BACKGROUND:Inter-limb asymmetry is a common phenomenon observed during human growth and development.Prolonged specialized training can lead to specific adaptations in inter-limb asymmetry among athletes.OBJECTIVE:To review the formation causes,manifestations,and impacts of inter-limb asymmetry on sports performance,and provide an overview of the relevant assessment methods and intervention strategies.METHODS:A literature search was conducted in the CNKI,WanFang,PubMed,and Web of Science databases from their inception to September 2024.The search terms included"asymmetry,asymmetries,asymmetric,asymmetrical,imbalance,strength,power,force,jump,sprint,athletic performance,anthropometry,injury"in English and Chinese.After excluding duplicate publications,irrelevant content,and conference papers,a total of 131 articles were finally included for analysis.RESULTS AND CONCLUSION:(1)Inter-limb asymmetry can be influenced by various factors including genetics,task demands,training regimens,injuries,fatigue,and limb preference.These factors lead to being primarily manifested in anatomical structure,strength performance,and task-specific asymmetry.(2)An increase in inter-limb asymmetry can result in impaired performance in bilateral in-phase symmetric movements.However,the relationship between increased inter-limb asymmetry and bilateral out-of-phase symmetric movements remains unclear and requires further investigation.(3)Training interventions have been shown to effectively mitigate inter-limb asymmetry,with unilateral training demonstrating superior outcomes compared with bilateral training.The choice of training methods and content should be tailored to meet the specific demands of the sport.(4)To further clarify the relationship between inter-limb asymmetry and athletic performance,it is recommended that future research adopt the concept of"task specificity"in inter-limb asymmetry.This includes standardizing study designs,selecting sensitive testing methods and indicators,unifying calculation methods to provide more high-quality evidence,and establishing categorized warning threshold standards for inter-limb asymmetry in different sports.

ObjectiveThis study aims to systematically analyze the blood-absorbed components and metabolic profiles of Xiebaisan（XBS） in normal and chronic bronchitis （CB） mice using ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS）， while comparing differences between the two states. MethodsThirty female BABL/c mice were randomly divided into the normal group， the normal drug administration group， the CB group， the CB drug administration group and the dexamethasone group， with 6 mice in each group. The CB mouse model was established by inducing with ovalbumin （OVA）. The mice in the normal drug administration group and the CB drug administration group started to be gavaged with XBS（13.2 g·kg^-1） from the 21^st day， and the dexamethasone group mice were simultaneously gavaged with dexamethasone （0.5 mg·kg^-1） until the end of the 35^th day of the experiment. Subsequently， serum samples were collected and evaluated for their efficacy， based on the pharmacological evaluation indicators， to determine the efficacy of XBS in treating CB. Then the UPLC-Q-Exactive Orbitrap MS was employed to identify and analyze the chemical constituents， blood-absorbed components， and metabolites of XBS. Chemometric analysis was conducted to reveal metabolic profile differences under "dual states". Concurrently， Real-time PCR technology was utilized to detect the expression levels of key liver metabolic enzymes CYP2E1， CYP3A1， UGT1A1， and UGT1A6. ResultsA total of 28 prototype components and 158 metabolites （including 48 phase Ⅰ metabolites and 110 phase Ⅱ metabolites） of XBS were unambiguously identified in the serum of normal mice. Additionally， a comprehensive characterization was performed on a total of 32 prototype components and 178 metabolites （including 50 phase Ⅰ metabolites and 128 phase Ⅱ metabolites） of XBS in the serum of CB mice. Among them， 27 prototype components were detected in both states， including 12 flavonoids， 2 alkaloids， 3 triterpenes， 4 organic acids， 3 amides， 1 stilbene and 2 other compounds. The chemometrics analysis revealed no significant difference in the prototype components and metabolites of XBS between normal and CB mice； however， there was a significant increase in the in-vivo exposure of XBS in CB mice. Compared to normal mice， the levels of phase Ⅰ metabolites such as oxidation， reduction and methylation of blood components of XBS as well as phase Ⅱ metabolites of glucuronidation showed significant changes in CB mice. Real-time PCR further confirmed that these alterations were attributed to the upregulation of CYP2E1 （P<0.05）， CYP3A1 （P>0.05）， UGT1A1 （P<0.01） and UGT1A6 （P<0.01） enzymes expression in the liver of CB mice. ConclusionThis study elucidated the disparities in the levels of the blood-absorbed components and metabolic profiles of XBS in normal and CB mice， especially in oxidation， reduction， methylation in phase Ⅰ metabolism and glucoaldehyde acidification in phase Ⅱ metabolism. And there are related to the differences in the expression levels of phase Ⅰ and phase Ⅱ metabolic enzymes CYP2E1， CYP3A1， UGT1A1 and UGT1A6 in the liver.

