TAF15 downregulation contributes to the benefits of physical training on dendritic spines and working memory in aged mice.

Moderate physical training has been shown to hinder age-related memory decline. While the benefits of physical training on hippocampal memory function are well-documented, little is known about its impact on working memory, which is linked to the prelimbic cortex (PrL), one major subdivision of the prefrontal cortex. Here, we examined the effects of physical training on spatial working memory in a well-established animal model of physical training, starting at 16 months of age and continuing for 5 months (running wheel 1 h/day and 5 days/week). This training strategy improved spatial working memory in aged mice (22-month-old), which was accompanied by an increased spine density and a lower TAF15 expression in the PrL. Specifically, physical training affected both thin and mushroom-type spines on PrL pyramidal cells, and prevented age-related loss of spines on selective segments of apical dendritic branches. Correlation analysis revealed that increased TAF15-expression was detrimental to the dendritic spines. However, physical training downregulated TAF15 expression in the PrL, preserving the dendritic spines on PrL pyramidal cells and improving working memory in trained aged mice. When TAF15 was overexpressed in the PrL via a viral approach, the benefits of physical training on the dendritic spines and working memory were abolished. These data suggest that physical training at a moderate pace might downregulate TAF15 expression in the PrL, which favors the dendritic spines on PrL pyramidal cells, thereby improving spatial working memory.

Design of Long-Life Wireless Near-Field Hydrogen Gas Sensor.

A compact wireless near-field hydrogen gas sensor is proposed, which detects leaking hydrogen near its source to achieve fast responses and high reliability. A semiconductor-type sensing element is implemented in the sensor, which can provide a significant response in 100 ms when stimulated by pure hydrogen. The overall response time is shortened by orders of magnitude compared to conventional sensors according to simulation results, which will be within 200 ms, compared with over 25 s for spatial concentration sensors under the worst conditions. Over 1 year maintenance intervals are enabled by wireless design based on the Bluetooth low energy protocol. The average energy consumption during a single alarm process is 153 µJ/s. The whole sensor is integrated on a 20 × 26 mm circuit board for compact use.

An Overview of Heavy Chain Ferritin in Cancer.

As a spherical protein that acts as a repository for intracellular iron, Ferritin is the most important iron storage form and is known to influence tumor immunity. Unbound ferritin is composed of 24 subunits, made up of ferritin light chain (FTL) and ferritin heavy chain (FTH). Ferritin can be automatically put together to form hollow nanocages that measure 12 nm around the outside and 8 nm around the inside. Cancer causes the second-most deaths worldwide, effective elimination of tumor cells while protecting normal cells is the foundation of modern tumor therapy. To this end, the innate tumor-targeting activity of human FTH1, first identified ten years ago, is highly appealing. Unmodified human FTH1 binds to its receptor, transferrin receptor 1 (TfR1), which is frequently overexpressed in cancer cells. FTH1-TfR1 binding permits improved drug efficacy by promoting ferritin-mediated targeted delivery. In addition, FTH is also associated with the prognosis of multiple typies of cancer. The level of FTH1 is significantly and positively correlated with the infiltration of tumor-associated macrophages. FTH1 also plays an important role in regulating the tumor immunity of solid cancer. As such, FTH1 has been extensively applied in the targeted delivery of anticancer drugs, diagnostic molecules (e.g., radioisotopes and fluorophones), and inorganic nanoparticles (NPs) to tumors.This article reviews the role of FTH in cancer and its potential as a therapeutic target.

Quantum Error-Correcting Codes Based on Orthogonal Arrays.

In this paper, by using the Hamming distance, we establish a relation between quantum error-correcting codes ((N,K,d+1))s and orthogonal arrays with orthogonal partitions. Therefore, this is a generalization of the relation between quantum error-correcting codes ((N,1,d+1))s and irredundant orthogonal arrays. This relation is used for the construction of pure quantum error-correcting codes. As applications of this method, numerous infinite families of optimal quantum codes can be constructed explicitly such as ((3,s,2))s for all si≥3, ((4,s2,2))s for all si≥5, ((5,s,3))s for all si≥4, ((6,s2,3))s for all si≥5, ((7,s3,3))s for all si≥7, ((8,s2,4))s for all si≥9, ((9,s3,4))s for all si≥11, ((9,s,5))s for all si≥9, ((10,s2,5))s for all si≥11, ((11,s,6))s for all si≥11, and ((12,s2,6))s for all si≥13, where s=s1⋯sn and s1,…,sn are all prime powers. The advantages of our approach over existing methods lie in the facts that these results are not just existence results, but constructive results, the codes constructed are pure, and each basis state of these codes has far less terms. Moreover, the above method developed can be extended to construction of quantum error-correcting codes over mixed alphabets.

