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Abstract Once considered unconventional cellular structures, membraneless organelles (MLOs), cellular substructures involved in biological processes or pathways under physiological conditions, have emerged as central players in cellular dynamics and function. MLOs can be formed through liquid-liquid phase separation (LLPS), resulting in the creation of condensates. From neurodegenerative disorders, cardiovascular diseases, aging, and metabolism to cancer, the influence of MLOs on human health and disease extends widely. This review discusses the underlying mechanisms of LLPS, the biophysical properties that drive MLO formation, and their implications for cellular function. We highlight recent advances in understanding how the physicochemical environment, molecular interactions, and post-translational modifications regulate LLPS and MLO dynamics. This review offers an overview of the discovery and current understanding of MLOs and biomolecular condensate in physiological conditions and diseases. This article aims to deliver the latest insights on MLOs and LLPS by analyzing current research, highlighting their critical role in cellular organization. The discussion also covers the role of membrane-associated condensates in cell signaling, including those involving T-cell receptors, stress granules linked to lysosomes, and biomolecular condensates within the Golgi apparatus. Additionally, the potential of targeting LLPS in clinical settings is explored, highlighting promising avenues for future research and therapeutic interventions.

In this study, we investigated the oxidation of the Mg-11Y-1Al alloy at 500 °C in an Ar-20%O2 environment. Multiscale analysis showed the network-like long-period stacking ordered (LPSO) phase transformed into needle-like LPSO and polygonal Mg24Y5 phases, leading to the formation of a high-dense network of needle-like oxides at the oxidation front. These oxides grew laterally along the oxide/matrix interfaces, forming a thicker, continuous scale that effectively blocked elemental diffusion. Hence, the preferential oxidation along the needle-like LPSO is believed to accelerate the formation of a thicker and continuous oxide scale, further improving the oxidation resistance of the Mg-11Y-1Al alloy.

Thoracic aortic aneurysm/dissection (TAAD) is a severe vascular condition associated with life-threatening complications, and its underlying molecular mechanisms remain largely unexplored. Previous research indicates that the aberrant activation of cytosolic DNA and its receptors plays a crucial role in vascular inflammation and dysfunction. Specifically, Absent in Melanoma 2 (AIM2), an intracellular DNA receptor, can trigger the inflammasome pathway, leading to extracellular matrix destruction. In this investigation, we delved into the mechanism underlying AIM2 activation in TAAD development and explored the potential of exosomes to impede TAAD progression by suppressing AIM2 expression. Our findings revealed that heightened AIM2 expression and activation contribute to TAAD development by fostering vascular inflammation and disrupting vascular homeostasis. Activated AIM2 induces pyroptosis through the recruitment of the deubiquitination enzyme USP21, which stabilizes AIM2 by reducing its ubiquitination and degradation. Moreover, we demonstrated that exosome-derived miR-485-5p exerts an anti-inflammatory and protective effect on the thoracic aorta by inhibiting AIM2 activation. This study introduces novel perspectives for the treatment of TAAD.

Abstract To serve in a more aggressive chlorine (Cl−) ions-containing environment, a chlorine ions insensitivity Mg-Nd-Zr alloys is fabricated, exhibiting a stable corrosion resistance in either 3.5wt.% or 10 wt.% NaCl solution. Unlike pure Mg who exhibit a negligible protection of the matrix, a distinct “hindering effect” of Cl− diffusion caused by doping elements within the corrosion film was observed. Its underlying mechanism is demonstrated by X-ray photoelectron spectroscopy (XPS) and Density functional theory (DFT) analysis. The introducing with Nd and Zr elements can effectively passivate vacancies and alter diffusion energy of chlorine ions.

