Search Results (5,214)

This paper investigates the role of digital marketing signals as alternative data for understanding financial and operational dynamics in the beverage supply chain. Drawing on web analytics covering multiple actors across a five-month horizon, we analyze traffic composition, user engagement, and acquisition channels through a panel econometric framework. Descriptive statistics reveal pronounced heterogeneity in channel reliance, with some firms emphasizing organic search visibility while others depend more on paid campaigns or social referrals. Correlation patterns indicate strong substitution between organic and paid search, while display advertising is positively associated with session depth, suggesting that differentiated digital strategies influence user engagement. Analysis of variance confirms significant structural differences across firms, with an effect size exceeding 0.90. A two-way fixed-effects regression demonstrates that brand-specific factors explain the vast majority of variation in digital visibility, overshadowing short-term fluctuations. These results highlight the potential of web-derived marketing metrics to serve as leading indicators of supply chain finance outcomes such as revenue growth, working-capital efficiency, and investor sentiment. By integrating digital signals into financial econometrics, this study contributes to emerging research on alternative data in supply chain contexts and offers practical implications for managers, investors, and policymakers. Full article

Background: Urban freight transport is essential for the functioning of cities. The COVID-19 pandemic accelerated the growth of e-commerce, creating new challenges for courier services. While consumer satisfaction has been extensively studied, little attention has been paid to courier drivers’ own perceptions and preferences. This study aims to fill that gap. Methods: A questionnaire survey was conducted among 139 drivers employed in eight courier companies in Serbia. Data were analyzed using parametric statistical methods (Independent Samples T-Test, Paired-Samples T-Test, and One-way ANOVA), with additional post hoc tests to explore group differences. Results: Statistically significant differences were observed across demographic, operational, and safety-related factors (gender, age, residence, occupation, license ownership, delivery area, and type of goods). A strong preference emerged for passenger vehicles as the safest mode of delivery, highlighting a misalignment between current operational practices and drivers’ safety perceptions. Conclusions: The findings emphasize the importance of tailoring delivery strategies to demographic and operational contexts. Practical recommendations include improving transport safety, optimizing delivery zones, and addressing driver satisfaction as a determinant of service quality. The study contributes new insights into last-mile delivery by focusing on the perspectives of courier drivers rather than consumers. Full article

Spatializing crop yield statistical data with administrative divisions as the basic unit helps reveal the spatial distribution characteristics of crop yield and provides necessary spatial information to support field management and government decision-making. However, owing to an insufficient understanding of the factors affecting yield, accurately depicting its spatial differences remains challenging. Taking Hailun city, Heilongjiang Province, as an example, this study proposes a yield downscaling method based on the standardized deviation from the mean of the comprehensive crop condition index (CCCI) during key phenological periods of the growing season. First, Sentinel-2 remote sensing data were used to retrieve crop condition parameters during key phenological periods, and the CCCI was constructed using the correlation between crop condition parameters in key phenological periods and statistical yield as the weight. Subsequently, regression analysis and the entropy weight method were applied to determine the spatiotemporal dynamic weights of the CCCI during key phenological stages and to calculate the standardized deviation from the mean. By combining these two components, the comprehensive spatial difference index of the crop growth condition (CSDICGC) was derived, which offered a new way to characterize the discrepancies between the pixel-level yield and statistical yield, thereby downscaling the yield statistical data from the administrative unit to the pixel scale. The results indicated that this method achieved a regional accuracy close to 100%, with a strong fit at the pixel scale. Pixel-level accuracy validation against ground-truth maize yield data resulted in an R² of 0.82 and a mean relative error (MRE) of 4.75%. The novelty of this study was characterized by the integration of multistage crop condition parameters with dynamic spatiotemporal weighting to overcome the limitations of single-index methods. The crop yield statistical data downscaling spatialization method proposed in this paper is simple and efficient and has the potential to be popularized and applied over relatively large regions. Full article

Greater Casablanca, one of Africa’s largest metropolitan regions, is undergoing significant spatial and demographic transformation. Yet, the underlying patterns of these dynamics remain poorly understood. This study investigates population dynamics and spatial inequalities in Greater Casablanca between 2014 and 2024. The analysis combines geospatial data, regression modeling, and clustering techniques to explore the interplay between demographic change, housing affordability, public-transport accessibility, and economic activity, providing a data-driven perspective on how these factors shape spatial inequalities and the region’s urban development trajectory. The results reveal a clear core–periphery divide. The central prefecture has lost population despite continued land consumption, while peripheral communes have experienced rapid demographic and economic expansion. This growth is strongly associated with affordable housing and high rates of new-firm formation, but it occurs where transport access remains weakest. Cluster analysis identifies four socio-spatial types, ranging from a shrinking but well-served core to fast-growing, poorly connected peripheries. The study underscores the need for integrated policy interventions to improve transport connectivity, implement inclusive housing strategies, and manage economic decentralization in ways that foster balanced and sustainable metropolitan development. By situating Greater Casablanca’s trajectory within global urbanization debates, this research extends core–periphery and shrinking-city frameworks to a North African context and provides evidence-based insights to support progress towards Sustainable Development Goal 11. Full article

