Search Results (139)

We present archival photometry from the Gravitational-wave Optical Transient Observer (GOTO) for four Galactic novae discovered between 2017 and 2024, spanning some of the faintest ZTF24aaomlxy and PGIR22akgylf (at a marginal near-limit level consistent with the practical limiting magnitude of calibrated L to the brightest V1405 Cas and V1674 Her recent eruptions. For each object, we extract GOTO measurements obtained at or near the pre-eruption state, excluding data points with observational uncertainties exceeding 0.5 mag (except for the faintest PGIR22akgylf). The resulting light curves show that GOTO can detect nova progenitors close to its observable limiting depth at calibrated L magnitudes approaching the survey’s practical limiting magnitude, providing meaningful constraints on quiescent brightness, possibly for systems that were only sparsely monitored using surveys such as ZTF and PGIR. These detections demonstrate that wide-field imaging originally designed for gravitational-wave follow-up can yield meaningful limits on both faint and fast-evolving nova progenitors. Simultaneously, we improve the sky positions of five Galactic novae—ZTF24aaomlxy, V3732 Oph, V2000 Aql, V3666 Oph, and V659 Sct—whose published coordinates are affected by crowding or limited precision. Using high-cadence photometry from ZTF and AAVSO, we identify the actual eruption source in each field and obtain revised coordinates that differ by several arcseconds. These findings highlight the importance of time-domain archives for identifying faint nova progenitors and improving astrometric accuracy across the Galactic nova population. Full article

Background: Fructans are fructose-based polysaccharides with diverse biological activities; however, their direct activity on skin cells remains unresolved. This study investigated the biological activity of fructan extracted from rakkyo (Allium chinense) (RF) and examined its effects on extracellular matrix (ECM) metabolism, particularly collagen and hyaluronan synthesis, in human dermal fibroblasts. Methods: RF was prepared from fresh rakkyo bulbs by aqueous extraction, alkaline clarification, and membrane filtration. The average molecular weight and structural characteristics of RF were analyzed using size-exclusion chromatography and ¹³C NMR spectroscopy. Normal human dermal fibroblasts (NHDFs) were treated with RF by culturing cells in RF-supplemented medium (0.1–1.0 mg/mL). Cell viability and viable cell number were evaluated using the thiazolyl blue tetrazolium bromide and trypan blue exclusion assays, respectively. Expression of ECM-related genes was analyzed by qRT-PCR, and collagen and hyaluronan production were quantified by Sirius Red staining and ELISA. Results: RF had an average molecular weight of approximately 11,500 Da and consisted of nearly equal proportions of inulin- and levan-type fructans. RF (≤1 mg/mL) increased the number of viable cells and markedly upregulated collagen, type I, alpha 1 (COL1A1) and hyaluronic acid synthase 2 (HAS2) expression while downregulating Hyal1 expression. After 9 days of treatment, the cumulative production of type I collagen and hyaluronic acid increased by 3.8- and 1.3-fold, respectively, as compared with controls. Upregulation of lysyl oxidase (LOX) mRNA suggested enhanced collagen cross-linking, whereas MMP-1 showed only modest induction. Conclusions: Rakkyo-derived fructan directly stimulates collagen and hyaluronan synthesis in dermal fibroblasts, likely through regulation of ECM-related genes. These results suggest that rakkyo-derived fructan modulates ECM-related readouts in NHDFs under controlled in vitro conditions. Further validation in more complex skin models and in vivo studies is necessary. Full article

