Efficacy and safety of anlotinib combined with the STUPP regimen in patients with newly diagnosed glioblastoma: a multicenter, single-arm, phase Ⅱ trial

Objective:Glioblastomas are highly vascularized malignant tumors.We determined the efficacy and safety of the anti-angiogenic multi-kinase inhibitor,anlotinib,for a newly diagnosed glioblastoma.Methods:This multicenter,single-arm trial(NCT04119674)enrolled 33 treatment-naïve patients with histologically proven glioblastomas between March 2019 and November 2020.Patients underwent treatment with the standard STUPP regimen[fractionated focal irradiation in daily fractions of 1.8-2 Gy given 5 d/w×6 w(total=54-60 Gy)]or radiotherapy plus continuous daily temozolomide(TMZ)(75 mg/m^(2)of body surface area/d,7 d/w from the first to the last day of radiotherapy),followed by 6 cycles of adjuvant TMZ(150-200 mg/m^(2)×5 d during each 28-d cycle)plus anlotinib(8 mg/d on d 1-14 of each 3-w cycle for 2 cycles during concomitant chemoradiotherapy,8 maximal cycles as adjuvant therapy,followed by maintenance at 8 mg/d.The primary endpoint was progression-free survival(PFS).Secondary endpoints included overall survival(OS)and adverse events(AEs).Results:Thirty-three patients received the planned treatment.The median PFS was 10.9 months(95%CI,9.9-18.7 months)and the 12-month PFS rate was 48.5%.The median OS was 17.4 months(95%CI,14.5-21.1 months)and the 12-month OS rate was 81.8%.The most common AEs included hypertriglyceridemia[58%(n=19)],hypoalbuminemia[46%(n=15)],and hypercholesterolemia[46%(n=15)]during concurrent chemoradiotherapy and leukopenia[73%(n=24)],hypertriglyceridemia[67%(n=22)],and neutropenia[52%(n=17)]during adjuvant therapy.Five patients discontinued treatment due to AEs.HEG1(HR,5.6;95%CI,1.3-23.7;P=0.021)and RP1L1 alterations(HR,11.1;95%CI,2.2-57.2;P=0.004)were associated with a significantly shorter PFS.Conclusions:Anlotinib plus the STUPP regimen has promising anti-tumor activity against glioblastoma and manageable toxicity.HEG1 and RP1L1 alterations might be novel predictive biomarkers of the response to anlotinib.

Absence of BCS–BEC crossover in FeSe_(0.45)Te_(0.55) superconductor

In iron-based superconductor Fe(Se,Te), a flat band-like feature near the Fermi level was observed around the Brillouin zone center in the superconducting state. It is under debate whether this is the evidence on the presence of the BCS–BEC[Bardeen–Cooper–Schrieffer(BCS), Bose–Einstein condensation(BEC)] crossover in the superconductor. High-resolution laser-based angle-resolved photoemission measurements are carried out on high quality single crystals of FeSe_(0.45)Te_(0.55) superconductor to address the issue. By employing different polarization geometries, we have resolved and isolated the dyz band and the topological surface band, making it possible to study their superconducting behaviors separately. The dyz band alone does not form a flat band-like feature in the superconducting state and the measured dispersion can be well described by the BCS picture. We find that the flat band-like feature is formed from the combination of the dyz band and the topological surface state band in the superconducting state. These results reveal the origin of the flat band-like feature and rule out the presence of BCS-BEC crossover in Fe(Se,Te) superconductor.

Evolution of microstructure and texture of AZ80 magnesium alloy under hot torsion with constant decreasing temperature rate

Hot torsion tests for AZ80 magnesium alloy were carried out in the temperature range of 380℃-260℃,with a constant decreasing temperature rate of 10℃/s in order to weaken the basal texture and refine the grains.The results indicated that the average grain sizes were refined forming gradient structure with increasing specimen radial position from center(12.2-5.4μm),and that the initial basal texture intensity of the extruded magnesium alloy was weakened from 46.2 to 8.3.Furthermore,the extension twins(ETs)could be disintegrated from the twins forming separated twins with smaller sizes.Interestingly,ETs with the same twin variant intersecting with each other could be coalesced forming grains with similar orientation,while ETs with different twin variants were separated by twins boundaries contributing to grain refinement.Moreover,in addition to the conventional continuous dynamic recrystallized(CDRX)grains with 30˚orientation rotated around C-axis of the parent grains,CDRXed grains with 30˚rotation around a-axis and random rotation axis were also discerned.Besides,the CDRX evolution induced twins were also elaborated,exhibiting the complex competition between CDRX and twining.Hot torsion deformation with constant decreasing temperatures rate is an effective way of grain refinement and texture modification.

