Network Formation Research Articles

Background: Pulmonary arterial hypertension (PAH) is a severe disease affecting the pulmonary arteries, causing increased blood pressure due to lumen narrowing. Aberrant proliferation of endothelial cells (ECs) and smooth muscle cells (SMCs), along with pro-inflammatory mediators and perivascular immune cell accumulation, contributes to arterial remodeling. Hypothesis: We hypothesized that the cytosolic RNA receptor melanoma differentiation-associated protein 5 (MDA5) contributes to PAH by dysregulating pulmonary vascular cell function and immune cell response. Methods: Lung tissue sections from control and PAH patients underwent immunofluorescence staining and confocal microscopy. siRNA targeting IFIH1 (gene for MDA5) was used for gene silencing in pulmonary artery ECs. BrdU incorporation and DNA staining analyzed the cell cycle; a Matrigel assay examined network formation, and a gap closure assay measured migration . Ifih1 -/- mice were exposed to the hypoxia/SU5416 (HX/Su) protocol for 21 days. Media wall thickness was quantified in histological sections. Immunohistochemistry assessed perivascular immune cell accumulation. PCR from lung tissue showed pro-inflammatory mRNA expression. Results: In lung tissue from control patients, MDA5 immunoreactivity was widely distributed throughout the pulmonary artery wall, with the strongest expression observed in immune cells. In the remodeled pulmonary arteries of PAH patients, MDA5 immunostaining was reduced in ECs. In cultured human pulmonary artery ECs, gene silencing of IFIH1 disrupted cell cycle progression, network formation, and gap closure. Bulk RNA sequencing analysis revealed the differential expression of 2,533 genes, affecting gene ontologies such as cell death and survival, as well as cell cycle. After exposing whole-body Ifih1 -/- mice to the Hx/Su protocol, we detected reduced right ventricular systolic pressure and pulmonary artery media wall thickness compared to wild-type mice. Pro-inflammatory mediators, interferon-regulated genes, and perivascular accumulation of CD11b-positive myeloid cells were decreased in the lung tissue of Hx/Su-exposed Ifih1 -/- mice. Conclusions: Our data suggest a protective effect of whole-body MDA5 knockout in mice, which may be due to a reduction in pro-inflammatory mediators and perivascular immune cell accumulation. Whether a decrease of MDA5 in ECs promotes or protects against PH will need further investigation.

Background: Irreversible myocardial injury and replacement fibrosis following myocardial infarction (MI) constitute key drivers of cardiac dysfunction. Consequently, promoting endogenous cardiomyocytes (CMs) regeneration represents a critical imperative. While mitochondria play pivotal roles in maintaining CMs functionality, the mechanisms governing mitochondrial regulation of CMs proliferative capacity remain incompletely elucidated. Aims: Our study aims to elucidate the role played by mitochondria in mammalian heart regeneration and the related regulatory mechanisms. Methods and Results: We first characterized the mitochondria of heart at different developmental stages, revealing that mitochondrial distribution dynamically correlate with CMs proliferative capacity. Notably, highly proliferative CMs exhibited pronounced mitochondrial perinuclear polarity distribution. Through optogenetic manipulation to alter mitochondrial distribution, we demonstrated that perinuclear mitochondrial clustering constitutes a key determinant of CMs proliferation. Further analysis identified that mitochondria and nucleus can form significant contact sites in highly proliferative CMs. Mechanistically, we identified that nuclear membrane-localized mitofusin 2 (MFN2) orchestrates mitochondrial perinuclear aggregation through spatial coupling, and efficiently promotes retrograde shuttling of the citrate to the nucleus. Additionlly, we found that intranuclear citrate cleavage is mediated by the nuclear enrichment of ATP citrate lyase (ACLY) , which could locally generate large amounts of acetyl-CoA, and in turn mediated histone acetylation modifications, particularly the acetylation of histone H3 lysine9 (H3K9ac) and histone H3 lysine27 (H3K27ac). By modulating citrate-derived acetyl coenzyme A in vivo and in vitro experiments, we confirmed that ACLY mediates the formation of the metabolism-epigenetic modification network, and enhances the transcriptional activity of cell cycle regulatory genes ( Ccna1, Ccne1 ) and pluripotency genes ( Erbb4, Mef2a ), exerting essential regulatory functions in mammalian CMs proliferation and myocardial injury repair. Conclusions: Our study demonstrated that mitochondrial perinuclear polarity distribution, essential for mammalian heart regeneration, promotes retrograde citrate transport into the nucleus. Nuclear ACLY then generates acetyl-CoA locally for histone acetylation, enhancing gene transcriptional activity and stimulating CMs proliferation.

