Search

The adjustment of the electronic structure of Co using Ce allows Ce–Co/N/C to show excellent ORR performance (E1/2 = 0.893 V).

This work comprehensively introduces recent innovative work on metal-related electrocatalysts for Li–CO2 batteries.

Exposure to micro- and nanoplastics (MNPs) is inevitable due to their omnipresence in the environment. A growing body of studies has advanced our understanding of the potential toxicity of MNPs but knowledge gaps still exist regarding the adverse effects of MNPs on the cardiovascular system and underlying mechanisms, particularly in humans. Here, we reviewed up-to-date data published in the past 10 years on MNP-driven cardiovascular toxicity and mechanisms. Forty-six articles concerning ADME (absorption, distribution, and aggregation behaviors) and toxicity of MNPs in the circulatory system of animals and human cells were analyzed and summarized. The results showed that MNPs affected cardiac functions and caused toxicity on (micro)vascular sites. Direct cardiac toxicity of MNPs included abnormal heart rate, cardiac function impairment, pericardial edema, and myocardial fibrosis. On (micro)vascular sites, MNPs induced hemolysis, thrombosis, blood coagulation, and vascular endothelial damage. The main mechanisms included oxidative stress, inflammation, apoptosis, pyroptosis, and interaction between MNPs and multiple cellular components. Cardiovascular toxicity was determined by the properties (type, size, surface, and structure) of MNPs, exposure dose and duration, protein presence, the life stage, sex, and species of the tested organisms, as well as the interaction with other environmental contamination. The limited quantitative information on MNPs' ADME and the lack of guidelines for MNP cardiotoxicity testing makes risk assessment on cardiac health impossible. Furthermore, the future directions of cardiovascular research on MNPs are recommended to enable more realistic health risk assessment.

Aggregate of therapeutic antibodies is usually considered as one of the most important critical quality attributes (CQA). The propensity of aggregates formation for bevacizumab is higher than other monoclonal antibody (mAb) drugs due to its tendency of self-association via the non-covalent interaction between the Fab arm of one bevacizumab molecule and the K445 residue on the heavy chain of another bevacizumab molecule. HLX04 has been developed as a biosimilar to bevacizumab (Avastin®) by Shanghai Henlius Biotech. To perform a head-to-head similarity evaluation with respect to aggregates or higher molecular weight species (HMWS) between HLX04 and Avastin®, we developed a robust high performance liquid chromatography (SEC-HPLC) method for aggregates analysis. Our characterization data indicated that HMWS of bevacizumab were mainly composed of dimers, and the dimer formation-dissociation equilibrium was influenced by protein concentration and storage temperature. Based on the characterization data of aggregates, we optimized the key parameters for SEC-HPLC based aggregates analysis method including mobile phase components and pH, autosampler temperature, as well as incubation conditions for sample pretreatment. The developed method was applied in HLX04 and Avastin® aggregates assessment and the similarity were confirmed among HLX04, China-sourced, and Europe-sourced Avastin® using both the pharmaceutical dosage forms and forced degradation samples. The method was also validated per ICH Q2 (R1) guidelines by challenging the parameters including specificity, accuracy, precision, linearity, range, limit of quantitation, and robustness. The validated method was applied in release test and stability study of HLX04 samples generated from commercial manufacturing process.

BackgroundImmunosuppressive tumor microenvironment (ITM) remains an obstacle that jeopardizes clinical immunotherapy.MethodsTo address this concern, we have engineered an exosome inherited from M1-pheototype macrophages, which thereby retain functions and ingredients of the parent M1-phenotype macrophages. The delivered RSL3 that serves as a common ferroptosis inducer can reduce the levels of ferroptosis hallmarkers (eg, glutathione and glutathione peroxidase 4), break the redox homeostasis to magnify oxidative stress accumulation, promote the expression of ferroptosis-related proteins, and induce robust ferroptosis of tumor cells, accompanied with which systematic immune response activation can bbe realized. M1 macrophage-derived exosomes can inherit more functions and genetic substances than nanovesicles since nanovesicles inevitably suffer from substance and function loss caused by extrusion-arised structural damage.ResultsInspired by it, spontaneous homing to tumor and M2-like macrophage polarization into M1-like ones are attained, which not only significantly magnify oxidative stress but also mitigate ITM including M2-like macrophage polarization and regulatory T cell decrease, and regulate death pathways.ConclusionsAll these actions accomplish a synergistic antitumor enhancement against tumor progression, thus paving a general route to mitigate ITM, activate immune responses, and magnify ferroptosis.