BACKGROUND:Inter-limb asymmetry is a common phenomenon observed during human growth and development.Prolonged specialized training can lead to specific adaptations in inter-limb asymmetry among athletes.OBJECTIVE:To review the formation causes,manifestations,and impacts of inter-limb asymmetry on sports performance,and provide an overview of the relevant assessment methods and intervention strategies.METHODS:A literature search was conducted in the CNKI,WanFang,PubMed,and Web of Science databases from their inception to September 2024.The search terms included"asymmetry,asymmetries,asymmetric,asymmetrical,imbalance,strength,power,force,jump,sprint,athletic performance,anthropometry,injury"in English and Chinese.After excluding duplicate publications,irrelevant content,and conference papers,a total of 131 articles were finally included for analysis.RESULTS AND CONCLUSION:(1)Inter-limb asymmetry can be influenced by various factors including genetics,task demands,training regimens,injuries,fatigue,and limb preference.These factors lead to being primarily manifested in anatomical structure,strength performance,and task-specific asymmetry.(2)An increase in inter-limb asymmetry can result in impaired performance in bilateral in-phase symmetric movements.However,the relationship between increased inter-limb asymmetry and bilateral out-of-phase symmetric movements remains unclear and requires further investigation.(3)Training interventions have been shown to effectively mitigate inter-limb asymmetry,with unilateral training demonstrating superior outcomes compared with bilateral training.The choice of training methods and content should be tailored to meet the specific demands of the sport.(4)To further clarify the relationship between inter-limb asymmetry and athletic performance,it is recommended that future research adopt the concept of"task specificity"in inter-limb asymmetry.This includes standardizing study designs,selecting sensitive testing methods and indicators,unifying calculation methods to provide more high-quality evidence,and establishing categorized warning threshold standards for inter-limb asymmetry in different sports.

AIM: To investigate the correlation between different severity grades of obstructive sleep apnea-hypopnea syndrome(OSAHS)and visual field defects as well asvisual evoked potential(VEP)parameters in patients with anterior ischemic optic neuropathy(AION). METHODS: A retrospective case-control study. Patients diagnosed with AION complicated by OSAHS at the Department of Ophthalmology, the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, between June 2022 and October 2025 were selected as the study subjects. According to the AHI and mSaO2, the patients were divided into three groups: a mild group(AHI 5-15 events/h, mSaO2 85%-90%), moderate group(AHI 16-30 events/h, mSaO2 80%-85%), and severe group(AHI >30 events/h, mSaO2 <80%). General demographic data, retinal nerve fiber layer(RNFL)thickness, visual field defect indicators including mean defect(MD)and pattern standard deviation(PSD), as well as VEP parameters(P100 latency and amplitude)were compared among the three groups. RESULTS: This study included a total of 110 patients with AION complicated by OSAHS. Based on the severity of OSAHS, the patients were divided into a mild group of 37 patients(21 men and 16 women, mean age 62.15±9.37 y), a moderate group of 35 patients(20 men, 15 women; mean age 61.82±8.94 y), and a severe group of 38 patients(22 men, 16 women; mean age 63.02±9.61 y). There were no significant differences among the three groups in terms of age, sex, TG, TC, LDL-C, HDL-C levels, or AION severity(all P>0.05); however, there were significant differences in history of hypertension, history of diabetes, systolic blood pressure, diastolic blood pressure, and FPG levels(all P<0.05). The mean RNFL thickness in the severe group(63.27±5.58 μm)was significantly lower than that in the moderate group(74.14±6.28 μm)and the mild group(83.22±7.02 μm), and the moderate group was lower than the mild group(all P<0.05); The MD value(-11.57±1.82 dB)and PSD value(7.35±0.87 dB)in the severe group were both higher than those in the moderate group [(-7.62±1.31 dB),(4.89±0.62 dB)] and the mild group [(-4.38±1.05 dB),(2.57±0.45 dB)](all P<0.05); the P100 latency in the severe group(132.41±8.57 ms)was longer than that in the moderate group(118.75±7.32 ms)and the mild group(105.62±6.14 ms), and the amplitude(7.65±1.53 μV)was lower than that of the moderate group(11.24±1.89 μV)and the mild group(15.38±2.11 μV)(all P<0.05). Spearman's correlation analysis revealed that the severity of OSAHS was negatively correlated with the MD value(rs=-0.901, P<0.05)and positively correlated with the PSD value and P100 latency(rs=0.947, 0.807, P<0.05), and was negatively correlated with P100 amplitude(rs=-0.878, P<0.05). CONCLUSION:The severity of OSAHS is closely associated with RNFL thickness, visual field defects, and VEP parameters in patients with AION; the more severe the OSAHS, the more pronounced the structural and functional damage to the optic nerve. Monitoring AHI and mSaO2 can aid in assessing the condition of patients with AION and developing personalized intervention plans.

