NR2F2 alleviates pulmonary fibrosis by inhibition of epithelial cell senescence.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fatal, and aging-associated interstitial lung disease with a poor prognosis and limited treatment options, while the pathogenesis remains elusive. In this study, we found that the expression of nuclear receptor subfamily 2 group F member 2 (NR2F2), a member of the steroid thyroid hormone superfamily of nuclear receptors, was reduced in both IPF and bleomycin-induced fibrotic lungs, markedly in bleomycin-induced senescent epithelial cells. Inhibition of NR2F2 expression increased the expression of senescence markers such as p21 and p16 in lung epithelial cells, and activated fibroblasts through epithelial-mesenchymal crosstalk, inversely overexpression of NR2F2 alleviated bleomycin-induced epithelial cell senescence and inhibited fibroblast activation. Subsequent mechanistic studies revealed that overexpression of NR2F2 alleviated DNA damage in lung epithelial cells and inhibited cell senescence. Adenovirus-mediated Nr2f2 overexpression attenuated bleomycin-induced lung fibrosis and cell senescence in mice. In summary, these data demonstrate that NR2F2 is involved in lung epithelial cell senescence, and targeting NR2F2 may be a promising therapeutic approach against lung cell senescence and fibrosis.

Hibiscus manihot L. flower extract induces anticancer activity through modulation of apoptosis and autophagy in A549 cells.

Lung cancer is a major public health issue and heavy burden in China and worldwide due to its high incidence and mortality without effective treatment. It's imperative to develop new treatments to overcome drug resistance. Natural products from food source, given their wide-ranging and long-term benefits, have been increasingly used in tumor prevention and treatment. This study revealed that Hibiscus manihot L. flower extract (HML) suppressed the proliferation and migration of A549 cells in a dose and time dependent manner and disrupting cell cycle progression. HML markedly enhanced the accumulation of ROS, stimulated the dissipation of mitochondrial membrane potential (MMP) and that facilitated mitophagy through the loss of mitochondrial function. In addition, HML induced apoptosis by activation of the PTEN-P53 pathway and inhibition of ATG5/7-dependent autophagy induced by PINK1-mediated mitophagy in A549 cells. Moreover, HML exert anticancer effects together with 5-FU through synergistic effect. Taken together, HML may serve as a potential tumor prevention and adjuvant treatment for its functional attributes.

Directed Differentiation of Human Induced Pluripotent Stem Cells to Heart Valve Cells.

BACKGROUND: A main obstacle in current valvular heart disease research is the lack of high-quality homogeneous functional heart valve cells. Human induced pluripotent stem cells (hiPSCs)-derived heart valve cells may help with this dilemma. However, there are no well-established protocols to induce hiPSCs to differentiate into functional heart valve cells, and the networks that mediate the differentiation have not been fully elucidated. METHODS: To generate heart valve cells from hiPSCs, we sequentially activated the Wnt, BMP4, VEGF (vascular endothelial growth factor), and NFATc1 signaling pathways using CHIR-99021, BMP4, VEGF-165, and forskolin, respectively. The transcriptional and functional similarity of hiPSC-derived heart valve cells compared with primary heart valve cells were characterized. Longitudinal single-cell RNA sequencing was used to uncover the trajectory, switch genes, pathways, and transcription factors of the differentiation. RESULTS: An efficient protocol was developed to induce hiPSCs to differentiate into functional hiPSC-derived valve endothelial-like cells and hiPSC-derived valve interstitial-like cells. After 6-day differentiation and CD144 magnetic bead sorting, ≈70% CD144+ cells and 30% CD144- cells were obtained. On the basis of single-cell RNA sequencing data, the CD144+ cells and CD144- cells were found to be highly similar to primary heart valve endothelial cells and primary heart valve interstitial cells in gene expression profile. Furthermore, CD144+ cells had the typical function of primary heart valve endothelial cells, including tube formation, uptake of low-density lipoprotein, generation of endothelial nitric oxide synthase, and response to shear stress. Meanwhile, CD144- cells could secret collagen and matrix metalloproteinases, and differentiate into osteogenic or adipogenic lineages like primary heart valve interstitial cells. Therefore, we identified CD144+ cells and CD144- cells as hiPSC-derived valve endothelial-like cells and hiPSC-derived valve interstitial-like cells, respectively. Using single-cell RNA sequencing analysis, we demonstrated that the trajectory of heart valve cell differentiation was consistent with embryonic valve development. We identified the main switch genes (NOTCH1, HEY1, and MEF2C), signaling pathways (TGF-ß, Wnt, and NOTCH), and transcription factors (MSX1, SP5, and MECOM) that mediated the differentiation. Finally, we found that hiPSC-derived valve interstitial-like cells might derive from hiPSC-derived valve endothelial-like cells undergoing endocardial-mesenchymal transition. CONCLUSIONS: In summary, this is the first study to report an efficient strategy to generate functional hiPSC-derived valve endothelial-like cells and hiPSC-derived valve interstitial-like cells from hiPSCs, as well as to elucidate the differentiation trajectory and transcriptional dynamics of hiPSCs differentiated into heart valve cells.

