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Natural products with dual anti-SARS-CoV-2 activity and selective cytotoxicity against leukemia cells from Rhaponticum carthamoides
Abstract Rhaponticum carthamoides ( Leuzea carthamoides ) is a Siberian medicinal plant known for a variety of beneficial effects and traditionally used in Russia and Eastern Europe. However, its potential as a source of antiviral agents and compounds with selective cytotoxicity against cancer cells remains underexplored. In this study, nine flavonoids, including ( 2R )-eriodictyol 5-O-β-glucopyranoside, ( 2S )-eriodictyol 5-O-β-glucopyranoside, eriodictyol 7-O-β-glucopyranoside, eriodictyol, quercetagetin 7-O-β-glucopyranoside, 6-hydroxykaempferol 7-O-β-glucopyranoside, 6-methoxyquercetin 7-O-β-glucopyranoside, spinacetin 7-O-β-glucopyranoside and 6-methoxykaempferol 3-O-β-glucopyranoside were isolated and characterized from the plant’s leaves. Their individual structures were determined by 2D NMR spectroscopy techniques and mass spectrometry. The compounds were tested for cytotoxic activity against an acute myeloid leukemia (AML) cell line (MOLM-13), and two non-malignant cell lines representing kidney epithelium (NRK) and cardiomyocyte (H9c2). Three compounds, quercetagetin 7-O-β-glucopyranoside, 6-methoxyquercetin 7-O-β-glucopyranoside, and spinacetin 7-O-β-glucopyranoside showed selective cytotoxicity towards MOLM-13 cells at 28–50 µM concentrations with little or no effect on the non-malignant cells. Notably, spinacetin 7-O-β-glucopyranoside was effective against MOLM-13 cells without affecting the viability of the non-malignant NRK and H9c2 cells, and it showed synergistic activity with the bench-mark AML drug daunorubicin. In SARS-CoV-2 pseudovirus neutralization assays, spinacetin 7-O-β-glucopyranoside and 6-methoxykaempferol 3-O-β-glucopyranoside demonstrated significant antiviral activity against variant Omicron (XBB 1.5) and some antiviral activity against Delta (B.1.617.2.) in A549 ACE2/TMPRSS2 cells. These findings identify spinacetin 7-O-β-glucopyranoside as a promising dual-acting compound with both anti-leukemic and antiviral properties, emphasizing the relevance of natural products in modern drug discovery.
Excitonic energy transfer in red algal Photosystem I reveals an evolutionary bridge between cyanobacteria and plants
Photosystem I (PSI) converts light into chemical energy with near-unity quantum efficiency, yet its energy-transfer and charge-separation mechanisms remain debated. Evolution has diversified PSI architectures: Cyanobacterial PSI trimers confine red-shifted pigments to the core, whereas plant PSI-Light Harvesting Complex Isupercomplexes incorporate extensive peripheral red and charge-transfer states that reshape trapping. The unicellular red alga Cyanidioschyzon merolae exemplifies functional diversification across distinct evolutionary branches, combining a photosystem II and plant-like monomeric PSI core associated with a varying number of light harvesting antenna subunits, Light Harvesting Complexes from Red Lineage (LHCR). This hybrid organization functionally bridges mechanistic models across different lineages. We applied two-dimensional electronic spectroscopy at ultralow temperatures (8 and 80 K) to disentangle overlapping excitation pathways in C. merolae PSI. Cryogenic measurements suppressed thermal broadening, resolving five dynamical components: subpicosecond equilibration (0.3 to 0.8 ps) across the core–LHCR interface, subsequent population transfer (2.6 to 4 ps) into progressively lower-energy manifolds, and slower feeding (18 to 53 ps) into red pools distributed across both core and antenna. On the longest timescales (hundreds of ps), a persistent ground-state bleach signifies excitons stabilized in terminal sinks. Notably, comparison of 8 K and 80 K spectra reveals that excitations are heterogeneously partitioned among multiple sinks at low disorder, whereas modest thermal activation (kT ∼ 55 cm −1 ) promotes selective convergence into core-associated red chlorophylls. Atomistic excitonic modeling with time-nonlocal master equations supports these observations, revealing temperature-dependent energy redistribution. Overall, C. merolae PSI expands the kinetic funnel by distributing trapping sites, enhancing spectral coverage while maintaining high efficiency, which is an important functional diversification during evolution.