Objective To investigate the effects of whole breast combined with regional nodal hypofractionated radiotherapy compared with conventional fractionated radiotherapy on peripheral lymphocyte count (PLC) and neutrophil-to-lymphocyte ratio (NLR) in patients with breast cancer after breast-conserving surgery. Methods This retrospective study enrolled 94 patients with breast cancer who underwent breast-conserving surgery in Tangshan People’s Hospital between April 2022 and April 2024. All patients received whole breast combined with regional nodal radiotherapy. These patients were divided into hypofractionated radiotherapy group (n = 42) and conventional fractionated radiotherapy group (n = 52) according to radiotherapy regimen. Differences in PLC and NLR before and after radiotherapy between the two groups were compared using the t-test. Results Before radiotherapy, the baseline PLC and NLR were comparable between the two groups (P > 0.05). After radiotherapy, PLC decreased and NLR increased in both groups (P < 0.05). The PLC in the hypofractionated radiotherapy group was significantly higher than that in the conventional fractionated radiotherapy group (0.95 ± 0.30 vs. 0.77 ± 0.26, P = 0.002), and the NLR was significantly lower in the hypofractionated radiotherapy group than in the conventional fractionated radiotherapy group (2.86 ± 1.27 vs. 3.67 ± 1.59, P = 0.010). Conclusion Compared with conventional fractionated radiotherapy, whole breast combined with regional nodal hypofractionated radiotherapy has less impact on PLC and NLR in patients with breast cancer after breast-conserving surgery.

ObjectiveThrough multimodal research methods including medication rule mining， network pharmacology， molecular docking and dynamics simulation， and in vivo animal experiments， this study aims to speculate and verify the core composition （Ginseng Radix et Rhizoma Rubra-Salviae Miltiorrhizae Radix et Rhizoma-Notoginseng Radix et Rhizoma） and efficacy （Qi-invigorating and blood-activating） of the drug combination in Yitangkang Compound for improving diabetic cardiomyopathy （DCM）， investigate the interaction relationship and binding strength between core active ingredients of the drug combination and key signaling pathway targets， and further explore the mechanism by which the Qi-invigorating and blood-activating drug combination regulates the calcium signaling pathway to improve cardiac function in DCM rats. MethodsThe Ancient and Modern Medical Cases Cloud Platform was used to construct a DCM prescription database， and the "Analysis Method" module of the platform was applied to mine and summarize medication rules， thereby determining the core composition of the Qi-invigorating and blood-activating drug combination in Yitangkang. Drug-active ingredient-signaling pathway-core target-disease analysis and visualization were conducted by combining network pharmacology with the Traditional Chinese Medicine System Pharmacology Platform （TCMSP） database， SwissTargetPrediction platform， GeneCards database， MetaScape database， CytoScape software， etc. Then， molecular docking was performed via the CB-Dock2 platform， and molecular dynamics simulation of the high-binding-strength docking complexes was carried out by Gromacs software. Finally， in vivo animal experiments were carried out. Twenty-eight Sprague Dawley （SD） rats meeting the research criteria were divided into a normal group， a model group， a drug combination group （3.3 g·kg^-1）， and a Yitangkang group （20 g·kg^-1）. A type 2 diabetes mellitus （T2DM） rat model was established by high-fat diet feeding combined with intraperitoneal injection of streptozotocin （STZ）， followed by continuous feeding for eight weeks until the DCM model was successfully established. During this period， the traditional Chinese medicine （TCM） compound and drug combination were administered for prevention and treatment intervention. Meanwhile， changes in blood glucose， body weight， and heart index of each group were monitored. Cardiac function was assessed by echocardiography， and electrophysiological signals were detected by an electrocardiogram. The heart tissue was observed for pathological changes by hematoxylin-eosin （HE） and Masson staining， and the expression of L-type calcium channel （CACNA1C）， calmodulin （CALM1）， calcium/calmodulin-dependent protein kinase Ⅱδ （CAMK2D）， and neuronal nitric oxide synthase （NOS1） proteins in the calcium signaling pathway of myocardial tissue was detected by Western blot. ResultsIn 62 DCM prescriptions， Ginseng Radix et Rhizoma Rubra， Salviae Miltiorrhizae Radix et Rhizoma， and Notoginseng Radix et Rhizoma were used most frequently. Their meridian tropism mainly involved the spleen， heart， and lung， and their sweet and warm properties were prominent. The drugs for tonifying or blood-activating and stasis-resolving ranked top. In association rule analysis， （Ginseng Radix et Rhizoma Rubra， Salviae Miltiorrhizae Radix et Rhizoma）-Notoginseng Radix et Rhizoma had the highest lift. Network pharmacology obtained 75 active ingredients of the drug combination， 714 drug combination action targets， 2 702 disease targets， and 286 intersection targets. Protein-protein interaction （PPI） network predicted nine interaction component-targets （nine active ingredients and four calcium signaling pathway target genes）. Molecular docking showed the four complexes with the lowest binding energy were 2f3z-ginsenoside Re， 1cll-quercetin， 9blh-（6S）-6-（hydroxymethyl）-1，6-dimethyl-8，9-dihydro-7H-naphtho［8，7-g］benzofuran-10，11-dione， and 5vv0-miltionone Ⅱ. Dynamics simulation showed the CALM1-quercetin complex had the strongest binding affinity. The animal experiment results revealed that compared with the normal group， the model group showed significant changes in blood glucose， body weight， myocardial tissue morphology， heart index， cardiac function， electrophysiological indexes， and the expression levels of CACNA1C， CALM1， CAMK2D， and NOS1 proteins （P<0.05， P<0.01）. Compared with the model group， the Yitangkang group had a certain improvement effect on the above indexes （P<0.05， P<0.01）. Compared with the Yitangkang group， the drug combination group showed no significant difference in improving myocardial tissue morphology， heart index， cardiac function， electrophysiological indexes， and the expression of CACNA1C， CALM1， CAMK2D， and NOS1 proteins， except for blood glucose and body weight. ConclusionGinseng Radix et Rhizoma Rubra， Salviae Miltiorrhizae Radix et Rhizoma， and Notoginseng Radix et Rhizoma are the core Qi-invigorating and blood-activating drug combination in Yitangkang Compound. They have a good preventive and therapeutic effect on STZ-induced DCM in rats， and their mechanism of action may be related to the regulation of the calcium signaling pathway.

Ten novel xanthones, garpedunxanthones A-G (1-5, 6a/6b, 7a/7b) and nujiangxanthone Q (8), along with sixteen known analogs (9-24), were isolated from Garcinia pedunculata and G. nujiangensis. Their structures were elucidated through high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) data, comprehensive nuclear magnetic resonance (NMR) spectroscopic analyses, and electronic circular dichroism (ECD) calculations. All compounds without cytotoxicity were assessed for anti-inflammatory properties by measuring the inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 cells. Structure-activity relationships are also discussed. Compounds 7b, 19, and 21 exhibited significant anti-inflammatory activity with IC₅₀ values of 16.44 ± 0.69, 14.28 ± 0.78, and 10.67 ± 3.28 μmol·L^-1, respectively. Enzyme-linked immunosorbent assay (ELISA) demonstrated that compounds 7b, 19, and 21 inhibited the expression of pro-inflammatory cytokines TNF-α and IL-6 in a dose-dependent manner. The inhibitory effect of compound 21 on IL-6 at 20 μmol·L^-1 was comparable to that of the positive control. In network pharmacology studies, potential targets of compounds and inflammation were identified from PharmMapper and GeneCards databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the overlapped targets were intricately associated with major pathogenic processes linked to inflammation, including positive regulation of mitogen-activated protein kinase (MAPK) cascade, protein kinase activity, NO synthase regulator activity, MAPK signaling pathway, and EGFR tyrosine kinase inhibitor resistance.
