Matrix Modulation Research Articles

Interplays Between Matrix Metalloproteinases and Neurotropic Viruses: An Overview.

Matrix metalloproteinases (MMPs) are a diverse group of proteases involved in various physiological and pathological processes through modulation of extracellular matrix (ECM) components, cytokines, and growth factors. In the central nervous system (CNS), MMPs play a major role in CNS development, plasticity, repair, and reorganisation contributing to learning, memory, and neuroimmune response to injury. MMPs are also linked to various neurological disorders such as Alzheimer's disease, Parkinson's disease, cerebral aneurysm, stroke, epilepsy, multiple sclerosis, and brain cancer suggesting these proteases as key regulatory factors in the nervous system. Moreover, MMPs have been involved in the pathogenesis of neurotropic viral infections via dysregulation of various cellular processes, which may highlight these factors as potential targets for the treatment and control of neurological complications associated with viral pathogens. This review provides an overview of the roles of MMPs in various physiological processes of the CNS and their interactions with neurotropic viral pathogens.

Research on Traffic Marking Segmentation Detection Algorithm Based on Feature Fusion

Identifying road markings is a very important part of the vehicle environment sensing system and plays a crucial role in a vehicle’s correct understanding of a current traffic situation. However, road traffic markings are interfered with by a variety of factors, such as being obscured and the viewpoint of the vehicle sensors, resulting in large errors in the existing detection methods. In order to make the target detection task applicable to irregular objects or to detection tasks with higher accuracy requirements while reducing the waste of computational resources, this paper improves the accuracy of traffic marking segmentation detection by designing a multi-type traffic marking segmentation detection model based on image segmentation algorithms and designing a segmentation guidance matrix module based on a rank guidance matrix computation method. By constructing a comprehensive traffic marking detection model, a unified road traffic marking detection is achieved. Finally, the new traffic marking datasets ApolloScape-Precise and ApolloScape-Large are constructed based on the existing ApolloScape dataset, and experimental validation is carried out on these two datasets. The results show that the index MIoU (Mean Intersection over Union) of traffic marking segmentation detection reaches 61.44% and 70.15%, thus achieving a more perfect road traffic marking detection and right-of-way information perception and proving the effectiveness of the integrated traffic marking detection method designed in this paper.

Immunotherapeutic potential of collagen V oral administration in mBSA/CFA-induced arthritis.

We hypothesized that after synovial injury, collagen V (Col V) expose occult antigens, and Col V autoantibodies develop, indicating the loss of immune tolerance against this molecule, thus leading to damage to mesenchymal-derived cells as well as the extracellular matrix in experimental arthritis. Thus, the present study investigated the effects of oral administration of Col V on the synovium after the development of inflammation in mBSA/CFA-induced arthritis. After fourteen days of intraarticular administration of mBSA, 10 male Lewis rats were orally administered Col V (500 μg/300 μL) diluted in 0.01 N acetic acid (IA-Col V group). The arthritic group (IA group, n = 10) received only intraarticular mBSA. An intra-articular saline injection (20 μL) was given to the control group (CT-Col V, n = 5). IA group presented damaged synovia, the expansion of the extracellular matrix by cellular infiltrate, which was characterized by T and B lymphocytes, and fibroblastic infiltration. In contrast, after Col V oral immunotherapy IA-Col V group showed a significant reduction in synovial inflammation and intense expression of IL-10+ and FoxP3+ cells, in addition to a reduction in Col V and an increase in Col I in the synovia compared to those in the IA group. Furthermore, an increase in IL-10 production was detected after IA-Col V group spleen cell stimulation with Col V in vitro. PET imaging did not differ between the groups. The evaluation of oral treatment with Col V, after mBSA/CFA-induced arthritis in rats, protects against inflammation and reduces synovial tissue damage, through modulation of the synovial matrix, showing an immunotherapeutic potential in inhibiting synovitis.

