Search Results (476)

This study provides new evidence on how production digitalization investment affects firm financial performance across diverse European regions. A panel of 14,935 firm-year observations from 30 countries (2012–2022), including a focused Baltic subsample, is used alongside a refined digital capital intensity metric based on depreciated plant and machinery value. The results indicate a positive association between digital investment and operating revenue across Europe, with significantly stronger effects observed in the Baltic region. Interaction models reveal higher marginal returns for Baltic firms, suggesting that digital capital delivers amplified value in economies with lower digital saturation but greater absorptive urgency. Employee-related costs consistently predict revenue outcomes, underscoring their role in translating digital assets into performance. Intangible fixed assets exhibit a positive impact in Baltic labor-scale models but weaker effects elsewhere, indicating that institutional maturity mediates knowledge capital productivity. Implications: (1) digital investment yields asymmetric returns; (2) workforce investment enhances digital ROI; and (3) policy should prioritize organizational readiness alongside infrastructure. This study contributes by introducing a replicable proxy for production-level digitalization and by providing rare comparative evidence on digital returns in transitional versus mature European economies. Full article

Fragmented, sector-by-sector governance is poorly suited to cascading risks that couple climate, food, water, health, biodiversity, soils, energy, and environmental quality. This paper addresses the translation gap between integrative security–sustainability paradigms and the routine machinery of government, including planning, budgeting, procurement, and accountability. We develop the Spheres of Security (SOS) model as a conceptual–operational method organised around four overlapping spheres (biophysical, economic, social, and governance) and a repeatable cycle—diagnose → co-design → deliver → demonstrate → adapt—illustrated through two stylised vignettes (urban heat and health; watershed food–water–energy). SOS introduces an auditable overlap rule and an Overlap Score, supported by lean assurance, to make verified multi-sphere co-benefits commissionable and to surface trade-offs transparently within normal, accountable institutions (consistent with weak securitisation). We provide implementation guidance, including minimum institutional preconditions and staged entry-point options for jurisdictions where pooled budgets and full administrative integration are not immediately feasible. Full article

Cyanobacteria harbor sophisticated molecular defense systems that have evolved over billions of years to protect against viral invasion and foreign genetic elements. These ancient photosynthetic organisms possess a diverse array of restriction-modification (R-M) systems and CRISPR-Cas arrays that present challenges for genetic engineering, but also offer unique opportunities for cancer-targeted biotechnological applications. These systems exist in prokaryotes mainly as defense mechanisms but they are currently used in molecular applications as gene editing tools. Moreover, latest developments in nucleases such as zinc finger nucleases (ZFNs), TALENs (transcription-activator-like effector nucleases) are discussed. A comprehensive genomic analysis of 126 cyanobacterial species found 89% encode multiple R-M systems, averaging 3.2 systems per genome, creating formidable barriers to transformation but also providing molecular machinery that could be harnessed for precise recognition and targeting of cancer cells. This review critically examines the dual nature of these defense systems, their ecological functions, and the emerging strategies to translate their molecular precision into advanced anticancer therapeutics. Hence, the review main objectives are to explore the recent understanding of these mechanisms and to exploit the knowledge gained in opening new avenues for cancer-focused targeted interventions, while acknowledging the significant challenges to translate these systems from laboratory curiosities to practical applications. Full article

Cancer progression is driven not only by biochemical signals but also by abnormal physical forces within a stiffened tumor microenvironment. This review re-examines the anticancer compound sulforaphane (SFN) through the integrative lens of tumor biomechanics. We propose SFN functions as a “mechano-modulator,” whose pleiotropic effects converge to disrupt pro-invasive mechanotransduction. SFN targets key force-sensitive pathways (e.g., YAP/TEAD, Rho/ROCK), destabilizes invasion machinery (cytoskeleton, invadopodia), and promotes tissue-level changes such as extracellular matrix remodeling. While preclinical evidence for this mechano-modulatory role is compelling, this perspective also highlights the critical need for clinical validation and discusses the key translational challenges. By systematically linking SFN’s molecular actions to the biophysics of tumor progression, this synthesis provides a novel framework for understanding its efficacy and outlines a rational path for its future development as a mechano-inspired therapeutic. Full article