Ni electrodes with 3D-ordered surface structures for boosting bubble releasing toward high current density alkaline water splitting.

The performance of alkaline water electrolysis (AWE) at high current densities is limited by gas bubble generation on the surface of electrodes, which covers active sites and blocks mass transfer, resulting in lower AWE efficiency. Here, we utilize electro-etching to construct Ni electrodes with hydrophilic and aerophobic surfaces to improve the efficiency of AWE. Ni atoms on the Ni surface can be exfoliated orderly along the crystal planes by electro-etching, forming micro-nano-scale rough surfaces with multiple crystal planes exposed. The 3D-ordered surface structures increase the exposure of active sites and promote the removal of bubbles on the surface of the electrode during the AWE process. In addition, experimental results from high-speed camera reveal that rapidly released bubbles can improve the local circulation of electrolyte. Lastly, the accelerated durability test based on practical working condition demonstrates that the 3D-ordered surface structures are robust and durable during the AWE process.

Nanoparticles advanced from preclinical studies to clinical trials for lung cancer therapy.

Lung cancer is the leading cause of cancer mortality. As a heterogeneous disease, it has different subtypes and various treatment modalities. In addition to conventional surgery, radiotherapy and chemotherapy, targeted therapy and immunotherapy have also been applied in the clinics. However, drug resistance and systemic toxicity still cannot be avoided. Based on the unique properties of nanoparticles, it provides a new idea for lung cancer therapy, especially for targeted immunotherapy. When nanoparticles are used as carriers of drugs with special physical properties, the nanodrug delivery system ensures the accuracy of targeting and the stability of drugs while increasing the permeability and the aggregation of drugs in tumor tissues, showing good anti-tumor effects. This review introduces the properties of various nanoparticles including polymer nanoparticles, liposome nanoparticles, quantum dots, dendrimers, and gold nanoparticles and their applications in tumor tissues. In addition, the specific application of nanoparticle-based drug delivery for lung cancer therapy in preclinical studies and clinical trials is discussed.

Catalytic [2,3]-sigmatropic rearrangement of sulfonium ylides derived from azoalkenes: non-carbenoid Doyle-Kirmse reaction.

The Sc(III)-catalyzed [2,3]-sigmatropic rearrangement of sulfonium ylides derived from azoalkenes has been established. Owing to the absence of a carbenoid intermediate, this protocol represents the first non-carbenoid variant of the Doyle-Kirmse reaction. Under mild conditions, a variety of tertiary thioethers have been readily prepared in good to excellent yields.

The effect of narcotics on ferroptosis-related molecular mechanisms and signalling pathways.

Ferroptosis is a novel programmed cell death form characterized by iron-mediated reactive oxygen species-induced lipid peroxidation and subsequent cell damage that is distinct from apoptosis, necroptosis, pyroptosis, and autophagy. Most studies on ferroptosis are based on its function and mechanism, but there have been relatively few studies on the effects of drugs, especially anaesthetics, on ferroptosis. Therefore, we summarized the recent literature on the effects of anaesthetics on ferroptosis to understand the underlying mechanism. In particular, we focused on the targets of various anaesthetics in different mechanisms of ferroptosis and the effects of ferroptosis induction or inhibition by narcotics on various diseases. The aims of this review are to provide a relatively reasonable drug regimen for clinicians, to explore potential ferroptosis protection drugs and targets, to reduce perioperative complications and to improve the postoperative performance of patients, especially those who are critically ill.

Strategies to improve the effect of mesenchymal stem cell therapy on inflammatory bowel disease.