Lutein-stevioside nanoparticle attenuates H_(2)O_(2)-induced oxidative damage in ARPE cells

In order to improve the bioavailability of lutein(LUT),a novel lutein-stevio side nanoparticle(LUT-STE)were prepared previously,but the information about LUT-STE on protecting of eye health was limited.This study investigated the effect of LUT-STE on antioxidant activity of H_(2)O_(2)-induced human retinal pigment epithelial(ARPE)cells.LUT and LUT-STE(final concentration of 5μg/mL)significantly enhanced cell viability from(74.84±5.10)%to(81.92±10.01)%(LUT)and(89.33±4.34)%(LUT-STE),and inhibited the cell apoptosis(P<0.05).After pretreatment with LUT-STE in ARPE cells,the levels of superoxide dismutase(SOD),catalase(CAT)and glutathion peroxidase(GSH-Px)in ARPE cells were significantly increased(P<0.05),the contents of reactive oxygen species(ROS)and malondialdehyde(MDA)were decreased.In addition,the vascular endothelial growth factor(VEGF)levels were inhibited by 13.61%and 17.39%,respectively,pretreatment with LUT and LUT-STE.Western blotting results showed that the pretreatment with LUT-STE inhibited the expression of caspase-9 and caspase-3 and up-regulated Bcl-2/Bax pathway to inhibit H_(2)O_(2)-induced apoptosis.In summary,the novel delivery LUT-STE had more pronounced inhibitory effect on H_(2)O_(2)-induced damage in human ARPE cells.

Negligible normal fluid in superconducting state of heavily overdoped Bi_(2)Sr_(2)CaCu_(2)O_(8+δ) detected by ultra-low temperature angle-resolved photoemission spectroscopy

In high temperature cuprate superconductors,it was found that the superfluid density decreases with the increase of hole doping.One natural question is whether there exists normal fluid in the superconducting state in the overdoped region.In this paper,we have carried out high-resolution ultra-low temperature laser-based angle-resolved photoemission measurements on a heavily overdoped Bi2212 sample with a T_(c) of 48 K.We find that this heavily overdoped Bi2212 remains in the strong coupling regime with 2Δ_(0)/(k_(B)T_(c))=5.8.The single-particle scattering rate is very small along the nodal direction(~5 meV) and increases as the momentum moves from the nodal to the antinodal regions.A hard superconducting gap opening is observed near the antinodal region with the spectral weight at the Fermi level fully suppressed to zero.The normal fluid is found to be negligibly small in the superconducting state of this heavily overdoped Bi2212.These results provide key information to understand the high T_(c) mechanism in the cuprate superconductors.

A brief review on the recent development of phonon engineering and manipulation at nanoscales

Phonons are the quantum mechanical descriptions of vibrational modes that manifest themselves in many physical properties of condensed matter systems. As the size of electronic devices continues to decrease below mean free paths of acoustic phonons, the engineering of phonon spectra at the nanoscale becomes an important topic. Phonon manipulation allows for active control and management of heat fow, enabling functions such as regulated heat transport. At the same time, phonon transmission, as a novel signal transmission method, holds great potential to revolutionize modern industry like microelectronics technology, and boasts wide-ranging applications. Unlike fermions such as electrons, polarity regulation is difficult to act on phonons as bosons, making the development of effective phonon modulation methods a daunting task.This work reviews the development of phonon engineering and strategies of phonon manipulation at different scales, reports the latest research progress of nanophononic devices such as thermal rectifiers, thermal transistors, thermal memories, and thermoelectric devices,and analyzes the phonon transport mechanisms involved. Lastly, we survey feasible perspectives and research directions of phonon engineering. Thermoelectric analogies, external field regulation, and acousto-optic co-optimization are expected to become future research hotspots.

Cloning, Characterization and Transformation of Methyltransferase 2a Gene (Zmet2a) in Maize (Zea mays L.)