Abstract Introducing particles to dynamic covalent networks is a common approach to improve their performance. However, network formation can be impacted by their size and functionality. The influence can be predicted by common theories for small molecular precursors, but it is unclear whether they are applicable to precursors bearing numerous reactive groups and micrometer-scale dimensions. In this work, an experimental study was undertaken using dynamic covalent networks formed by the Diels–Alder reaction between furan and maleimide groups. The gelation behavior of the Diels–Alder networks was studied using rheometry to track their network formation at 40 °C with varying maleimide-functionalized microsphere loading. The highly functional microspheres can interact with the furan precursor, aiding in the formation of the Diels–Alder networks. A 5 wt% microsphere sample can reduce the gelation time by 23% and facilitate network formation in an unbalanced stoichiometry near the critical composition to form a percolating network. Graphical abstract

Despite demonstrating bistability in spin-crossover (SCO) materials, the absence of long-range magnetic order and poor electrical conductivity limit their prospect in spintronic and nanoelectronic applications. Intending to create hybrid devices made of SCO-2D architecture, here, we report an easily processable Fe-based SCO nanostructures grown on 2D reduced graphene oxide (rGO). X-ray photoelectron spectra of the hybrid clearly reveal the formation of new bonding state with possible charge transfer between rGO and SCO nanoparticles. This interfacial charge transfer enhances intermolecular interactions, resulting in increased cooperativity within the heterostructure. The temperature dependent Mössbauer spectra analysis distinctly uncovers the proportion of Fe (II) spin states within the hybrid nanocomposite samples, highlighting how the formation of a 2D network of SCO clusters enhances the cooperativity. Notably, both the thermal hysteresis and the mean spin-transition temperature are tunable through the application of a magnetic field, underscoring significant magnetic interactions. The inherently low conductivity of pristine SCO nanostructures is addressed by embedding them within a conductive rGO matrix. This facilitates the electrical detection of magnetic bistability through high-spin/low-spin conductance switching, even in the absence of an external magnetic field. As a result, spin functionality is integrated into the conductance behavior, paving the way for hybrid 2D spintronic devices. Finally, ab-inito calculations, on the experimentally motivated model systems provide insights into the microscopic mechanism confirming the enhanced magnetic interaction in the hybrid architecture facilitated by interfacial charge transfer.

Bile leakage is a major complication following hepatectomy; these often lead to surgical site infections, liver failure, and even death. Biomaterials, including fibrinogen-based collagen fleece (TachoSil) and fibrin glue, are ineffective for bile sealing. Synthetic sealants, including cyanoacrylate and polymer-based materials, independent of coagulation, are inadequate for bile leakage management. Therefore, in the present study, a novel hydrogel-based sealant (DCSN_100_25) is developed using 3 types of poly(ethylene glycol) (PEG) with a dual-stage cross-linking mechanism, termed the delayed cross-linked single network (DCSN). This design facilitates rapid initial solidification followed by gradual network formation, ensuring immediate sealing and stable adhesion to the amputated liver tissue surface. Experiments using in vivo rat hepatectomy models demonstrated that DCSN_100_25 achieved hemostasis within 1 min, outperforming conventional sealants, such as SURGICEL and TachoSil, and effectively preventing both bleeding and bile leakage. Furthermore, in vivo safety assessments confirmed its safety profile, with PEG brushes remaining on the liver tissue and exhibiting minimal inflammation and no chronic liver damage. These findings suggest that DCSN_100_25 is a promising surgical sealant that effectively manages bile leakage and enhances hepatectomy safety.