Cluster roots of white lupin are induced by low phosphorus (LP) to efficiently access unavailable P, but how soilborne microbes are associated with cluster root formation (CRF) is unclear. We investigated the roles of soilborne bacteria in CRF response to LP by high-throughput sequencing and root-bacteria interactions. Cluster root number was significantly decreased in plants grown in sterilized soil compared with nonsterilized soil. Proteobacteria was enriched in CR, as shown by microbiome analysis of soil (bulk, rhizosphere, and rhizosheath) and roots (main, lateral, and CR). Large-scale gene expression level implicated ethylene mediation in CRF. Klebsiella pneumoniae (P7), a soilborne bacterium belonging to Proteobacteria, was isolated from CR. Among 11 isolated strains, P7 exhibited the highest 1-aminocyclopropane-1-carboxylate deaminase (ACCD) activity; this enzyme inhibits the biosynthesis of ethylene in plants by the cleavage of the ethylene precursor 1-aminocyclopropane-1-carboxylic acid and promotes CRF under LP. We constructed an ACCD-deficit mutant accd in the P7 genetic background. The loss-of-function mutation failed to promote CRF under LP conditions. Also, auxin responses may be involved in K. pneumoniae-ethylene-mediated CRF. Overall, we propose that the soilborne bacterium K. pneumoniae promotes CRF of white lupin in response to LP by ethylene mediation.

All-solid-state electrolytes have attracted widely attentions due to their adequate safety assurance, which demonstrates great potential in high energy batteries with lithium metal anode. In the view of practical application, the inorganic-organic solid composite electrolytes (SCEs) show most promising because of their excellent processability. However, poor ionic conductivity and unstable interface between electrodes and solid electrolytes hinder their development. In this review, we summarized the strategies to improve the ionic conductivity of the active inorganic fillers based SCEs and interface compatibility between electrodes and solid electrolytes. Tuning the physical-chemical properties (concentration, geometry, orientation and etc.) of the fillers, surface decoration and small-molecular additives can regulate polymer crystallization kinetics and trigger fast Li-ions transport pathways, which promotes the ionic conductivity. To ameliorate interfacial performance, the approaches mainly involve designing multilayered SCE with symmetric or asymmetric configuration, utilizing chemical interactions and liquid phase therapy, and blending of polymers with various molecular weights and functional groups to ameliorate interface contact, prevent the interface reaction and inhibit lithium dendrites. We hope this review can provide deeply understanding and guidance on the design of SCEs for all-solid-state lithium metal batteries.

Purpose To establish a novel circRNA–miRNA–mRNA network associated with the poor prognosis of hepatocellular carcinoma (HCC). Materials and Methods Quantitative real-time PCR was used to verify the differentially expressed circRNA. Moreover, the competing endogenous RNA networks were established using bioinformatics methods. Meanwhile, the prognostic value and potential mechanism of ceRNA network in hepatocellular carcinoma (HCC) were analyzed. Results This work found that circ_0130911 was highly expressed in HCC tissues and early recurring HCC. Further, we effectively constructed a ceRNA network. The ceRNA network regulated by circ_0130911 might influence the prognosis of HCC by regulating cell cycle-related pathways. Conclusion The ceRNA network proposed here can be used as a novel biomarker for the prognosis of HCC, thereby providing new insights for the targeted therapy of HCC.

The effect of different SNPs in HIF-1α and cancer susceptibility remain indistinct. Here, we evaluated the association between all identified SNPs (rs11549465, rs11549467 and rs2057482) in HIF-1α and the overall risk of cancer in all case-control studies published before April 2020. A total of 54 articles including 56 case-control studies were included in this analysis. We found that variant genotypes of rs11549465 and rs11549467 were associated with a significantly increased overall cancer risk. In contrast, the variant T allele of rs2057482 showed a significantly reduced risk of overall cancer. In addition, variant genotypes of the three studied SNPs exhibited a significant association with cancer risk in Asians and specific cancer types. Meanwhile, HIF-1α was significantly highly expressed in head and neck squamous cell carcinoma and pancreatic cancer tissues. More importantly, survival analysis indicated that the high expression of HIF-1α was associated with a poor survival in patients with lung cancer. These findings further provided evidence that different SNPs in HIF-1α may exhibit different effects on overall cancer risk; these effects were ethnicity and type-specific. Further studies with functional evaluations are required to confirm the biological mechanisms underlying the role of HIF-1α SNPs in cancer development and progression.