Tribo-charge enhanced and cellulose based biodegradable nanofibrous membranes with highly fluffy structure for air filtration and self-powered respiration monitoring systems.

Recently, the demand for healthcare products especially wearable smart masks is increasing. The biosafety and degradability of smart masks are crucial for human health and environmental protection. However, the development of biodegradable and biocompatible fibrous membranes with high filtration efficiency and low pressure drop is still a challenge. How to realize the collaborative improvement between air filtration efficiency and pressure drop of the nanofibrous membrane is still a challenge. Here, a tribo-charge enhanced and biodegradable nanofibrous membranes (TCB NFMs) with highly fluffy structure for air filtration and self-powered respiration monitoring systems is reported for the first time. The filtration efficiency and pressure drop of the prepared membranes for 0.3 µm NaCl particulates is 99.971% and 41.67 Pa. The TCB NFMs based smart mask possesses a series of satisfactory and excellent characteristics, such as self-powered, biodegradable, biocompatible, high filtration efficiency, and low pressure drop, which is highly promising for application in air filtration systems and intelligent wearable respiration monitoring systems.

Amorphous MnO2 Lamellae Encapsulated Covalent Triazine Polymer-Derived Multi-Heteroatoms-Doped Carbon for ORR/OER Bifunctional Electrocatalysis.

The intelligent construction of non-noble metal materials that exhibit reversible oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) with bifunctional electrocatalytic performance is greatly coveted in the realm of zinc-air batteries (ZABs). Herein, a crafted structure-amorphous MnO2 lamellae encapsulated covalent triazine polymer-derived N, S, P co-doped carbon sphere (A-MnO2 /NSPC) is designed using a self-doped pyrolysis coupled with an in situ encapsulation strategy. The customized A-MnO2 /NSPC-2 demonstrates a superior bifunctional electrocatalytic performance, confirmed by a small ΔE index of 0.64 V for ORR/OER. Experimental investigations, along with density functional theory calculations validate that predesigned amorphous MnO2 surface defects and abundant heteroatom catalytic active sites collectively enhance the oxygen electrocatalytic performance. Impressively, the A-MnO2 /NSPC-based rechargeable liquid ZABs show a large open-circuit potential of 1.54 V, an ultrahigh peak power density of 181 mW cm-2 , an enormous capacity of 816 mAh g-1 , and a remarkable stability for more than 1720 discharging/charging cycles. Additionally, the assembled flexible all-solid-state ZABs also demonstrate outstanding cycle stability, surpassing 140 discharging/charging cycles. Therefore, this highly operable synthetic strategy offers substantial understanding in the development of magnificent bifunctional electrocatalysts for various sustainable energy conversions and beyond.

Bimetallic-Coordinated Covalent Triazine Framework-Derived FeNi Alloy Nanoparticle-Decorated Coral-Like Nanocarbons for Oxygen Electrocatalysis.