Exosomes are nanoscale extracellular vesicles that mediate intercellular communication by transporting microRNAs, proteins, and lipids. Generated through Endosomal Sorting Complex Required for Transport (ESCRT)-dependent mechanisms or ESCRT-independent pathways, exosomes are released when multivesicular bodies fuse with the plasma membrane. The ESCRT-dependent pathway involves sequential protein complexes (ESCRT-0, I, II, III) that recognize and sort ubiquitinated cargo, induce membrane budding, and facilitate vesicle scission. In contrast, the ESCRT-independent pathway relies on membrane lipids such as ceramide and proteins like tetraspanins (CD9, CD63, CD81) to promote vesicle formation without ESCRT machinery. Furthermore, post-translational modifications, including ubiquitination, sumoylation, and phosphorylation, further serve as molecular switches, modulating the affinity of ESCRT complexes or cargo proteins for membrane domains and affecting ILV formation rates. In reproductive medicine, exosomes regulate oocyte maturation, embryo–endometrial crosstalk, placental development, and maternal–fetal communication. Altered exosomal signaling contributes to obstetric complications, including preeclampsia, gestational diabetes mellitus, and preterm birth, whereas distinct exosomal miRNA signatures serve as potential diagnostic biomarkers. In gynecology, dysregulated exosomes are implicated in endometriosis, polycystic ovary syndrome, premature ovarian insufficiency, and gynecological malignancies. In contrast, mesenchymal stem cell-derived exosomes show therapeutic promise in restoring ovarian function and enhancing fertility outcomes. The distinctive molecular profiles of circulating exosomes enable minimally invasive diagnosis, while their biocompatibility and ability to cross biological barriers position them as vehicles for targeted drug delivery. Characterization of accessible data provides non-invasive opportunities for disease monitoring. However, clinical translation faces challenges, including standardization of isolation protocols, establishment of reference ranges for biomarkers, and optimization of therapeutic dosing. This review summarizes exosome biogenesis, characterization methods, physiological functions, and clinical applications in obstetrics and gynecology, with an emphasis on their diagnostic and therapeutic potential. Future directions include large-scale biomarker validation studies, engineering approaches to enhance exosome targeting, and integration with precision medicine platforms to advance personalized reproductive healthcare. Full article

Long Terminal Repeat (LTR) retrotransposons (LTR-RTEs) comprise up to 90% of some plant genomes and drive genome diversification through their amplification. Novel insertions arise during the final stages of the LTR-RTE life cycle, which depends on both LTR-RTE-encoded proteins and host cellular factors. The LTR-RTE elements require host transcriptional machinery for RNA production, followed by nuclear processing/export, translation, virus-like particle assembly, reverse transcription, and genomic integration. This review addresses the following question: What host proteins promote LTR-RTE transposition in plants? Our analysis of recent literature on host factors and cellular compartments implicated in the retrotransposition cycle reveals the extensive integration of LTR-RTEs into host processes. Nonetheless, the precise mechanisms remain poorly resolved, especially in plants with their rich repertoire of LTR-RTEs. We propose integrating plant mobilomics with transposition reporters, genome editing, synthetic biology, and interactomics to elucidate plant-specific mechanisms. Full article

The autophagy–lysosome system is a master regulator of cellular homeostasis, integrating quality control, metabolism, and cell fate through the selective degradation of cytoplasmic components. Disruption of either autophagic flux or lysosomal function compromises this degradative pathway and leads to diverse pathological conditions. Emerging evidence identifies the autophagy–lysosome network as a central signaling hub that connects metabolic balance to disease progression, particularly in neurodegenerative disorders and cancer. Although cancer and neurodegenerative diseases exhibit seemingly opposite outcomes—uncontrolled proliferation versus progressive neuronal loss—both share common mechanistic foundations within the autophagy–lysosome axis. Here, we synthesize recent advances on the roles of autophagy and lysosomal mechanisms in neurodegenerative diseases and cancer, especially on how defects in lysosomal acidification, membrane integrity, and autophagosome–lysosome fusion contribute to toxic protein accumulation and organelle damage in Alzheimer’s and Parkinson’s diseases, while the same machinery is repurposed by tumor cells to sustain anabolic growth, stress tolerance, and therapy resistance. We also highlight emerging lysosome-centered therapeutic approaches, including small molecules that induce lysosomal membrane permeabilization, nanomedicine-based pH correction, and next-generation protein degradation technologies. Finally, we discuss the major challenges and future opportunities for translating these mechanistic insights into clinical interventions. Full article

RNA viruses, such as SARS-CoV-2 and influenza, pose a persistent threat to global public health. Their high mutation rates undermine the effectiveness of conventional direct-acting antivirals (DAAs) and facilitate drug resistance. As obligate intracellular parasites, RNA viruses rely extensively on host cellular machinery and metabolic pathways throughout their life cycle. This dependency has prompted a strategic shift in antiviral research—from targeting the mutable virus to targeting relatively conserved host dependency factors (HDFs). In this review, we systematically analyze how RNA viruses exploit HDFs at each stage of infection: utilizing host receptors for entry; remodeling endomembrane systems to establish replication organelles; hijacking transcriptional, translational, and metabolic systems for genome replication and protein synthesis; and co-opting trafficking and budding machinery for assembly and egress. By comparing strategies across diverse RNA viruses, we highlight the broad-spectrum potential of HDF-targeting approaches, which offer a higher genetic barrier to resistance, providing a rational framework for developing host-targeting antiviral therapies. Full article