Continued population growth demands a significant increase in agricultural production to ensure food security. However, agricultural output is limited by environmental crises and the negative impacts of open-field farm practices. As an alternative, vertical farming techniques, such as aeroponics, can be utilized to optimize the use of resources. However, the uneven size and distribution of spray droplets in aeroponics, issues that affect root development and nutrient delivery, continue to be problematic in spray performance analysis. In aeroponics, nutrient solutions are delivered to plant roots through pressurized nozzles, and the effectiveness of this delivery depends on the spray characteristics. Variations in flow rates directly affect droplet size, density, and coverage, which in turn influence nutrient uptake and crop growth. In this study, the flow rate was adjusted (3, 4.5, and 6 L/min) to quantitatively analyze spray performance using water-sensitive paper (WSP) as a deposit collector via a quick assessment method. Subsequently, image-processing techniques such as threshold segmentation and morphological operations were applied to isolate individual spray droplets on the WSP images. This technique enabled the quantification of the droplet’s coverage area, size, density, and uniformity to effectively evaluate spray performance. One-way ANOVA indicated that all the spray parameters varied significantly with respect to the flow rate (p < 0.05): For example, the average diameters of the droplets increased from 0.73 mm at 3 L/min to 1.29 mm at 6 L/min. The droplets’ densities decreased from 85.53 drops/cm² to 30.00 drops/cm² across the same flow range. The average uniformity index improved from 30.53 to 15.95 as the flow rate increased. These results indicate that the application of WSP is an effective and scalable approach for analyzing spray performance in aeroponics, as WSP can be rapidly digitized with simple tools, such as a cell phone camera, avoiding the limitations of flatbed scanners or specialized imaging systems. Full article

Background/Objectives: Trophoblast cell surface antigen 2 (Trop2), a transmembrane glycoprotein overexpressed in a broad spectrum of epithelial malignancies but minimally expressed in normal tissues, has emerged as a clinically relevant prognostic biomarker and therapeutic target, particularly in breast cancer. This study aims to develop an enhanced way of targeting Trop2 expression in tumors and blocking it using extracellular vesicles (EVs) bioengineered to express a nanobody sequence against Trop2 (NB60 E). Methods: Here, a plasmid construct was designed to express the Trop2 sequence, NB60, flanked with HA tag and myc epitope and a PDGFR transmembrane domain in the C-terminal region, and was transfected into HEK293T cells for EVs isolation. The potency of NB60 E to knock down Trop2 in letrozole-resistant breast cancer cells (LTLT-Ca and MDA-MB-468 cells) was initially investigated. Thereafter, the effects of NB60 E on the cell viability and downstream signaling pathway of Trop2 via MTT assay and Western blotting were determined. Lastly, we also examined whether NB60 E treatment in Jurkat T cells affects IL-6, TNF-α, and IL-2 cytokine production by enzyme-linked immunosorbent assay (ELISA). Results: Results revealed treatment with NB60 E significantly reduced surface Trop2 expression across both cell lines by 23.5 ± 1.5% in MDA-MB-468, and 61.5 ± 1.5% in LTLT-Ca, relative to the HEK293T-derived control EVs (HEK293T E). NB60 E treatment resulted in a marked reduction in LTLT-Ca cell viability by 52.8 ± 0.9% at 48 h post-treatment. This was accompanied by downregulation of key oncogenic signaling molecules: phosphorylated ERK1/2 (p-ERK 1/2) decreased by 30 ± 4%, cyclin D1 by 67 ± 11%, phosphorylated STAT3 (p-STAT3) by 71.8 ± 1.6%, and vimentin by 40.8 ± 1.4%. ELISA analysis revealed significant decreases in IL-6 (−57.5 ± 1.5%, 7.4 ± 0.35 pg/mL) and TNF-α (−32.1 ± 0.3%, 6.1 ± 1.2 pg/mL) levels, coordinated by an increase in IL-2 secretion (22.1 ± 2.7%, 49.2 ± 1.1 pg/mL). Quantitative analysis showed marked reductions in the number of nodes (−45 ± 4.4%), junctions (−55 ± 3.5%), and branch points (−38 ± 1.2%), indicating suppression of angiogenic capacity. In vivo experiment using near-infrared Cy7 imaging demonstrated rapid and tumor-selective accumulation of NB60 E within 4 h post-administration, followed by efficient systemic clearance by 24 h. The in vivo results demonstrate the effectiveness of NB60 E in targeting Trop2-enriched tumors while being efficiently cleared from the system, thus minimizing off-target interactions with normal cells. Lastly, Trop2 expression in LTLT-Ca tumor xenografts revealed a significant reduction of 41.0 ± 4% following NB60 E treatment, confirming efficient targeted delivery. Conclusions: We present a first-in-field NB60 E-grafted EV therapy that precisely homes to Trop2-enriched breast cancers, silences multiple growth-and-invasion pathways, blocks angiogenesis, and rewires cytokine crosstalk, achieving potent antitumor effects with self-clearing, biomimetic carriers. Our results here show promising potential for the use of NB60 E as anti-cancer agents, not only for letrozole-resistant breast cancer but also for other Trop2-expressing cancers. Full article