Cost analysis of a sequential antimicrobial therapy protocol in patients with pneumonia: A multicenter study
Pneumonia is one of the leading causes of hospitalization and mortality due to infectious diseases and is also responsible for a substantial proportion of antimicrobial prescriptions. This study aimed to analyze the clinical outcomes and the economic implications associated with a sequential antimicrobial in hospitalized patients with pneumonia. This was a multicenter, retrospective, observational cost analysis study conducted in four private Brazilian hospitals between January 2022 and December 2023. A total of 185 medical records from patients undergoing the sequential therapy protocol were included. Clinical outcomes, length of hospital stay, acceptability among physicians of pharmacist-led interventions for switching the route of administration, and the direct costs related to medications and human resources were assessed according to a microcosting methodology. Among the included patients, 74.6% transitioned to the oral route, and 88.4% showed a positive clinical outcome. Sequential therapy was associated with a significant reduction in mean length of stay (10.1 vs. 14.7 days; p = 0.024) and was associated with 55% lower treatment costs, corresponding to an estimated cost avoidance of US$ 4,529.96. The findings suggest that sequential antimicrobial therapy is an safe and economically advantageous strategy that contributes to the rational use of antimicrobials and the optimization of hospital resources.
RadCube MAGIC observations of complex field aligned currents associated with a supersubstorm during the May 2024 geomagnetic storm
Abstract Geomagnetic storms are a key driver of space weather impacts. The enhancement of ionospheric currents during these events can produce geomagnetically induced currents (GICs) that may interfere with the operation of ground infrastructure such as power grids, pipelines, and railway networks. It is therefore critical to understand how, why, and when very intense GICs may occur during an extended geomagnetic storm interval. Supersubstorms are extremely intense substorms which may occur during the main or recovery phases of geomagnetic storms. These rare events bear special investigation because they may have a significant impact on GIC formation during extreme geomagnetic storms. Multiple supersubstorms were observed during the May 2024 geomagnetic storm, and here we report new observations of supersubstorm field aligned currents (FACs), observed in situ by the MAGnetometer from Imperial College (MAGIC) instrument on the RadCube technology demonstration CubeSat. These measurements provide new insight into the detailed structure of supersubstorm FACs, complementing global FAC maps, and reveal an extended spatial region containing magnetic fluctuations across a broad range of spatial/temporal scales, including intense localised current spikes. As well as revealing new details about supersubstorm-related FACs, these observations illustrate the need for dense constellations of low-Earth-orbit satellite-based magnetometers for space weather monitoring.
Intentional incisions on Neolithic Obsidian arrowheads from Central Anatolia: A techno-functional and iconographic approach
Incised obsidian arrowheads form a rare and geographically restricted artifact class, known exclusively from Neolithic Central Anatolia between the late 8th and 7th millennia BCE. These artifacts, marked by deliberate incisions, have been variously interpreted as symbolic or identity-related. This study presents a comprehensive techno-functional and iconographic analysis of eleven newly identified specimens from Tepecik-Çiftlik (Cappadocia, Türkiye), adding to the regional corpus of 43 known examples. The incised arrowheads were found in dwelling sites, a chipped stone workshop, and during surveys.Provenance analysis by macroscopic characterization confirms their production from local Cappadocian obsidian sources (Göllüdağ, Nenezi Dağ). The incisions are highly variable, and show no correlation with raw material, chaîne opératoire , typology, or use-wear. Incisions were executed both before and after final retouching, suggesting no fixed production stage. Comparative analysis reveals parallels between sites, indicating a possible shared but flexible iconographic repertoire. The rarity of these artifacts, their relation to domestic contexts, and their absence beyond Central Anatolia point to the hypothesis of a shared cultural practice. The analysis of these incised arrowheads, along with the limited archaeological and ethnographic comparisons available, calls for a cautious interpretation. While they have been suggested as personal or collective markers (e.g., hunters’ marks), this hypothesis requires further evidence. The expanded dataset from Tepecik-Çiftlik refines the understanding of this peculiar practice, highlighting its persistence despite broader cultural change.