P-type organic electrode materials, characterized by fast kinetics and high redox potential, hold great promise for aqueous zinc-ion batteries (ZIBs), but suffer from low capacity and limited cycling stability in practical applications. Herein, we demonstrate that the introduction of electroactive chelating groups can significantly improve both the capacity and cycling stability of p-type triphenylamine derivative-based electrodes. The electroactive chelating groups promote a higher proportion of electroactive sites within the cathode material. The combined in/ex situ spectroscopic analysis and theoretical investigations show that electroactive chelating groups facilitate the formation of stable zinc-supramolecular network, which effectively mitigates the dissolution of electrode materials and the decomposition of the aqueous electrolyte during cycling. The as-synthesized poly(1,4-naphthoquinone-1,3,5-tri(4-aminophenyl)benzene) exhibits a high reversible capacity of 311 mAhg-1 at 50mAg-1 and superior rate performance (199 mAhg-1 at 10 Ag-1) in aqueous electrolyte. Moreover, it demonstrates excellent stability, retaining 83% to 96% of its capacity over 5000 cycles in various aqueous electrolytes, representing a new record for p-type and bipolar-type organic electrode materials. This work provides valuable insights into the design of organic electrode materials for high-performance ZIBs.

Gluten-free (GF) pasta alternatives are frequently limited in variety, availability, and physicochemical qualities when compared with wheat pasta. Egg white protein (EWP) serves as a nutritional and texturizing agent but its role in modulating the structural and functional properties of heat-moisture-treated (HMT) rice-flour based GF pasta remains underexplored. This study aimed to investigate the effects of EWP (2.5%, 5%, 7.5%, and 10%), with and without transglutaminase (TG) (0% and 1%) on the quality of HMT rice-flour-based pasta. The incorporation of egg white protein (with or without TG) restructured the protein-starch matrix, increasing optimal cooking time, water absorption, and swelling index. The EWP-enriched formulation increased firmness and chewiness to wheat-like levels while lowering cooking loss (CL) to less than 8% (threshold for 'good quality' pasta). At 10%, EWP (with or without TG) in the formulation enabled rice pasta to qualify as a protein source under EU regulations with reduced starch digestibility. Microstructurally, EWP with and without TG reduced starch crystallinity but promoted β-sheet network formation. Although TG reinforced the rice-EWP matrix by creating a denser network and delaying starch digestion, the overall pasta properties of EWP with TG remained similar to those without TG, with only minor differences. Overall, this study shows that EWP (with or without TG) can successfully improve HMT rice flour-based pasta, resulting in a wheat-like texture, low CL, and slower starch digestion. These findings support the scalable production of nutritionally enhanced GF pasta, particularly for gluten-sensitive and health-conscious consumers. © 2025 Society of Chemical Industry.

Exogenous addition of glutamic-based organic nitrogen stimulates straw decomposition by altering bacterial community assemblage and network formation

Hybrid biofabrication of multilayered 3D neuronal networks with structural and functional interlayer connectivity.

Solvent-polarity-engineered hyaluronic acid aerogels: Synthesis of transparent nanofiber network for thermal insulation.

Preparation of soybean protein isolate-lactose glycation conjugate gels: synergistic mechanism of cold plasma treatment and lactose glycosylation.

The role of recommendation algorithms in the formation of disinformation networks

Synergistic ultrasound and oat β-glucan treatment improves structural conformation and gelation behavior of skipjack tuna myofibrillar protein.

Carboxylated cellulose nanocrystals-driven heat-induced soy protein isolate amyloid fibril gel: Network structure and formation mechanism.

Insights into viscosity, rheology, microstructure, and in vitro digestibility of Cyperus esculentus starch-Sanxan Gum mixtures.

