Search Results (506)

Background: Pancreatic cancer (PC) and colorectal cancer (CRC) are among the most lethal malignancies, with growing evidence pointing to the gut microbiota’s role in their progression. This study aimed to explore the anticancer potential of two microbiota-derived postbiotics, N-acetylcysteine (NAC) and tetrahydro β-carboline carboxylic acid (THC), in targeting some hallmark traits of PC and CRC, both as standalone agents and in combination with standard chemotherapeutics (gemcitabine for PC and 5-fluorouracil (5-FU) for CRC). Methods: Cell viability assays and IC₅₀ determination was assessed using either the Muse™ Count & Viability Kit or the Sulforhodamine B assay; cell death was determined by Annexin V/Propidium Iodide and cell cycle assessed by Propidium Iodide was analyzed by flow cytometry. Results: Here, we found that NAC selectively reduced the viability of PC cells BxPC-3 without triggering apoptosis, while effectively inducing apoptosis in PC cells Panc-1 and in CRC cell lines. THC exhibited stronger anticancer activity, inhibiting proliferation and promoting apoptosis in all tested PC and CRC cells, even at lower concentrations. Combination treatments yielded promising enhancement effects. NAC enhanced the cytotoxicity of gemcitabine in Panc-1 cells through increased apoptosis. NAC, when combined with 5-FU, also increased apoptosis of CRC cells. THC further potentiated gemcitabine’s impact on Panc-1 cells by increasing apoptosis and by inducing cell cycle changes in BxPC-3. In the CRC model, THC co-treatment with 5-FU reduced cell viability and increased apoptosis in all cells. Conclusions: These findings provide preliminary in vitro evidence supporting the potential of integrating microbiota-derived postbiotics with conventional chemotherapy both in PC and CRC. Full article

The aggressiveness of pancreatic ductal adenocarcinoma (PDAC) has been linked to cancer stem cells (CSCs) and telomerase activity; however, the mechanism underlying this association remains unclear. In this study, we engineered dual transcriptional reporters (SORE6-GFP and TERT-BFP) to isolate SOX2⁺OCT4⁺TERT^high subpopulations from AsPC-1 and BxPC-3 cells. We combined Fluorescence-Activated Cell Sorting with functional assays, RNA-seq, and network analysis. Clinically, tumors co-expressing high SOX2/OCT4/TERT levels were associated with reduced overall survival, whereas single-gene elevations were not prognostic. We identified a minority SOX2⁺OCT4⁺TERT^high fraction (~9%) enriched for pluripotency transcripts (SOX2, OCT4, NANOG, and ALDH1A1), which exhibited the highest proliferative, migratory, and invasive capacities. Transcriptomic profiling of SOX2⁺OCT4⁺TERT^high cells showed enrichment of KRAS, telomere maintenance, epithelial–mesenchymal transition, and developmental pathways (WNT and Hedgehog). Connectivity profiling highlighted actionable vulnerabilities, including NF-κB, WNT, and telomerase inhibition pathways. Together, these data define an aggressive telomerase-engaged, pluripotency-driven CSC-like state in PDAC and suggest testable therapeutic strategies that target TERT^high dependencies. Full article

Inoculated fermentation can enhance the flavor, nutrition, and functionality of juice. The lactic acid bacteria (LAB) are commonly used as starter cultures. This study screened LAB for orange juice fermentation and optimized fermentation factors using response surface methodology (RSM) to improve GABA content in orange juice. A total of 52 LAB strains were screened, and Lacticaseibacillus paracasei ZY (Lcb. paracasei ZY) and Lacticaseibacillus rhamnosus SN12 (Lcb. rhamnosus SN12) presented higher GABA yields and adaptability to substrates. The optimized fermentation factors for GABA enhancement in orange juice were as follows: initial pH of 5.5, fermentation temperature of 37 °C, soluble solids content of 12.0 °Bx, inoculum ratio of Lcb. paracasei ZY to Lcb. rhamnosus SN12 as 1:1, inoculum size of 6 Log CFU/mL, and fermentation time of 96 h. Under these optimized conditions, the GABA content reached 0.89 g/L, representing a 39.06% increase compared to uninoculated orange juice. This indicates that RSM-based optimization is conducive to increasing GABA content in orange juice and provides a scientific basis for the development of GABA-enriched functional fermented juices. Full article