It is highly desirable to fabricate transition bimetallic alloy-embedded porous nanocarbons with a unique nanoarchitecture for the oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) in rechargeable zinc-air batteries. In this work, we introduce a template-assisted in situ alloying synthesis of FeNi alloy nanoparticle-decorated coral-like nanocarbons (FeNi-CNCs) as efficient OER/ORR dual-functional electrocatalysts. The present materials are produced through polycondensation of a covalent triazine framework (CTF), the coordination of Ni and Fe ions, and sequential pyrolytic treatment. Through the pyrolysis process, the nanolamellar FeNi-CTF precursors can be facilely converted into FeNi alloy nanoparticle-decorated nanocarbons. These nanocarbons possess a distinctive three-dimensional (3D) coral-like nanostructure, which is favorable for the transport of oxygen and the diffusion of electrolyte. As a result, FeNi-CNC-800 with the highest efficiency exhibited remarkable electrocatalytic performance and great durability. Additionally, it also can be assembled into rechargeable zinc-air batteries that can be assembled in both liquid and solid forms, offering a superior peak power density, large specific capacity, and outstanding reusability during charging/discharging cycles (e.g., 5160 charging-and-discharging cycles at 10 mA cm-2 for the liquid forms). These traits make it a highly promising option in the burgeoning field of wearable energy conversion.

Cellular Senescence: A Troy Horse in Pulmonary Fibrosis.

Pulmonary fibrosis (PF) is a chronic interstitial lung disease characterized by myofibroblast abnormal activation and extracellular matrix deposition. However, the pathogenesis of PF remains unclear, and treatment options are limited. Epidemiological studies have shown that the average age of PF patients is estimated to be over 65 years, and the incidence of the disease increases with age. Therefore, PF is considered an age-related disease. A preliminary study on PF patients demonstrated that the combination therapy of the anti-senescence drugs dasatinib and quercetin improved physical functional indicators. Given the global aging population and the role of cellular senescence in tissue and organ aging, understanding the impact of cellular senescence on PF is of growing interest. This article systematically summarizes the causes and signaling pathways of cellular senescence in PF. It also objectively analyzes the impact of senescence in AECs and fibroblasts on PF development. Furthermore, potential intervention methods targeting cellular senescence in PF treatment are discussed. This review not only provides a strong theoretical foundation for understanding and manipulating cellular senescence, developing new therapies to improve age-related diseases, and extending a healthy lifespan but also offers hope for reversing the toxicity caused by the massive accumulation of senescence cells in humans.

ADRB2 inhibition combined with antioxidant treatment alleviates lung fibrosis by attenuating TGFß/SMAD signaling in lung fibroblasts.

Idiopathic pulmonary fibrosis is a progressive and fatal interstitial lung disease with a poor prognosis and limited therapeutic options, which is characterized by aberrant myofibroblast activation and pathological remodeling of the extracellular matrix, while the mechanism remains elusive. In the present investigation, we observed a reduction in ADRB2 expression within both IPF and bleomycin-induced fibrotic lung samples, as well as in fibroblasts treated with TGF-ß1. ADRB2 inhibition blunted bleomycin-induced lung fibrosis. Blockage of the ADRB2 suppressed proliferation, migration, and invasion and attenuated TGF-ß1-induced fibroblast activation. Conversely, the enhancement of ADRB2 expression or functionality proved capable of inducing fibroblast-to-myofibroblast differentiation. Subsequent mechanistic investigation revealed that inhibition of ADRB2 suppressed the activation of SMAD2/3 in lung fibroblasts and increased phos-SMAD2/3 proteasome degradation, and vice versa. Finally, ADRB2 inhibition combined with antioxidants showed increased efficacy in the therapy of bleomycin-induced lung fibrosis. In short, these data indicate that ADRB2 is involved in lung fibroblast differentiation, and targeting ADRB2 could emerge as a promising and innovative therapeutic approach for pulmonary fibrosis.

Effects of groundwater depth on groundwater recharge and soybean growth dynamics in Northeast China Plain.