There are many studies on the association between miR-608 rs4919510 polymorphism and susceptibility to colorectal cancer (CRC). However, the role of rs4919510 in CRC development and its underlying ...

Aging is associated with neurological impairment and cognitive decline. Flavonoids are very promising in anti-aging research in mouse models. Ribes meyeri anthocyanins are rich in abundant flavonoids, but their anti-aging biological activities remain unknown. In this study, we prepared an R. meyeri anthocyanin extract and analyzed its effects on neural stem cell (NSC) senescence in vivo and in vitro. We isolated mouse NSCs and used cell counting kit-8 (CCK-8), cell cycle, reactive oxygen species (ROS), and immunofluorescence methods to analyze the anti-aging effects of R. meyeri anthocyanins as well as naringenin (Nar), which metabolic analysis revealed as an important flavonoid in R. meyeri anthocyanins. RNA-sequencing (RNA-seq) and enzyme-linked immuno sorbent assay (ELISA) methods were also used to investigate Nar-specific mechanisms of anti-aging. After R. meyeri anthocyanin treatment, NSC proliferation accelerated, and NSCs had decreased senescence markers, and reduced P16ink4a expression. R. meyeri anthocyanin treatment also reversed age-dependent neuronal loss in vivo and in vitro. Nar blocked mNSC aging in vitro and improved spatial memory and cognitive abilities in aging mice through downregulation of plasma TNF-α protein. These findings suggest that R. meyeri anthocyanins increase NSC proliferation and improve neurogenesis with aging via Nar-induced reductions in TNF-α protein levels in vivo.

Human adipose-derived mesenchymal stem cells (hADSCs) are an ideal source of seed cells for regenerative applications and tissue engineering. However, long-term in vitro culture of hADSCs reduces their quantity and quality, which lessens their value in research and clinical applications. The molecular mechanisms underlying this biological process are poorly defined. Recently identified microRNAs (miRNAs) have emerged as critical modulators of cellular senescence. In this study, we examined the changes in hADSCs undergoing senescence. Significant miR-483-3p upregulation was noted during in vitro passaging of hADSCs, which correlated with the adipogenic differentiation and cellular senescence. Knockdown of miR-483-3p retarded the adipogenic differentiation potential of hADSCs and reduced cellular senescence. Dual-luciferase reporter assays identified insulin-like growth factor-1 (IGF1) as the target gene of miR-483-3p. IGF1 inhibition confirmed its inhibitory effects on replicative senescence in hADSCs. In conclusion, our study revealed essential regulatory roles of miR-483-3p in the adipogenesis and aging of hADSCs mediated by targeting IGF1.

BackgroundBlocking signaling by epidermal growth factor receptor (EGFR), can effectively inhibit the proliferation and differentiation of non-small-cell lung cancer (NSCLC). Additionally, an increasing number of NSCLC patients have treatment limitations caused by EGFR overexpression or mutations. Therefore, we constructed a nanotherapy platform consisting of cetuximab (CTX) to target EGFR-sensitive NSCLC with an iron tetroxide core loading the sound-sensitive agent IR780 for dual-mode imaging diagnosis by combining targeting and sonodynamic therapy (SDT) to reshape the tumor microenvironment (TME), enhance the SDT antitumor effects and improve the therapeutic effects of EGFR sensitivity.MethodsIR780@INPs were prepared by reverse rotary evaporation, CTX was adsorbed/coupled to obtain IR780@INPs-CTX, and the morphology and structure were characterized. Intracellular ROS levels and cell apoptosis first verified its killing effects against tumor cells. Then, a nude mouse lung cancer subcutaneous xenograft model was established with HCC827 cells. A real-time fluorescence IVIS imaging system determined the targeting and live distribution of IR780@INPs-CTX in the transplanted tumors and the imaging effects of the T2 sequence of the INPs by magnetic resonance imaging (MRI) 0 h, 2 h, 4 h and 6 h after administration to confirm drug efficacy.ResultsIn vitro, US+IR780@INPs-CTX produced a large amount of ROS after SDT to induce cell apoptosis, and significant cell death after live/dead staining was observed. In vivo fluorescence imaging showed the IR780@INPs-CTX was mainly concentrated in the tumor with a small amount in the liver. MRI displayed rapid enrichment of the IR780@INPs into tumor tissue 0h after injection and the T2 signal intensity gradually decreases with time without obvious drug enrichment in the surrounding tissues. In vivo, at the end of treatment, the US+IR780@INPs-CTX group showed disappearance or a continued decrease in tumor volume, indicating strong SDT killing effects.ConclusionThe combination of CTX and SDT is expected to become a novel treatment for EGFR-sensitive NSCLC.