Precipitation strengthening represents a crucial strengthening approach in the realm of metals, with particular significance for magnesium. In this study, a complex LPSO–precipitate structure, which is constituted of the principal secondary phases in Mg rare earth (RE) alloys, namely the Long-Period Stacking Ordered (LPSO) phase and the aging precipitate, was successfully fabricated within a Mg-11Y-1Al alloy. Subsequently, an in-depth investigation was conducted regarding the interaction between dislocations and this LPSO–precipitate structure under varying temperature conditions. The findings revealed that, at room temperature (RT), the aging precipitates effectively hindered the movement of basal dislocations, and the activation of non-basal dislocations is rather difficult, resulting in the alloy’s high strength and low plasticity. When the temperature was elevated to 200 °C, although non-basal slip could be initiated, the LPSO–precipitate structure was capable of blocking both basal and non-basal slips. Consequently, the alloy still demonstrated high strength and low plasticity. As the temperature further increased to 250 °C, dislocations could cut through the aging precipitate particles, and the interior of the grains could provide partial deformation. Hence, the tensile elongation of the alloy was significantly enhanced, increasing from 4% to 12% as the temperature was elevated from 200 °C to 250 °C. These results suggest that the LPSO–precipitate structure still exerts a remarkable strengthening effect at 200 °C. When the temperature reaches 250 °C, the plasticity of the alloy is improved but its strength decreases. The research outcomes presented in this paper offer a novel perspective for the precise tailoring of mechanical properties through precipitation strengthening within Mg-RE alloys.

The strategy of rare-earth elements addition into Mg alloys has been successfully developed and applied to enhance the mechanical performance and corrosion resistance of Mg alloys. Although this strategy has also been applied to enhance their high-temperature oxidation resistance, the mechanistic understanding of the beneficial effects remains elusive. Here, the oxidation of Mg–4Nd and Mg-4Nd–1Y alloys in Ar–20%O2 at 500 °C was studied and compared. It was found that even though a continuous layer of Nd2O3 did not form, the Nd addition could still enhance the oxidation tolerance of Mg–4Nd alloy by facilitating the generation of a more continuous and intact oxide scale and working as oxygen sinks to delay the violent oxidation of Mg. The formation of a continuous Y2O3 layer on Mg-4Nd–1Y alloy suggests that Y was more capable of facilitating the external oxidation due to its much faster diffusion rate in Mg matrix than that of Nd. However, the Nd addition could decrease the critical content of Y necessary for the oxidation transition from internal to external because of the synergistic effect of the Nd and Y addition. The dissolution of the thermal unstable Mg12Nd precipitates resulted in a localized increase of Nd content, accelerating the oxidation by increasing the preferential oxidation of Nd. Hence, in the design of oxidation-resistant Mg alloys, the addition of RE elements with faster diffusion rate and the addition of multiple alloy elements are preferred. In addition, the number of thermal unstable precipitates needs to be strictly controlled.

The local deformation behavior and dynamic recrystallization of a shock compressed Mg-1Zn alloy was investigated through EBSD and TEM. Since dislocation slipping and twinning were locally suppressed during high strain-rate deformation, a more flexible kinking deformation was activated to adjusted local orientation and facilitate slipping and twinning within the kinks. Meanwhile, due to the slow heat dissipation that resulted in a local temperature elevating, the kink bands were evolved into deformation bands with recrystallized nano-grains. Such a finding provides a new perspective for kinking-facilitated nanocrystallization in Mg alloys and other anisotropic metallic materials.

Abstract The ribosome is a multi-unit complex that translates mRNA into protein. Ribosome biogenesis is the process that generates ribosomes and plays an essential role in cell proliferation, differentiation, apoptosis, development, and transformation. The mTORC1, Myc, and noncoding RNA signaling pathways are the primary mediators that work jointly with RNA polymerases and ribosome proteins to control ribosome biogenesis and protein synthesis. Activation of mTORC1 is required for normal fetal growth and development and tissue regeneration after birth. Myc is implicated in cancer development by enhancing RNA Pol II activity, leading to uncontrolled cancer cell growth. The deregulation of noncoding RNAs such as microRNAs, long noncoding RNAs, and circular RNAs is involved in developing blood, neurodegenerative diseases, and atherosclerosis. We review the similarities and differences between eukaryotic and bacterial ribosomes and the molecular mechanism of ribosome-targeting antibiotics and bacterial resistance. We also review the most recent findings of ribosome dysfunction in COVID-19 and other conditions and discuss the consequences of ribosome frameshifting, ribosome-stalling, and ribosome-collision. We summarize the role of ribosome biogenesis in the development of various diseases. Furthermore, we review the current clinical trials, prospective vaccines for COVID-19, and therapies targeting ribosome biogenesis in cancer, cardiovascular disease, aging, and neurodegenerative disease.