To explore the groundwater recharge rate and soybean growth dynamics under different groundwater depths, we conducted a field experiment with four groundwater depth treatments (1 m, D1; 2 m, D2; 3 m, D3; 4 m, D4) through the groundwater simulation system in 2021 and 2022 and explored the relationships between groundwater depth and groundwater recharge, irrigation, growth dynamics of soybean plants, and yield. We used the Logistic regression model to simulate the dynamics of soybean growth indices, including plant height, leaf area index, and dry matter accumulation. The results showed that compared with D1 treatment, the amount of groundwater recharge under D2, D3, and D4 treatments decreased by 81.1%, 96.8%, 97.5% and 80.7%, 96.7%, 97.3% in the two years, respectively. The groundwater in D1 treatment could meet water needs of soybean throughout the whole growth period, except that irrigation was needed in the sowing stage. The amount of irrigation under D1 treatment was decreased by 91.7%, 93.0%, 94.2%, and 90.9%, 92.9%, 94.0% in the two years, respectively, compared with D2, D3, D4 treatments. Among the four treatments, D1 treatment took the shortest time for entering the rapid growth stage and reach the maximum growth rate, which had the highest maximum growth rate. At the mature stage of soybean, the dry matter distribution ratio of stem in D1 treatment was the highest. D1 treatment promoted the translocation of post-flowering assimilates in soybean, and its post-flowering assimilate contribution to seeds increased by 15.5%, 16.2%, 32.6% and 45.5%, 48.7%, 63.3% in the two years, respectively, compared with D2, D3, D4 treatments. D1 treatment had the highest plant height, leaf area index, and dry matter accumulation, follo-wed by D4 treatment, while D3 treatment had the lowest. Soybean yield, number of pods per plant, number of grains per plant, and 100-grain weight all decreased and then increased with increasing groundwater depth, following an order of D1>D4>D2>D3. Soybean yield was significantly positively correlated with groundwater recharge, which was positively correlated with plant height, leaf area index, and dry matter accumulation. Our results indicated that the D1 treatment with adequate groundwater recharge increased plant height, leaf area index, and dry matter accumulation, coordinated the distribution and translocation of dry matter among all plant parts in the late soybean growth period, and ultimately achieved the highest yield. When groundwater depth was deep (D4), groundwater recharge was small. In such case, the growth and development status and yield of soybean could also reach a high level if there was sufficient water supply.

Self-healing polymers through hydrogen-bond cross-linking: synthesis and electronic applications.

Recently, polymers capable of repeatedly self-healing physical damage and restoring mechanical properties have attracted extensive attention. Among the various supramolecular chemistry, hydrogen-bonding (H-bonding) featuring reversibility, directionality and high per-volume concentration has become one of the most attractive directions for the development of self-healing polymers (SHPs). Herein, we review the recent advances in the design of high-performance SHPs based on different H-bonding types, for example, H-bonding motifs and excessive H-bonding. In particular, the effects of the structural design of SHPs on their mechanical performance and healing efficiency are discussed in detail. Moreover, we also summarize how to employ H-bonding-based SHPs for the preparation of self-healable electronic devices, focusing on promising topics, including energy harvesting devices, energy storage devices, and flexible sensing devices. Finally, the current challenges and possible strategies for the development of H-bonding-based SHPs and their smart electronic applications are highlighted.

Machine learning identifies ferroptosis-related genes as potential diagnostic biomarkers for osteoarthritis.