Inflammatory bowel disease (IBD) includes Crohn's disease and ulcerative colitis and is an idiopathic, chronic inflammatory disease of the colonic mucosa. The occurrence of IBD, causes irreversible damage to the colon and increases the risk of carcinoma. The routine clinical treatment of IBD includes drug treatment, endoscopic treatment and surgery. The vast majority of patients are treated with drugs and biological agents, but the complete cure of IBD is difficult. Mesenchymal stem cells (MSCs) have become a new type of cell therapy for the treatment of IBD due to their immunomodulatory and nutritional functions, which have been confirmed in many clinical trials. This review discusses some potential mechanisms of MSCs in the treatment of IBD, summarizes the experimental results, and provides new insights to enhance the therapeutic effects of MSCs in future applications.

Immunotherapeutic Strategies for Head and Neck Squamous Cell Carcinoma (HNSCC): Current Perspectives and Future Prospects.

Neoantigens are abnormal proteins produced by genetic mutations in somatic cells. Because tumour neoantigens are expressed only in tumour cells and have immunogenicity, they may represent specific targets for precision immunotherapy. With the reduction in sequencing cost, continuous advances in artificial intelligence technology and an increased understanding of tumour immunity, neoantigen vaccines and adoptive cell therapy (ACT) targeting neoantigens have become research hotspots. Approximately 900,000 patients worldwide are diagnosed with head and neck squamous cell carcinoma (HNSCC) each year. Due to its high mutagenicity and abundant lymphocyte infiltration, HNSCC naturally generates a variety of potential new antigen targets that may be used for HNSCC immunotherapies. Currently, the main immunotherapy for HNSCC is use of immune checkpoint inhibitors(ICIs). Neoantigen vaccines and adoptive cell therapy targeting neoantigens are extensions of immunotherapy for HNSCC, and a large number of early clinical trials are underway in combination with immune checkpoint inhibitors for the treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). In this paper, we review recent neoantigen vaccine trials related to the treatment of HNSCC, introduce adoptive cell therapy targeting neoantigens, and propose a potential treatment for HNSCC. The clinical application of immune checkpoint inhibitor therapy and its combination with neoantigen vaccines in the treatment of HNSCC are summarized, and the prospect of using neoantigen to treat HNSCC is discussed and proposed.

Research Progress on Radiotherapy Combined with Immunotherapy for Associated Pneumonitis During Treatment of Non-Small Cell Lung Cancer.

Radiation pneumonitis is a common and serious complication of radiotherapy for thoracic tumours. Although radiotherapy technology is constantly improving, the incidence of radiation pneumonitis is still not low, and severe cases can be life-threatening. Once radiation pneumonitis develops into radiation fibrosis (RF), it will have irreversible consequences, so it is particularly important to prevent the occurrence and development of radiation pneumonitis. Immune checkpoint inhibitors (ICIs) have rapidly altered the treatment landscape for multiple tumour types, providing unprecedented survival in some patients, especially for the treatment of non-small cell lung cancer (NSCLC). However, in addition to its remarkable curative effect, ICls may cause immune-related adverse events. The incidence of checkpoint inhibitor pneumonitis (CIP) is 3% to 5%, and its mortality rate is 10% to 17%. In addition, the incidence of CIP in NSCLC is higher than in other tumour types, reaching 7%-13%. With the increasing use of immune checkpoint inhibitors (ICls) and thoracic radiotherapy in the treatment of patients with NSCLC, ICIs may induce delayed radiation pneumonitis in patients previously treated with radiation therapy, or radiation activation of the systemic immune system increases the toxicity of adverse reactions, which may lead to increased pulmonary toxicity and the incidence of pneumonitis. In this paper, the data about the occurrence of radiation pneumonitis, immune pneumonitis, and combined treatment and the latest related research results will be reviewed.

Erratum to "Evaluation of the Mechanism of Modified Lingguizhugan Decoction in the Treatment of Nonalcoholic Fatty Liver Disease".

[This corrects the article DOI: 10.1155/2022/4576679.].

Analysis of the Therapeutic Effect of Changyanning on Intestinal Flora in Inflammatory Bowel Disease.