Abstract Tumor development relies on the stemness of cancer stem cells, which is regulated by environmental cues. Previous studies have shown that zyxin can inhibit the expression of genes for embryonic stem cell status. In the present study, the expression levels of zyxin protein in cancer tissues and adjacent noncancerous tissues from 73 gastric cancer patients with different clinical stages were analyzed by Western blot. We showed that the relative expression levels of zyxin in gastric cancer tissues (cancer tissues/adjacent tissues) were significantly downregulated in advanced clinical stages. Overexpression of zyxin inhibited the stemness and epithelial–mesenchymal transition (EMT) processes in gastric cancer cells. Zyxin also inhibited the proliferation, migration, and invasion but increased the sensitivity of cancer cells to drugs. Overexpression of zyxin in MKN45 cells inhibited tumor growth in nude mice. We show that the interactions between zyxin and SIRT1 led to the upregulation of SIRT1, reduced acetylation levels of histone H3 K9 and K23, decreased transcription levels of SNAI 1/2, and inhibition of the EMT process. This study demonstrated that zyxin negatively regulates the progression of gastric cancer by inhibiting the stemness of cancer stem cells and EMT. Our findings shed new light on the pathogenesis of gastric cancer.

High-strength Mg alloys are often sought-after for automotive and aerospace applications, but they have an inferior corrosion resistance. Here, the authors develop a Mg-11Y-1Al (wt. %) alloy that shows both significantly improved mechanical properties and corrosion resistance.

Abstract The regenerative capacity of skeletal muscle is dependent on satellite cells. The circadian clock regulates the maintenance and function of satellite cells. Cryptochrome 2 (CRY2) is a critical component of the circadian clock, and its role in skeletal muscle regeneration remains controversial. Using the skeletal muscle lineage and satellite cell‐specific CRY2 knockout mice (CRY2scko), we show that the deletion of CRY2 enhances muscle regeneration. Single myofiber analysis revealed that deletion of CRY2 stimulates the proliferation of myoblasts. The differentiation potential of myoblasts was enhanced by the loss of CRY2 evidenced by increased expression of myosin heavy chain (MyHC) and myotube formation in CRY2−/− cells versus CRY2+/+ cells. Immunostaining revealed that the number of mononucleated paired box protein 7 (PAX7+) cells associated with myotubes formed by CRY2−/− cells was increased compared with CRY2+/+ cells, suggesting that more reserve cells were produced in the absence of CRY2. Loss of CRY2 leads to the activation of the ERK1/2 signaling pathway and ETS1, which binds to the promoter of PAX7 to induce its transcription. CRY2 deficient myoblasts survived better in ischemic muscle. Therefore, CRY2 is essential in regulating skeletal muscle repair.

Extracellular vesicles (EVs) are membranous vesicles secreted from cells to the outside and are widely present in body fluids. The most commonly used method to isolate EVs is ultracentrifugation. EVs contain lipids, proteins, genetic material, and organelles, which can be used as communication carriers between different cells and potential disease biomarkers. EVs secreted by different cells (cancer cells, adipocytes, mesenchymal stem cells, immune cells et al.) play different functions. With the development of technology, EVs can also be engineered to deliver drugs. EVs also play an important role in the progression, prevention, diagnosis, and treatment of Corona Virus Disease 2019 (COVID-19).

Abstract Inflammasomes are protein complexes of the innate immune system that initiate inflammation in response to either exogenous pathogens or endogenous danger signals. Inflammasome multiprotein complexes are composed of three parts: a sensor protein, an adaptor, and pro-caspase-1. Activation of the inflammasome leads to the activation of caspase-1, which cleaves pro-inflammatory cytokines such as IL-1β and IL-18, leading to pyroptosis. Effectors of the inflammasome not only provide protection against infectious pathogens, but also mediate control over sterile insults. Aberrant inflammasome signaling has been implicated in the development of cardiovascular and metabolic diseases, cancer, and neurodegenerative disorders. Here, we review the role of the inflammasome as a double-edged sword in various diseases, and the outcomes can be either good or bad depending on the disease, as well as the genetic background. We highlight inflammasome memory and the two-shot activation process. We also propose the M- and N-type inflammation model, and discuss how the inflammasome pathway may be targeted for the development of novel therapy.

