Iron oxide nanoparticles (IONs) have been widely explored for biomedical applications due to their high biocompatibility, surface-coating versatility, and superparamagnetic properties. Upon exposure to an external magnetic field, IONs can be precisely directed to a region of interest and serve as exceptional delivery vehicles and cellular markers. However, the design of nanocarriers that achieve an efficient endocytic uptake, escape lysosomal degradation, and perform precise intracellular functions is still a challenge for their application in translational medicine. This review highlights several aspects that mediate the activation of the endosomal pathways, as well as the different properties that govern endosomal escape and nuclear transfection of magnetic IONs. In particular, we review a variety of ION surface modification alternatives that have emerged for facilitating their endocytic uptake and their timely escape from endosomes, with special emphasis on how these can be manipulated for the rational design of cell-penetrating vehicles. Moreover, additional modifications for enhancing nuclear transfection are also included in the design of therapeutic vehicles that must overcome this barrier. Understanding these mechanisms opens new perspectives in the strategic development of vehicles for cell tracking, cell imaging and the targeted intracellular delivery of drugs and gene therapy sequences and vectors.

Due to their highly hydrophilic nature and compositional versatility, hydrogels have assumed a protagonic role in the development of physiologically relevant tissues for several biomedical applications, such as in vivo tissue replacement or regeneration and in vitro disease modeling. By forming interconnected polymeric networks, hydrogels can be loaded with therapeutic agents, small molecules, or cells to deliver them locally to specific tissues or act as scaffolds for hosting cellular development. Hydrogels derived from decellularized extracellular matrices (dECMs), in particular, have gained significant attention in the fields of tissue engineering and regenerative medicine due to their inherently high biomimetic capabilities and endowment of a wide variety of bioactive cues capable of directing cellular behavior. However, these hydrogels often exhibit poor mechanical stability, and their biological properties alone are not enough to direct the development of tissue constructs with functional phenotypes. This review highlights the different ways in which external stimuli (e.g., light, thermal, mechanical, electric, magnetic, and acoustic) have been employed to improve the performance of dECM-based hydrogels for tissue engineering and regenerative medicine applications. Specifically, we outline how these stimuli have been implemented to improve their mechanical stability, tune their microarchitectural characteristics, facilitate tissue morphogenesis and enable precise control of drug release profiles. The strategic coupling of the bioactive features of dECM-based hydrogels with these stimulation schemes grants considerable advances in the development of functional hydrogels for a wide variety of applications within these fields.

Magnetite nanoparticles (MNPs) have gained significant attention in several applications for drug delivery. However, there are some issues related to cell penetration, especially in the transport of cargoes that show limited membrane passing. A widely studied strategy to overcome this problem is the encapsulation of the MNPs into liposomes to form magnetoliposomes (MLPs), which are capable of fusing with membranes to achieve high delivery rates. This study presents a low-cost microfluidic approach for the synthesis and purification of MLPs and their biocompatibility and functional testing via hemolysis, platelet aggregation, cytocompatibility, internalization, and endosomal escape assays to determine their potential application in gastrointestinal delivery. The results show MLPs with average hydrodynamic diameters ranging from 137 ± 17 nm to 787 ± 45 nm with acceptable polydispersity index (PDI) values (below 0.5). In addition, we achieved encapsulation efficiencies between 20% and 90% by varying the total flow rates (TFRs), flow rate ratios (FRRs), and MNPs concentration. Moreover, remarkable biocompatibility was attained with the obtained MLPs in terms of hemocompatibility (hemolysis below 1%), platelet aggregation (less than 10% with respect to PBS 1×), and cytocompatibility (cell viability higher than 80% in AGS and Vero cells at concentrations below 0.1 mg/mL). Additionally, promising delivery results were obtained, as evidenced by high internalization, low endosomal entrapment (AGS cells: PCC of 0.28 and covered area of 60% at 0.5 h and PCC of 0.34 and covered area of 99% at 4 h), and negligible nuclear damage and DNA condensation. These results confirm that the developed microfluidic devices allow high-throughput production of MLPs for potential encapsulation and efficient delivery of nanostructured cell-penetrating agents. Nevertheless, further in vitro analysis must be carried out to evaluate the prevalent intracellular trafficking routes as well as to gain a detailed understanding of the existing interactions between nanovehicles and cells.

Glioblastoma is incurable and resistant to therapy despite genomic stability under treatment ^1–8 , suggesting that non-genetic cellular plasticity is a central driver of progression. Whether such plasticity reflects stochastic state switching or is governed by predictable gene regulation has remained unclear ^9–13 . Here we introduce scDORI (single-cell deep multi-omic regulatory inference)—a deep-learning framework that infers enhancer-driven gene-regulatory networks at single-cell resolution—and apply it to single-nucleus multiome profiles of more than one million cells from primary glioblastomas. Integrating computational inference with systematic perturbation screens across patient-derived models, we show that a structured regulatory program with an asymmetric interplay of activators and repressors governs cellular plasticity in glioblastoma. The resulting transition landscape is hierarchical and predictable, but permits cross-lineage trajectories that are absent from normal neurodevelopment. Within this landscape, low-plasticity states such as the neuronal-like state are not stable differentiation end points but actively maintained configurations, stabilized by a network of safeguard repressors that silence alternative fates. We identify MYT1L as the dominant member of this network, and show that it binds to and represses master regulators of every alternative state to consolidate neuronal-like identity. MYT1L restricted plasticity even under standard-of-care therapy and suppressed tumour growth and invasion in vivo. Conversely, loss of MYT1L reactivated plasticity and accelerated malignant features, indicating that low-plasticity identity requires continuous repression. These findings reframe malignant cell state stability as a balance between activation and continuous repression, and nominate safeguard repressors as candidate therapeutic targets that are distinct from differentiation-inducing activators, with potential relevance across cancers in which phenotypic switching drives therapy resistance.

En este libro se explora la agroindustria panelera a través de una cuidadosa recopilación de resultados de investigación en diversas áreas del conocimiento: 1) Cultivo y manejo agronómico, 2) Transformación, industrialización y diversificación de uso de la panela, y 3) Análisis socioeconómico y ambiental de la agroindustria panelera. La obra se presenta como una valiosa fuente de referencia, con capítulos estructurados en formato de artículos científicos, por lo cual ofrece información rigurosa y de alta calidad. Este enfoque garantiza que el libro se convierta en una herramienta invaluable para todos los actores implicados en la agroindustria panelera, abarcando desde los productores hasta los investigadores y los responsables de tomar decisiones. De esta manera, la obra se posiciona como una guía esencial para comprender los desafíos y oportunidades que enfrenta este sector en su evolución continua, ofreciendo una visión completa y actualizada que contribuye al desarrollo y la innovación dentro de la agroindustria.