Research Purposes. Inflammatory bowel disease (IBD) is an autoimmune disease coinduced by genes, environment, and immune response, mainly including ulcerative colitis (UC) and Crohn's disease (CD). There are a large number and variety of intestinal bacteria in the human intestinal tract. These bacteria maintain a balance with the human environment and participate in the normal physiological processes of the human body. They play a unique role in defending against pathogen invasion, maintaining the homeostasis of the human immune system and metabolizing substances. Intestinal flora imbalance may be one of the pathogenic factors of IBD, and restoring the disturbed intestinal flora has become a research hotspot in the prevention and treatment of IBD. Changyanning is mainly composed of Dijincao grass, yellow hairy ear grass, camphor tree roots, maple leaves, and so on. Clinical studies have shown that Changyanning alone or in combination has a significant effect on ulcerative colitis, but the treatment mechanism is not yet clear. In this study, we established an IBD animal model to explore the therapeutic mechanism of Changyanning on inflammatory bowel disease and its effect on intestinal flora. Research Methods. Male C57BL/6 SPF mice were given free access to 4% dextran sulfate sodium (DSS) solution for 7 days to establish an ulcerative colitis model. After the model was established, different doses of Changyanning tablets, Changyanning granules, and sulfasalazine were given by gavage for 7 days. The relieving effects of the above drugs on the symptoms of inflammatory bowel disease were evaluated by evaluating the mouse/rat body weight, survival rate, disease activity index, colon length, pathological tissue score, and other indicators. Results. The DSS-induced IBD mouse model showed significant increases in weight loss, DAI score, and pathological score. Both Changyanning tablets and granules can relieve the weight loss of mice, restore the colon length, and protect the colon tissue structure of mice. In reducing DAI and pathological scores in mice, Changyanning granules had a better effect. In conclusion, Changyanning can significantly improve the quality of life of IBD model animals, relieve intestinal inflammatory response, and relieve colonic edema, ulceration, and necrosis. The results show that Changyanning has a certain therapeutic effect on IBD. This study also provides experimental evidence for the application of Changyanning in the treatment of IBD, which is of great significance to its clinical application. The trail is registered in ChiCTR with number (TRN) ChiCTR2000028830.

Evaluation of the Mechanism of Modified Lingguizhugan Decoction in the Treatment of Nonalcoholic Fatty Liver Disease.

Nonalcoholic steatohepatitis (NASH) may develop into cirrhosis and liver cancer, which imposes a great burden to individuals and society. Lingguizhugan decoction is a commonly used dampness dispelling medication in traditional Chinese medicine and is often used to treat those with phlegm and retained fluid from various causes and pathogeneses. The objective of this study was to explore the effect and mechanism of modified Lingguizhugan decoction (MLGZG) on lipid metabolism and the inflammatory response to identify a theoretical basis to promote its clinical application in NASH therapy. After treatment with MLGZG for 8 weeks, the weight of high-fat-diet (HFD)-fed NASH rats was significantly higher than that of rats in the normal group, and the weights in each dose group were significantly lower than those in the model group. The treatment groups (low, medium, and high doses) had different degrees of improvement in the changes in hepatocyte tissue structure, steatosis, and inflammatory infiltration. Compared with that in the normal group, the expression of TNF receptor-associated factor-3 (TRAF-3) and nuclear factor κB (NFκB) in the model group significantly increased to varying degrees. Compared with the NASH group, the treatment groups (low, middle, and high doses) showed modified lipid metabolism gene expression and decreased inflammatory factor expression levels. Modified Lingguizhugan decoction can improve the general condition of rats with nonalcoholic fatty liver disease by reducing the expression levels of TRAF3, NF-κB, the Toll-like receptor 4 (TLR-4) pathway, and related proteins, as well as the expression levels of lipid metabolism genes and cytokines.

Human pluripotent stem cell-derived ectomesenchymal stromal cells promote more robust functional recovery than umbilical cord-derived mesenchymal stromal cells after hypoxic-ischaemic brain damage.