Melatonin, an indolic neuromodulator with putative oncostatic and proposed anti-inflammatory properties, primarily demonstrated in preclinical models, is produced at extrapineal sites—most notably in the gut. Its canonical actions are mediated by high-affinity GPCRs (MT1/MT2) and by NQO2, a cytosolic enzyme with a melatonin-binding site (historically termed “MT3”). A growing body of work highlights a bidirectional interaction between the gut microbiota and host melatonin. We integrated two lines of work: (i) three clinical cohorts—cardiac arrhythmias (n = 111; 46–75 y), epilepsy (n = 77; 20–59 y), and stage III–IV solid cancers (25–79 y)—profiled with stool 16S rRNA sequencing, SCFA measurements, and circulating melatonin/urinary 6-sulfatoxymelatonin and (ii) an age-spanning cognitive cohort with melatonin phenotyping, microbiome analyses, and exploratory immune/metabolite readouts, including a novel observation of melatonin binding on bacterial membranes. Across all three disease cohorts, we observed moderate-to-severe dysbiosis, with reduced alpha-diversity and shifted beta-structure. The core dysbiosis implicated tryptophan-active taxa (Bacteroides/Clostridiales proteolysis and indolic conversions) and depletion of SCFA-forward commensals (e.g., Faecalibacterium, Blautia, Akkermansia, and several Lactobacillus/Bifidobacterium spp.). Synthesised literature indicates that typical human gut commensals rarely secrete measurable melatonin in vitro; rather, their metabolites (SCFAs, lactate, and tryptophan derivatives) regulate host enterochromaffin serotonin/melatonin production. In arrhythmia models, dysbiosis, bile-acid remodelling, and autonomic/inflammatory tone align with melatonin-sensitive antiarrhythmic effects. Epilepsy exhibits circadian seizure patterns and tryptophan–metabolite signatures, with modest and heterogeneous responses to add-on melatonin. Cancer cohorts show broader dysbiosis consistent with melatonin’s oncostatic actions. In the cognitive cohort, the absence of dysbiosis tracked with preserved learning across ages, and exploratory immunohistochemistry suggested melatonin-binding sites on bacterial membranes in ~15–17% of samples. A unifying microbiota–tryptophan–melatonin axis plausibly integrates circadian, electrophysiologic, and immune–oncologic phenotypes. Practical levers include fiber-rich diets (to drive SCFAs), light hygiene, and time-aware therapy, with indication-specific use of melatonin. Our conclusions regarding microbiota–melatonin crosstalk rely primarily on local paracrine effects within the gut mucosa (where melatonin concentrations are 10–400× plasma levels), whereas systemic chronotherapy conclusions depend on circulating melatonin amplitude and phase. This original research article presents primary data from four prospectively enrolled clinical cohorts (total n = 577). Full article

Glacier inventories are critical for monitoring glacier response to climate change, providing constraints for glacier modeling studies and for assessing the impacts of glacier retreat on ecosystems and human societies. In the Bhutanese Himalaya, an up-to-date glacier inventory and a systematic analysis of decadal-scale glacier changes is lacking. Here, we present three glacier inventories (1976, 1998, and 2024) for this region. Manual mapping of glacier outlines from multi-source satellite imagery and the Copernicus digital elevation model (DEM) are used to derive a glacier inventory with associated topographic attributes. We found that 1871 glaciers existed in this region in 1976, covering an area of 2297.07 ± 117.15 km². By 1998 this number had reduced to 1803 glaciers, covering 2106.99 ± 90.60 km². In 2024, only 1697 glaciers remained, covering 1584.18 ± 36.37 km². A total of 89 (1976–1998) and 435 (1998–2024) glaciers became extinct in the Bhutanese Himalaya during these two time periods, and glacier area decrease accelerated from ~0.38% yr⁻¹ to ~0.95% yr⁻¹. Lake-terminating glaciers retreated almost three times faster (~32.2 m yr⁻¹) than land-terminating (~10.4 m yr⁻¹) glaciers during the observation period. Debris-covered glacier area increased from 112.79 ± 11.50 km² in 1976 to 128.89 ± 10.50 km² in 2024. Glaciers on the South Bhutanese Himalaya (draining into Bhutan) experienced faster glacier retreat than the glaciers of the North Bhutanese Himalaya (draining into the Tibetan Autonomous Region). ERA5-Land reanalysis data show that summer decadal average temperature in this region increased by 0.003 °C yr⁻¹ between 1976 and 1998 and 0.020 °C yr⁻¹ between 1998 and 2024, with the increase in warming rate coinciding with accelerated glacier retreat after 1998. Our updated glacier inventories will be useful for assessments of global sea level change, mountain hazards, and water resources. Full article