Static recrystallization of a high strain rate compressed Mg-1 Zn (wt.%) alloy was investigated using electron backscattered diffraction (EBSD). A novel 53°〈101¯0〉 structure was observed in the as-deformed alloy, which showed a {101¯2}-{101¯2} double twin relationship with the matrix. When the as-deformed alloy was annealed at 200 °C, the {101¯1} compression twins and {101¯1}-{101¯2} double twins showed a higher priority to recrystallize. In addition, the coarse {101¯2} tension twins and their inner double twins were preferentially to recrystallize, while the lenticular tension twins had little impact on the recrystallization. Therefore, obtaining more compression twins or coarse twins instead of lenticular tension twins can be an effective approach to manipulate recrystallization process in deformed Mg alloys.

Summary: Skeletal muscle regeneration relies on satellite cells that can proliferate, differentiate, and form new myofibers upon injury. Emerging evidence suggests that misregulation of satellite cell fate and function influences the severity of Duchenne muscular dystrophy (DMD). The transcription factor Pax7 determines the myogenic identity and maintenance of the pool of satellite cells. The circadian clock regulates satellite cell proliferation and self-renewal. Here, we show that the CLOCK-interacting protein Circadian (CIPC) a negative-feedback regulator of the circadian clock, is up-regulated during myoblast differentiation. Specific deletion of Cipc in satellite cells alleviates myopathy, improves muscle function, and reduces fibrosis in mdx mice. Cipc deficiency leads to activation of the ERK1/2 and JNK1/2 signaling pathways, which activates the transcription factor SP1 to trigger the transcription of Pax7 and MyoD. Therefore, CIPC is a negative regulator of satellite cell function, and loss of Cipc in satellite cells promotes muscle regeneration.

In this paper, microstructure evolution and hardness of Mg-3Gd alloy treated by femtosecond (fs) laser shock peening (LSP) with direct and confined ablation modes were investigated in detail. Under a relatively low pulse energy of 430 µJ with a repetition of 1 kHz, the surface hardness of sample has been enhanced by 70% effectively. Compared with ns-LSP with pulse fluence of 71.7 J/cm2, fs-LSP with pulse fluence of 34.2 J/cm2 is superior in the hardness increment, both of which are in the same order of magnitude. A distinct grain refinement of surface layer has been discovered and results in the increase of hardness. Nonuse of absorption and confining layers and the employment of the industry commercial fs laser with high repetition can inspire big potential LSP application in special metal material. Keywords: Laser shock peening, Femtosecond laser, Mg–3Gd alloy hardness, Surface treatment

Recent studies have shown that the hydrogels formed by composite biomaterials are better choice than hydrogels formed by single biomaterial for tissue repair. We explored the feasibility of the composite hydrogel formed by silk fibroin (SF) and silk sericin (SS) in tissue repair for the excellent mechanical properties of SF, and cell adhesion and biocompatible properties of SS. In our study, the SF SS hydrogel was formed by SF and SS protein with separate extraction method (LiBr dissolution for SF and hot alkaline water dissolution for SS), while SF-SS hydrogel was formed by SF and SS protein using simultaneous extraction method (LiBr dissolution for SF and SS protein). The effects of the two composite hydrogels on the release of inflammatory cytokines from macrophages and the wound were analyzed. Moreover, two hydrogels were used to encapsulate and deliver human umbilical cord mesenchymal stem cell derived exosomes (UMSC-Exo). Both SF SS and SF-SS hydrogels promoted wound healing, angiogenesis, and reduced inflammation and TNF-α secretion by macrophages. These beneficial effects were more significant in the experimental group treated by UMSC-Exo encapsulated in SF-SS hydrogel. Our study found that SF-SS hydrogel could be used as an excellent alternative to deliver exosomes for tissue repair.

Mg-Y based alloys exhibit a promising combination of strength and deformability through tuning precipitation and solute strengthening mechanisms and tailoring the activity of non-basal dislocations. Understanding the precipitation sequence of Mg-Y based alloys and its dependence on Yttrium concentration in the matrix will provide a guideline for fine tuning structure, morphology and distribution of precipitates in Mg-Y based alloys. In this paper, we explore the precipitation behaviors of Mg-11Y (wt%) and Mg-11Y-1Al (wt%) alloys using aberration-corrected scanning transmission electron microscopy, and rationalize the experimental observations based on first-principles density functional theory calculations. The precipitation sequence during ageing at 225 °C is identified to be SSSS → clusters/G.P. Zones →β′ (Mg7Y) → β′′/βt′′ (Mg3Y). A novel βt′′ phase forms through in-situ transformation from the β′ phase, which shares the same Mg3Y composition with D019-β′′ phase and exhibits the same cbco-structure as β′ phase in Mg-Y based alloys.