In this work, three novel optimization algorithms—collectively referred to as the BxR algorithms—and their multi-objective versions, referred to as the MO-BxR algorithms, are applied to diverse heat transfer systems. Five representative case studies are presented: two single-objective problems involving a heat exchanger network and a jet-plate solar air heater; a two-objective optimization of Y-type fins in phase-change thermal energy storage units; and two three-objective problems involving TPMS–fin three-fluid heat exchangers and Tesla-valve evaporative cold plates for LiFePO₄ battery modules. The proposed algorithms are compared with leading evolutionary optimizers, including IUDE, εMAgES, iL-SHADEε, COLSHADE, and EnMODE, as well as NSGA-II, NSGA-III, and NSWOA. The results demonstrated improved convergence characteristics, better Pareto front diversity, and reduced computational burden. A decision-making framework is also incorporated to identify balanced, practically feasible, and engineering-preferred solutions from the Pareto sets. Overall, the results demonstrated that the BxR and MO-BxR algorithms are capable of effectively handling diverse thermal system designs and enhancing heat transfer performance. Full article

To investigate the role of bacteria associated with pine wood nematodes (PWNs), Bursaphelenchus xylophilus (Steiner & Buhrer) Nickle, we isolated two dominant bacterial strains (Agrobacterium radiobacter Bx.F4 and Delftia tsuruhatensis Bx.Q2) from B. xylophilus with different pathogenicity (highly pathogenic F and weakly pathogenic Q) identified in previous studies. In this study, Agrobacterium radiobacter Bx.F4 and Delftia tsuruhatensis Bx.Q2 were inoculated, respectively, to aseptic PWNs to identify the effects of dominant nematode-associated bacteria on the motility, egg laying, population growth, lifespan, feeding ability, and pathogenicity of PWNs. The results showed that Agrobacterium radiobacter Bx.F4 could significantly enhance the motility, egg-laying, population growth, lifespan, feeding ability, and pathogenicity of PWNs, while Delftia tsuruhatensis Bx.Q2 exhibited the opposite effects. Furthermore, using RNA-sequencing analysis, we found that the longevity regulatory pathways, along with the JNK, Wnt, and FOXO signaling pathways related to these genes were clearly enriched. These results indicate that dominant bacterial strains associated with B. xylophilus may regulate various metabolic activities within the nematode, thereby exerting a significant influence on its physiological state and pathogenicity. This also provides a potential strategy for the biocontrol of pine wilt disease (PWD). Full article

Background and Objectives: GLP-1 receptor agonists (GLP-1 RAs; ATC A10BJ) and dual GLP-1/GIP agonist (ATC A10BX16) have expanded rapidly due to strong evidence in type 2 diabetes, obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). Their high acquisition costs and accelerating uptake make them key drivers of pharmaceutical expenditure. This study quantified national utilization and expenditure trends for antihyperglycemic drugs in Croatia (2017–2024), with a focus on GLP-1 RA and dual GLP-1/GIP agonists. Materials and Methods: Aggregate national data on dispensed medicines, valued at wholesale pharmacy prices, were obtained from HALMED’s annual ATC/DDD reports. Utilization was expressed as defined daily doses per 1000 inhabitants per day (DDD/1000/day). We analyzed the total A10 and key subclasses. The dual GLP-1/GIP agonist was only marketed in 2024. Compound annual growth rates (CAGR) were calculated. Results: The total antihyperglycemic utilization increased from 66.9 to 96.8 DDD/1000/day (a 44.7% rise), while the total A10 expenditure increased from EUR 54.2 million to EUR 96.5 million, indicating that expenditure growth outpaced utilization growth. GLP-1 receptor agonist expenditure increased from EUR 5.2 million (2018) to EUR 28.6 million (2024) (CAGR 33.0%), reaching 29.8% of total A10 expenditure in 2024. Expenditure for GLP-1-based agents grew faster than their DDD volume because per-DDD acquisition costs are substantially higher than for SGLT-2 inhibitors. These growth patterns are consistent with trajectories reported in higher-uptake EU health systems, suggesting convergence rather than an outlier position for Croatia. Conclusions: Croatia experienced a rapid shift towards GLP-1 RA-based antihyperglycemic pharmacotherapy, with GLP-1-based therapies exerting a disproportionate budget impact. For payers, these surveillance data support budget forecasting and negotiation of pricing and reimbursement conditions; clinicians can use them to benchmark and optimize evidence-aligned prescribing; and policymakers can apply them to monitor the diffusion and fiscal impact of high-cost therapies. Routine national ATC/DDD analysis, complemented by HZZO claims and primary-care datasets, is essential for guiding future pricing, reimbursement and formulary decisions. Full article