On Nilpotent Elements and Armendariz Modules

For a left module MR over a non-commutative ring R, the notion for the class of nilpotent elements (nilR(M)) was first introduced and studied by Sevviiri and Groenewald in 2014 (Commun. Algebra, 42, 571–577). Moreover, Armendariz and semicommutative modules are generalizations of reduced modules and nilR(M)=0 in the case of reduced modules. Thus, the nilpotent class plays a vital role in these modules. Motivated by this, we present the concept of nil-Armendariz modules as a generalization of reduced modules and a refinement of Armendariz modules, focusing on the class of nilpotent elements. Further, we demonstrate that the quotient module M/N is nil-Armendariz if and only if N is within the nilpotent class of MR. Additionally, we establish that the matrix module Mn(M) is nil-Armendariz over Mn(R) and explore conditions under which nilpotent classes form submodules. Finally, we prove that nil-Armendariz modules remain closed under localization.

Adaptive compressed learning boosts both efficiency and utility of differentially private federated learning

In the federated learning (FL) research field, current research is confronted with several pivotal challenges, e.g., data privacy, model utility and communication efficiency. Furthermore, these challenges are further amplified by statistical data heterogeneous in the FL system. Thus, a novel Communication-efficient and Utility-assured Gaussian differential privacy-based Personalized Federated Adaptive Compressed Learning method, called CUG-PFACL, is proposed. Specifically, an end-to-end local adaptive compressed learning strategy is designed, including three crucial modules, namely the measurement matrix, the personalized compressed data transformation and the local model. Especially, jointly training the measurement matrix module and the personalized compressed data transformation module can mitigate the inherent statistical heterogeneity while preserving all important characteristics of the compressed private data of each local client, and alleviate the additional heterogeneity induced by Gaussian differential privacy in each global communication round. Numerous experimental simulation and comparisons demonstrate that CUG-PFACL has three notable advantages: data privacy guarantee, enhanced personalized model utility and high-efficient communication.

On-chip multifunctional metasurfaces with full-parametric multiplexed Jones matrix

On-chip metasurface for guided wave radiation works as an upgrade of conventional grating couplers, enriching the interconnection between guided wave and free-space optical field. However, the number of controllable parameters in equivalent Jones matrix of on-chip metasurface is limited that restricts the channels for multiplexing. Here, a supercell design based on detour phase and geometric phase has been proposed to reach full-parametric modulation of Jones matrix. As proof of concept, four independent sets of amplitude-phase channels have been experimentally demonstrated through a single on-chip metasurface. Moreover, through joint modulation of three phase mechanisms including detour phase, geometric phase and propagation phase, the Jones matrix could be decoupled from forward- and backward-propagating guided waves for direction multiplexing. This work paves the way for guided wave radiation towards high-capacity multiplexing and may further extend its application in optical communications, optical displays and augmented/virtual reality.

Inhalable nano-structured microparticles for extracellular matrix modulation as a potential delivery system for lung cancer

The use of inhalable nanoparticulate-based systems in the treatment of lung cancer allows for efficient localized delivery to the lungs with less undesirable systemic exposure. For this to be attained, the inhaled particles should have optimum properties for deposition and at the same time avoid pulmonary clearance mechanisms. Drug delivery to solid tumors is furthermore challenging, due to dense extracellular matrix (ECM) formation, which hinders the penetration and diffusion of therapeutic agents. To this end, the aim of the current work is to develop an ECM-modulating nano-structured microparticulate carrier, that not only enables the delivery of therapeutic nanoparticles (NPs) to the lungs, but also enhances their intratumoral penetration. The system is composed of acetalated maltodextrin (AcMD) NPs embedded into a water-soluble trehalose/leucine matrix, in which collagenase was loaded with different mass concentrations (10 %, 30 % and 50 %). The collagenase-containing AcMD nano-structured microparticles (MPs) exhibited suitable median volume diameters (2.58 ± 1.35 to 3.01 ± 0.68 µm), hollow corrugated morphology, sufficient redispersibility, low residual moisture content (2.71 ± 0.17 % to 3.10 ± 0.20 %), and favorable aerodynamic properties (Mass median aerodynamic diameter (MMAD): 1.93 ± 0.06 to 2.80 ± 0.10 µm and fine particle fraction (FPF): 68.02 ± 6.86 % to 69.62 ± 2.01 %). Importantly, collagenase retained as high as 89.5 ± 6.7 % of its enzymatic activity after spray drying. MPs containing 10 % mass content of collagenase did not show signs of cytotoxicity on either human lung adenocarcinoma A549 cells or lung MRC-5 fibroblasts. The nanoparticle penetration was tested using adenocarcinoma A549/MRC-5 co-culture spheroid model, where the inclusion of collagenase resulted in deeper penetration depth of AcMD-NPs.