Microvascular network formation is governed by a variety of factors, with interstitial flow (IF) playing a pivotal role. However, the impact of multidirectional IF (MDIF) on microvascular network development remains insufficiently explored. In this study, we developed a platform consisting of a Square chip capable of generating MDIF and a deep learning-based Vasculature-on-a-Chip Analysis Tool (VoCAT) for high-efficient analysis of vascular morphology on the chip. Using this platform, we demonstrated that microvascular networks formed on the Square chip exhibited intricate structural features with enhanced functionality. We also demonstrated its utility in modeling a tumor microenvironment with complex microvascular networks and observed enhanced tumor cell migration. This study provides the first evidence that MDIF promotes microvascular network formation, offering new perspectives for advanced in vitro vascular and disease research.

A stiff bioink for hybrid bioprinting of vascularized bone tissue with enhanced mechanical properties.

Glioblastoma, an aggressive brain tumor that largely depends on angiogenesis, has limited treatment options and poor prognosis. This study explores the therapeutic potential of fimepinostat, a dual HDAC/PI3K inhibitor, as a single agent alone and in combination of temozolomide in glioblastoma using preclinical tumor and angiogenesis models. We show that fimepinostat at nanomolar concentrations inhibited proliferation and induced apoptosis in a panel of glioblastoma cell lines. In addition, fimepinostat inhibited capillary network formation of microvascular endothelial cells derived from patients, indicating that fimepinostat inhibits glioblastoma angiogenesis. Combination index analysis indicates that fimepinostat and temozolomide is synergistic in inhibiting glioblastoma. Consistent with the in vitro findings, fimepinostat significantly inhibited glioblastoma growth in mice without causing any toxicity. The combination of fimepinostat and temozolomide significantly inhibited tumor growth and prolonged survival compared to monotherapy or control. Mechanism studies confirmed that fimepinostat acts on glioblastoma cells through suppressing Akt/MYC. Our findings suggest that dual targeting of tumor and angiogenesis by fimepinostat may provide an alternative approach for anti-glioblastoma therapy.

Disruption of mitochondrial homeostasis and apoptosis by oryzalin exposure in zebrafish embryos.

In vitro red blood cell (RBC) production offers a promising complement to conventional blood donation, particularly for patients with rare blood types. Previously, we developed imBMEP-A, the first erythroid cell line derived from reticulocyte progenitors, which maintains robust hemoglobin expression and erythroid differentiation in the presence of erythropoietin (EPO) despite its immortalized state. However, clinical translation remains hindered by the inability to scale up production due to impaired in vitro enucleation of RBC progenitor cell lines. Enhancing enucleation efficiency in imBMEP-A cells involved CRISPR/Cas9-mediated knockout (K.O.) of miR-30a-5p, a key enucleation inhibitor, moderately increasing rates to 3.3 ± 0.4%- 8.9 ± 1.7%. Further investigation of enucleation inefficiencies led to transcriptome and proteome comparisons between imBMEP-miR30a-K.O. cells and hematopoietic stem cells (HSCs). These analyses revealed altered gene expression and protein abundances linked to metabolic transitions, apoptosis promotion, and cytoskeletal regulation. Notably, forced expression of the proto-oncogene c-Myc, required for cell immortalization, emerged as a key driver of these physiological changes. Counteracting these effects required optimization of imBMEP-A cells by activating BCL-XL transcription and knocking out SCIN, which encodes the actin-severing protein scinderin. While BCL-XL is upregulated in normal erythropoiesis, it is downregulated in imBMEP-A. Conversely, SCIN, typically absent in erythroid cells, is highly expressed in imBMEP-A, disrupting actin organization. These interventions improved viability, restored actin network formation, and increased terminal erythropoiesis, yielding 22.1 ± 1.7% more orthochromatic erythroblasts. These findings establish a foundation for optimizing imBMEP-A cells for therapeutic use and advancing the understanding the pathophysiology of erythroleukemia.