Background: Osteoarthritis (OA) is one of the most common forms of degenerative arthritis and a major cause of pain and disability. Ferroptosis, a novel mode of cell death, has been verified to participate in the development of OA, but its mechanism is still unclear. This paper analyzed the ferroptosis-related genes (FRGs) in OA and explored their potential clinical value. Methods: We downloaded data through the GEO database and screened for DEGs. Subsequently, FRGs were obtained using two machine learning methods, LASSO regression and SVM-RFE. The accuracy of the FRGs as disease diagnosis was identified using ROC curves and externally validated. The CIBERSORT analyzed the immune microenvironment rug regulatory network constructed through the DGIdb. The competitive endogenous RNA (ceRNA) visualization network was constructed to search for possible therapeutic targets. The expression levels of FRGs were verified by qRT-PCR and immunohistochemistry. Results: In this study, we found 4 FRGs. The ROC curve showed that the combined 4 FRGs had the highest diagnostic value. Functional enrichment analysis showed that the 4 FRGs in OA could influence the development of OA through biological oxidative stress, immune response, and other processes. qRT-PCR and immunohistochemistry verified the expression of these key genes, further confirming our findings. Monocytes and macrophages are heavily infiltrated in OA tissues, and the persistent state of immune activation may promote the progression of OA. ETHINYL ESTRADIOL was a possible targeted therapeutic agent for OA. Meanwhile, ceRNA network analysis identified some lncRNAs that could regulate the FRGs. Conclusion: We identify 4 FRGs (AQP8, BRD7, IFNA4, and ARHGEF26-AS1) closely associated with bio-oxidative stress and immune response, which may become early diagnostic and therapeutic targets for OA.

Distinct mononuclear diploid cardiac subpopulation with minimal cell-cell communications persists in embryonic and adult mammalian heart.

A small proportion of mononuclear diploid cardiomyocytes (MNDCMs), with regeneration potential, could persist in adult mammalian heart. However, the heterogeneity of MNDCMs and changes during development remains to be illuminated. To this end, 12 645 cardiac cells were generated from embryonic day 17.5 and postnatal days 2 and 8 mice by single-cell RNA sequencing. Three cardiac developmental paths were identified: two switching to cardiomyocytes (CM) maturation with close CM-fibroblast (FB) communications and one maintaining MNDCM status with least CM-FB communications. Proliferative MNDCMs having interactions with macrophages and non-proliferative MNDCMs (non-pMNDCMs) with minimal cell-cell communications were identified in the third path. The non-pMNDCMs possessed distinct properties: the lowest mitochondrial metabolisms, the highest glycolysis, and high expression of Myl4 and Tnni1. Single-nucleus RNA sequencing and immunohistochemical staining further proved that the Myl4+Tnni1+ MNDCMs persisted in embryonic and adult hearts. These MNDCMs were mapped to the heart by integrating the spatial and single-cell transcriptomic data. In conclusion, a novel non-pMNDCM subpopulation with minimal cell-cell communications was unveiled, highlighting the importance of microenvironment contribution to CM fate during maturation. These findings could improve the understanding of MNDCM heterogeneity and cardiac development, thus providing new clues for approaches to effective cardiac regeneration.

Long-term outcomes and potential mechanisms of offspring exposed to intrauterine hyperglycemia.

Diabetes mellitus during pregnancy, which can be classified into pregestational diabetes and gestational diabetes, has become much more prevalent worldwide. Maternal diabetes fosters an intrauterine abnormal environment for fetus, which not only influences pregnancy outcomes, but also leads to fetal anomaly and development of diseases in later life, such as metabolic and cardiovascular diseases, neuropsychiatric outcomes, reproduction malformation, and immune dysfunction. The underlying mechanisms are comprehensive and ambiguous, which mainly focus on microbiota, inflammation, reactive oxygen species, cell viability, and epigenetics. This review concluded with the influence of intrauterine hyperglycemia on fetal structure development and organ function on later life and outlined potential mechanisms that underpin the development of diseases in adulthood. Maternal diabetes leaves an effect that continues generations after generations through gametes, thus more attention should be paid to the prevention and treatment of diabetes to rescue the pathological attacks of maternal diabetes from the offspring.

Activity and Characterization of Tocopherol Oxidase in Corn Germs and Its Relationship with Oil Color Reversion.

