referred to as CPCJ0, CPCJ20, CPCJ40, and CPCJ60, respectively. Triplicate groups of rockfish were carefully hand-fed the diets to satiation throughout the feeding experiment. The rockfish fed the CPCJ60 diet produced significantly higher weight gain (WG) (p < 0.002) and specific growth rate (SGR) (p < 0.003) than those fed the Con, CPCJ0, and CPCJ20 diets but showed no significant (p > 0.05) differences compared to those fed the CPCJ40 diet. Both the WG (Y = 0.9367X + 17.0500, p < 0.0001, Adjusted R² = 0.8468) and SGR (Y = 0.0005X + 0.0165, p < 0.0001, Adjusted R² = 0.8580) of the rockfish increased linearly with increased dietary JMM inclusion levels when 10% of the FM was replaced by CPC. The rockfish fed the CPCJ60 diet showed a significantly higher feed consumption (FC) (p < 0.03) compared to those fed the CPCJ0 diet. Among the dietary treatments, however, no significant (p > 0.05) differences were found in the feed utilization, proximate composition, amino and fatty acid profiles, and blood chemistry of the rockfish. The CPCJ60 diet resulted in the highest economic profit index (EPI) among the dietary treatments. Conclusively, JMM was found to be effective in improving the FC of rockfish fed the diets replacing 10% of the FM with CPC. Furthermore, the WG and SGR of the rockfish fed the diets replacing 10% of the FM with CPC improved linearly with elevated JMM inclusion. Thus, incorporating 60% of JMM into the diets substituting 10% of the FM with CPC was the most recommended strategy according to the growth performance and FC of the rockfish, providing the highest EPI for fish farmers. Full article

Aconitum pendulum Busch (Tiebangchui), a traditional Chinese medicinal herb, is recognized for its diverse pharmacological properties and for its significant toxicity. The Zanba stir-frying processing method is commonly employed to mitigate toxicity and enhance efficacy; however, the underlying chemical principles remain insufficiently studied. In order to address this issue, a phytochemical investigation was conducted on the diterpenoid alkaloids present in Zanba-processed Tiebangchui. Eleven diterpenoid alkaloids were isolated by means of chromatographic techniques, including silica gel column chromatography. Their structures were elucidated by extensive spectroscopic analysis (single-crystal X-ray diffraction, IR, HR-ESI-MS) and comparison with literature data. The compounds were identified as 12-epi-turpelline (1), 12-epi-napelline (2), 12-acetyl-napelline (3), azitine (4), flavaconitine (5), nagarutine C (6), nagarutine D (7), 16-epi-pyroaconine (8), spicatine B (9), 3-deoxyaconitine (10), and napelline (11). Notably, compound 1 was characterized as a novel alkaloid. Additionally, compounds 3–9 were isolated from this processed material for the first time. These findings provide crucial chemical insights into the detoxification mechanism of Zanba processing. Subsequent pharmacological evaluation revealed that compounds 10 and 11 exhibit notable anti-inflammatory activities. Moreover, given the structural analogy between the novel alkaloid 1 and the active compound 11, compound 1 is proposed as a promising lead for future structure–activity relationship studies and semi-synthetic modification. Full article

Tuberculosis remains a major public health concern in Uganda, one among the thirty high TB burden countries globally. Despite national progress, gaps persist due to asymptomatic disease, diagnostic limitations, and uneven access to healthcare within the country. This study implemented the Epi-control platform, an AI-driven predictive modelling tool, to predict community-level hotspots and support data-driven active case-finding (ACF). Using retrospective chest X-ray screening data, we integrated demographic, environmental, and human development indicators from open-source databases to model TB risk at sub-parish level. A proprietary Bayesian modelling framework was deployed and validated by comparing TB yields between predicted hotspots and non-hotspot locations. Across Uganda, the model identified significantly higher TB yields in hotspot areas (risk ratio = 1.69, 95% CI 1.41–2.02; p < 0.001). The Central and Western regions showed the highest concentrations of hotspots, consistent with their population density and urbanization patterns. The results show that the model prioritized areas with higher observed ACF yield in this retrospective dataset, supporting its potential operational use for screening prioritization under similar implementation conditions. The results demonstrate that AI-based predictive modelling can enhance the efficiency of ACF by targeting high-risk areas for screening. Integrating such predictive tools within national TB programmes may support screening planning and resource prioritization; prospective evaluation and external validation are needed to assess generalisability and incremental impact. Full article

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