Mammalian mitochondrial permeability transition pore (MPTP), across the inner and outer membranes of mitochondria, is a nonspecific channel for signal transduction or material transfer between mitochondrial matrix and cytoplasm such as maintenance of Ca2+ homeostasis, regulation of oxidative stress signals, and protein translocation evoked by some of stimuli. Continuous MPTP opening has been proved to stimulate neuronal apoptosis in ischemic stroke. Meanwhile, inhibition of MPTP overopening-induced apoptosis has shown excellent efficacy in the treatment of ischemic stroke. Among of which, the potential molecular mechanisms of drug therapy for stroke has also been gradually revealed by researchers. The characteristics of multi-components or multi-targets for ethnic drugs also provide the possibility to treat stroke from the perspective of mitochondrial MPTP. The advantages mentioned above make it necessary for us to explore and clarify the new perspective of ethnic medicine in treating stroke and to determine the specific molecular mechanisms through advanced technologies as much as possible. In this review, we attempt to uncover the relationship between abnormal MPTP opening and neuronal apoptosis in ischemic stroke. We further summarized currently authorized drugs, ethnic medicine prescriptions, herbs, and identified monomer compounds for inhibition of MPTP overopening-induced ischemic neuron apoptosis. Finally, we strive to provide a new perspective and enlightenment for ethnic medicine in the prevention and treatment of stroke by inhibition of MPTP overopening-induced neuronal apoptosis.

Maternal nicotine exposure causes alteration of gene expression and cardiovascular programming. The discovery of nicotine-medicated regulation in cardiogenesis is of major importance for the study of cardiac defects. The present study investigated the effect of nicotine on cardiac gene expression and epigenetic regulation during myocardial differentiation. Persistent nicotine exposure selectively inhibited expression of two cardiac genes, Tbx5 and Gata4, by promoter DNA hypermethylation. The nicotine-induced suppression on cardiac differentiation was restored by general nicotinic acetylcholine receptor inhibition. Consistent results of Tbx5 and Gata4 gene suppression and cardiac function impairment with decreased left ventricular ejection fraction were obtained from in vivo studies in offspring. Our results present a direct repressive effect of nicotine on myocardial differentiation by regulating cardiac gene suppression via promoter DNA hypermethylation, contributing to the etiology of smoking-associated cardiac defects.

While angiotensin II (ang II) has been implicated in the pathogenesis of cardiac cachexia (CC), the molecules that mediate ang II's wasting effect have not been identified. It is known TNF-α level is increased in patients with CC, and TNF-α release is triggered by ang II. We therefore hypothesized that ang II induced muscle wasting is mediated by TNF-α. Ang II infusion led to skeletal muscle wasting in wild type (WT) but not in TNF alpha type 1 receptor knockout (TNFR1KO) mice, suggesting that ang II induced muscle loss is mediated by TNF-α through its type 1 receptor. Microarray analysis identified cholesterol 25-hydroxylase (Ch25h) as the down stream target of TNF-α. Intraperitoneal injection of 25-hydroxycholesterol (25-OHC), the product of Ch25h, resulted in muscle loss in C57BL/6 mice, accompanied by increased expression of atrogin-1, MuRF1 and suppression of IGF-1/Akt signaling pathway. The identification of 25-OHC as an inducer of muscle wasting has implications for the development of specific treatment strategies in preventing muscle loss.

BackgroundExosomes derived from mesenchymal stem cells (MSCs) were proved to boost cell proliferation and angiogenic potency. We explored whether cardiac stem cells (CSCs) preconditioned with MSC exosomes could survive and function better in a myocardial infarction model. Methods and ResultsDiI‐labeled exosomes were internalized with CSCs. They stimulated proliferation, migration, and angiotube formation of CSCs in a dose‐dependent manner. In a rat myocardial infarction model, MSC exosome–preconditioned CSCs had significantly better survival, enhanced capillary density, reduced cardiac fibrosis, and restored long‐term cardiac function. MicroRNA profiling analysis revealed that a set of microRNAs were significantly changed in CSCs after MSC exosome treatment. ConclusionsPretreatment of CSCs with MSC exosomes provided a promising strategy to improve survival and angiogenic potency of CSCs.