Electrospinning, Forcespinning^®, and melt electrowriting are becoming increasingly important fiber-based fabrication technologies for tissue engineering and drug delivery applications. Despite their scientific and industrial relevance, their patent landscape has not been systematically examined, which limits the understanding of technological dynamics and translational applications. This study addresses this gap through a patentometric analysis conducted within a Competitive Technology Intelligence framework. A total of 3557 active and granted Extended Patent Families from 2020 to 2024 were analyzed to identify temporal patterns, geographic distribution, key innovators, industrial sectors, and primary application areas. The results showed that the overall patent activity increased until 2022 before experiencing a slight decline. China dominates the landscape, accounting for approximately 62% of applications filed, largely driven by academic institutions such as Shanghai University. Leading industries include special-purpose machinery, medical and dental technology, and textiles. According to International Patent Classification codes, filament formation (D01D5/00) is prevalent, while electrospinning—specifically IPC D04H1/728—represents the most active and influential of the three technologies. These findings exhibit the technological dynamics shaping fiber-based fabrication platforms and underscore their growing relevance in pharmaceutical innovation. The identified trends position these technologies as foundational for next-generation biomaterial design, offering valuable insights for researchers, industry stakeholders, and policymakers. Full article

Orthoebolaviruses (OEV) are highly pathogenic viruses responsible for the Ebola virus disease (EVD). To establish a successful infection, OEV hijacks the host cell machinery, which in turn responds to infection by activating cellular antiviral pathways. These processes are regulated via post-translational modifications (PTMs) of both cellular and viral proteins. The most common PTMs include phosphorylation, ubiquitination, acetylation, methylation, and glycosylation. These modifications regulate stability, activity, and interactions between proteins that control the immune response, cell metabolism, and cell death, among others. PTMs are critical during the viral replication cycle as they can be either proviral, facilitating adequate virus replication inside the infected cell, or antiviral, most commonly hindering essential viral processes such as viral genome transcription or replication. Here, we review the different roles of PTMs known to occur during OEV infection in both viral and cellular proteins. Understanding how OEV modulates the fate of host cell proteins through specific PTMs can provide a basis for the development of novel therapeutic strategies. Full article

Cancer therapy resistance emerges from highly integrated molecular systems that enable tumor cells to evade cell death and survive cytotoxic therapeutic stress. High Mobility Group Box 1 (HMGB1) is increasingly gaining recognition as a central coordinator of these resistance programs. This review delineates how HMGB1 functions as a molecular switch that dynamically redistributes between cellular compartments in response to stress, with each localization enabling a distinct layer of resistance. In the nucleus, HMGB1 enhances chromatin accessibility and facilitates the recruitment of DNA repair machinery, strengthening resistance to radio- and chemotherapeutic damage. Cytosolic HMGB1 drives pro-survival autophagy, maintains redox stability, and modulates multiple regulated cell death pathways, including apoptosis, ferroptosis, and necroptosis, thereby predominantly shifting cell-fate decisions toward survival under therapeutic pressure. Once released into the extracellular space, HMGB1 acts as a damage-associated molecular pattern (DAMP) that activates key pro-survival and inflammatory signaling pathways, establishing microenvironmental circuits that reinforce malignant progression and therapy escape. HMGB1 further intensifies resistance through upregulation of multidrug resistance transporters, amplifying drug efflux. Together, these compartmentalized functions position HMGB1 as a central node in the networks of cancer therapy resistance. Emerging HMGB1-targeted agents, ranging from peptides and small molecules to receptor antagonists and nanoformulations, show promise in reversing resistance, but clinical translation will require precise, context- and redox-informed HMGB1 targeting to overcome multifactorial resistance program in refractory cancers. Full article