Combination therapy with doxorubicin and Berberis asiatica induces mitochondrial-mediated apoptosis and inhibits the PI3K/Akt pathway in non-Hodgkin lymphoma
The unique Efg1 fungal virulence regulon in the catheterized bladder environment
Urinary catheterization, a frequent procedure in hospitals, nursing homes, and other healthcare facilities, is a primary driver of nosocomial infections. The most common of these are catheter-associated urinary tract infections (CAUTIs), which often progress to severe complication, sepsis, and ultimately death. The fungus Candida albicans is a primary causative agent of CAUTIs; yet, its tissue-specific pathogenesis remains poorly understood, which complicates development of efficient treatments. While Efg1 is a known virulence driver in CAUTI, its specific downstream targets within the unique bladder environment have not been defined. Here, we identify and validate the EFG1 regulon that is active during conditions that mimic the human catheterized bladder and, additionally, confirm the regulon by transcriptional profiling of catheters retrieved from patients with C. albicans infection. We found that this urine-specific signature is highly conserved in clinical samples, with Efg1-dependent genes being among the most robustly induced transcripts during active human infection. Furthermore, we characterized two of these key factors, ECE1 and EED1 , validating their roles in infection both in vitro in human urine and in vivo using a CAUTI mouse model. Elucidating this tissue-specific regulon offers a strategic roadmap for the development of targeted therapies to mitigate these ever-increasing life-threatening fungal infections.
Factors affecting lung cancer stage at diagnosis and receipt of surgery in Ontario: A population-based analysis
Lung cancer is the leading cause of cancer mortality in Canada, with most cases diagnosed at advanced stage. Despite universal healthcare, social determinants of health may impact stage at diagnosis and access to treatment. We examined the association between these factors, stage at diagnosis, and receipt of surgery in Ontario. We conducted a population-based retrospective cohort study of adults diagnosed with lung cancer in Ontario from 2007–2023 using linked administrative health data. Stage was obtained from the Ontario Cancer Registry. Factors included income, primary care attachment, immigration status, geographic region, and distance to the nearest cancer centre. Logistic regression identified factors associated with stage IV diagnosis. Among 106,867 patients with available stage data, 52.6% were diagnosed with stage IV disease; 19.1% were stage I. Patients without a family physician were significantly more likely to present with stage IV cancer compared with those fully rostered (62.1% vs 51.5%; adjusted OR 1.55, p < 0.001). Females had lower likelihood of stage IV diagnosis than males (OR 0.85, p < 0.001). Increasing household income was associated with reduced likelihood of stage IV disease (OR 0.92 for highest vs lowest quintile, p < 0.001). Immigrants were less likely to be diagnosed with stage IV cancer than non-immigrants (OR 0.77, p = 0.001). Frailty was associated with higher odds of stage IV disease (OR 1.01, p = 0.009). Surgical resection was performed in 56.1% of patients with stage I disease and 1.4% with stage IV disease. Receipt of surgery decreased with advancing age (27.0% < 50 years vs 7.3% ≥ 80 years), higher comorbidity burden (25.4% with 0 vs 5.0% with ≥5 comorbidities), and lack of primary care attachment. Marked social inequities in lung cancer stage at diagnosis and surgical treatment persist in Ontario. Interventions addressing primary care attachment and upstream social determinants may improve early detection and access to curative therapy.
Fast and lightweight 6D object pose estimation for efficient robotic grasping
Statutory construction and interpretation for AI
AI systems are increasingly governed by natural language rules, yet a key challenge arising from reliance on language remains underexplored: interpretive ambiguity. As in legal systems, ambiguity arises both from how these rules are written and how they are applied. But while legal systems use institutional safeguards to manage such ambiguity, such as transparent appellate review policing interpretive constraints, rule-based AI alignment pipelines lack comparable protections. Different interpretations of the same rule can lead to inconsistent model behavior. Drawing on U.S. legal theory, we identify key gaps in current rule-based alignment pipelines by examining how legal systems constrain ambiguity at both the rule creation and rule application steps. We then propose a computational framework that formalizes interpretive ambiguity as constrained entropy minimization and introduces two law-inspired mechanisms: 1) a rule refinement pipeline that minimizes interpretive disagreement by revising ambiguous rules (analogous to agency rulemaking or iterative legislative action), and 2) prompt-based interpretive constraints that reduce disagreement during rule application (analogous to legal canons that guide judicial discretion). We evaluate our framework on a 5,000-scenario subset of the WildChat dataset and show that both interventions significantly improve judgment consistency across a panel of reasonable interpreters. Our approach offers a step toward systematically managing interpretive ambiguity, an essential step for building more robust, law-following AI systems.