Aims: Hypoxic-ischaemic encephalopathy (HIE) is one of the most serious complications in neonates and infants. Mesenchymal stromal cell (MSC)-based therapy is emerging as a promising treatment avenue for HIE. However, despite its enormous potential, the clinical application of MSCs is limited by cell heterogeneity, low isolation efficiency and unpredictable effectiveness. In this study, we examined the therapeutic effects and underlying mechanisms of human pluripotent stem cell-derived ectomesenchymal stromal cells (hPSC-EMSCs) in a rat model of HIE. Methods: hPSC-EMSCs were induced from either human embryonic stem cells or induced pluripotent stem cells. Stem cells or the conditioned medium (CM) derived from stem cells were delivered intracranially or intranasally to neonatal rats with HIE. Human umbilical cord-derived MSCs (hUC-MSCs) were used as the therapeutic comparison control and phosphate-buffered saline (PBS) was used as a negative control. Lesion size, apoptosis, neurogenesis, astrogliosis and microgliosis were evaluated. The rotarod test and Morris water maze were used to determine brain functional recovery. The PC-12 cell line, rat primary cortical neurons and neural progenitor cells were used to evaluate neurite outgrowth and the neuroprotective and neurogenesis effects of hPSC-EMSCs/hUC-MSCs. RNA-seq and enzyme-linked immunosorbent assays were used to determine the secretory factors that were differentially expressed between hPSC-EMSCs and hUC-MSCs. The activation and suppression of extracellular signal-regulated kinase (ERK) and cAMP response element-binding protein (CREB) were characterised using western blotting and immunofluorescent staining. Results: hPSC-EMSCs showed a higher neuroprotective potential than hUC-MSCs, as demonstrated by a more significant reduction in lesion size and apoptosis in the rat brain following hypoxia-ischaemia (HI). Compared with PBS treatment, hPSC-EMSCs promoted endogenous neurogenesis and alleviated astrogliosis and microgliosis. hPSC-EMSCs were more effective than hUC-MSCs. hPSC-EMSCs achieved a greater recovery of brain function than hUC-MSCs and PBS in rats with HIE. CM derived from hPSC-EMSCs had neuroprotective and neurorestorative effects in vitro through anti-apoptotic and neurite outgrowth- and neurogenesis-promoting effects. Direct comparisons between hPSC-EMSCs and hUC-MSCs revealed the significant enrichment of a group of secretory factors in hPSC-EMSCs, including nerve growth factor (NGF), platelet-derived growth factor-AA and transforming growth factor-ß2, which are involved in neurogenesis, synaptic transmission and neurotransmitter transport, respectively. Mechanistically, the CM derived from hPSC-EMSCs was found to potentiate NGF-induced neurite outgrowth and the neuronal differentiation of NPCs via the ERK/CREB pathway. Suppression of ERK or CREB abolished CM-potentiated neuritogenesis and neuronal differentiation. Finally, intranasal delivery of the CM derived from hPSC-EMSCs significantly reduced brain lesion size, promoted endogenous neurogenesis, mitigated inflammatory responses and improved functional recovery in rats with HIE. Conclusion: hPSC-EMSCs promote functional recovery after HI through multifaceted neuromodulatory activities via paracrine/trophic mechanisms. We propose the use of hPSC-EMSCs for the treatment of HIE, as they offer an excellent unlimited cellular source of MSCs.

Hesperetin ameliorates hepatic oxidative stress and inflammation via the PI3K/AKT-Nrf2-ARE pathway in oleic acid-induced HepG2 cells and a rat model of high-fat diet-induced NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver disease. Dietary supplementation has become a promising strategy for managing NAFLD. Hesperetin, a citrus flavonoid, is mainly found in citrus fruits (oranges, grapefruit, and lemons) and possesses multiple pharmacological properties, including anti-cancer, anti-Alzheimer and anti-diabetic effects. However, the anti-NAFLD effect and mechanisms of hesperetin remain unclear. In this study, we investigated the therapeutic effect of hesperetin against NAFLD and the underlying mechanism in vitro and in vivo. In oleic acid (OA)-induced HepG2 cells, hesperetin upregulated antioxidant levels (SOD/GPx/GR/GCLC/HO-1) by triggering the PI3 K/AKT-Nrf2 pathway, alleviating OA-induced reactive oxygen species (ROS) overproduction and hepatotoxicity. Furthermore, hesperetin suppressed NF-κB activation and reduced inflammatory cytokine secretion (TNF-α and IL-6). More importantly, we revealed that this anti-inflammatory effect is attributed to reduced ROS overproduction by the Nrf2 pathway, as pre-treatment with Nrf2 siRNA or an inhibitor of superoxide dismutase (SOD) or/and glutathione peroxidase (GPx) abolished hesperetin-induced NF-κB inactivation and reductions in inflammatory cytokine secretion. In a rat model of high-fat diet (HFD)-induced NAFLD, we confirmed that hesperetin relieved hepatic steatosis, oxidative stress, inflammatory cell infiltration and fibrosis. Moreover, hesperetin activated the PI3 K/AKT-Nrf2 pathway in the liver, increasing antioxidant expression and inhibiting NF-κB activation and inflammatory cytokine secretion. In summary, our results demonstrate that hesperetin ameliorates hepatic oxidative stress through the PI3 K/AKT-Nrf2 pathway and that this antioxidative effect further suppresses NF-κB-mediated inflammation during NAFLD progression. Thus, our study suggests that hesperetin may be an effective dietary supplement for improving NAFLD by suppressing hepatic oxidative stress and inflammation.