Xanthones/therapeutic use* ; Garcinia ; Anti-Inflammatory Agents/therapeutic use* ; Plant Preparations/therapeutic use* ; Structure-Activity Relationship ; Nitric Oxide/metabolism* ; RAW 264.7 Cells ; Animals ; Mice ; Enzyme-Linked Immunosorbent Assay ; Mitogen-Activated Protein Kinase Kinases/metabolism* ; Circular Dichroism

Gastric cancer (GC) is characterized by high morbidity and mortality rates. Chinese agarwood comprises the resin-containing wood of Aquilaria sinensis (Lour.) Gilg., traditionally utilized for treating asthma, cardiac ischemia, and tumors. However, comprehensive research regarding its anti-GC effects and underlying mechanisms remains limited. In this study, Chinese agarwood petroleum ether extract (CAPEE) demonstrated potent cytotoxicity against human GC cells, with half maximal inhibitory concentration (IC₅₀) values for AGS, HGC27, and MGC803 cells of 2.89, 2.46, and 2.37 μg·mL^-1, respectively, at 48 h. CAPEE significantly induced apoptosis in these GC cells, with B-cell lymphoma-2 (BCL-2) associated X protein (BAX)/BCL-2 antagonist killer 1 (BAK) likely mediating CAPEE-induced apoptosis. Furthermore, CAPEE induced G₀/G₁ phase cell cycle arrest in human GC cells via activation of the deoxyribonucleic acid (DNA) damage-p21-cyclin D1/cyclin-dependent kinase 4 (CDK4) signaling axis, and increased Fe²⁺, lipid peroxides and reactive oxygen species (ROS) levels, thereby inducing ferroptosis. Ribonucleic acid (RNA) sequencing, real-time quantitative polymerase chain reaction (RT-qPCR), and Western blotting analyses revealed CAPEE-mediated upregulation of heme oxygenase-1 (HO-1) in human GC cells. RNA interference studies demonstrated that HO-1 knockdown reduced CAPEE sensitivity and inhibited CAPEE-induced ferroptosis in human GC cells. Additionally, CAPEE administration exhibited robust in vivo anti-GC activity without significant toxicity in nude mice while inhibiting tumor cell growth and promoting apoptosis in tumor tissues. These findings indicate that CAPEE suppresses human GC cell growth through upregulation of the DNA damage-p21-cyclin D1/CDK4 signaling axis and HO-1-mediated ferroptosis, suggesting its potential as a candidate drug for GC treatment.
Animals ; Humans ; Mice ; Antineoplastic Agents, Phytogenic ; Apoptosis/drug effects* ; Cell Line, Tumor ; Cyclin D1/genetics* ; Cyclin-Dependent Kinase 4/genetics* ; DNA Damage/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Ferroptosis/drug effects* ; G1 Phase Cell Cycle Checkpoints/drug effects* ; Heme Oxygenase-1/genetics* ; Mice, Inbred BALB C ; Mice, Nude ; Plant Extracts/pharmacology* ; Stomach Neoplasms/physiopathology* ; Thymelaeaceae/chemistry* ; Up-Regulation/drug effects*

Objective:To discuss the optimal doping concentration of vanadium(V)and silicon(Si)co-doped TiO? coating(V-Si TiO?)formed on titanium surface by electrochemical treatment,to evaluate its antibacterial effect under visible light irradiation,and to clarify its visible light response mechanism.Methods:The medical pure titanium sheets were subjected to micro-arc oxidation followed by high-temperature calcination,and V-Si TiO2 coatings with different doping concentrations were prepared by adjusting the ratio of V to Si in the electrolyte.The experiment was divided into 1V:10Si(V5Si50)group,2V:10Si(V10Si50)group,and 3V:10Si(V15Si50)group;control group was set up(contains only bacterial culture medium).The optimal doping concentration was screened based on comprehensive evaluation of surface morphology,ion release,photocatalytic ability,and biocompatibility;cell counting kit-8(CCK-8)method was used to detect the proliferation activities and the survival rates of the cells in various group.Subsequently,the optimized coating was characterized and compared by scanning electron microscope(SEM),atomic force microscopy(AFM),digital eddy current coating thickness gauge,X-ray diffraction(XRD),X-ray photoelectron spectroscope(XPS),and ultraviolet-visible absorption spectroscopy(UV-vis).The experiment was divided into PT group(blank control),PEO group(no element doping),V10 group(V doping),Si50 