Estrogen receptors and extracellular matrix: the critical interplay in cancer development and progression.

Cancer remains a significant global health concern. Breast cancer is a multifaceted and prevalent disease influenced by several factors, among which estrogen receptors (ERs) and the extracellular matrix (ECM) play pivotal roles. ERs, encompassing ERα and ERβ, exert significant diversity on tumor behavior, cell signaling, invasion, and metastatic potential, thus guiding breast cancer prognosis. Understanding the multifunctional connections between ERs and ECM that mediate the dynamics of tumor microenvironment is vital for unraveling the complexity of breast cancer pathobiology and identifying novel therapeutic targets. This critical review delves into the intricate nature of ERs, emphasizing their structural isoforms and the consequential impact on breast cancer outcomes. A detailed examination of ER-mediated cell signaling pathways reveals how differential expression of ERα and ERβ isoforms influence breast cancer cell behavior. The functional ERs-matrix interactions emerge as a pivotal factor in modulating epigenetic mechanisms of breast cancer cells, orchestrating changes in cellular phenotype and expression patterns of matrix modulators. Specifically, ERα isoforms are shown to regulate ECM signaling cascades, while the effects of ECM components on ERα activity highlight a bidirectional regulatory axis. The diversity of ERβ isoforms is also highlighted, illustrating their distinct contribution to ECM-mediated cellular responses. This review underscores the complex interplay between ERα/β isoforms and the ECM, shedding light onto the potential therapeutic strategies targeting these interactions to improve breast cancer management.

Abstract B041: Fibroblast STAT3 Signaling in Pancreatic Cancer: Implications for Immunotherapy and Tumor Microenvironment Modulation

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer distinguished by a dense stromal microenvironment. The current investigation delves into the fibroblast-specific STAT3 signaling in the PDAC tumor microenvironment (TME) and its effects on immune cell infiltration and extracellular matrix (ECM) modulation. An association was identified between heightened levels of phosphorylated STAT3 (pSTAT3) in tumor-associated fibroblasts (CAFs) and a more unfavorable prognosis, particularly among male patients. Comparative analysis of gene expression patterns in normal fibroblasts and those deficient in STAT3, extracted from mouse models of pancreatic cancer, unveiled distinct gene expression profiles related to the inflammatory signaling pathway (IL6, ADM, CXCL11, CD80, VEGFA, TGFB1, STC1, STC2). Utilizing ChIP-Seq analysis with an anti-pSTAT3 antibody, it was confirmed that STAT3 binds to the regulatory regions of these genes, supporting its regulatory role in the inflammatory signaling pathway. Moreover, the absence of STAT3 in CAFs resulted in a decline in M2 macrophages and an upsurge in M1 macrophages within the TME, indicating a potential function of STAT3 in influencing macrophage polarization. Noteworthy observations also revealed that STAT3 signaling in CAFs impacts ECM remodeling, as illustrated by reduced collagen deposition. Furthermore, the deficiency of STAT3 in CAFs led to a notable reduction in the quantity of neutrophils within the TME in our mouse model. Additionally, a plausible involvement of STAT3 in neutrophil recruitment and activation through the CXCL1/CXCR2 axis was indicated. Alterations in the infiltration of neutrophils and macrophages due to the absence of STAT3 could profoundly influence the immune response against PDAC. The modified composition of ECM following STAT3 deletion might also impact the infiltration and functioning of immune cells. These outcomes underscore the significance of STAT3 signaling in CAFs as a promising therapeutic target in PDAC, offering potential for modulating the tumor microenvironment, augmenting anti-tumor immunity, and advancing patient outcomes. Citation Format: Samaneh Saberi, Cameron Bumbleburg, Caroline Everett, Julia E Lefler, Victoria Jordan, Lu Han, Sudarshana Sharma, Michael C. Ostrowski. Fibroblast STAT3 Signaling in Pancreatic Cancer: Implications for Immunotherapy and Tumor Microenvironment Modulation [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B041.