Background/Objectives: Oxidative stress plays a significant role in the development and progression of age-related macular degeneration (AMD). Retinal pigment epithelium (RPE) cells are specialized multifunctional cells indispensable for the maintenance of vision. The dysfunction and death of RPE cells in the macula characterize the onset and development of AMD. Of the various toxic agents that impact the health of the RPE, particular focus has been given to various forms of lipoproteins and their cytotoxic derivatives normally present in the retina. Oxidized low-density lipoprotein (OxLDL), derived from LDL in a pro-oxidative environment, is found adjacent to RPE cells as part of drusen, extracellular deposits that are a hallmark feature of AMD. OxLDL is a potent inflammatory agent and it has been implicated in cardiovascular and neurodegenerative conditions. The cellular molecular mechanisms triggered by OxLDL are only partially understood. The focus of this study was to characterize changes in the proteome of RPE cells after exposure to OxLDL, with a focus on the characterization and quantification of ubiquitinated proteins. Methods: Identification and quantification were performed with a high-resolution LC-MS/MS-based proteomics workflow after immune-enrichment for ubiquitinated peptides. Results: In total, out of the more than 1000 RPE ubiquitinated peptides quantified, OxLDL treatment caused a significant increase in ubiquitinated peptides compared to LDL and untreated cells. Principal component analysis (PCA) of the differentially ubiquitinated proteins (265) reduced the data complexity in two main groups of variables (proteins). Conclusions: Gene ontology enrichment analysis of the grouped proteins with the highest loading contribution to principal component 1 (PC1) and principal component 2 (PC2) revealed significant ubiquitination changes upon OxLDL treatment in proteins of the ubiquitin–proteasome system (UPS) responsible for proteasome-mediated catabolic processes and in protein members of the cellular translation machinery. Full article

Chronic kidney disease is a significant global health burden and a leading cause of cardiovascular morbidity and mortality. Diabetes mellitus is the primary cause of kidney disease, driving the progression of both micro- and macrovascular complications. Sustained hyperglycemia initiates a cascade of deleterious molecular and cellular events, including mitochondrial dysfunction, inflammation, oxidative stress, and dysregulated apoptosis and autophagy, which collectively contribute to the progression of renal injury. Beyond these well-established mechanisms, a compelling body of evidence highlights the pivotal role of epigenetic alterations (such as DNA methylation, histone post-translational modifications, and non-coding RNAs) in mediated long-term kidney damage. The interplay between transcriptional and epigenetic regulation underlies the phenomenon of the “metabolic memory”, wherein cellular dysfunction persists even after glycemic control is achieved. This review synthesizes the current knowledge on mechanisms sustaining metabolic and epigenetic memory, with a particular focus on the epigenetic machinery that establishes and maintains these signals, a concept increasingly termed “epigenetic memory.” Given their reversible nature, epigenetic determinants are emerging as promising biomarkers and a compelling therapeutic avenue. Targeting these “epifactors” offers a novel strategy to halt progression to end-stage renal disease, thereby paving the way for precision medicine approaches in diabetes-related renal disease. Full article

Reflecting on the digital unconscious may mean proposing a reflection on non-mastery in a field—digital creation of images and sounds, or the use of the digital in audiovisual creation—where resides the idea that digital machinery gives immense power to the artist who can now, thanks to calculation and data storage, surpass the usual limitations that human capacities have otherwise imposed on creation. On the contrary, we should take into account not only what digital machines reveal about us or from which unconscious patterns our work with them emerges, but how we deal with them as machines. Are we so aware of what we expect from technologies, or of what we project onto them? Pierre Schaeffer (the inventor of musique concrète but also a media theorist in his own right), who wrote on that topic 50 years ago can be of help here. This paper mainly relies on his text “Le machinisme artistique” (“Artistic Machinism”), published as a chapter at the beginning of Machines à communiquer in 1970 (his book on media theory and practice, not yet translated into English) and proposes, with this approach in mind, an examination of several uses and conceptions of the digital image today, with particular reference to the movie Oppenheimer. Full article

Cancer stem cells (CSCs) represent a small but critical subpopulation of tumor cells that drive therapy resistance, relapse and metastasis. Gastric cancer stem cells (GCSCs) have been identified through surface markers and transcriptional signatures, revealing their central role in tumor progression. Recently, N⁶-methyladenosine (m⁶A) RNA modification has emerged as a crucial epitranscriptomic regulator of CSC biology. The m⁶A machinery, including “writers” (METTL3, METTL14, WTAP, VIRMA), “erasers” (FTO, ALKBH5) and “readers” (YTHDFs/ YTHDCs, IGF2BPs, hnRNPA2B1), orchestrates RNA stability, splicing, translation and decay, thereby influencing self-renewal and oncogenic signaling. In GCSCs, m⁶A controls pluripotency factors, oncogenic transcripts and non-coding RNAs, collectively reinforcing stemness and malignant potential. Mounting evidence implicates dysregulated m⁶A effectors as not only key drivers of GCSC biology but also as promising biomarkers for patient stratification and therapeutic targets capable of selectively eliminating CSCs. Harnessing this knowledge could enable earlier diagnosis, more accurate patient stratification and more precise treatments. However, challenges remain regarding the resolution of m⁶A profiling, therapeutic selectivity to avoid unwanted toxicity and biomarker validation for clinical use. This review summarizes the discovery and features of CSCs, highlights the functional role of m⁶A in GCSCs, and explores diagnostic and therapeutic opportunities while outlining key difficulties for clinical translation. Full article