group(Si doping),and V10Si50 group(2V:10Si).The ability of the coating materials to degrade methylene blue(MB)and generation of reactive oxygen species(ROS)under visible light were detected.For antibacterial experiments,Staphylococcus aureus(S.aureus)and Escherichia coli(E.coli)were used.The colony counts on plates in various groups were recorded after visible light irradiation for 2 h and dark treatment for 2 h,respectively.The ROS levels were detected using 2',7'-dichlorofluorescein diacetate(DCFH-DA)ROS probe.ROS scavenging experiment was performed using the optimal doping concentration V10Si50 group,and the two kinds of bacteria were divided into blank control group,N-acetylcysteine(NAC)group,V10Si50 group,and NAC+V10Si50 group.The colony counts on plates in various groups were recorded after visible light irradiation for 2 h.Results:The V concentration of 0.01 mol·L?1 and Si concentration of 0.05 mol·L?1 in the electrolyte solution were the optimal doping concentrations for the V-Si TiO? coating.The SEM observation results showed that compared with V5Si50 group and V15Si50 group,the surface pore size of the coating material in V10Si50 group was significantly decreased(P<0.05),and the coating thickness was significantly increased(P<0.05);its crystal structure was mainly anatase type,and the MB degradation rate of the coating material in V10Si50 group after 9 h of visible light catalysis was significantly increased(P<0.05).Compared with control group,the cell proliferation activity and cell survival rate in V10Si50 group were significantly increased at 1,2,and 4 d of cell culture(P<0.05);at 2 and 4 d of cell culture,the cell proliferation activity and cell survival rate in V5Si50 group and V15Si50 group were significantly decreased(P<0.05).Compared with PT,PEO,and Si50 groups,the colony counts of two kinds of the bacteria in V10 group and V10Si50 group after visible light irradiation for 2 h were significantly decreased(P<0.05).Compared with PT group and PEO group,the ROS levels in two kinds of the bacteria in V10Si50 group after 2 h of irradiation were significantly increased(P<0.05).Compared with V10Si50 group,the colony counts of two kinds of the bacteria in NAC+V10Si50 group were significantly increased(P<0.05).Conclusion:A reasonably loaded V-Si TiO? coating material(V10Si50)was screened out,which maintained good biological activity and significantly enhanced the antibacterial effect under visible light irradiation.

Although clinical evidence suggests that nonalcoholic fatty liver disease is an established major risk factor for heart failure, it remains unexplored whether sleep disorder-caused hepatic damage contributes to the development of cardiovascular disease (CVD). Here, our findings revealed that sleep fragmentation (SF) displayed notable hepatic detrimental phenotypes, including steatosis and oxidative damage, along with significant abnormalities in cardiac structure and function. All these pathological changes persisted even after sleep recovery for 2 consecutive weeks or more, displaying memory properties. Mechanistically, persistent higher expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) in the liver was the key initiator of SF-accelerated damage phenotypes. SF epigenetically controlled the acetylation of histone H3 lysine 27 (H3K27ac) enrichment at the Nox4 promoter and markedly increased Nox4 expression in liver even after sleep recovery. Moreover, fine coordination of the circadian clock and hepatic damage was strictly controlled by BMAL1-dependent Sirtuin 1 (Sirt1) transcription after circadian misalignment. Accordingly, genetic manipulation of liver-specific Nox4 or Sirt1, along with pharmacological intervention targeting NOX4 (GLX351322) or SIRT1 (Resveratrol), could effectively erase the epigenetic modification of Nox4 by reducing the H3K27ac level and ameliorate the progression of liver pathology, thereby counteracting SF-evoked sustained CVD. Collectively, our findings may pave the way for strategies to mitigate myocardial injury from persistent hepatic detrimental memory in diabetic patients.