DNA methylation is an important epigenetic regulatory mechanism,it regulates gene expression by recruiting proteins involved in gene repression or by inhibiting the binding of transcription factor(s)to DNA.In this study,a novel methyltransferase 2a gene(Zmet2a)was cloned in maize and identified by polymerase chain reaction-base(PCR-base)using a bioinformatics strategy.The Zmet2a cDNA sequence is 2739 bp long and translates to 912 amino acid peptides.The Zmet2a protein revealed that it contains BAH and CHROMO structural domains,is a non-transmembrane protein that is hydrophilically unstable,and has no signal peptide structure.Meanwhile,we verified the biological roles of Zmet2a using transgenic Arabidopsis overexpressing Zmet2a and Zmet2a-knockout maize.Transgenic Zmet2a Arabidopsis thaliana showed highly significant advancement inflowering time,and Zmet2a-knockout maize showed advancement inflowering time,with significant changes in several traits.Altogether,these report the role of Zmet2a in the regulation offlowering time,which will lay a foundation for revealing the biological function and epigenetic regulation mechanism of Zmet2a in the growth,development andflowering of maize.

Context-Oriented Multi-RAT User Association and Resource Allocation with Triple Decision in 5G Heterogeneous Networks

In the upcoming 5 G heterogeneous networks, leveraging multiple radio access technologies(RATs) shows to be a crucial issue in achieving RAT multiplexing gain to meet the explosive traffic demand. For always best connection(ABC), users tend to activate parallel transmission across all available RATs. However from a system-wide perspective, this might not be optimal given the context of network load, interference and diverse service requirements. To intelligently determine how to use these multi-RAT access resources concurrently, this paper proposes a joint multi-RAT user association and resource allocation strategy with triple decision and integrated context awareness of users and networks. A dynamic game based ant colony algorithm(GACA) is designed to simultaneously maximize the system utility and the fairness of resource allocation. Simulation results show that it's more reasonable to make multi-RAT association decision from a system-wide viewpoint than from an individual one. Compared to max-SNR based and ABC based strategies, the proposed method alleviates network congestion and optimizes resource allocation. It obtains 39%~70% performance improvement.

透明质酸对膝关节骨性关节炎相关细胞因子及生物标志物的影响

骨性关节炎(OA)是一种由不同病因引起的综合征最终聚集在同一致病途径上,产生软骨、软骨下骨和滑膜的特征性变化。OA由于软骨破坏及其代谢改变,可在其体液中寻找反映软骨结构变化的相关细胞因子和特异性生物标志物,这对于OA的诊疗及预后评估起到积极的指导作用。关节腔注射透明质酸(HA)是治疗膝关节OA最常用的有效方法,其可刺激内生HA分泌,润滑关节组织,也可有效防止软骨降解。此外,关节腔注射HA可以降低金属蛋白酶含量,减少促炎介质的产生,从而减少参与OA发病机制的因素,改善关节炎症症状和关节软骨的损伤。

PD-1抑制剂诱发的药物免疫相关不良反应事件的研究

近年来出现的肿瘤免疫治疗彻底改变传统的癌症治疗方法。免疫疗法是免疫抑制剂针对免疫检查点进行调节,免疫抑制剂包括细胞毒性T淋巴细胞抗原肿瘤4(CTLA-4)抑制剂、程序性死亡蛋白1(PD-1)抑制剂和程序性死亡蛋白配体1(PD-L1)抑制剂。PD-1/PD-L1抑制剂通过阻断PD-1/PD-L1途径以调节免疫耐受的重要抑制通路,在机体中参与维持对自身抗原的免疫耐受。然而,免疫系统平衡的转变也会对多个组织器官产生免疫相关不良事件(irAEs)。irAEs不同于传统的化疗药物或靶向治疗的副作用,且目前在其诊断和管理方面经验相对较少。因此,irAEs构成免疫疗法中真正的挑战,并且任何新的改变都可能是与治疗相关的。最常见的irAEs发生在皮肤、胃肠道,其次是肺、内分泌系统、肌肉骨骼、肾、神经、血液和心血管。IrAEs通常持续时间长、可控,但有时可能导致免疫治疗的中断,甚至可能发生致命不良事件。该文针对目前PD-1抑制剂所产生的irAEs做一综述。

大学生信息素养影响因素及培养策略研究——基于三维重叠空间的分析

构建教育与人力资源强国对大学生信息素养培养提出更高要求,因此探索大学生信息素养影响因素并提供合适的培养策略,对提高大学生信息素养具有重要意义。文章通过对调查数据进行结构方程模型和三维重叠空间分析发现:大学生学习兴趣、自我效能感、自主学习能力显著正向影响信息素养;学习积极特质在学习动机特质和信息素养之间存在完全中介作用;在高信息素养群体与低信息素养群体的重叠空间中,低分群体更有潜力培养为高信息素养者。文章最后提出从改善大学生学习积极特质、改进学习动机特质、针对三维重叠空间中的低分群体等方面提升大学生信息素养水平的策略和建议。

