Search Results (49,227)

Based on a sample of Chinese listed firms from 2010 to 2024, this study employs a complex adaptive systems (CAS) lens to investigate the spillover effects of core-firm digital transformation (CDT) on innovation within supply chain networks. It reveals that CDT fosters supplier innovation while impeding customer innovation. Heterogeneity analysis shows that the spillover effect is more pronounced when suppliers (customers) are non-state-owned, larger, more competitive, and have more able managers. Mechanism analysis suggests that the spillover effect is realized through resource and competition mechanisms. This study contributes to the literature by integrating CAS theory with established supply chain management perspectives to provide a systemic understanding of digital transformation’s ripple effects, offering valuable insights for both managers navigating digital ecosystem evolution and policymakers designing industrial innovation strategies. Full article

Despite decades of structural and kinetic characterization, the full spectral molecular vibrations that accompany the catalysis in alkaline phosphatase (ALP) have remained largely unexplored. In this study, we combine in situ real-time attenuated total reflection Fourier transform infrared (ATR-FTIR) measurements over a large energy range to track the hydrolysis of p-nitrophenyl phosphate (PNPP) and inorganic phosphate (Pi) over a large range of enzyme concentrations. From the static spectra of the pure components (ALP, PNPP, PNP, Pi), we identify their characteristic vibrational frequencies and use them as reference points for the time-resolved spectra. The reaction reveals a monotonic growth of the inorganic-phosphate band at 1077 cm⁻¹. At the highest alkaline phosphatase concentration, we resolve two blue shifts in the nitro/aromatic region (1510 → 1518 cm⁻¹; 1494 → 1499 cm⁻¹), two red shifts in the fingerprint region (1345 → 1340 cm⁻¹; 1294 → 1290 cm⁻¹), and a splitting of the ~1592 cm⁻¹ band into 1595 and 1583 cm⁻¹. In conclusion, by anchoring the time-resolved spectra to the static spectra of individual constituents, we were able to resolve the infrared readout of the enzymatic reaction, offering a generalizable approach for FTIR-based tracking of catalytic processes. Full article

Background/Objectives: Research on noble metal nanoparticles (NPs) has increased over the past three decades, with advancements in synthesis techniques refining their physicochemical characteristics, including size, shape, and surface chemistry. Bimetallic NPs (BNPs) offer synergistic properties contributed by both metals. Gold (Au) and palladium (Pd) NPs possess low toxicity, high biocompatibility and loading, ease of synthesis and surface modification. Doxorubicin (DOX) and 5-fluorouracil (5-FU) are potent chemotherapeutic drugs but are rapidly metabolised in the body, producing severe side effects, limiting their use. Hence, innovative strategies to mitigate this is needed. Methods: In this study, AuPd NPs in a core-shell formation were chemically synthesized. The AuPd NPs were conjugated to 5-FU and DOX-encapsulated CS complexes and decorated with the targeting moiety transferrin (Tf). Results: Transmission electron microscopy and nanoparticle tracking analysis confirmed that the BNPs were spherical, with an average size of 73.4 nm. Functionalized BNPs were able to encapsulate more than 70% of 5-FU and DOX, resulting in a controlled drug release profile at pH 4.2. Cytotoxicity levels in human cancer cells, HeLa (cervical carcinoma) and MCF-7 (breast adenocarcinoma), as well as in non-cancer HEK293 (embryonic kidney) cells, revealed that the Tf-targeted nanocomplexes were HeLa cell-specific, with no significant cytotoxicity in the HEK293 cells. Tf-mediated cellular uptake was confirmed by receptor competition studies in the HeLa cells. Apoptosis and oxidative stress analysis confirmed cell death by apoptosis, consistent with the action of 5-FU and DOX. Conclusions: This study highlighted the potential of this BNP-nanocomplex as a suitable vehicle for drug delivery. Full article

Organic light-emitting diodes (OLEDs) have the advantages of high efficiency and high color purity, which gives them great potential and application prospects in the field of display technology, and thus they have been of wide interest for scholars and industry. Due to their nature, when using the first generation of fluorescent materials, only 25% of the excitons are used, while the rest are wasted, meaning the device efficiency does not exceed 25%. The second generation of phosphorescent materials solves this problem by utilizing 25% singlet excitons while utilizing 75% triplet excitons, achieving 100% internal quantum efficiency. Therefore, a third generation of materials, namely Thermally Activated Delayed Fluorescence (TADF) materials, has been developed, and these are able to use the small singlet–triplet energy gap to allow excitons on the triplet state to upconvert back to the single state, which improves the utilization of triplet excitons. These TADF materials can also reach 100% maximum internal quantum efficiency, but they have many problems, such as low color purity and serious efficiency roll-off. Therefore, researchers have designed hyperfluorescent materials, which possess high efficiency, high color purity, and a long lifetime, showing tremendous potential and application prospects in the field of display technology. This report takes hyperfluorescent OLEDs as the entry point and the molecular design and luminescence mechanism of hyperfluorescent materials are reviewed, considering blue, green, red, and white light. Full article