Background: No machine learning (ML) models for sepsis prediction have been specifically developed for patients with prolonged or chronic critical illness (PCI/CCI). Objective: This study aimed to develop and validate an ML-based sepsis prediction model for this cohort. Methods: We analyzed ICU admissions from the Russian Intensive Care Dataset (RICD, 575 patients with PCI/CCI) and two public ICU datasets from the PhysioNet (>40,000 patients with acute critical illness). Models were trained within a right-aligned prediction framework using a case–crossover–control sampling approach and a 6 h prediction window. Two strategies were evaluated: (1) a PCI/CCI-focused model trained on RICD with external testing on PhysioNet data and (2) a universal model trained on combined RICD and PhysioNet cohorts. Models were developed with tree-based algorithms (XGBoost, LightGBM, Random Forest, AdaBoost), with internal and external validation. Primary outcome was model discrimination (AUROC). Subgroup analyses were performed for sepsis phenotypes. Results: The PCI/CCI-focused XGBoost model achieved an AUROC of 0.82 in the RICD cohort but failed to generalize to external ICU populations (AUROC 0.47). A universal model trained on mixed data demonstrated reduced discrimination in PCI/CCI patients (AUROC mean difference 0.02, p = 0.0012). Respiratory rate, heart rate, body temperature, and age were among the most important features. Predictive performance was higher in hypoinflammatory sepsis phenotype (AUROC 0.84 vs. 0.81 for hyperinflammatory, p < 0.001). Despite worthless positive predictive value (up to 21%) for PCI/CCI-focused model, negative predictive value exceeded 97%. Conclusions: A right-aligned ML model tailored to PCI/CCI demonstrated strong internal performance for sepsis exclusion but limited cross-population generalizability, underscoring the need for population-specific prediction models and prospective validation before clinical application. Full article

This article examines the challenges associated with implementing and applying the new valuation approaches introduced by IPSAS 46 in the public sector, specifically fair value and current operational value. The analysis is based on thematic survey data collected from professionals engaged in public sector accounting and reporting, as well as a diverse range of documentary sources. Although the study does not include a factor analysis and its conclusions are limited to the Georgian context, thematic grouping revealed key determinants influencing the implementation of IPSAS: professional competence, resource availability, and managerial attitudes towards development and perceived need. Additional situational limitations existed, as the study was conducted prior to the official translation of IPSAS 46 and its incorporation into the national guidance. Despite these constraints, the findings may hold relevance for other countries facing similar challenges of limited resources, professional capacity, and managerial attitudes. The study provides recommendations for integrating IPSAS 46 principles into local standards. Full article

Background: Targeting cancer tumors using PLGA (Poly(D, L-lactide-co-glycolide)) nanoparticles (NPs) requires clathrin-mediated endocytosis (CME) and lysosomal degradation to provide release within cancer cells. However, Caveolae-mediated endocytosis (CavME) provides lysosomal escape, which is favorable in oral applications. Macropinocytosis (MPC) is a non-targeted way of endocytosis, used by immune cells. Methods: In this proof-of-concept study, we investigated how polysaccharide surface coatings modulate the endocytic uptake of FITC-labeled PLGA nanomicelles (FPM) in MCF-7 breast cancer cells using spectrophotometry. This research involved the surface modification of FPM using polysaccharides: cellulose (FPCM) as a polyglucan and Halomonas Levan (FPLM) as a polyfructan, to modify the NP and cell-surface association. Results: MPC was found to be the major internalization pathway for the nanomicelles ~200 nm. However, after surface modification, FPCM and FPM remained highly MPC-dependent with additional CavME/CME involvement, whereas FPLM showed relatively reduced MPC dependence and a higher CME contribution. Conclusion: Overall, the results indicate that simple polysaccharide coatings can bias the relative use of MPC, CME, and CavME for PLGA nanomicelles in MCF-7 cells, providing a basis for pathway-oriented nanocarrier design. Validation by flow cytometry, studies in additional breast cancer cell lines, and transporter-level investigations will be needed to generalize and refine these findings. Full article