RegQTL, a novel concept, indicates that different genotypes of some SNPs have differential effects on the expression patterns of miRNAs and their target mRNAs. We aimed to identify the association between regQTL-SNPs and lung cancer risk and to explore the underlying mechanisms. The two-stage case–control study included the first stage in a Chinese population (626 lung cancer cases and 667 healthy controls) and the second stage in a European population (18,082 lung cancer cases and 13,780 healthy controls). Functional annotations were conducted based on the GTEx and the TCGA databases. Functional experiments were performed to explore the underlying biological mechanisms in vitro and vivo. After strict screening, five candidate regQTL-SNPs (rs7110737, rs273957, rs6593210, rs3768617, and rs6836432) were selected. Among them, the variant T allele of rs3768617 in LAMC1 was found to significantly increase the risk of lung cancer (first stage: P = 0.044; second stage: P = 0.007). The eQTL analysis showed that LAMC1 expression level was significantly higher in subjects with the variant T allele of rs3768617 (P = 1.10 × 10–14). In TCGA paired database, the regQTL annotation indicated the different expression patterns between LAMC1 and miRNA-548b-3p for the distinct genotypes of rs3768617. Additionally, LAMC1 knockdown significantly inhibited malignant phenotypes in lung cancer cell lines and suppressed tumor growth. A novel regQTL-SNP, rs3768617, might affect lung cancer risk by modulating the expression patterns of miRNA-548b-3p and LAMC1. RegQTL-SNPs could provide a new perspective for evaluating the regulatory function of SNPs in lung cancer development.

Genetically arming new chimeric antigen receptors (CARs) on T cells is a prevalent method to fulfill CAR-T immunotherapy. However, this approach fails to completely address the poor infiltration, complex immunosuppressive tumor microenvironment (ITM), and insufficient immune cells, which are recognized as the three dominant hurdles to discouraging the trafficking and persistence of CAR-T and immune checkpoint blockade (ICB) immunotherapies against solid tumors. To address the three hurdles, a sonoimmunity-engineered nanoplatform is designed in which a rattle-type-structured carrier enables intraparticle-double-scattering to generate massive reactive oxygen species (ROS) during the sonodynamic process. Abundant ROS accumulation can directly kill tumor cells, release antigens, and activate systematic immune responses for expanding effector T or CAR-T cells, while alleviating ITM via immunosuppressive macrophage polarization and reduction in pro-tumorigenic cytokine secretion. Furthermore, the co-loaded phosphodiesterase-5 inhibitors release nitric oxide (NO) to impel vascular normalization and open the infiltration barrier (IB) for allowing more T cells to enter into the tumor. Systematic experiments demonstrate the feasibility of such intraparticle-double-scattering-decoded sonogenetics in the sonoimmunity-engineered nanoplatforms for expanding effector T or CAR-T cells, thereby promoting their infiltration into tumors and alleviating ITM. These compelling actions lead to excellent CAR-T and ICB immunotherapies against solid tumors with repressed tumor metastasis.

Direct, rapid and sensitive detection of physiologically-relevant active small molecules (ASMs) in complex biological samples is highly desirable. Herein, we present an electrochemical sensing platform by combining three-dimensional macroscopic graphene (3DG) and vertically-ordered mesoporous silica-nanochannel film (VMSF), which is able to directly detect ASMs in complex samples with high sensitivity and no need of tedious pretreatment. Free-standing and macroscopic 3DG serves as the supporting electrode and O2-plasma treatment is proposed as a simple and green approach to improve its hydrophilicity and electrochemical activity. The plasma-treated 3DG (pl-3DG) is suitable for stable modification of VMSF using electrochemically assisted self-assembly (EASA) method, conferring the electrode (VMSF/pl-3DG) with excellent anti-fouling properties. As the proof-of-concept demonstration, VMSF/pl-3DG sensor exhibits fast and ultrasensitive determination of uric acid (UA) with ultralow limit of detection (LOD, 23 nM) owing to high active surface, unhindered mass transfer, good electrical transfer of 3DG and signal amplification of VMSF nanochannel. Direct determination of UA in biological sample (serum) is also realized without the need of tedious pretreatment.