The detection of zeranol in grazing cattle could be explained by the metabolization of the mycotoxin, zearalenone (ZEA), which was proven to be naturally contaminating the grasses harboring the Fusarium species. Previous studies have suggested that members of the Fusarium incarnatum–equiseti species complex (FIESC) could be responsible for this contamination. Therefore, the objective of this study is to determine the species composition of FIESC isolates isolated from natural and cultivated pastures previously intended for livestock feed in Argentina and to analyze their ability to produce ZEA. Twenty-five Fusarium isolates were characterized by a phylogenetic analysis of the translation elongation factor 1α, and their ZEA production was quantified by cultivation in rice and subsequent analysis by UPLC-MS/MS. The phylogenetic analysis revealed a high genetic diversity identifying five isolates as species already described in the FIESC and six linages which could represent putative new phylogenetic species. In addition, 76% of the isolates were able to produce ZEA, even in high quantities. In conclusion, grasses used for grazing cattle in Argentina harbor a high diversity of FIESC species, many of which are potentially new and capable of producing ZEA, confirming their role as a likely source of this mycotoxin contamination in pastures and improving our understanding of mycological risk in livestock production systems. Full article

Background/Objectives: Low-grade inflammation and microbial imbalance have been thought to play a role in the pathogenesis of Symptomatic Uncomplicated Diverticular Disease (SUDD). We aimed to assess the efficacy of a cranberry formulation in reducing the inflammatory state of the colon and symptoms in SUDD patients. Methods: Twenty patients were enrolled in a prospective, multi-center, open-label, pilot study. We enrolled SUDD patients in whom fecal calprotectin (FC) was assessed at baseline and during the follow-up, with a baseline value ≥ 50 µg/g. Patients were treated with a gastroresistant formulation of cranberry (Vaccinium macrocarpon), one tablet/day for 4 weeks, followed by an 8-week observation period. The primary endpoint was to assess the efficacy of this gastroresistant cranberry formulation in reducing the inflammatory state of the colon by FC assessment. The secondary main endpoint was to assess the impact of this formulation on SUDD symptoms (assessed by the Visual Analog Scale, VAS). Intention-to Treat (ITT) and Per-Protocol (PP) analyses were performed. Results: At baseline, the mean FC value was 110 ± 118 μg/g; it was 72 ± 24 μg/g and 82 ± 19 μg/g after 4 weeks of treatment, and after a further 8 weeks of observation, it was significantly reduced on both ITT (p = 0.0001) and PP (p = 0.001). About the secondary main endpoint (namely symptoms of SUDD), the mean values according to the VAS were reduced significantly both at the end of the treatment and after 8 weeks post treatment. Conclusions: This gastroresistant formulation of cranberry may be able to reduce inflammation and symptoms in SUDD patients. Furthermore, large studies have to confirm these preliminary and promising results. Full article