Background/Objectives: Accurate prognostication for patients with chronic critical illness (CCI) following brain injury remains challenging. Conventional scoring systems like the Acute Physiology and Chronic Health Evaluation II (APACHE II) and the Nutrition Risk in the Critically Ill (NUTRIC) score are validated as “left-side” models for risk stratification at intensive care unit (ICU) admission but may not capture the evolving trajectory of prolonged illness. This study aimed to evaluate the prognostic performance of APACHE II and NUTRIC as “right-side” models—assessed at intervals closer to the outcome—by testing the hypothesis that their predictive accuracy for in-hospital mortality improves when measured nearer to the time of death. Methods: In this real-world data analysis study, data were extracted from the electronic health records (Russian Intensive Care Dataset [RICD] v. 2.0) of 328 adult patients with CCI following brain injury. The discriminative ability of repeatedly assessed APACHE II and NUTRIC scores for predicting mortality was analyzed by calculating the area under the receiver operating characteristic curve (AUROC) for three predefined intervals before death: within ≤7 days, 8–14 days, and ≥15 days. Results: Among the 328 patients (median age 64 years; 18.3% in-hospital mortality), a total of 380 paired score assessments were analyzed. The predictive performance for both scores was highest within 7 days of death (APACHE II AUROC: 0.883; NUTRIC AUROC: 0.839). Discriminatory ability declined at 8–14 days (APACHE II AUROC: 0.807; NUTRIC AUROC: 0.778) and was poorest at ≥15 days before death (APACHE II AUROC: 0.671; NUTRIC AUROC: 0.681). The NUTRIC score consistently demonstrated higher AUROC values than APACHE II across all intervals, though the differences were not statistically significant. Conclusions: In patients with CCI following brain injury, the prognostic accuracy of APACHE II and NUTRIC scores is time-dependent, peaking immediately before death and offering poor long-term prediction from admission. These findings underscore the limitation of static, admission-based models and highlight the necessity for developing dynamic, personalized and time-sensitive prognostic tools tailored to the evolving course of chronic critical illness. Full article

Background: Advances in intensive care have markedly improved survival from acute critical illness. Nevertheless, the subsequent trajectory of these patients is heterogeneous: while most recover and are eventually discharged, approximately 10% remain dependent on life-support systems, forming a distinct group classified as chronic critical illness (CCI). These patients experience prolonged ICU stays, high mortality, and poor long-term outcomes. Prognostication in CCI remains challenging, as traditional severity scores based on admission data seem to lose prognostic accuracy progressively over longer ICU stays. This is particularly relevant in traumatic brain injury (TBI), where patients constitute a significant proportion of the CCI population and require specialized prognostic approaches. Objective: To develop and validate prognostic models for in-hospital mortality in patients with TBI who progress to chronic critical illness, comparing the performance of a traditional admission-based (left-aligned) model with a novel dynamic (right-aligned) model utilizing data from the week preceding the outcome. Methods: A real-world data analysis was conducted using the Russian Intensive Care Dataset (RICD v2.0). The cohort included 430 ICU admissions of adult TBI patients with a stay of ≥7 days. Multivariable logistic regression was used to develop two nomograms: one using parameters from ICU admission and another using data from 7 days prior to discharge or death. Model performance was assessed via ROC analysis, sensitivity, specificity, and predictive values. Results: The left-aligned model, based on admission data (coronary artery disease, multiorgan failure, CRP), showed moderate discriminative capacity (AUROC 0.720). In contrast, the right-aligned model, incorporating dynamic parameters from the pre-outcome period (lymphocyte count, platelet count, urea, CRP), demonstrated excellent predictive performance (AUROC 0.889), with 90.0% sensitivity and 98.6% negative predictive value. A high score on the right-aligned nomogram was associated with a 19.7-fold increased risk of mortality within the subsequent week. Conclusions: For patients with CCI following TBI, a dynamic prognostic model based on data from the immediate pre-outcome period significantly outperforms traditional admission-based models. The high negative predictive value of the right-aligned model provides a reliable tool for identifying patients with a low short-term risk of mortality, supporting a paradigm shift towards dynamic risk stratification in chronic critically ill patients. Full article