Six-long non-coding RNA signature predicts recurrence-free survival in hepatocellular carcinoma

BACKGROUND Recent evidence shows that long non-coding RNAs(lncRNAs) are closely related to hepatogenesis and a few aggressive features of hepatocellular carcinoma(HCC). Increasing studies demonstrate that lncRNAs are potential prognostic factors for HCC. Moreover, several studies reported the combination of lncRNAs for predicting the overall survival(OS) of HCC, but the results varied. Thus,more effort including more accurate statistical approaches is needed for exploring the prognostic value of lncRNAs in HCC.AIM To develop a robust lncRNA signature associated with HCC recurrence to improve prognosis prediction of HCC.METHODS Univariate COX regression analysis was performed to screen the lncRNAs significantly associated with recurrence-free survival(RFS) of HCC in GSE76427 for the least absolute shrinkage and selection operator(LASSO) modelling. The established lncRNA signature was validated and developed in The Cancer Genome Atlas(TCGA) series using Kaplan-Meier curves. The expression values of the identified lncRNAs were compared between the tumor and non-tumor tissues. Pathway enrichment of these lncRNAs was conducted based on the significantly co-expressed genes. A prognostic nomogram combining the lncRNA signature and clinical characteristics was constructed.RESULTS The lncRNA signature consisted of six lncRNAs: MSC-AS1, POLR2 J4, EIF3 J-AS1,SERHL, RMST, and PVT1. This risk model was significantly associated with the RFS of HCC in the TCGA cohort with a hazard ratio(HR) being 1.807(95%CI[confidence interval]: 1.329-2.457) and log-rank P-value being less than 0.001. The best candidates of the six-lncRNA signature were younger male patients with HBV infection in relatively early tumor-stage and better physical condition but with higher preoperative alpha-fetoprotein. All the lncRNAs were significantly upregulated in tumor samples compared to non-tumor samples(P < 0.05). The most significantly enriched pathways of the lncRNAs were TGF-β signaling pathway, cellular apoptosis-associated pathways, etc. The nomogram showed great utility of the lncRNA signature in HCC recurrence risk stratification.CONCLUSION We have constructed a six-lncRNA signature for prognosis prediction of HCC.This risk model provides new clinical evidence for the accurate diagnosis and targeted treatment of HCC.

Active corrosion protection of super-hydrophobic corrosion inhibitor intercalated Mg-Al layered double hydroxide coating on AZ31 magnesium alloy

Magnesium alloys,the advanced lightweight structural materials,have been successfully applied in the manufacturing field.Unfortunately,their poor corrosion resistance restrains the potential wide applications.In this work,anti-corrosion coatings were fabricated via the insitu growth of the corrosion inhibitors intercalated magnesium-aluminum layered double hydroxide(Mg-Al LDH)on AZ31 magnesium alloy and then post-sealing it by a super-hydrophobic coating.SEM,XRD,EDS,FTIR,XPS and contact angle test were conducted to analyze physical/chemical features of these coatings.Potentiodynamic polarization curves and electrochemical impedance spectroscopy were recorded to assess the anti-corrosion performance of prepared coatings.Surprisingly,Mg-Al LDH with molybdate intercalation and lauric acid modification achieves the excellent corrosion inhibition performance(99.99%)due to the multicomponent synergistic effect such as the physical protection of Mg-Al LDH,the corrosion inhibition of molybdate and super-hydrophobic properties of lauric acid.This work presents a scientific perspective and novel design philosophy to fabricate the efficient anti-corrosion coating to protect magnesium alloys and then expand their potential applications in other field.

Procalcitionin as a diagnostic marker to distinguish upper and lower gastrointestinal perforation