Osteoporosis is highly prevalent in postmenopausal women, causing chronic pain, fractures, and limited mobility that burden individuals and society. While resistance exercise benefits bone health, its role in osteoporotic bone injury healing and underlying mechanisms remain unclear. This study aimed to explore the effects of 10-week weight-bearing ladder climbing exercise on ovariectomy (OVX)-induced osteoporosis and subsequent bone injury healing, and to investigate whether these effects are associated with the myostatin (MSTN) and Wnt/β-catenin pathways. Fifty-four 12-week-old female SD rats were randomized into Sham, OVX, and OVX + EX groups. Rats in the OVX and OVX + EX groups underwent ovariectomy to induce postmenopausal osteoporosis, and those in the OVX + EX group received 10-week weight-bearing ladder climbing. After the exercise intervention, 6 rats in each group were sacrificed; the remaining rats underwent femoral midshaft drilling to establish bone injury. The improvement in osteoporosis was evaluated via Micro-CT, biomechanical tests, RT-qPCR for mRNA detection, and Western blot for measuring protein levels of MSTN and Wnt/β-catenin pathway-related molecules at post-exercise and 21 days post-injury. Bone healing was reflected by the bone volume fraction at the bone injury site detected via Micro-CT at 10 and 21 days post-injury. This exercise significantly enhanced muscle strength and improved femoral bone mineral density (BMD), trabecular microstructure, and biomechanical properties in OVX rats. Meanwhile, the level of MSTN in the OVX + EX group was decreased, the expression of its downstream signaling pathways was inhibited, and the mRNA and protein expressions of Wnt/β-catenin were upregulated. Moreover, 21 days after exercise intervention, the biomechanical properties and bone microstructure of the OVX + EX group were still significantly superior to those of the OVX group, and the aforementioned molecular regulatory effect remained. In addition, pre-conducted exercise was able to promote increases in bone volume fraction at the bone injury site 10 and 21 days after drilling, which was conducive to bone injury healing. Ten-week weight-bearing ladder climbing ameliorates OVX-induced bone loss and promotes osteoporotic bone repair via regulating the MSTN/ActRIIB/Smad3 and Wnt/β-catenin pathways, providing evidence for exercise as a safe non-pharmacological intervention. Full article

Background: Electrochemotherapy (ECT) is a clinically validated local ablative treatment increasingly recognized for its ability to induce immunogenic cell death and stimulate antitumor immunity. Its combination with immune checkpoint inhibitors, such as anti-PD-1 antibodies, may enhance systemic immune responses and improve therapeutic efficacy, particularly in poorly immunogenic tumors. Methods: We evaluated the antitumor effectiveness of ECT combined with a murine analog of the anti-PD-1 antibody in four syngeneic murine tumor models with differing histology and immune status: WEHI fibrosarcoma, CT26 and MC38 colorectal carcinoma, and 4T1 mammary carcinoma. In vitro cytotoxicity assays assessed tumor cell sensitivity to ECT, while in vivo experiments evaluated complete response (CR) rates, immune cell infiltration, and long-term immune memory through secondary tumor challenge. Immunohistochemical analysis of CD4⁺, CD8⁺, and granzyme B⁺ effector cells. Results: In vitro, WEHI cells exhibited the highest sensitivity to ECT. In vivo, ECT monotherapy induced CRs in 100% of WEHI tumors, 60% of CT26, 17% of 4T1, and 15% of MC38. The addition of anti-PD-1 significantly enhanced outcomes in less responsive models, increasing CRs to 90% in CT26, 91% in MC38, and 53% in 4T1. Combination therapy promoted pronounced infiltration of CD4⁺, CD8⁺, and granzyme B⁺ T cells and the formation of tertiary lymphoid structure, particularly in MC38 tumors. Secondary challenge experiments confirmed long-term immune memory in CT26 and MC38 models and induced memory in 4T1, which was absent following monotherapy. Conclusions: ECT synergizes with PD-1 blockade to potentiate local and systemic antitumor immunity, overcoming immune resistance in poorly immunogenic tumors. These findings support further clinical development of ECT in combination with immune checkpoint inhibitors as a component of personalized cancer immunotherapy. Full article

This paper presents the design of G-IDSS (Graph-based InnoCyPES Data Storage Service): a novel, distributed data storage service that is built around a P2P network overlay to support handling distributed data. G-IDSS is accessible through a standard command-line interface and is based on a graph database to support the schema-less management of the distributed data stored among peers. The mechanisms to facilitate the execution of complex queries requiring distributed data integration and fusion are also presented and discussed. Besides the design, this work also provides relevant details related to the implementation of G-IDSS, reflecting several use cases that demand data that are distributed across different, even geographically spread, locations. G-IDSS scales to thousands of peers in an overlay, it is able to run distributed queries and can integrate data that are stored in different sources. Full article