Colorectal carcinoma (CRC) is characterized by mutations in p53 and the Wnt signaling pathway, and immunotherapy has shown limited efficacy in microsatellite-stable CRC. Here, CEABP1, a binding protein for the CRC biomarker carcinoembryonic antigen (CEA), was designed de novo through the AI-based computational generation methods RFDiffusion/ProteinMPNN and stringent in silico selection, for targeted delivery of purified p53 protein and transcription factor T-cell factor (TCF)/lymphoid enhancer-binding factor (LEF) transcription factor decoy (TFD) DNA into CRC cells. The cell-penetrating peptide (CPP) p28 was employed to deliver the p28-p53-CEABP1 protein, which significantly enhanced p53’s inhibition of CRC cell proliferation and xenograft tumor growth. Codelivery of the p14ARF protein together with p53 prolonged the effective antitumor duration of p53. In addition, the DNA binding domain of Max was fused with CPP and CEABP1 to deliver TCF/LEF TFD DNA, comprising concatenated consensus binding motifs for TCF/LEF and Max, into CRC cells to inhibit Wnt target gene transcription, leading to marked suppression of CRC cell proliferation and xenograft tumor growth. These findings paved the way for the development of precision anticancer therapeutics using designed binding proteins of tumor biomarkers for targeted delivery of tumor suppressor proteins and TFD DNA. Full article

Understanding how complex biological forms emerge and evolve remains a central question in evolutionary and developmental biology. To explore this complexity, we introduce a minimal two-dimensional, cellular automaton (CA)-based model that captures key features of biological development—such as spatial growth, self-organization, and differentiation—while remaining computationally tractable and evolvable. Unlike most abstract genotype–phenotype mapping models, our approach generates emergent morphological complexity through spatially explicit rule-based interactions governed by a simple genetic vector, resulting in self-organized patterns reminiscent of biological morphogenesis. Using simulations, we show that, as observed in empirical studies, the resulting phenotypic distribution is highly skewed: simple forms are common, while complex ones are rare. The model exhibits a strongly non-linear genotype-to-phenotype mapping in such a way that small genetic changes can lead to disproportionately large morphological shifts. Notably, transitions toward complexity are less frequent than regressions to simplicity, reflecting evolutionary asymmetries observed in natural systems. We further demonstrate that, by allowing for mutations in the generative rules, our model is capable of adaptive evolution and even reproducing generic features of tumoral growth. These findings suggest that even minimal developmental rules can give rise to rich, hierarchical patterns and complex evolutionary dynamics, positioning our CA-based model as a powerful tool for investigating how developmental constraints and biases shape morphological evolution. Full article

Selecting an appropriate rootstock for a specific scion cultivar is an efficient way to improve both yield and berry quality in viticulture. This study aimed to provide practical guidance for rootstock selection in the cultivation of the table grape cultivar ‘Fengguang’. The mature scions of this cultivar were grafted onto hardwood cuttings of eight different resistant rootstocks, which included 101-14M, 110R, 188-08, 3309C, 5BB, 5C, SO4, and Beta, with the own-rooted vines as control. Graft compatibility, growth vigor, yield performance, and fruit quality were compared and analyzed among the different grafting combinations. The results suggested that vines on 101-14M, 5BB, and Beta obtained higher germination rates of scions, better healing rates of the mating interface, and greater generation rates of root callus. Among these, vines on 5BB exhibited the largest scion trunk cross-sectional diameter. Furthermore, SO4 demonstrated the most significant improvement in yield, with an average increase of 13.54% compared to the control. Regarding berry quality, 101-14M significantly enhanced berry mass, pressure resistance, and flesh firmness relative to the controls, with average improvements of 7.67%, 11.34%, and 29.86%, respectively. Based on a comprehensive evaluation of yield and fruit quality indicators, 101-14M gained the highest value. In conclusion, 101-14M is preferentially recommended for grafting cultivation of ‘Fengguang’ vines. These findings could provide practical guidance for the cultivation of table grape cultivars. Full article