Thrombospondins: Conserved mediators and modulators of metazoan extracellular matrix.

This review provides a personal overview of significant scientific developments in the thrombospondin field during the course of my career. Thrombospondins are multidomain, multimeric, calcium-binding extracellular glycoproteins with context-specific roles in tissue organisation. They act at cell surfaces and within ECM to regulate cell phenotype and signalling, differentiation and assembly of collagenous ECM, along with tissue-specific roles in cartilage, angiogenesis and synaptic function. More recently, intracellular, homeostatic roles have also been identified. Resolution of structures for the major domains of mammalian thrombospondins has facilitated major advances in understanding thrombospondin biology from molecule to tissue; for example, in illuminating molecular consequences of disease-causing coding mutations in human pseudoachrondroplasia. Although principally studied in vertebrates, thrombospondins are amongst the most ancient of animal ECM proteins, with many invertebrates encoding a single thrombospondin and the thrombospondin gene family of vertebrates originating through gene duplications. Moreover, thrombospondins form one branch of a thrombospondin superfamily that debuted at the origin of metazoans. The super-family includes additional sub-groups, present only in invertebrates, that differ in N-terminal domain organisation, share the distinctive TSP C-terminal region domain architecture and, to the limited extent studied to date, apparently contribute to tissue development and organisation. Finally, major lines of translational research are discussed, related to fibrosis; TSP1, TSP2 and inhibition of angiogenesis; and the alleviation of chronic cartilage tissue pathologies in pseudoachrondroplasia.

Lipoxin A4 modulates the PKA/CREB and NF-κB signaling pathway to mitigate chondrocyte catabolism and apoptosis in temporomandibular joint osteoarthritis

Temporomandibular joint osteoarthritis (TMJ-OA) is characterized by the degradation of the extracellular matrix (ECM) in cartilage and the apoptosis of chondrocytes, which is caused by inflammation and disruptions of chondrocyte metabolism and inflammation. Lipoxin A4 (LXA4), a specialized pro-resolving mediator, has been shown to inhibit inflammation and regulate the balance between ECM synthesis and degradation. However, the therapeutic effects of LXA4 on TMJ-OA and its underlying mechanisms remain unclear. Interleukin-1 beta (IL-1β)-induced chondrocyte and surgically induced TMJ-OA rat models were established in this study. The viability of chondrocytes treated with LXA4 was evaluated with the cell counting kit-8 (CCK-8) assay, while protein levels were assessed by western blot analysis, and the apoptosis rate was evaluated with terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labelling (TUNEL) staining. Histological analysis was conducted to evaluate the impact of LXA4 on cartilage degradation in TMJ-OA rat models. In vitro, the qRT-PCR and western blot analysis demonstrated that LXA4 facilitated the upregulation of collagen proteins (Collagen II) and decreased expression of matrix metalloproteinases (MMP-3, and MMP-13) associated with ECM modulation. LXA4 enhanced the TMJ-OA chondrocyte viability and decreased apoptotic rate. In vivo, histology and immunohistochemistry (IHC) analysis revealed that intraperitoneal injection of LXA4 contributed to the amelioration of chondrocyte injuries and deceleration of TMJ-OA. Transcriptomic sequencing revealed that cAMP signaling pathway was up-regulated and NF-κB signaling pathway was down-regulated in LXA4 treated group. LXA4 inhibited the phosphorylation of P65 and inhibitor of nuclear factor kappa B (IκBα) proteins while enhancing the phosphorylation PKA and CREB. This study demonstrates the potential of LXA4 as a therapeutic agent for suppressing chondrocyte catabolism and apoptosis by increasing PKA/CREB activity and decreasing NF-κB signaling.