This review summarizes a growing collection of data on adult neurogenesis in various vertebrate species, with a focus on teleost fish and mammals. Teleost fish serve as exceptional models for studying the dynamics of the cell cycle and the functions of adult neural stem progenitor cells (aNSPCs) throughout the central nervous system (CNS). New information about the characteristics of cells in various areas of the telencephalon of non-model objects—juvenile masu salmon Oncorhynchus masou and chum salmon Oncorhynchus keta—during postembryonic ontogenesis and after traumatic injury expands the current understanding of the issue. The expression of molecular markers of adult-type glial precursors in the model zebrafish and non-model objects, juveniles O. masou and O. keta, was presented. Immunohistochemical (IHC) verification of BrdU and PCNA made it possible to identify a population of rapidly and slowly proliferating cells in the pallium of intact O. masou and after traumatic brain injury (TBI). In salmonids, unlike in mammals, progenitor cells are able to differentiate into neurons after injury. The expression of vimentin and GFAP in the aNSCPs has functional specificity. A comparative analysis of the expression of Pax transcription factors in various vertebrates and juveniles O. masou is presented. Pax genes maintain cells in an undifferentiated state and ensure the spatiotemporal formation of mature cell types in changing developing neurogenic niches. The functions of glutamine synthetase (GS) and H₂S in the brains of vertebrates and juvenile chum salmon under intact conditions and after TBI are characterized. In fish, unlike mammals, as a result of TBI, neuronal conduction is restored in the injury area, whereas in mammals the regenerative process is complicated by neuroinflammation and culminates in the formation of a glial scar. Full article

p53 has long been studied as a major regulator in cellular pathways, resulting in a plethora of information on the structure and function of this protein as a frequently mutated tumor suppressor. Recent studies have demonstrated how the p53 transcription activation domain (TAD) interacts with the BH3-binding pocket of BCL-2 to regulate cell survival/death. While the in vitro studies on p53 and BCL-2 have frequently used truncated and stabilized proteins of p53 to ensure crystallization, these mutated proteins are not naturally observed in cells. Thus, it becomes important to find a way in silico to simulate how a full-length monomer with the unaltered sequence of wild-type (WT) or missense mutant (MT) p53 interacts with BCL-2. Our objective is to provide a predictive insight into how p53 monomers might interact with BCL-2 through the combination of previously published algorithms. Using pre-established computational techniques in silico, the interactions between p53 variants and BCL-2 were compared to existing crystals to ensure the validity of the current method, and the affinities were predicted to explore the strength of these interactions. Here, we found that this protocol was able to replicate some of the amino acid interactions identified in the previous literature, as well as identify affinities between each WT/MT p53 and BCL-2. Most major MT p53 variants are predicted to directly interact with BCL-2, but have a decrease in affinity compared to WT p53, suggesting a potential increase in BCL-2 survival activity. Together, the method described here can potentially be useful as a predictive workflow to inform future studies in vitro and in vivo. Full article

Background: Clinical pharmacists are increasingly demonstrating their value within primary care; this process directly improves patient experiences and outcomes. However, many undergraduate pharmacy students have little or no experience in this area, so that when they first qualify from training, their previous lack of exposure could affect future patient care in this environment. Aim: This study aims to evaluate how pharmacy undergraduate students’ learning and development of competencies are managed and received by general practitioner (GP) educators, clinical tutors, students, and patients in a general practice setting. Design and setting: The General Practice Pharmacy Educational Placement (GPEP) for undergraduates was designed and delivered in half-a-day each week across five weeks in general practice. Students observed patient consultations, interviewed patients, conducted medication reviews, used medicines reconciliation techniques, and also produced patient care plans. Method: Students participating in GPEP completed both pre- and post-course questionnaires rating eight learning outcomes, using a five-point Likert scale. Data analysis incorporated multivariate principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) strategies, and thematic analysis was applied to student focus groups, patient interviews, and GP staff interviews. Following the patient medication interview, students recorded findings and potential interventions for consideration. Results: A total of 112/157 students (71%) completed the questionnaires (June 2016–March 2019), with significant statistical differences in student confidence (p < 0.0005 for all learning outcomes). Thematic analysis revealed largely positive attitudes towards GPEP. Healthcare professionals highlighted benefits and challenges of GPEP. More than 40 issues relating to medicines optimisation and patient safety were identified, with some requiring immediate interventions from GP teams. Conclusions: GPEP demonstrated a positive clinical impact, improving patient safety. The undergraduate activities may encourage students to consider roles in primary and community care, enabling a resilient and able future workforce. Full article