The role of HMW-GSs in soft wheat quality remains inadequately understood. In Chinese soft wheat variety Ningmai 9, a nonsense mutation (Glu-B1x, 1Bx7null) reduced dough tenacity while enhancing dough extensibility under both low (LN) and high nitrogen (HN) inputs. The improved extensibility in the NIL carrying 1Bx7null was primarily due to a reduced glutenin/gliadin ratio, with HN further increasing extensibility compared to LN. Notably, the NIL under HN exhibited better cookie quality than WT under LN without yield loss (p < 0.05). A CAPS marker was developed based on a C-to-T SNP at 514 bp in the CDS of 1Bx7null, reliably distinguishing 1Bx7 and 1Bx7null alleles. This allele-marker combination shows promising potential for soft wheat breeding. Future studies should explore the effects of allele 1Bx7null across diverse genetic backgrounds and soft wheat products. Full article

A promising strategy for pancreatic cancer therapy involves developing nanocarriers capable of simultaneously delivering various antitumor substances with diverse physicochemical properties, often resulting in synergistic effects. In the present work, novel biocomposites were developed using amphiphilic N-vinylpyrrolidone polymer incorporating bortezomib (BTZ) and modified with either the DR5-selective TRAIL cytokine (DR5-B) or its fusion with the iRGD effector peptide (DR5-B-iRGD), resulting in AmphPVP-BTZ-DR5-B and AmphPVP-BTZ-DR5-B-iRGD formulations. The release of BTZ was most extensive at acidic pH 5.6, mimicking endolysosomal compartments, while at near-neutral pH 7.4 and alkaline pH 8.2 the release was slower and less complete, indicating a smart pH-responsive behavior suitable for triggered release in the tumor microenvironment. Both AmphPVP-BTZ-DR5-B and AmphPVP-BTZ-DR5-B-iRGD significantly inhibited the growth of pancreatic adenocarcinoma cell lines PANC-1, BxPC-3, and MIA PaCa-2 and induced more rapid internalization of the DR5 receptor in MIA PaCa-2 cells than unmodified particles and free DR5-B or DR5-B-iRGD. Importantly, AmphPVP-BTZ-DR5-B-iRGD exhibited a more pronounced DR5 internalization rate and cytotoxic effect than AmphPVP-BTZ-DR5-B owing to the presence of fusion protein with internalizing iRGD peptide. Both biocomposites induced cell death via the apoptotic pathway while exhibiting minimal cytotoxic effects on healthy cells. Therefore, biocomposites incorporating BTZ and functionalized with DR5-selective TRAIL variants DR5-B or DR5-B-iRGD represent a promising avenue for future studies in pancreatic cancer animal models. Full article

Pollinators play a crucial role in global biodiversity, providing essential ecosystem services such as crop pollination. However, their abundance and diversity have been gradually decreasing in recent years. Despite increasing interest in sustainable agriculture, information on vegetable crops that attract insect pollinators remains limited. We hypothesize that variation in floral traits among vegetable crop cultivars, especially nectar volume, nectar sugar concentration, and pollen characteristics, significantly influences visitation patterns and species composition. To test this, we evaluated multiple cultivars of six vegetable crops (cowpea, sweet potato, eggplant, green bean, mustard, and chickpea) over two years, focusing on five key pollinator groups (honey bees, bumble bees, carpenter bees, sweat bees, and wasps). Cowpea and sweet potato consistently attracted the most pollinators, whereas chickpea attracted the fewest. In 2022, nectar volume was highest in sweet potato (16.45 ± 0.37 µL) and lowest in chickpea (1.18 ± 0.75 µL). Similarly, in 2023, sweet potato recorded the highest nectar volume (8.33 ± 2.95 µL), and chickpea the lowest (0.02 ± 0.01 µL). However, chickpea (31.00 ± 1.58 °Bx) and mustard (30.10 ± 1.12 °Bx) recorded the highest nectar sugar concentration in both years, and chickpea and eggplant produced significantly more pollen grains. A significant positive correlation was observed between nectar volume and pollinator abundance. Comprehensively, this two-year study demonstrates the complex relationship between floral traits and pollinator preferences. These findings offer growers practical guidance on selecting vegetable intercrops that attract specific pollinators, thereby enhancing pollination services, supporting biodiversity, and improving the yield of pollinator-dependent crops. Full article