Color reversion has long been a major problem for the vegetable oil industry, and the enzymatic oxidation of γ-tocopherol is thought to trigger this phenomenon. In this study, first, the extraction, purification, and detailed characterization of tocopherol oxidase from fresh corn germs were performed. Then, the relationship between the enzyme reaction of γ-tocopherol and oil color reversion was verified. The results showed that the membrane-free extracts of raw corn germ performed specific catalysis of tocopherol in the presence of lecithin. In terms of the oxidation product, tocored (the precursor of color reversion) was detected in the mixture after the catalytic reactions, indicating that this anticipated enzyme reaction was probably correlated with the color reversion. Furthermore, the optimal pH and temperature for the tocopherol oxidase enzyme were 4.6 and 20 °C, respectively. In addition, ascorbic acid at 1.0 mM completely inhibited the enzymatic reaction.

Di-n-butyl phthalate stress hampers compost multifunctionality by reducing microbial biomass, diversity and network complexity.

Phthalates are common pollutants in agriculture. Here, the influence of di-n-butyl phthalate (DBP) on multifunctionality of composting was assessed. Results indicated that DBP stress (100 mg/kg) hampered multifunctionality from the thermophilic phase onwards and resulted in a 6.5 % reduction of all assessed functions. DBP stress also significantly reduced microbial biomass (P < 0.05), altered microbial composition (P < 0.05), and decreased network complexity (P < 0.01). Multifunctionality was found to be strongly correlated (P < 0.001) with microbial biomass, diversity, and network complexity. In addition, keystone taxa responsive to DBP were identified as Streptomyces, Thermoactinomyces, Mycothermus, and Lutispora. These taxa were significantly (P < 0.001) affected by DBP stress, and a correlation between them and multifunctionality was shown. This study contributes to a better understanding of the negative implications of phthalates during composting processes, which is of great significance to the development of new treatment strategies for agricultural waste.

Selective Cleavage of the Strong or Weak C-C Bonds in Biphenylene Enabled by Rare-Earth Metals.

Selective cleavage of C-C bonds within arene rings is of great interest but remains elusive, especially for the molecules possessing the active and inert C-C bonds. Here, we report that the active and inert C-C bonds of biphenylene could be controllably cleaved by the reaction of biphenylene, potassium graphite, and rare-earth complexes with different metal centers. For scandium, the bond activation occurs at the Caryl-Caryl single bond, yielding 9-scandafluorene. For Lu, the reaction goes through ring contraction of the aromatic ring in biphenylene to provide benzopentalene dianionic lutetium. The origin of the selectivity and the reaction mechanism were illustrated by the isolation of intermediates and DFT calculations.

Intrinsic properties and extrinsic factors of food matrix system affecting the effectiveness of essential oils in foods: a comprehensive review.

Essential oils (EOs) have been proved as natural food preservatives because of their effective and wide-spectrum antimicrobial activity. They have been extensively explored for potential applications in food industry, and substantial progresses have been achieved. However well EOs perform in antibacterial tests in vitro, it has generally been found that a higher level of EOs is needed to achieve the same effect in foods. Nevertheless, this unsimilar effect has not been clearly quantified and elaborated, as well as the underlying mechanisms. This review highlights the influence of intrinsic properties (e.g., oils and fats, carbohydrates, proteins, pH, physical structure, water, and salt) and extrinsic factors (e.g., temperature, bacteria characteristics, and packaging in vacuum/gas/air) of food matrix systems on EOs action. Controversy findings and possible mechanism hypotheses are also systematically discussed. Furthermore, the organoleptic aspects of EOs in foods and promising strategies to address this hurdle are reviewed. Finally, some considerations about the EOs safety are presented, as well as the future trends and research prospects of EOs applications in foods. The present review aims to fill the evidenced gap, providing a comprehensive overview about the influence of the intrinsic and extrinsic factors of food matrix systems to efficiently orientate EOs applications.

Both intrinsic properties and extrinsic factors of food matrix affect the EOs action.EOs influence on the food organoleptic aspects were reviewed.Promising strategies for overcoming the organoleptic aspects of EOs were listed.Future research prospects are outlined to accelerate EOs application in foods.

Injectable Hydrogels Encapsulating Dual-Functional Au@Pt Core-Shell Nanoparticles Regulate Infarcted Microenvironments and Enhance the Therapeutic Efficacy of Stem Cells through Antioxidant and Electrical Integration.