Natural shampoos are increasingly designed to provide multifunctional benefits beyond cleansing, including hair conditioning, scalp protection, and reduced irritation potential. POLEVAN^®, a proprietary levan-based polysaccharide produced enzymatically from sugar, offers a combination of oligo- and polysaccharide fractions with potential cosmetic applications. This study evaluated POLEVAN^® in shampoo formulations for three targeted effects: improving hair glossiness, enhancing scalp moisturization, and boosting foam while enabling reduced surfactant levels. Glossiness was assessed ex vivo using damaged hair tresses. Moisturization was assessed in a randomized clinical trial, comparing the test formulation with hyaluronic acid (HA), employing corneometer readings and Trans Epidermal Water Loss (TEWL) measurements. The study was subject-blinded, and all outcomes were determined solely through quantitative, device-based measurements, minimizing observer bias. Foaming performance was tested using the Shaking Cylinder Method. Shampoos containing 2% POLEVAN^® significantly increased hair glossiness by 24% (p = 0.0375) versus a non-significant increase without POLEVAN^®. Moisturization studies showed no significant difference between POLEVAN^® and HA in maintaining hydration or preventing TEWL over 4 weeks. Foam analysis demonstrated that addition of POLEVAN^® allowed up to 50% reduction in surfactant content without compromising foam generation or stability. These results highlight POLEVAN^® as a multifunctional natural ingredient capable of improving sensory and performance attributes of shampoos while supporting gentler formulations. Full article

Mountain glaciers are sensitive indicators of climate variability, and their retreat since the end of the Little Ice Age (LIA) has strongly reshaped alpine environments worldwide. In the Greater Caucasus, glacier shrinkage has accelerated over the past century, yet detailed multi-temporal reconstructions remain limited for many glaciers. Here, we reconstruct the post-LIA evolution of Tsaneri–Nageba Glacier, one of largest ice bodies in the Georgian Caucasus, and document the development of its newly formed proglacial lake. Using a combination of geomorphological mapping, historical maps, multi-temporal satellite imagery, Uncrewed Aerial Vehicle (UAV) photogrammetry, and sonar bathymetry, we quantify glacier change from ~1820 to 2025 and provide the first direct measurements of a proglacial lake in the Tsaneri–Nageba system—and indeed in the Georgian Caucasus as a whole. Our results reveal that Tsaneri–Nageba Glacier has shrunk from ~48 km² at its LIA maximum to ~30.6 km² in 2025, a loss of −43.5% (or −0.21% yr⁻¹). The pace of shrinkage intensified after 2000, with the steepest losses recorded between 2014 and 2025. Terminus positions shifted up-valley by nearly 3.9 km (Tsaneri) and 4.3 km (Nageba), accompanied by fragmentation of the former compound valley glacier into smaller ice bodies. Long-term meteorological records confirm strong climatic forcing, with pronounced summer warming since the 1990s and declining winter precipitation. A proglacial lake started to form in mid-summer 2015, which by 03/09/15 had a surface area of ~14,366 m², expanding to ~106,945 m² by 10/07/2025. The lake is in contact with glacier ice and is thus prone to calving. It is dammed by unconsolidated moraines and bounded by steep, active slopes, making it susceptible to generating a glacial lake outburst flood (GLOF). By providing the first quantitative measurements of a proglacial lake in the region, this study establishes a baseline for future monitoring and risk assessment. The findings highlight the urgency of integrating glaciological, geomorphological, and hazard studies to support community safety and water resource planning in the Caucasus. Full article