Resting-state fMRI studies have demonstrated that Alzheimer's disease (AD) is associated with aberrant organization and function of large-scale brain networks. However, the nature of the disruption of cross-network interactions in the key neurocognitive networks in the brain remains unclear. In this paper, we examined the 'triple-network model', including the default mode network (DMN), salience network (SN), and central executive network (CEN), to identify the cross-network interactions in late mild cognitive impairment (LMCI) and AD. With resting-state fMRI, we tested cross-network functional connectivity among the DMN, SN, and CEN in 33 AD patients, 24 LMCI, and 25 well-matched normal control subjects. Then, we identified the most influential brain regions affected by AD and LMCI. Finally, we investigated the relationship between aberrant functional connectivity and clinical cognitive dysfunction. We found the cross-network functional connectivity of the SN-centered 'triple-network model' was significantly impaired in the AD group and the alterations were negatively correlated with the Mini-Mental State Examination (MMSE) scores. For the LMCI group, the functional connectivity of the SN-centered 'triple-network model' also changed compared to AD; however, we found no correlation with MMSE score. As predicted, the abnormal connections among the three networks mainly overlap with the key nodes of the three networks. Overall, our findings suggested that the interactions of the SN-centered 'triple-network model' are impaired in AD patients and that these alterations contribute to the decline in cognitive function. This 'triple-network model' provides new insights into AD and provides more information about the dysregulation of brain networks in AD.

Recently, a novel technology for noninvasive deep brain stimulation (NDBS) with temporally interfering electric fields was developed. This noninvasive technology is able to perform one-point temporal interference (TI) stimulation and stimulates the hippocampus without affecting the overlying cortex in mice. In this study, we introduce the concept of multi-point temporal interference (MTI) stimulation, which can simultaneously stimulate multiple nodes in the brain network to modulate its function. For the sake of realizing MTI stimulation, we proposed the scheme with each electrode carrying different frequency currents, which has higher usability with respect to the scheme by adding more electrode pairs. Additionally, to optimize the MTI stimulation, we selected the proper current frequencies and amplitudes, which were verified by geometrical model, magnetic resonance imaging (MRI) human head model, and tissue phantom. Finally, we tested the independence between the two stimulation points in MTI stimulation. The MTI stimulation can be generated by our method with proper parameters in geometrical model, MRI human head model, and tissue phantom. The stimulation points in MTI stimulation are all steerable, and furthermore can be controlled independently. Our results suggest that MTI stimulation can be used to simultaneously stimulate multiple target nodes of the brain network in deep brain areas noninvasively, which paves the way for the modulation of the brain in research and clinical neurobiology.

How to effectively evaluate and identify the potential default risk of borrowers and calculate the default probability of borrowers before issuing loans is the basis and important link of the credit risk management of modern financial institutions. This paper mainly studies the statistical analysis of historical loan data of banks and other financial institutions with the help of the idea of non-balanced data classification, and uses machine learning algorithms (not statistical algorithms) such as random forest, logical regression and decision tree to establish loan default prediction model. The experimental results show that neural network and random forest algorithm outperform decision tree and logistic regression classification algorithm in prediction performance. In addition, by using the random forest algorithm to rank the importance of features, the features that have a greater impact on the final default can be obtained, so as to make a more effective judgment on the loan risk in the financial field.

There are many studies on the association between miR-608 rs4919510 polymorphism and susceptibility to colorectal cancer (CRC). However, the role of rs4919510 in CRC development and its underlying mechanism remain unclear. We first evaluated the gene that may be regulated by the variation of rs4919510 through a two-stage expression quantitative trait loci analysis and then compared the expression of that identified gene in CRC tissues and adjacent nontumor tissues. Next, methyl thiazolyl tetrazolium (MTT) assay, transwell assay, and flow cytometry analyses were performed to investigate the

In order to ensure the safe transmission of the brine pipeline, this paper designs a leakage detection terminal based on STM32F7. This terminal uses GPS to added time stamps to the collected data. And each distributed terminal uses second pulse signal of GPS to realize the function of synchronously collecting signals. Finally, the data is transmitted to the cloud computing platform through the 4G wireless transmission module system. This paper uses the S transform algorithm to analyze the characteristics of these transmitted data. S transform algorithm fully extracts the characteristics of the data in the time-frequency-mode domain. The simulation results show that the data generates high-frequency signals at default point. Through the whole system, it can effectively realize real-time monitoring.