AIM To assess the accuracy of serum procalcitionin(PCT)as a diagnostic marker in verifying upper and lower gastrointestinal perforation(GIP).METHODS This retrospective study included 46 patients from the surgical intensive care unit(ICU)of the Second Affiliated Hospital of Harbin Medical University who were confirmed to have GIP between June 2013 and December 2016.Demographic and clinical patient data were recorded on admission to ICU.Patients were divided into upper(n=19)and lower(n=27)GIP groups according to the perforation site(above or below Treitz ligament).PCT and WBC count was obtained before laparotomy and then compared between groups.Meanwhile,the diagnostic accuracy of PCT was analyzed.RESULTS Patients with lower GIP exhibited significantly higher APACHE II score,SOFA score and serum PCT level than patients with upper GIP(P=0.017,0.004,and0.001,respectively).There was a significant positive correlation between serum PCT level and APACHE II score or SOFA score(r=0.715 and r=0.611,respectively),while there was a significant negative correlation between serum PCT level and prognosis(r=-0.414).WBC count was not significantly different between the two groups,and WBC count showed no significant correlation with serum PCT level,APACHE II score,SOFA score or prognosis.The area under the receiver operating characteristic curve of PCT level to distinguish upper or lower GIP was 0.778.Patients with a serum PCT level above 17.94 ng/d L had a high likelihood of lower GIP,with a sensitivity of 100%and a specificity of 42.1%.CONCLUSION Serum PCT level is a reliable and accurate diagnostic marker in identifying upper or lower GIP before laparotomy.

LAG-3 expression on tumor-infiltrating T cells in soft tissue sarcoma correlates with poor survival

Objective: To elucidate the role and prognostic significance of lymphocyte activation-gene-3(LAG-3) in soft tissue sarcoma(STS).Methods: The expression of LAG-3 in patient and matched normal blood samples was analyzed by flow cytometry. The localization and prognostic values of LAG-3^+ cells in 163 STS patients were analyzed by immunohistochemistry. In addition, the expression of tumor-infiltrating CD3^+ T, CD4^+ T, and CD8^+ T cells and their role in the prognosis of STS were evaluated by immunohistochemistry. The effect of LAG-3 blockade was evaluated in an immunocompetent MCA205 fibrosarcoma mouse model.Results: Peripheral CD8^+ and CD4^+ T cells from STS patients expressed higher levels of LAG-3 than those from healthy donors.LAG-3 expression in STS was significantly associated with a poor clinical outcome(P = 0.038) and was correlated with high pathological grade(P < 0.001), advanced tumor stage(P = 0.016). Additionally, LAG-3 expression was highly correlated with CD8^+ T-cell infiltration(r = 0.7034, P < 0.001). LAG-3 was expressed in murine tumor-infiltrating lymphocytes, and its blockade decreased tumor growth and enhanced secretion of interferon-gamma by CD8^+ and CD4^+ T cells.Conclusions: LAG-3 blockade may be a promising strategy to improve the effects of targeted therapy in STS.

Structure and function of the contactin-associated protein family in myelinated axons and their relationship with nerve diseases

The contactin-associated protein （Caspr） family participates in nerve excitation and conduction, and neurotransmitter release in myelinated axons. We analyzed the structures and functions of the Caspr family- CNTNAP1 （Casprl）, CNTNAP2 （Caspr2）, CNTNAP3 （Caspr3）, CNTNAP4 （Caspr4） and CNTNAP5 （Caspr5）, Casprl-5 is not only involved in the formation of myelinated axons, but also participates in maintaining the stability of adjacent connections. Casprl participates in the formation, differentiation, and proliferation of neurons and astrocytes, and in motor control and cognitive function. We also analyzed the relationship between the Caspr family and neurodegenerative diseases, multiple sclerosis, and autoimmune encephalitis. However, the effects of Caspr on disease course and prognosis remain poorly understood. The effects of Caspr on disease diagnosis and treatment need further investigation.

Double-Edge Intelligent Integrated Satellite Terrestrial Networks

The efficient integration of satellite and terrestrial networks has become an important component for 6 G wireless architectures to provide highly reliable and secure connectivity over a wide geographical area.As the satellite and cellular networks are developed separately these years,the integrated network should synergize the communication,storage,computation capabilities of both sides towards an intelligent system more than mere consideration of coexistence.This has motivated us to develop double-edge intelligent integrated satellite and terrestrial networks(DILIGENT).Leveraging the boost development of multi-access edge computing(MEC)technology and artificial intelligence(AI),the framework is entitled with the systematic learning and adaptive network management of satellite and cellular networks.In this article,we provide a brief review of the state-of-art contributions from the perspective of academic research and standardization.Then we present the overall design of the proposed DILIGENT architecture,where the advantages are discussed and summarized.Strategies of task offloading,content caching and distribution are presented.Numerical results show that the proposed network architecture outperforms the existing integrated networks.