P163 EMPAGLIFLOZIN AND ITS CARDIOPROTECTIVE EFFECTS IN THE HEART DURING VOLUME OVERLOAD IN AN EXPERIMENTAL MODEL INDUCED BY AORTOCAVAL FISTULA

Mitral regurgitation causes volume overload of the heart, and due to the deregulation of extracellular matrix proteins, the electrical communication between cardiomyocytes provided by connexin channels is disturbed. The aim of this study was to investigate the effect of cardiac volume overload (VO) on its functional parameters, structural remodeling, and connexin43 (Cx43), a protein ensuring electrical synchronization of the heart, and the cardioprotective effect of empagliflozin. Cardiac VO was induced by surgical aortocaval fistula (ACF) in adult, 6-month-old male Wistar rats. Mitral regurgitation and VO developed within four weeks. Subsequently, empagliflozin was administered daily for five weeks at a dose of 10 mg/kg of body weight. Echocardiographic examination showed increased cardiac output and increased Vmax of the aortic valve, decreased ejection fraction and fractional shortening due to ACF-VO. Echocardiographic parameters showed an increase in the diameter of the left ventricle in both systole and diastole, as well as an increase in the volume of the left ventricle at the end of systole and diastole. Empagliflozin normalized the negative parameters in the ACF-VO group. Myocardial protein Cx43 levels were reduced by ACF-VO but normalized by empagliflozin treatment. In addition, empagliflozin suppressed the ACF-VO-induced increase in interstitial collagen detected by van Gieson staining. These findings were consistent with increased protein expression of MMP-2, which is involved in structural remodeling of the extracellular matrix, and was normalized by empagliflozin. Protein kinase C epsilon levels associated with Cx43 and extracellular matrix modulation were reduced by ACF-VO and normalized by empagliflozin. However, protein levels of pro-apoptotic and pro-hypertrophic protein kinase C delta were increased by ACF-VO and normalized by empagliflozin. Protein expression of transforming growth factor beta as well as fibroblast growth factor 21 was increased by ACF-VO and normalized by empagliflozin. The results indicate a cardioprotective effect of empagliflozin due to suppression of myocardial structural remodeling and preservation of Cx43 in an experimental model simulating volume overload. The research was supported by grants APVV-21-0410,VEGA-2/0006/23,VEGA-2/0133/24,VEGA-2/0002/20

ATM Activation is Key in Vasculogenic Mimicry Formation by Glioma Stem-like Cells

Objective Vasculogenic mimicry (VM) is a novel vasculogenic process integral to glioma stem cells (GSCs) in glioblastoma (GBM). However, the relationship between VM and ataxia-telangiectasia mutated (ATM) serine/threonine kinase activation, which confers chemoradiotherapy resistance, remains unclear.Methods We investigated VM formation and phosphorylated ATM (pATM) levels by CD31/GFAPperiodic acid-Schiff dual staining and immunohistochemical staining in 145 GBM specimens. Glioma stem-like cells (GSLCs) derived from the formatted spheres of U87 and U251 cell lines and their pATM level and VM formation ability were examined using western blot and three-dimensional culture. For the examination of the function of pATM in VM formation by GSLCs, ATM knockdown by shRNAs and deactivated via ATM phosphorylation inhibitor KU55933 were studied.Results VM and high pATM expression occurred in 38.5% and 41.8% of tumors, respectively, and were significantly associated with reduced progression-free and overall survival. Patients with VM-positive GBMs exhibited higher pATM levels (rs = 0.425, P = 0.01). The multivariate analysis established VM as an independent negative prognostic factor (P = 0.002). Furthermore, GSLCs expressed high levels of pATM and formed vascular-like networks in vitro. ATM inactivation or knockdown hindered VM-like network formation concomitant with the downregulation of pVEGFR-2, VE-cadherin, and laminin B2.Conclusion VM may predict a poor GBM prognosis and is associated with pATM expression. We propose that pATM promotes VM through extracellular matrix modulation and VE-Cadherin / pVEGFR-2 activation, thereby highlighting ATM activation as a potential target for enhancing anti-angiogenesis therapies for GBM.