Preoperative anxiety: Is it affected by preoperative counseling and surgical technique?
Background Preoperative anxiety (PA) is a common psychological response that can adversely affect patient satisfaction and surgical complications and outcomes. To reduce these effects, several studies were conducted to identify the factors that influence the severity of PA; however; none of the studies have examined the relationship between the PA and factors related to preoperative surgical and anesthetic counseling and the type of surgical technique. Methods A cross-sectional questionnaire-based study was carried out between November 2023-January 2024, involving patients aged 18 years or older who were scheduled for surgical procedures at our institute. Anxiety levels were assessed using the Amsterdam Preoperative Anxiety and Information Scale (APAIS). PA was stratified into low (<11) and high (≥11) anxiety based on the total anxiety (both anesthesia- and surgery-related) scores. Results The prevalence of clinically significant PA was 39.7%. In addition to the previously identified factors such as female gender, younger age and unemployment status, other factors which were also associated with higher PA included fewer pre-operative surgical consultations, longer duration of each surgical consultation, undergoing laparoscopic procedures instead of open surgery, referral to an internist for further evaluation of preexisting medical conditions and use of general anesthesia or uncertainty about the type of anesthesia (P < 0.05 for all). However, the number of anesthetic consultations and the surgeon’s level of experience were not significantly associated with PA. Interestingly, using illustrations and figures during consultations was also associated with higher PA (P < 0.05) while searching the internet for more information, did not have an effect. Conclusions Preoperative anxiety remains a significant concern and was associated with factors related to gender, employment status, preoperative surgical and anesthetic counseling, surgical technique and type of anesthesia. These findings might help in formulating targeted interventions to reduce preoperative anxiety and improve surgical outcomes.
Dyeing performance of Lawsonia inermis leaf extract on mulberry silk fibre: effect of cocoon stifling and mordanting method
Abstract The present study evaluated the influence of cocoon stifling and mordanting methods on the dyeing performance of Lawsonia inermis leaf extract on raw mulberry silk fibre. Silk fibres obtained through open sun drying, open sun drying with black cloth, barrel steaming, and hot air oven drying were dyed using henna extract (15%) with ferrous sulphate (3%) mordant under pre-, simultaneous-, post-, and without-mordanting methods. Significant differences were observed in percent dye absorption, colour coordinates, colour strength, and fastness properties among treatments. The highest dye absorption (78.73 ± 3.43%) was recorded in silk obtained through open sun drying with black cloth under post-mordanting, whereas simultaneous mordanting showed the highest ΔE (64.66 ± 3.85) and colour strength (K/S 3.76 ± 0.52). Mordanted samples exhibited better dye fixation and colour fastness than unmordanted samples. The study demonstrates that cocoon stifling history significantly affects the dyeability of silk fibre and confirms the potential of henna as a sustainable natural dye for eco-friendly silk coloration.
Glucocorticoid receptors in oligodendrocyte precursor cells regulate hippocampal network plasticity and stress-induced behavior in mice
Glucocorticoid receptors (GRs) are key mediators of how the stress hormone glucocorticoids (GCs) shape postnatal brain development and adaptive plasticity. Because GC signaling is critical during this period, postnatal GC concentrations are tightly regulated in the brain, whereas excessive levels of circulating GCs can disrupt developmental trajectories and increase the risk of psychiatric disorders later in life. GR function influences multiple neural cell types, but its cell-specific roles, particularly early in development, remain poorly understood. Oligodendrocyte precursor cells (OPCs), which generate myelinating oligodendrocytes and actively modulate neuronal networks, express GRs and can therefore respond to fluctuations in GC levels. Although excessive GC exposure during early life adversity has been linked to changes in OPC development, the physiological role of GR signaling specifically within OPCs remains unclear. To address this, we conditionally deleted GRs in postnatal OPCs in mice to investigate the role of physiological GC signaling in OPC proliferation and maturation, as well as in neuronal network activity and behavior. This deletion resulted in reduced oligodendrocyte and myelinated axon density in the hippocampus, sex-specific alterations in hippocampal activity and long-term potentiation following acute challenge, and impairments in memory formation in adulthood. Our findings reveal an OPC-specific role for GRs and suggest that physiological GR activity in the oligodendrocyte lineage contributes to normal hippocampal plasticity, learning, and memory.