The global need for tissue and organ transplantation paved the way for plant-based scaffolds as cheap, ethical, and valuable alternatives to synthetic and animal-derived matrices for tissue regeneration. Over the years, the field has outgrown its initial scope, including the development of tissue models, platforms for drug testing and delivery, biosensors, and laboratory-grown meat. In this scoping review, we aimed to shed light on the frequency of the use of different plant matrices, the main techniques for decellularization, the functionalization methods for stimulating mammalian cell attachment, and the main results. To that purpose, we searched the keywords “decellularized” AND “scaffold” AND (“plant” OR “vegetable”) in online-available databases (Science Direct, Scopus, PubMed, and Sage Journals). From the selection and study of 71 articles, we observed a multitude of plant sources and tissues, along with a large and inhomogeneous body of protocols used for decellularization, functionalization and recellularization of plant matrices, which all led to variable results, with different extents of success (mostly in vitro). Since the field of plant-based scaffolds shows high potential for growth in the next few years, driven by emerging biotechnological applications, we conclude that future research should focus on plant sources with low economic and environmental impacts while also pursuing the standardization of the methods involved and a much deeper characterization of the scaffold performance in vivo. Full article

Cytoskeleton-associated protein 4 (CKAP4) has emerged as a critical player in gastrointestinal (GI) cancer progression, diagnosis, and therapy. This comprehensive review synthesizes current knowledge on CKAP4′s multifaceted roles across GI malignancies, providing novel insights into its mechanisms of action and clinical potential. Its interaction with DKK1 and subsequent activation of the PI3K/AKT pathway underscores its role in promoting tumor growth. This review also highlights novel insights into CKAP4′s mechanisms of action beyond the well-established DKK1-CKAP4 axis, including its interaction with integrin β1 and involvement in angiogenesis through the FMNL2/EGFL6/CKAP4/ERK pathway. CKAP4′s impact on tumor microenvironment and immune evasion is elucidated, offering a new perspective on its contribution to cancer progression. In addition, CKAP4 arises as a promising serum biomarker for early detection and prognosis across multiple GI cancers, emphasizing its potential superiority over traditional markers. The therapeutic potential of targeting CKAP4 is extensively explored, including novel approaches like anti-CKAP4 antibodies and aptamers, and their synergistic effects with existing treatments. By integrating findings from esophageal, gastric, pancreatic, and colorectal cancers, this review provides a unique, comprehensive overview of CKAP4 in GI oncology, underscoring CKAP4′s potential to revolutionize GI cancer diagnosis and treatment and paving the way for future translational research. Full article

US food regulatory agencies have adopted a preference for researchers and testing labs to use ‘acid-adapted challenge cultures’ when performing inoculated validation studies of food processes that involve acidic treatments to accustom the cultures to acidic pH so that they will not be easily affected during processing. We evaluated acid adaptation in regard to the processing of South African style air-dried beef, notably biltong and droëwors, using a mixture of five serovars of Salmonella as well as a unique serovar isolated from dried beef (Salmonella Typhimurium 1,4,[5],12:i:-). Acid adaptation was obtained by growing cultures in tryptic soy (TS) broth containing 1% glucose. Non-adapted cultures were obtained by growth in TS broth without glucose or in TS broth with 1% glucose but buffered with 0.2 M phosphate buffer. Processes included biltong (dried solid beef) and droëwors (ground, sausage-style). Each trial was performed twice and triplicate samples were examined at each sampling point (i.e., n = 6). Statistical analysis was applied using analysis of variance (ANOVA) or one-way repeated measures (RM-ANOVA) and the Holm–Sidak test for pairwise multiple comparisons to determine significant differences (p < 0.05). We observed that in all processes examined (eight trials), treatments using acid-adapted cultures were more sensitive to the biltong and droëwors processes, giving greater reductions (5.3-log reduction) than when non-adapted cultures were used (3.8-log reduction). Acid adaptation leads to stressed conditions in Salmonella resulting in sensitization to the multiple hurdles found in biltong and droëwors processing (acid/vinegar, salt, desiccation). Based on our data, the use of non-adapted Salmonella cultures to achieve desired challenge culture process lethality could result in more robust processing conditions and a greater level of safety in these products as intended by US regulatory guidance. Full article