Background. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer that has a high level of morbidity and mortality. Long noncoding RNA (lncRNA) is a novel regulatory factor of tumour proliferation, apoptosis, and metastasis. Our previous studies indicated that lncRNA FOXP4-AS1 is a functional oncogene in HCC; thus, this study is aimed at further evaluating the clinical and biological function of FOXP4-AS1 in HCC. Material and Methods. First, we detected the expression of FOXP4-AS1 in HCC tissues and paracarcinoma normal tissues by qRT-PCR. Second, the prognostic effects of FOXP4-AS1 in patients with HCC were analysed in a training group and a verification group. Subsequently, to investigate the biological effects of FOXP4-AS1 on HCC cells, downexpression tests were further conducted. Results. The expression of FOXP4-AS1 was higher in HCC tissues than adjacent nontumourous tissues, whereas the low expression of FOXP4-AS1 was correlated with optimistic treatment outcomes, which suggested that FOXP4-AS1 may be an independent prognostic biomarker for HCC. Moreover, the downregulation of FOXP4-AS1 significantly reduced the cell proliferation and clonal abilities and inhibited the invasion, migration, and angiogenesis of hepatoma cells ( P < 0.05 ). Conclusion. These results revealed the clinical significance and biological function of FOXP4-AS1 in HCC development, which may provide a new direction for finding therapeutic targets and potential prognostic biomarkers of HCC.

Capillary electrophoresis sodium dodecyl sulfate (CE-SDS), either in reduced (rCE-SDS) or non-reduced (nrCE-SDS) form, is widely used for purity evaluation and impurity analysis of monoclonal antibody (mAb) drugs. The accuracy of the method may be interfered by artificial species resulted from sample preparation or electrophoresis operation if it is not well optimized. In a routine analysis of pertuzumab for both innovator Perjeta® and biosimilar HLX11 samples, a cluster of unknown peaks located between light chain (LC) and heavy chain (HC) were observed in rCE-SDS and making the purity of (LC + HC)% unacceptable. They can hardly be reduced by regular method optimization such as changing buffer pH, denaturing temperature or incubation time to achieve the (LC + HC)% expectation. Here, the peaks are first characterized and determined to be non-covalently formed LC-LC dimers by multiple techniques including reversed-phase liquid chromatography-mass spectrometry (LC–MS). These artifacts are then eliminated through enhancing capillary separation temperature to 60 °C and decreasing the separation voltage to 9.5 kV, an unusual CE-SDS operation setting. Finally, a developed rCE-SDS method is presented for successful evaluation of pertuzumab purity and impurities, which is further confirmed by an alternative reduced microchip-based gel electrophoresis. In summary, the developed method provided an accurate and reliable purity evaluation and size variant profiling for batch releasing, stability testing and quality study of reduced pertuzumab samples.

Growth differentiation factor 11 (GDF11) is a putative systemic rejuvenation factor. In this study, we characterized the mechanism by which GDF11 reversed aging of mesenchymal stem cells (MSCs). In culture, aged MSCs proliferate slower, and are positive for senescence markers SA-β-gal and P16 ink4a . They have shortened telomeres, decreased GDF11 expression, and reduced osteogenic potential. GDF11 can block MSC aging in vitro , and reverse age-dependent bone loss in vivo . The anti-aging effect of GDF11 is via activation of the Smad2/3-PI3K-AKT-mTOR pathway. Unexpectedly, GDF11 also upregulated a DNA demethylase Tet2, which served as a key mediator for GDF11 to autoregulate itself via demethylation of specific CpG sites within the GDF11 promoter. Mutation of Tet2 facilitates MSC aging by blocking GDF11 expression. Mutagenesis of Tet2-regulated CpG sites also blocks GDF11 expression, leading to MSC aging. Together, a novel mutual regulatory relationship between GDF11 and an epigenetic factor Tet2 unveiled their anti-aging roles. One Sentence Summary An epigenetic mechanism by which GDF11 rejuvenates mesenchymal stem cells