Recently, strong polymer‐based hydrogels have been intensively investigated. However, the development of tough protein hydrogels with controlled degradation for bone regeneration has rarely been ...reported. Here, regenerated silk fibroin/gelatin (RSF/G) hydrogels with both strength and controlled degradation are prepared via physically and chemically double‐crosslinked networks. As a representative example, the 9%RSF/3%G hydrogel shows approximately 80% elongation and a compressive and tensile modulus of up to 0.25 and 0.21 MPa, respectively. It also shows a degradation rate that can be adjusted to approximately three months in vivo, a value between that of the rapidly degrading gelatin hydrogel and the slowly degrading RSF hydrogel. The 9%RSF/3%G hydrogel has good biocompatibility and promotes the proliferation and differentiation of bone marrow–derived stem cells compared with the control and pure RSF hydrogels. At 12 weeks after implantation of the gel in a calvarial defect, micro‐computed tomography shows greater bone volume and bone mineral density in the 9%RSF/3%G group. More importantly, histology reveals more mineralization and enhancements in the quality and rate of bone regeneration with less of a tissue response in the 9%RSF/3%G group. These results indicate the promising potential of this tough protein hydrogel with controlled degradation for bone regeneration applications.
A novel facile strategy is developed to fabricate strong and tough hydrogels with controlled degradation by immersing an enzymatically crosslinked regenerated silk fibroin/gelatin (RSF/G) hydrogel in a salt solution, forming a double‐crosslinked network. The resulting 9%RSF/3%G hydrogel shows high strength, good biocompatibility, a suitable degradation rate, and capacity for promoting osteogenic differentiation and bone regeneration.
Ferroptosis is an iron-dependent regulated cell death driven by excessive lipid peroxidation. Inflammation is one common and effective physiological event that protects against various stimuli to ...maintain tissue homeostasis. However, the dysregulation of inflammatory responses can cause imbalance of the immune system, cell dysfunction and death. Recent studies have pointed out that activation of inflammation, including the activation of multiple inflammation-related signaling pathways, can lead to ferroptosis. Among the related signal transduction pathways, we focused on five classical inflammatory pathways, namely, the JAK-STAT, NF-κB, inflammasome, cGAS-STING and MAPK signaling pathways, and expounded on their roles in ferroptosis. To date, many agents have shown therapeutic effects on ferroptosis-related diseases by modulating the aforementioned pathways in vivo and in vitro. Moreover, the regulatory effects of these pathways on iron metabolism and lipid peroxidation have been described in detail, contributing to further understanding of the pathophysiological process of ferroptosis. Taken together, targeting these pathways related to inflammation will provide appropriate ways to intervene ferroptosis and diseases.
Ferroptosis was first coined in 2012 to describe the form of regulated cell death (RCD) characterized by iron-dependent lipid peroxidation. To date, ferroptosis has been implicated in many diseases, ...such as carcinogenesis, degenerative diseases (e.g., Huntington’s, Alzheimer’s, and Parkinson’s diseases), ischemia-reperfusion injury, and cardiovascular diseases. Previous studies have identified numerous targets involved in ferroptosis; for example, acyl-CoA synthetase long-chain family member 4 (ACSL4) and p53 induce while glutathione peroxidase 4 (GPX4) and apoptosis-inducing factor mitochondria-associated 2 (AIFM2, also known as FSP1) inhibit ferroptosis. At least three major pathways (the glutathione-GPX4, FSP1-coenzyme Q10 (CoQ10), and GTP cyclohydrolase-1- (GCH1-) tetrahydrobiopterin (BH4) pathways) have been identified to participate in ferroptosis regulation. Recent advances have also highlighted the crucial roles of posttranslational modifications (PTMs) of proteins in ferroptosis. Here, we summarize the recently discovered knowledge regarding the mechanisms underlying ferroptosis, particularly the roles of PTMs in ferroptosis regulation.
The interferon-regulatory factor (IRF) family comprises nine members in mammals. Although this transcription factor family was originally thought to function primarily in the immune system, ...contributing to both the innate immune response and the development of immune cells, recent advances have revealed that IRFs plays critical roles in other biological processes, such as metabolism. Accordingly, abnormalities in the expression and/or function of IRFs have increasingly been linked to disease. Herein, we provide an update on the recent progress regarding the regulation of immune responses and immune cell development associated with IRFs. Additionally, we discuss the relationships between IRFs and immunity, metabolism, and disease, with a particular focus on the role of IRFs as stress sensors. This article is part of a Special Issue entitled: Autophagy and protein quality control in cardiometabolic diseases.
•IRFs are involved not only in immunity, but also in metabolism, and related diseases.•The roles of IRFs in cardiovascular and cerebrovascular diseases are discussed.•IRFs are stress sensors.
Studies over the past decades have elucidated the critical role of autophagy in human health and diseases. Although the processes of autophagy in the cytoplasm have been well studied, the ...posttranscriptional and epigenetic regulation mechanisms of autophagy are still poorly understood. Protein methylation, including histone methylation and non-histone protein methylation, is the most important type of posttranscriptional and epigenetic modification. Recent studies have shown that protein methylation is associated with effects on autophagosome formation, autophagy-related protein expression, and signaling pathway activation, but the details are still unclear. Thus, it is important to summarize the current status and discuss the future directions of research on protein methylation in the context of autophagy.