Oxidized low density lipoprotein (OxLDL) has multiple proatherogenic effects, including induction of apoptosis. We have recently shown that OxLDL markedly downregulates insulin-like growth factor-1 receptor (IGF-1R) in human aortic smooth muscle cells, and that IGF-1R overexpression blocks OxLDL-induced apoptosis. We hypothesized that specific OxLDL-triggered signaling events led to IGF-1R downregulation and apoptosis. We examined OxLDL signaling pathways and found that neither IGF-1R downregulation nor the proapoptotic effect was blocked by inhibition of OxLDL-triggered extracellular signal-regulated kinase, p38 mitogen-activated protein kinase (MAPK), or peroxisome proliferator-activated receptor γ (PPARγ) signaling pathways, as assessed using specific inhibitors. However, antioxidants, polyethylene glycol catalase, superoxide dismutase, and Trolox completely blocked OxLDL downregulation of IGF-1R and OxLDL-induced apoptosis. Nordihydroguaiaretic acid, AA-861, and baicalein, which are lipoxygenase inhibitors and also have antioxidant activity, blocked IGF-1R downregulation and apoptosis as well as reactive oxygen species (ROS) production. These results suggest that OxLDL enhances ROS production possibly through lipoxygenase activity, leading to IGF-1R downregulation and apoptosis. Furthermore, anti-CD36 scavenger receptor antibody markedly inhibited OxLDL-induced IGF-1R downregulation and apoptosis as well as ROS production.In conclusion, our data demonstrate that OxLDL downregulates IGF-1R via redox-sensitive pathways that are distinct from OxLDL signaling through MAPK- and PPARγ-involved pathways but may involve a CD36-dependent mechanism.

BACKGROUND:Diabetes has been regarded as an inflammatory condition which is associated with left ventricular diastolic dysfunction (LVDD). The purpose of this study was to examine the expression levels of macrophage migration inhibitory factor (MIF) and G protein-coupled receptor kinase 2 (GRK2) in patients with early diabetic cardiomyopathy, and to investigate the mechanisms involved in MIF expression and GRK2 activation. METHODS:83 patients in the age range of 30-64 years with type 2 diabetes and 30 matched healthy men were recruited. Left ventricular diastolic function was evaluated by cardiac Doppler echocardiography. Plasma MIF levels were determined by ELISA. To confirm the clinical observation, we also studied MIF expression in prediabetic rats with impaired glucose tolerance (IGT) and relationship between MIF and GRK2 expression in H9C2 cardiomyoblasts exposed to high glucose. RESULTS:Compared with healthy subjects, patients with diabetes have significantly increased levels of plasma MIF which was further increased in diabetic patients with Left ventricular diastolic dysfunction (LVDD). The increased plasma MIF levels in diabetic patients correlated with plasma glucose, glycosylated hemoglobin and urine albumin levels. We observed a significant number of TUNEL-positive cells in the myocardium of IGT-rats but not in the control rats. Moreover, we found higher MIF expression in the heart of IGT with cardiac dysfunction compared to that of the controls. In H9C2 cardiomyoblast cells, MIF and GRK2 expression was significantly increased in a glucose concentration-dependant manner. Furthermore, GRK2 expression was abolished by siRNA knockdown of MIF and by the inhibition of CXCR4 in H9C2 cells. CONCLUSIONS:Our findings indicate that hyperglycemia is a causal factor for increased levels of pro-inflammatory cytokine MIF which plays a role in the development of cardiomyopathy occurring in patients with type 2 diabetes. The elevated levels of MIF are associated with cardiac dysfunction in diabetic patients, and the MIF effects are mediated by GRK2.

Myogenic regeneration relies on the proliferation and differentiation of satellite cells. TECRL (trans-2,3-enoyl-CoA reductase like) is an endoplasmic reticulum protein only expressed in cardiac and skeletal muscle. However, its role in myogenesis remains unknown. We show that TECRL expression is increased in response to injury. Satellite cell-specific deletion of TECRL enhances muscle repair by increasing the expression of EGR2 through the activation of the ERK1/2 signaling pathway, which in turn promotes the expression of PAX7. We further show that TECRL deletion led to the upregulation of the histone acetyltransferase general control nonderepressible 5, which enhances the transcription of EGR2 through acetylation. Importantly, we showed that AAV9-mediated TECRL silencing improved muscle repair in mice. These findings shed light on myogenic regeneration and muscle repair. [ABSTRACT FROM AUTHOR]