Comparative Transcriptome Analysis of Human and Mouse Canalicular Lungs in Fetal Diaphragmatic Hernia

BackgroundThe nitrofen model of congenital diaphragmatic hernia (CDH) is widely used in translational research. However, the molecular pathways associated with pulmonary hypoplasia in this model compared to the human CDH phenotype have not been well described. The aim of this study was to investigate differentially expressed genes (DEG) and signaling pathways in early stage fetal lungs in mouse and human CDH. MethodsCDH lung tissue was obtained from human fetuses (21–23 weeks gestation) and nitrofen mouse pups (E15.5). NovaSeq Flowcell RNA-seq was performed to evaluate differentially expressed transcriptional and molecular pathways (DEGs) in fetal mice with CDH, compared with age-matched normal mouse lungs and human CDH samples. ResultsThere were thirteen overlapping DEGs in human and mouse CDH lung samples compared to controls. These genes were involved in extracellular matrix, myogenesis, cilia, and immune modulation pathways. Human CDH was associated with an upregulation of collagen formation and extracellular matrix reorganization whereas mouse CDH was associated with an increase in muscular contraction. The most common cell types upregulated in human and mouse CDH samples were ciliated airway cells. ConclusionsThis study highlights the unique gene transcriptional patterns in early fetal mouse and human lungs with CDH. These data have implications when determining the translational potential of novel therapies in CDH using nitrofen-based animal models. Level of EvidenceLevel IV. Study TypeBasic science/case series.

Proteomics Analysis of the Protective Effect of Polydeoxyribonucleotide Extracted from Sea Cucumber (Apostichopus japonicus) Sperm in a Hydrogen Peroxide-Induced RAW264.7 Cell Injury Model.

Sea cucumber viscera contain various naturally occurring active substances, but they are often underutilized during sea cucumber processing. Polydeoxyribonucleotide (PDRN) is an adenosine A2A receptor agonist that activates the A2A receptor to produce various biological effects. Currently, most studies on the activity of PDRN have focused on its anti-inflammatory, anti-apoptotic, and tissue repair properties, yet relatively few studies have investigated its antioxidant activity. In this study, we reported for the first time that PDRN was extracted from the sperm of Apostichopus japonicus (AJS-PDRN), and we evaluated its antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS), and hydroxyl radical scavenging assays. An in vitro injury model was established using H2O2-induced oxidative damage in RAW264.7 cells, and we investigated the protective effect of AJS-PDRN on these cells. Additionally, we explored the potential mechanism by which AJS-PDRN protects RAW264.7 cells from damage using iTRAQ proteomics analysis. The results showed that AJS-PDRN possessed excellent antioxidant activity and could significantly scavenge DPPH, ABTS, and hydroxyl radicals. In vitro antioxidant assays demonstrated that AJS-PDRN was cytoprotective and significantly enhanced the antioxidant capacity of RAW264.7 cells. The results of GO enrichment and KEGG pathway analysis indicate that the protective effects of AJS-PDRN pretreatment on RAW264.7 cells are primarily achieved through the regulation of immune and inflammatory responses, modulation of the extracellular matrix and signal transduction pathways, promotion of membrane repair, and enhancement of cellular antioxidant capacity. The results of a protein-protein interaction (PPI) network analysis indicate that AJS-PDRN reduces cellular oxidative damage by upregulating the expression of intracellular selenoprotein family members. In summary, our findings reveal that AJS-PDRN mitigates H2O2-induced oxidative damage through multiple pathways, underscoring its significant potential in the prevention and treatment of diseases caused by oxidative stress.