Bacterial exopolysaccharides have emerged as versatile biopolymers for the design of advanced hydrogels with adjustable physico-chemical, mechanical, and biological properties. Among these, levan, a fructose-based exopolysaccharide synthesized by various microbial species, has attracted increasing attention due to its unique structural features, high biocompatibility, and inherent bioactivity. This review provides a comprehensive overview of hydrogel systems derived from bacterial exopolysaccharides, with a particular focus on levan-based hydrogels. We discuss the molecular structure, synthesis pathways, and physico-chemical characteristics of levan that underpin its hydrogel-forming ability. Emphasis is placed on design strategies, including chemical modification, crosslinking approaches, and composite formation, that enable fine-tuning of mechanical strength, swelling behavior, and degradation kinetics. This review further highlights biomedical applications of levan-based hydrogels, encompassing drug delivery, wound healing, rejuvenation, tissue engineering, regenerative medicine, and bioprinting, while addressing current limitations and future research directions. By elucidating the structure–function relationships and emerging fabrication methodologies, this review underscores the biomedical promise of levan as a sustainable and functional biopolymer for next-generation hydrogel technologies. Full article

Levan and levan-type fructooligosaccharides (L-FOSs) are non-digestible fructans with prebiotic properties that promote gut microbiota growth. This study presents the first genomic analysis of a Bacillus velezensis HL25 strain with high fructan-producing efficiency, revealing genes involved in sucrose utilization and fructan biosynthesis. A putative levansucrase operon was identified in the HL25 genome, consisting of the sacB levansucrase gene classified in GH68 subfamily 1 and the following three GH32 genes: endo-levanase (lev), β-fructofuranosidase (ffase), and sucrose-6-phosphate hydrolase (scrB). Remarkably, sugars involved in levan biosynthesis are proposed to be transported through three distinct systems: a multiple-component ABC sugar transporter, a glucose/H⁺ symporter, and glucose- and fructose-specific phosphotransferase systems (PTS). Subsequently, recombinant HL25SacB levansucrase exhibited optimal activity at 40 °C and pH 5.0 in 50 mM sodium acetate buffer. The enzyme demonstrates high specificity in converting sucrose into a mixture of short-chain FOSs (DP 2–4) and levan, achieving a 62.5% conversion rate at 30 °C with 200 g/L sucrose over 24 h. These findings demonstrate the potential of this B. velezensis HL25 strain as an efficient whole-cell biocatalyst and highlight the applicability of the recombinant HL25SacB enzyme as a promising tool for sustainable production of FOSs and levan. Full article

Objectives: Cyclosporin A (CsA) is an immunosuppressive drug that is highly effective. CsA, similar to other drugs with limited oral bioavailability due to poor membrane permeability, requires the use of absorption enhancers in its formulations. Phe-Cys-Ile-Gly-Arg-Leu (FCIGRL-OH), a peptide fragment of Zonula occludens toxin (ZOT), has been studied for its potential to enhance drug absorption by regulating intercellular tight junctions. This study aimed to evaluate the effects of four novel modified peptides, which have been substituted or dimerized at the C-terminus or cysteine moiety of FCIGRL-OH, as improved versions of FCIGRL-OH on the intestinal permeation of CsA. Methods: The four modified peptides used were FCIGRL-NH₂ (Pep-1), homo-dimer peptides derived from FCIGRL-OH and Pep-1 (Pep-2, Pep-3), and a peptide in which the cysteine in Pep-1 was replaced with N₃-substituted dipropionic acid (Pep-4). Pharmacokinetic analysis was performed following intraduodenal administration of CsA with each of four peptides in the presence of levan and benzalkonium chloride (BC) in rats. Results: Results showed that each of Pep-2, Pep-3, and Pep-4 significantly increased intestinal absorption of CsA in the presence of levan and BC. In particular, the area under the curve (AUC_0–360min) for CsA was significantly enhanced by 2.01-fold (p < 0.01) and 2.03-fold (p < 0.05) when treated with Pep-3 and Pep-4, respectively, at a dose of 10 mg·kg⁻¹. Additionally, the maximum plasma concentration (C_max) of CsA increased by 2.46-fold (p < 0.01) with Pep-3 and by 2.37-fold (p < 0.01) with Pep-4. Conclusions: These study findings indicate that Pep-2, particularly Pep-3 and Pep-4, are involved in tight junction opening as novel absorption enhancers for intestinal delivery of CsA. Full article