Comparison of the complete mitochondrial genome of Phyllophorus liuwutiensis (Echinodermata: Holothuroidea: Phyllophoridae) to that of other sea cucumbers.

Sea cucumber species are abundant (>1400 species) and widely distributed globally. mtDNA sequencing is frequently used to identify the phylogenetic and evolutionary relationships among species. However, there are no reports on the mitochondrial genome of Phyllophorus liuwutiensis. Here, we performed mtDNA sequencing of P. liuwutiensis to examine its phylogenetic relationships with other echinoderms. Its mitochondrial genome (15 969 bp) contains 37 coding genes, including 13 protein-coding genes, 22 tRNA genes and 2 rRNA genes. Except for one protein-coding gene (nad6) and five tRNA genes encoded on the negative strand, all other genes were encoded on the positive strand. The mitochondrial bases of P. liuwutiensis were composed of 29.55% T, 22.16% C, 35.64% A and 12.64% G. The putative control region was 703 bp in length. Seven overlapping regions (1-10 bp) were found. The noncoding region between the genes ranged from 1 to 130 bp in length. One putative control region has been found in the P. liuwutiensis mitogenome. All of the tRNA genes were predicted to fold into a cloverleaf structure. In addition, we compared the gene arrangements of six echinoderms, revealing that the gene order of P. liuwutiensis was a new arrangement.

Characterization of the complete mitochondrial genome of a holothurians species: Holothuria hilla (Holothuroidea: Holothuriidae).

Mitochondrial genome sequence is a great potential method to both resolve disputed taxonomic issues and to infer phylogenetic relationships among holothurians. In this study, we present the complete mitochondrial genome of Holothuria hilla which was 15,744 bp in length, containing 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and a putative control region. The gene content and arrangement were typical for Holothuroidea ground pattern. The overall base composition was 32.43% A, 27.20% T, 24.35% C and 16.02% G, showing a bias toward A + T (59.63%). The maximum-likelihood tree based on the concatenated 13 protein-coding genes revealed the phylogenetic relationships among the Holothuroidea species.

The complete mitochondrial genome sequence of Stichopus variegatus (Echinodermata: Holothuroidea) and phylogenetic studies of Echinodermata.

At present, there exist some confusing issues on the species classification and phylogeny in Echinodermata. In this study, we first determined and described the complete mitochondrial genome of Stichopus variegatus. The complete mitogenome sequence had a circular mapping molecular with the total length of 16,315 bp and contained 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and a putative control region. To further validate the newly determined sequences, phylogenetic trees involving all the Holothuroidea and other Echinodermata species available in GenBank Database were constructed. These results would be used for the species identification and further phylogenetic studies of Echinodermata.

Epigenetic memory gained by priming with osteogenic induction medium improves osteogenesis and other properties of mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are highly plastic cells that are able to transdifferentiate or dedifferentiate under appropriate conditions. In the present study, we reported here that after in vitro induction of osteogenic differentiation, MSCs could be reverted to a primitive stem cell population (dedifferentiated osteogenic MSCs, De-Os-MSCs) with improved cell survival, colony formation, osteogenic potential, migratory capacity and increased expression of Nanog, Oct4 and Sox2. Most importantly, our results showed great superiority of the De-Os-MSCs over untreated MSCs in ectopic bone formation in vivo. Furthermore, Nanog-knockdown in MSCs could reverse these enhanced properties in De-Os-MSCs in vitro, indicating a central role of Nanog in the transcriptional network. In addition, epigenetic regulations including DNA methylation and histone modifications may play important roles in regulating the de-osteogenic differentiation process. And we found decreased methylation and promoter accrual of activating histone marks, such as H3K4me3 and H4ac on both Nanog and Oct4 gene promoters. Taken together, our study demonstrated that epigenetic memory in De-Os-MSCs gained by priming with osteogenic induction medium favored their differentiation along osteoblastic lineage with improved cell survival and migratory abilities, which may have application potential in enhancing their regenerative capacity in mammals.