Transcription Factor 23 is an Essential Determinant of Murine Term Parturition.

Pregnancy involving intricate tissue transformations governed by the progesterone hormone (P4). P4 signaling via P4 receptors (PRs) is vital for endometrial receptivity, decidualization, myometrial quiescence, and labor initiation. This study explored the role of TCF23 as a downstream target of PR during pregnancy. TCF23 was found to be expressed in female reproductive organs, predominantly in uterine stromal and smooth muscle cells. Tcf23 expression was high during midgestation and was specifically regulated by P4, but not estrogen. The Tcf23 knockout (KO) mouse was generated and analyzed. Female KO mice aged 4-6 months exhibited subfertility, reduced litter size, and defective parturition. Uterine histology revealed disrupted myometrial structure, altered collagen organization, and disarrayed smooth muscle sheets at the conceptus sites of KO mice. RNA-Seq analysis of KO myometrium revealed dysregulation of genes associated with cell adhesion and extracellular matrix organization. TCF23 potentially modulates TCF12 activity to mediate cell-cell adhesion and matrix modulation in smooth muscle cells. Overall, TCF23 deficiency leads to impaired myometrial remodeling, causing parturition delay and fetal demise. This study sheds light on the critical role of TCF23 as a dowstream mediator of PR in uterine remodeling, reflecting the importance of cell-cell communication and matrix dynamics in myometrial activation and parturition.

N/S‐Doped Hierarchical Porous Bamboo Carbon Fibers with Ultra‐Large Surface Area and Highly Exposed Active Sites for Flexible Zinc‐Air Battery†

Comprehensive SummaryFacile mass transport channel and accessible active sites are crucial for binder‐free air electrode catalysts in rechargeable flexible zinc‐air battery (ZAB). Herein, a ZnS/NH3 dual‐assisted pyrolysis strategy is proposed to prepare N/S‐doped hierarchical porous bamboo carbon cloth (HP‐NS‐BCC) as binder‐free air electrode catalyst for ZAB. BCC fabric with abundant micropores is firstly used as flexible carbon support to facilitate the heteroatom‐doping and construct the hierarchical porous structure. ZnS nanospheres and NH3 activization together facilitate the electronic modulation of carbon matrix by N/S‐doping and optimize the macro/meso/micropores structure of carbon fibers. Benefiting from the highly‐exposed N/S‐induced sites with enhanced intrinsic activity, the optimized mass transport of biocarbon fibers, as well as the ultra‐large specific surface area of 2436.1 m2·g–1, the resultant HP‐NS‐BCC catalyst exhibits improved kinetics for oxygen reduction/evolution reaction. When applied to rechargeable aqueous ZABs, it achieves a significant peak power density of 249.1 mW·cm−2. As binder‐free air electrode catalyst, the flexible ZAB also displays stable cycling over 500 cycles with a minimal voltage gap of 0.42 V, showcasing promising applications in flexible electronic devices.

Nanostructural modulation of chitosan matrix for facilitating transport of organic molecules across the membrane by pervaporation

Chitosan, as the second most abundant biopolymer on earth, is constantly increasing attention from different fileds such as biomedicals, food, energy, and the environment. However, its application in membrane technology such as pervaporation is lacking of an effective membrane manufacture strategy to improve its separation efficiency. Herein, we use a chitosan-based membrane subjected to neutralization and crosslinking procedures in contrasting solvents—specifically, water and ethanol—to explore the impact of polymer-solvent interactions on the effective nanogaps between polymer nanofibers. Under identical conditions, the procedures conducted in water yield hydrated membranes, while those in ethanol resulted in anhydrous membranes. In hydrated membranes, strong hydrogen bonds formed between water and amine groups block nanogaps amongst polymer nanofibers, significantly impeding molecular transport. Conversely, the absence of such strong hydrogen bonds in anhydrous membrane avoided this effect. This study highlights the potential of controlling the transport of organic molecules by tuning the nanogaps within the membrane matrix. This was achieved through a novel strategy involving washing the chitosan-based membranes with pure ethanol to remove free acids, followed by direct crosslinking in a glutaraldehyde ethanol solution. This strategy was able to double the membrane selectivity despite a 25 % reduction in methanol permeance.