Soil salinity affects large areas of the world and results in horticultural and biodiversity losses in tropical regions. Garcinia humilis (Vahl) C.D. Adams, fam. Clusiaceae, commonly known as achachairu, is a neotropical evergreen fruit tree native to the Amazonian forests in Bolivia. Its tolerance and responses to soil salinity exclusive of other stressors and within a range of salinity levels have not been reported. This study assessed the physiological, biochemical, and morphological responses of G. humilis to different levels of elevated soil salinity induced by saline irrigation. Physiological variables measured included net CO₂ assimilation (A_n), stomatal conductance of H₂O (g_s), intercellular CO₂ concentration, leaf chlorophyll index (LCI), and the ratio of variable to maximum chlorophyll fluorescence (F_v/F_m). Leaf and root nutrient analyses were performed to assess nutrient imbalances and the accumulation of toxic ions. Antioxidant responses, including superoxide dismutase, catalase, peroxidase, guaiacol peroxidase, ascorbate peroxidase, ascorbic acid, monodehydroascorbate reductase, dehydroascorbate reductase, glutathione, and glutathione reductase; reactive oxygen species (ROS) such as hydrogen peroxide and superoxide radical; and lipid peroxidation as indicated by malonaldehyde were also measured. The results indicate that G. humilis tolerates elevated soil salinity induced by saline irrigation with an electrical conductivity of at least 6 dS m⁻¹, which results in stress responses without fatal consequences. Soil salinity induced by saline irrigation of 6 dS m⁻¹ reduced A_n and g_s by approximately 50% during a 30-day period, but there was no evidence of physiological damage based on the LCI or F_v/F_m. The levels of Na⁺ and Cl⁻ did not reach toxic levels, and the plants were able to prevent damaging imbalances of plant nutrients, indicating an ion-avoidance strategy. Increased antioxidant response to soil salinity induced by saline irrigation possibly prevented ROS and lipid peroxidation damage. G. humilis appears to be moderately tolerant of soil salinity induced by saline irrigation of at least 30 days at 6 dS m⁻¹. Full article

In forest soils, nitrogen (N) is present in inorganic and organic forms. The organic forms include monomeric amino acids, but also polymers such as chitin. Ectomycorrhizal fungi are known to take up both inorganic and organic N forms, and to depolymerize large organic compounds; however, it is unknown if the compounds are used for growth. The aim of this investigation was to determine the growth of a range of ectomycorrhizal fungi on inorganic and organic N sources. Seven ectomycorrhizal fungi and one endophyte originating from mountain regions either in Austria, Mongolia, or Slovenia were grown in in-vitro cultures containing ammonium, nitrate, or chitin. Four ectomycorrhizal fungi were used to investigate growth on amino acids. All fungi, except Paxillus involutus, utilized nitrate as a N source. All fungi also grew on both chitin and N-acetylglucosamine, the amino sugar precursor of chitin. Paxillus involutus and Melanogaster broomeanus showed enhanced growth on chitin-containing media. Amanita muscaria, Rhizopogon roseolus, and Suillus granulatus, but not Paxillus involutus, were able to utilize the amino acids glycine and glutamate, as well as the tripeptide triglycine. The ability to utilize the different N sources was independent of the origin of the fungi. Full article

Diabetic foot ulcers (DFUs) represent 6.3% of the various complications of type 2 diabetes mellitus, with a risk of development of up to 34%. Several factors contribute to the formation of ulcers, which are very difficult to treat as they hinder efficient wound healing. Patients experience persistent pain, which leads to the consumption of various medications (polypharmacy) due to the lesions not resolving. Conversely, this can increase the risk of various factors, including a chronic inflammatory state, which hinders the body’s own regenerative processes. Until now, treatment options have been limited to washing the wound and stimulating new tissue growth, but this is a painful and unsuccessful process. One of the treatment options is therefore cell therapy with mesenchymal stem cells, which have immunomodulatory characteristics and allow tissue regeneration, although the effect directly in pain is not totally clear. We have previously reported in our working group that patients with ulcers treated with mesenchymal stem cells (MSCs) have been able to integrate into their daily lives, although the pain related to the inflammatory state and polypharmacy has not been studied. Objective: This study investigates how the local administration of MSCs improves the condition of an ulcer by inducing tissue regeneration. It also shows how the concentration of systemic inflammatory biomarkers is modified in direct correlation with pain and the consumption of medications over time. Methods: Local administration of MSCs at 7 and 14 days, measuring pro- and anti-inflammatory cytokines relative to the healthy control group, evaluating wound healing, and monitoring the medications taken by the patient in conjunction with pain perception. Results: Cell administration showed that inflammatory molecules were reduced and anti-inflammatory molecules increased. This is reflected in the consumption of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in relation to wound improvement, with a decrease in pain medication consumption of less than 50%. We provide evidence that locally administered mesenchymal stem cells influence systemic inflammatory processes necessary for tissue recovery, impacting patients’ polypharmacy consumption due to reduced perceived pain. Conclusions: This report establishes a direct link between mesenchymal stem cells and pain relief in type 2 diabetes ulcers, potentially paving the way for new pain therapies. Full article