Beyond speed and strategy: A configurational analysis of collective attention to post-match institutional discourse in the UEFA Champions League
Post-match institutional communication has become a visible component of elite football events, yet comparable official messages can receive very different levels of public attention. This study examines UEFA Champions League post-match communication as a configurational problem rather than as a linear consequence of response speed or message strategy. Using 25 theoretically selected focal club-event observations from the 2017–2018–2022–2023 seasons, it calibrates one outcome set, High_News, from a Raw_Mentions-derived media-visibility proxy and four causal-condition sets: High_Delay, High_Shock, High_Stakes, and High_TemplateDeviation. The analysis uses conservative coding of template deviation, separating response latency from communication form. The intermediate solution identifies one stable high-stakes legacy pathway and one sensitivity-dependent crisis-minimalism pathway. The stable pathway combines non-delayed response, low outcome shock, high match stakes, and trophy/legacy-oriented template deviation. The crisis-minimalism pathway is retained in the baseline solution but is interpreted cautiously because it depends on medium-confidence coding and changes under strict recoding. The analysis of ~High_News confirms causal asymmetry: non-membership in the high-attention set is not simply the inverse of the pathway(s) associated with High_News. The findings contribute to sport communication research by showing how event structure and institutional discourse combine to produce bounded media visibility, while avoiding population-level claims about all football matches or internal platform algorithms.
Prenatal exposure to toxic and essential trace elements in Syrian newborns: a meconium biomonitoring study
Identification of a conserved gene family with an essential role in <i>Leishmania</i> parasite–insect vector adhesion
Adhesion to tissues and surfaces is used by pathogens to avoid clearance, maintain infections, and facilitate transmission. An important example is the adhesion of the Leishmania parasite to the stomodeal valve of its insect vector, the sand fly, which is important for life cycle progression, and occurs through its flagellum via a cytoskeletal adhesion complex. While three essential kinetoplastid-insect adhesion proteins (KIAPs) are known, the overall proteome of the adhesion complex is obscure. Using TurboID-tagged KIAP3 combined with proteomics and light microscopy, we have identified additional proteins associated with the adhered flagellum, including multiple members of the Adhesion Related NTPase-like Domain (ARND) family, of which the canonical member is KIAP4, described here. Phylogenetic analysis of the ARND family showed it is conserved across the kinetoplastids, and we demonstrate that Trypanosoma congolense paralogs localize to the adhered flagellum in that parasite. Deletion of KIAP4 severely impaired haptomonad adhesion, with the mutant parasites unable to colonize the sand fly stomodeal valve. Our work provides details of the molecular machinery essential for vector colonization and shows that these proteins have a conserved function in other kinetoplastid parasites.
Distribution and efficacy of ingested dsRNA targeting tissue-specific genes in the Argentine ant, Linepithema humile
With the increasing availability of genomic and transcriptomic information within Formicidae, the investigation of gene function has become possible within ants. However, eusocial life history renders the generation of mutagenic strains of ants difficult outside of specific ant lineages that can induce reproductive behavior in workers. RNA interference (RNAi) remains a practical option to investigate gene function within their genomic context in ant lineages that do not exhibit reproductive behavior in workers. This method can be leveraged to investigate the large odorant receptor (OR) gene families present in ant clades. However, ORs tend to be expressed in a tissue-specific fashion, and the capability of dsRNA to achieve knockdown of genes exhibiting localized expression remains uncertain. In this study, we use fluorescently labelled dsRNA to track the spread of dsRNA through the worker body, qPCR to verify that dsRNA can knockdown gene expression in the antennae, and behavioral trials to verify that knockdown of ORs affects nestmate recognition. Our results show ingested dsRNA is able to reach the antennae and knock down odorant coreceptor ( orco ) expression in the antennae. We determined that orally-administered dsRNA is capable of being spread systemically and knocking down tissue-specific genes. These findings show that RNAi may be useful in investigating the influence of ORs in eusocial insect nestmate recognition.