Amid ongoing educational reforms and the rapid advancement of the knowledge economy, innovative teaching behaviors are not only closely related to teachers’ professional growth and students’ academic achievement but are also regarded as the key driving force for the evolution of the educational system. Consequently, identifying effective ways to foster teachers’ innovative teaching behaviors has become a central concern in educational psychology and management. Grounded in the Job Demands–Resources framework, this study developed and tested a chained mediation model using survey data from 1165 Chinese elementary and secondary school teachers. The model examines how teachers’ emotional competence fosters innovative teaching behaviors and elucidates the underlying mechanisms. The results revealed that (1) emotional competence significantly and positively predicted innovative teaching behaviors, and (2) teaching efficacy and work vitality served not only as independent mediators but also as sequential mediators in this relationship. These findings extend the understanding of the antecedents of teachers’ innovative behaviors from an emotional perspective, demonstrating that emotional competence, as a critical psychological resource, can be transformed into innovative teaching behaviors through dual “cognitive–motivational” and “energy–motivational” pathways. This study offers both theoretical insights and practical implications for advancing teaching innovation by strengthening teachers’ emotional competence, teaching efficacy, and work vitality. Full article

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide exerting, among others, strong trophic and protective effects. It plays a role in several physiological functions, including glucose homeostasis. The protective effects of PACAP are mainly mediated via its specific PAC1 receptor by stimulating anti-inflammatory, anti-apoptotic and antioxidant pathways. The aim of the present review is to summarize data on the protective effects of PACAP in the three major complications of diabetes, retinopathy, nephropathy and neuropathy, as well as some other complications. In type 1 and type 2 diabetic retinopathy models and in glucose-exposed cells of the eye, PACAP counteracted the degeneration of retinal layers and inhibited apoptosis and factors leading to abnormal vessel growth. In models of nephropathy, kidney morphology was better retained after PACAP administration, with decreased apoptosis and fibrosis. In diabetic neuropathy, PACAP protected against axonal–myelin lesions and less activation in pain processing centers. This neuropeptide has several other beneficial effects in diabetes-induced complications like altered vascular response, cognitive deficits and atherosclerosis. The promising therapeutic effects of PACAP in several pathological conditions have encouraged researchers to design PACAP-related drugs and to develop ways to enhance tissue delivery. These intentions are expected to result in overcoming the hurdles preventing PACAP from being introduced into therapeutic treatments, including diabetes-related conditions. Full article

The digital economy is significantly transforming the global economic environment and has emerged as the primary driver behind China’s high-quality development. The comprehensive melding of the cultural and tourism sectors (CTI) serves as a strategic approach to boost regional competitiveness and enhance public welfare. This study investigates the mechanisms and boundary conditions through which the growth of the digital economy across China’s 31 provinces from 2011 to 2023 impacts CTI, aiming to address existing research gaps related to micro-level transmission mechanisms and the analysis of contextual variables. Utilizing a two-way fixed-effects moderated mediation model complemented by instrumental variable (IV-2SLS) regression for testing endogeneity, the research uncovers intricate interactions among the digital economy, CTI, and significant influencing factors. The results strongly suggest that advancements in the digital economy substantially facilitate the integration of cultural and tourism sectors. This beneficial effect is partially mediated through two primary channels: the construction of new infrastructure and enhancements in employment quality, underscoring the critical role of both material and human capital in digital empowerment. Significantly, this research uniquely identifies that new quality productive forces (NQP) have a notable negative moderating impact on the link between the digital economy and cultural–tourism integration. This indicates that in provinces exhibiting high levels of NQP, the positive influence of the digital economy on cultural–tourism integration is considerably diminished. This unexpected finding can be interpreted through mechanisms such as resource dilution, varied integration pathways or maturity effects, along with differences in developmental stages and priorities. Furthermore, it resonates well with the resource-based view, innovation ecosystem theory, and dynamic capability theory. Instrumental variable regression further substantiates the notable positive influence of the digital economy on the integration of cultural tourism. This approach effectively tackles potential endogeneity concerns and reveals the upward bias that may exist in fixed-effects models. The findings contribute significantly to theoretical frameworks by enhancing the understanding of the intricate mechanisms facilitating the digital economy and, for the first time, innovatively designating NQP as a surprising key boundary condition. This enriches theories related to industrial advancement and resource allocation in the digital age. On a practical note, the research provides nuanced and differentiated policy guidance aimed at optimizing pathways for integration across various Chinese provinces at different stages of development. Additionally, it underscores significant implications for other developing nations engaged in digital tourism growth, thereby improving its global relevance. Full article