Chalcopyrite and bornite are typical copper sulfide minerals; however, the interaction mechanisms between these minerals and conventional collectors—sodium butyl xanthate (BX) and ammonium dibutyl dithiophosphate (ADD)—when used in combination remain unclear. To address this issue, this study integrated flotation tests, FTIR spectroscopy, adsorption measurements, and AFM to investigate the effects of BX, ADD, and their mixture on the floatability of the two minerals. Flotation results showed that chalcopyrite exhibited excellent floatability in all collector systems, with above 90% recovery. Within the pH range of 3 to 11, BX outperformed ADD in enhancing bornite flotation. The BX/ADD mixture at a mass ratio of 3:1 had no significant effect on chalcopyrite recovery but significantly improved bornite recovery to 84.20% at pH 9. FTIR confirmed chemical adsorption of both collectors on the mineral surfaces. AFM further visualized stronger adsorption of BX on both chalcopyrite and bornite. Compared with single BX or ADD alone, the BX/ADD mixed collector exhibited more effective adsorption on chalcopyrite and bornite. The study provides guidance for reagent selection in the industrial flotation of chalcopyrite and bornite. Full article

Galectin-3 (Gal-3) is a histologic marker of pancreatic cancer and a potential therapeutic target. This study aimed to characterize a novel sulfated agarose-derived oligosaccharide (DP9) from marine algae, Gracilaria lemaneiformis, evaluate its Gal-3 inhibitory activity, and investigate its anti-pancreatic cancer mechanisms. Through controlled acid hydrolysis, a series of odd-numbered oligosaccharides (DP3-11) were obtained, in which DP9 showed the strongest Gal-3 inhibition in hemagglutination assays. Structural analysis confirmed DP9’s unique composition including an alternating β (1→4)-D-galactose and α (1→3)-3,6-anhydro-L-galactose backbone, featuring partial 6-O-methylation on β-D-galactose and 6-O-sulfation on 3,6-anhydro-α-L-galactose residues. Molecular docking revealed DP9’s binding to Gal-3’s carbohydrate recognition domain through key hydrogen bonds (His158, Arg162, Lys176, Asn179 and Arg186) and hydrophobic interactions (Pro117, Asn119, Trp181 and Gly235), with the sulfate group enhancing binding affinity. In vitro studies demonstrated DP9’s selective anti-pancreatic cancer activity against BxPC-3 cells, including inhibition of cell proliferation; S-phase cell cycle arrest; induction of apoptosis; and suppression of migration and invasion. Mechanistically, DP9 attenuated the Gal-3/EGFR/AKT/FOXO3 signaling pathway while showing minimal cytotoxicity to normal cells. This study first demonstrated that agarose-derived odd-numbered oligosaccharides (DP9) can serve as effective Gal-3 inhibitors, which proved its potential as a marine oligosaccharide-based therapeutic agent for pancreatic cancer. Full article

Although plant sap analysis is a practical, real-time approach to nutrient monitoring, current practice still relies on single-day diagnostics. Because management interventions and environmental drivers can rapidly modulate physiological processes that shape metabolite pools, we hypothesized that sap composition is not temporally stable but instead undergoes significant inter-day shifts under field conditions. To test this, we conducted a five-day field trial in broccoli, quantifying sap pH, EC, K⁺, NO₃⁻, and °Bx daily under five extraction methods. Extraction method had a negligible effect on inter-day shifts (%Δ), whereas chemical parameters differed markedly, ranking pH (0.8%) < °Bx (3.7%) < K⁺ (5.9%) < EC (6.2%) < NO₃⁻ (8.2%). The largest observed changes across successive days were 0.13 pH units, 0.49 °Bx, 6.94 mmol/L K⁺ (271 mg/L), 1.17 dS/m EC, and 11.98 mmol/L NO₃⁻ (743 mg/L). These results show that inter-day instability can bias single-day diagnostics, motivating adoption of new sampling strategies. We urge researchers and advisors to account for inter-day variation and incorporate multi-day sampling into experimental design and decision-making until predictive frameworks are available. Addressing this dimension will improve sap diagnostic reliability and support more sustainable, science-based nutrient management. Full article