Injectable functional biomaterials have made significant progress in cardiac regenerative. In addition, how to adjust the abominable infarction microenvironment and introduce therapeutic stem cells to improve the healing effect has become a hotspot. Herein, injectable stem cell vector is prepared by combining natural alginate hydrogel and Au@Pt nanoparticles (Au@Pt/Alg hydrogel) to encapsulate brown adipose stem cells (BASCs). Au@Pt nanoparticles with both antioxidative and conductive properties could effectively eliminate reactive oxygen species, enhance the frequency of action potential release of cardiomyocytes, and further reduce the inflammatory factors of macrophage in vitro. The Au@Pt/Alg hydrogel enhances the antioxidant, differentiation, and paracrine capability of BASCs. The effect of BASCs loaded Au@Pt/Alg hydrogel is evaluated in a rat myocardial infarction (MI) model. The antioxidant, anti-inflammatory, and heart electrical integration are showed in the MI model. More interestingly, Au@Pt/Alg hydrogel can effectively maintain the paracrine efficiency and pro-angiogenesis effects of BASCs in the infarcted area. This study led us to recognize the great value of Au@Pt/Alg hydrogels for their ability to actively regulate the microenvironment and carry stem cells for MI treatment.

A Conductive Bioengineered Cardiac Patch for Myocardial Infarction Treatment by Improving Tissue Electrical Integrity.

Conductive scaffolds are of great value for constructing functional myocardial tissues and promoting tissue reconstruction in the treatment of myocardial infarction (MI). Here, a novel scaffold composed of silk fibroin and polypyrrole (SP50) with a typical sponge-like porous structure and electrical conductivity similar to the native myocardium is developed. An electroactive engineered cardiac patch (SP50 ECP) with a certain thickness is constructed by applying electrical stimulation (ES) to the cardiomyocytes (CMs) on the scaffold. SP50 ECP can significantly express cardiac marker protein (α-actinin, Cx-43, and cTnT) and has better contractility and electrical coupling performance. Following in vivo transplantation, SP50 ECP shows a notable therapeutic effect in repairing infarcted myocardium. Not only can SP50 ECP effectively improves left ventricular remodeling and restore cardiac functions, such as ejection function (EF), but more importantly, improves the propagation of electrical pulses and promote the synchronous contraction of CMs in the scar area with normal myocardium, effectively reducing the susceptibility of MI rats to arrhythmias. In conclusion, this study demonstrates a facile approach to constructing electroactive ECPs based on porous conductive scaffolds and proves the therapeutic effects of ECPs in repairing the infarcted heart, which may represent a promising strategy for MI treatment.

Biomaterials based on hyaluronic acid, collagen and peptides for three-dimensional cell culture and their application in stem cell differentiation.

In recent decades, three-dimensional (3D) cell culture technologies have been developed rapidly in the field of tissue engineering and regeneration, and have shown unique advantages and great prospects in the differentiation of stem cells. Herein, the article reviews the progress and advantages of 3D cell culture technologies in the field of stem cell differentiation. Firstly, 3D cell culture technologies are divided into two main categories: scaffoldless and scaffolds. Secondly, the effects of hydrogels scaffolds and porous scaffolds on stem cell differentiation in the scaffold category were mainly reviewed. Among them, hydrogels scaffolds are divided into natural hydrogels and synthetic hydrogels. Natural materials include polysaccharides, proteins, and their derivatives, focusing on hyaluronic acid, collagen and polypeptides. Synthetic materials mainly include polyethylene glycol (PEG), polyacrylic acid (PAA), polyvinyl alcohol (PVA), etc. In addition, since the preparation techniques have a large impact on the properties of porous scaffolds, several techniques for preparing porous scaffolds based on different macromolecular materials are reviewed. Finally, the future prospects and challenges of 3D cell culture in the field of stem cell differentiation are reviewed. This review will provide a useful guideline for the selection of materials and techniques for 3D cell culture in stem cell differentiation.