Cardioprotective effects of Empagliflozin in cardiac volume overload-induced by aortocaval fistula in rats

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Slovak Research and Development Agency under the contract no. 21-0410 VEGA grants no. 2/0006/23 Heart failure is characterized by reduction in cardiac output and the occurrence of malignant arrhythmias, thereby contributing significantly to high morbidity and mortality worldwide. Myocardial structural remodelling is a key factor contributing to the development of these life-threatening events and belongs to unsolved clinical issues challenging to investigate in animal models. The aim of our study was to explore the impact of cardiac volume overload (VO) on structural remodelling and electrical coupling protein, connexin43 (Cx43) in the left and right heart ventricles as well as the efficacy of treatment with SGLT2i, Empagliflozin. Aortocaval fistula (ACF) was surgically induced in 6-month-old Wistar rats, to develop VO during 4 weeks, followed by oral administration of Empagliflozin 10 mg/kg/b.w. daily for 5 weeks. At the end of the experiment, biometric parameters were registered and left and right heart tissue samples were snap-frozen and kept at -80°C for western blot analysis and microscopic examination. Findings revealed an increase of heart, left and right ventricular mass due to ACF-VO versus sham controls, which was associated, with eccentric myocardial hypertrophy. Noteworthy, Empagliflozin reduced heart, left and right ventricular mass. Levels of myocardial protein Cx43, that determine electrical coupling among cardiomyocytes, were reduced by ACF-VO, while normalized by treatment with Empagliflozin. Moreover, treatment attenuated ACF-VO-induced increase of interstitial collagen visualized by van Gieson staining. It was in line with the protein expression of MMP-2, which is involved in structural remodeling. The protein levels of PKCε, concerned/associated with modulation of Cx43 and extracellular matrix, were decreased due to ACV-VO but normalized after treatment with Empagliflozin. On the other hand, protein levels of PKCδ, involved in proapoptotic and prohypertrophic pathways, were increased and normalized by Empagliflozin. The changes were more pronounced in the right ventricle compared to the left heart ventricle. In summary, our pilot results point out the benefit of Empagliflozin due to the suppression of myocardial structural remodelling and preservation of Cx43 in the rat ACF-VO model. Furthermore, this Empagliflozin-induced cardioprotection was associated with the normalization of Cx43, MMP-2, and PKC levels independent of glucose control. However, further analyses are needed to reveal the molecular mechanisms of the cardioprotective effects of Empagliflozin.

Ultrahigh energy density in dielectric nanocomposites by modulating nanofiller orientation and polymer crystallization behavior

High-energy density dielectrics for electrostatic capacitors are in urgent demand for advanced electronics and electrical power systems. Poly(vinylidene fluoride) (PVDF) based nanocomposites have attracted remarkable attention by intrinsic high polarization, flexibility, low density, and outstanding processability. However, it is still challenging to achieve significant improvement in energy density due to the common contradictions between electric polarization and breakdown strength. Here, we proposed a novel facile strategy that simultaneously achieves the construction of in-plane oriented BaTiO3 nanowires and crystallization modulation of PVDF matrix via an in-situ uniaxial stretch process. The polar phase transition and enhanced Young's modulus facilitate the synergetic improvement of electric polarization and voltage endurance capability for PVDF matrix. Additionally, the aligned distribution of nanowires could reduce the contact probability of nanowire tips, thus alleviating electric field concentration and hindering the conductive path. Finally, a record high energy density of 38.3 ​J/cm3 and 40.9 ​J/cm3 are achieved for single layer and optimized sandwich-structured nanocomposite, respectively. This work provides a unique structural design and universal method for dielectric nanocomposites with ultrahigh energy density, which presents a promising prospect of practical application for modern energy storage systems.