Hard Cr-Al-Si-B-(N) coatings were deposited in Ar and Ar–15%N₂ medium by d.c. magnetron sputtering of composite targets manufactured using self-propagating high-temperature synthesis. The structure of the coatings was studied by X-ray diffraction, scanning and transmission electron microscopy, energy dispersion spectroscopy, and glow discharge optical emission spectroscopy. The coating properties were determined by nanoindentation, scratch testing, and tribological pin-on-disc testing at room and elevated temperatures. The oxidation resistance and diffusion barrier properties of the coatings were also evaluated. The results obtained showed that non-reactive coatings had a coarse crystalline structure and contained Cr₅Si₃, CrB_x, and Cr₂Al phases. The introduction of nitrogen into the coating composition promoted crystallite refinement and structural amorphization. Non-reactive CrAl₄Si₁₁B₂₁ coatings had a maximum hardness up to 29 GPa and an elastic modulus up to 365 GPa. The introduction of nitrogen into the coating composition resulted in a 16–32% reduction in mechanical properties. The CrAl₆Si₁₂B₅N₂₅ coating, which exhibited maximal plasticity index H/E = 0.100 and resistance to plastic deformation H³/E² = 0.247 GPa, was characterized by a minimum wear rate Vw = 5.7 × 10⁻⁶ mm³N⁻¹m⁻¹ and a friction coefficient of 0.47. While the CrAl₁₈Si₁₁B₅N₂₆ coating demonstrated a record level of oxidation resistance and successfully resisted oxidation up to a temperature of 1300 °C. Full article

Pomegranate (Punica granatum L.) is a strategic crop for Mediterranean agriculture due to its adaptability to arid environments—an increasingly important trait in the context of climate change—and its rising market demand driven by nutritional and medicinal properties. To support breeding and conservation efforts, this study evaluated the genetic diversity and phenotypic traits of two Mediterranean germplasm collections from Elche (Spain) and Bari (Italy). A total of 184 accessions were analyzed using SSR markers and evaluated for key pomological and phenological traits, including fruit weight, skin and aril color, seed hardness, aril weight, titratable acidity, soluble solids content, and harvest time. Genetic analyses revealed high levels of diversity within and between collections, with clear population structure influenced by geographic origin. Phenotypic evaluation revealed considerable variation in agronomic and quality traits, and several accessions with notably desirable characteristics were identified. For example, Ovadan and Molla Nepes displayed very high soluble solids content (>19 °Bx), Sanrà Nero, Sanrà Rosso, and Tajikistan Dark Red exhibited titratable acidity exceeding 40 g/L citric acid, and De Marco reached aril weights of up to 0.60 g. The integration of molecular and morphological data provided valuable insights into the distinctiveness and breeding potential of the studied genotypes. Misclassifications were identified, as well as phenotypic differences attributable to environmental influences. These findings highlight the importance of characterizing regional germplasm to preserve local adaptations and support development of new cultivars adapted to changing environmental conditions. This work reinforces the role of European pomegranate collections as reservoirs of genetic resources for sustainable cultivation and future breeding programs. Full article

A nested semi-tube hollow-core anti-resonant fiber (HC-ARF) that can support the high-purity transmission of a few polarization-maintaining modes is designed in this paper. By employing bi-thickness hybrid silica/silicon anti-resonant tubes, the birefringence of the orthogonal polarized modes is significantly improved, and the weak coupling condition of the five lowest-order polarization maintaining modes, including the LP_{01_x}, LP_{01_y}, LP_{11a_x}, LP_{11b_x}, and LP_{11a_y}, can be met. The effective refractive index difference between each pair of the supported adjacent modes is larger than 1.0 × 10⁻⁴. With hybrid multi-layer nested semi-tubes, the confinement losses of the supported modes are all less than 1.50 × 10⁻¹ dB/m within a transmission band from 1.530 to 1.620 μm. The minimum confinement losses of the LP_{01_y}, LP_{01_x}, LP_{11a_y}, LP_{11a_x}, and LP_{11b_x} modes are 3.71 × 10⁻⁴ dB/m, 1.61 × 10⁻³ dB/m, 2.00 × 10⁻² dB/m, 1.30 × 10⁻¹ dB/m, and 4.20 × 10⁻² dB/m, respectively. Meanwhile, the unwanted higher-order modes are filtered out well to guarantee the modal purity. The minimum higher-order-mode extinction ratio of the lowest-loss LP₂₁ mode to the highest-loss LP₁₁ mode remains larger than 139 from 1.545 to 1.615 μm. The numerical results highlight the potential of the proposed polarization-maintaining few-mode hollow-core anti-resonant fibers in many application fields, such as short-range and high-capacity data transmission networks, fiber sensing systems, quantum communication systems, and so on. Full article