Effects of acute kidney injury on acute pancreatitis patients’ survival rate in intensive care unit: A retrospective study

BACKGROUND Acute kidney injury(AKI)is one of the most common acute pancreatitis(AP)-associated complications that has a significant effect on AP,but the factors affecting the AP patients’survival rate remains unclear.AIM To assess the influences of AKI on the survival rate in AP patients.METHODS A total of 139 AP patients were included in this retrospective study.Patients were divided into AKI group(n=72)and non-AKI group(n=67)according to the occurrence of AKI.Data were collected from medical records of hospitalized patients.Then,these data were compared between the two groups and further analysis was performed.RESULTS AKI is more likely to occur in male AP patients(P=0.009).AP patients in AKI group exhibited a significantly higher acute physiologic assessment and chronic health evaluation II score,higher Sequential Organ Failure Assessment score,lower Glasgow Coma Scale score,and higher demand for mechanical ventilation,infusion of vasopressors,and renal replacement therapy than AP patients in non-AKI group(P<0.01,P<0.01,P=0.01,P=0.001,P<0.01,P<0.01,respectively).Significant differences were noted in dose of norepinephrine and adrenaline,duration of mechanical ventilation,maximum and mean values of intra-peritoneal pressure(IPP),maximum and mean values of procalcitonin,maximum and mean serum levels of creatinine,minimum platelet count,and length of hospitalization.Among AP patients with AKI,the survival rate of surgical intensive care unit and in-hospital were only 23%and 21%of the corresponding rates in AP patients without AKI,respectively.The factors that influenced the AP patients’survival rate included body mass index(BMI),mean values of IPP,minimum platelet count,and hospital day,of which mean values of IPP showed the greatest impact.CONCLUSION AP patients with AKI had a lower survival rate and worse relevant clinical outcomes than AP patients without AKI,which necessitates further attention to AP patients with AKI in surgical intensive care unit.

Prognostic significance of preoperative platelet count in patients with gallbladder cancer

AIM:To investigate the prognostic value of preoperative platelet count(PLT) in patients with primary gallbladder cancer(GBC).METHODS:The clinical data of 223 GBC patients after surgery was retrospectively reviewed.A receiver operating characteristic(ROC) curve was plotted to verify the optimum cutoff point for PLT.Univariate and multivariate survival analyses were performed to identify the factors associated with the prognosis.RESULTS:The ROC curve showed that the optimum cutoff point for PLT was 178 × 109/L,and the entire cohort was stratified into group A with PLT > 178 × 109/L and group B with PLT ≤ 178 × 109/L.Group A had a better survival than group B(P < 0.001).There was an obvious difference between the two groups in terms of the differentiation degree,advanced tumor stage,lymph node metastasis(P < 0.001) and pathological type(P < 0.05).The univariate analysis demonstrated that tumor location,differentiation degree,TNM stage,Nevin stage,lymph node metastasis and PLT were associated with overall survival(P < 0.001).In the multivariate analysis,PLT(P = 0.032),lymph node metastasis(P = 0.007),tumor location(P < 0.001) and TNM stage(P = 0.005) were independent prognostic factors.CONCLUSION:PLT is closely correlated with GBC prognosis and could be used to identify the population with a poorer prognosis after surgery.

The epigenetic landscape of exercise in cardiac health and disease

With the rising incidence of cardiovascular diseases,the concomitant mortality and morbidity impose huge burdens on quality of life and societal costs.It is generally accepted that physical inactivity is one of the major risk factors for cardiac disease and that exercise benefits the heart in both physiological and pathologic conditions.However,the molecular mechanisms governing the cardioprotective effects exerted by exercise remain incompletely understood.Most recently,an increasing number of studies indicate the involvement of epigenetic modifications in the promotion of cardiac health and prevention of cardiac disease.Exercise and other lifestyle factors extensively induce epigenetic modifications,including DNA/RNA methylation,histone post-translational modifications,and non-coding RNAs in multiple tissues,which may contribute to their positive effects in human health and diseases.In addition,several studies have shown that maternal or paternal exercise prevents age-associated or high-fat dietinduced metabolic dysfunction in the offspring,reinforcing the importance of epigenetics in mediating the beneficial effects of exercise.It has been shown that exercise can directly modify cardiac epigenetics to promote cardiac health and protect the heart against various pathological processes,or it can modify epigenetics in other tissues,which reduces the risk of cardiac disease and affords cardioprotection through exerkines.An in-depth understanding of the epigenetic landscape of cardioprotective response to exercise will provide new therapeutic targets for cardiac diseases.This review,therefore,aimed to acquaint the cardiac community with the rapidly advancing and evolving field of exercise and epigenetics.