Smooth muscle cell (SMC) loss is the characteristic feature in the pathogenesis of aortic dissection (AD), and ferroptosis is a novel iron-dependent regulated cell death driven by the excessive lipid ...peroxidation accumulation. However, whether targeting ferroptosis is an effective approach for SMC loss and AD treatment remains unclear. Here, we found that the iron level, ferroptosis-related molecules TFR, HOMX1, ferritin and the lipid peroxidation product 4-hydroxynonenal were increased in the aorta of AD. Then, we screened several inhibitors of histone methyltransferases and found that BRD4770 had a protective effect on cystine deprivation-, imidazole ketone erastin- or RSL3-induced ferroptosis of SMCs. The classic ferroptosis pathways, System Xc--GPX4, FSP1-CoQ10 and GCH1-BH4 pathways which were inhibited by ferroptosis inducers, were re-activated by BRD4770 via inhibiting mono-, di- and tri- methylated histone H3 at lysine 9 (H3K9me1/2/3). RNA-sequencing analysis revealed that there was a positive feedback regulation between ferroptosis and inflammatory response, and BRD4770 can reverse the effects of inflammation activation on ferroptosis. More importantly, treatment with BRD4770 attenuated aortic dilation and decreased morbidity and mortality in a β-Aminopropionitrile monofumarate-induced mouse AD model via inhibiting the inflammatory response, lipid peroxidation and ferroptosis. Taken together, our findings demonstrate that ferroptosis is a novel and critical pathological mechanism that is involved in SMC loss and AD development. BRD4770 is a novel ferroptosis inhibitor and has equivalent protective effect to Ferrostatin-1 at the optimal concentration. Translating insights into the anti-ferroptosis effects of BRD4770 may reveal a potential therapeutic approach for targeting SMC ferroptosis in AD.
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•Ferroptosis is a novel and critical pathological mechanism involved in SMC loss and AD development.•BRD4770 is a novel inhibitor of ferroptosis and protects against SMC ferroptosis via maintaining redox homeostasis.•BRD4770 relieves BAPN-induced AD by inhibiting ferroptosis and inflammatory cell infiltration.
Recognition of multifrequency microwave (MW) electric fields is challenging because of the complex interference of multifrequency fields in practical applications. Rydberg atom-based measurements for ...multifrequency MW electric fields is promising in MW radar and MW communications. However, Rydberg atoms are sensitive not only to the MW signal but also to noise from atomic collisions and the environment, meaning that solution of the governing Lindblad master equation of light-atom interactions is complicated by the inclusion of noise and high-order terms. Here, we solve these problems by combining Rydberg atoms with deep learning model, demonstrating that this model uses the sensitivity of the Rydberg atoms while also reducing the impact of noise without solving the master equation. As a proof-of-principle demonstration, the deep learning enhanced Rydberg receiver allows direct decoding of the frequency-division multiplexed signal. This type of sensing technology is expected to benefit Rydberg-based MW fields sensing and communication.
Far-from-equilibrium dynamics that lead to self-organization are highly relevant to complex dynamical systems not only in physics but also in life, earth, and social sciences. However, it is ...challenging to find systems with sufficiently controllable parameters that allow quantitatively modeling of emergent properties. Here, we study a nonequilibrium phase transition and observe signatures of self-organized criticality in a dilute thermal vapor of atoms optically excited to strongly interacting Rydberg states. Electromagnetically induced transparency provides excellent control over the population dynamics and enables high-resolution probing of the driven-dissipative dynamics, which also exhibits phase bistability. Increased sensitivity compared to previous work allows us to reconstruct the complete phase diagram, including in the vicinity of the critical point. We observe that interaction-induced energy shifts and enhanced decay only occur in one of the phases above a critical Rydberg population. This case limits the application of generic mean-field models; however, a modified, threshold-dependent approach is in qualitative agreement with experimental data. Near threshold, we observe self-organized dynamics in the form of population jumps that return the density to a critical value.
Background
Plastic bronchitis (PB) is a rare, variable, and potentially fatal disease. This study aimed to assess the efficacy of fiberoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL) in ...treating children with PB.
Methods
In total, 15 children with PB, between 2012 and 2020, were enrolled in our study. Within 12 hours of admission, FOB and BAL were performed and reviewed under local anesthesia and sedation. Before and after FOB, clinical findings and chest imaging were evaluated.
Results
Regarding the onset of symptoms before FOB, all cases had prominent cough for 7.00 ± 4.55 days, and 14 had persistent high fever. In total, 13 cases had complete obstruction from bronchial casts, consistent with consolidated lesions; 2 had partial airway obstruction. Within 3 days, complete resolution was revealed in nine cases. Overall, six cases underwent repeated FOB (range, 2‐3 times) for persistent atelectasis and airway obstruction. Except for two cases with type 2 PB, cast histology confirmed type 1 PB for all cases. Only eight children had minor intra‐ and post‐procedure complications. Reverse transcription‐polymerase chain reaction for Mycoplasma pneumoniae in sputum and BAL samples were positive in 13 cases. Next‐generation sequencing of the BAL samples was positive for adenovirus and Human parainfluenza virus in one case, respectively. During 1 month to 7 years of follow‐up, no patient developed PB recurrence, asthmatic attacks, or chronic cough.
Conclusions
Early FOB and BAL were effective in alleviating clinical findings, atelectasis, and airway obstruction. Serial FOB could be performed in patients with recurrent symptoms.
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