Effects of mindfulness-based stress reduction on cancer-related fatigue in patients with breast cancer: a meta-analysis of randomized controlled trials.

Introduction: Mindfulness-based stress reduction (MBSR) has been widely used for improving psychological symptoms and sleep quality in breast cancer patients and has a positive impact on posttraumatic growth and immunology. Moreover, MBSR is increasingly being used in cancer-related fatigue (CRF) intervention studies for breast cancer patients, but conflicting results also exist. Objective: This study aimed to evaluate the effect of MBSR on CRF in patients with breast cancer. Methods: A comprehensive computer search of the Pubmed, Cochrane Library, Embase, Web of Science, China Biomedical Document Service System, China Knowledge Infrastructure Engineering, Wanfang Data Knowledge Service Platform, and VIP databases was performed. Randomized controlled trials (RCTs) published before April 10, 2023, were identified. The primary outcome was cancer-related fatigue associated with breast cancer. Two researchers independently screened the studies, extracted the data, and evaluated the methodological quality of the studies according to the inclusion and exclusion criteria. The Meta-analysis of the outcome indicators was performed using STATA 16.0 software. Results: A total of 13 studies were included, including 1992 patients (997 patients in the MBSR group and 1015 patients in the control group). Compared with conventional care, MBSR significantly alleviated the symptoms of CRF in breast cancer patients (SMD=-0.32, 95% CI [-0.42, -0.22], z=6.54, p<.01). Under the supervision of experts, the 8-week MBSR had a great influence on CRF, especially in the Asian population. Conclusions: MBSR is effective in the treatment of CRF induced by breast cancer, and no obvious adverse effects occur; thus, MBSR can be recommended as a beneficial adjuvant therapy for treating CRF in breast cancer patients. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021245365.

Path analysis of COVID-19 cognition, social support, and mental health of pregnant women with interventional prenatal diagnosis during the COVID-19 pandemic based on structural equation modeling.

This study aims to investigate the relationship between Corona Virus Disease 2019 (COVID-19) cognition, social support, and mental health among pregnant women proposed for undergoing interventional prenatal diagnosis in Sichuan Province during the COVID-19 pandemic. A total of 2270 pregnant women (2232 valid) who were proposed to undergo interventional prenatal diagnosis at a tertiary hospital prenatal diagnosis center in Sichuan Province from January to December 2022 were selected by Convenience sampling and surveyed using a self-administered general information questionnaire, social support rating scale, mental health questionnaire (including: Self-Rating Anxiety Scale, Self-Rating Depression Scale), and self-administered COVID-19 cognition questionnaire. Structural equation modeling showed that social support negatively predicted anxiety (ß = -0.34, t = -14.98, P < .001) and negatively predicted depressive status (ß = -0.21, t = -9.57, P < .001); COVID-19 cognition negatively predicted anxiety (ß = -0.76, t = -5.34, P < .001) and depression (ß = -0.40, t = -2.99, P < .01); anxiety positively predicted anxiety (ß = 0.73, t = 37.34, P < .001). The overall knowledge rate of COVID-19 cognition among 2232 pregnant women who were to undergo interventional prenatal diagnosis was 76.40%. The fit indices of the model were: CMIN/DF = 3.071, GFI = 0.999, AGFI = 0.993, CFI = 0.999, RMSEA = 0.030, NFI = 0.998, and TLI = 0.992, indicating that the model had a good fit and the model was scientifically valid. Pregnant women in Sichuan province who are to undergo prenatal interventional diagnosis have a medium level of COVID-19 awareness, and their level of COVID-19 awareness and social support will directly affect their anxiety and depression level, and their anxiety level will also affect their depression level. We should give more attention to pregnant women, especially those in particular situations such as advanced age, poor maternal history, family history of genetic disease, etc, they should be given adequate care and social support, and multiple channels and types of health education should be provided for the COVID-19 to improve the pregnant women's knowledge of COVID-19, which is important for improving the mental health of pregnant women.

An Improved and Simplified Agrobacterium-Mediated Genetic Transformation Protocol for Solanum nigrum with a Shorter Growth Time.

Solanum nigrum (Solanaceae family) is widely consumed as a fruit or local leafy vegetable after boiling; it also serves as a medicinal plant. Although Agrobacterium-mediated genetic transformation has been established in S. nigrum, the transformation period is long. Specifically, induction of roots takes approximately five weeks for tetraploid and hexaploid S. nigrum, and 7 weeks for diploid Solanum americanum. In this study, we developed an improved rooting-induced method that requires only about 1 week and avoids the use of tissue culture. After generating the transgenic shoots, they were directly transplanted into the soil to facilitate root formation. Remarkably, 100% of the transgenic shoots developed roots within 6 days. Our improved method is time-saving (saving more than 1 month) and simpler to operate. The improved rooting-induced step can be applied to induce roots in various plants using tissue culture, exemplified by the carnation (Dianthus caryophyllus L.). Furthermore, we applied the improved method to generate S. americanum plants expressing AcMYB110 from kiwifruit (Actinidia chinensis spp.). This method will contribute to speeding up gene functional analysis and trait improvement in S. nigrum and might have potential in fast plant molecular breeding processes in crops and rapid rooting induction in tissue culture.

Inspecting mother-to-infant microbiota transmission: disturbance of strain inheritance by cesarian section.

Introduction: The initial acquisition and subsequent development of the microbiota in early life is crucial to future health. Cesarean-section (CS) birth is considered to affect early microbial transmission from mother to infant. Methods: In this study, we collected fecal samples from 34 CS infants and their mothers from West China Second Hospital, Sichuan University to assess the microbiota developmental trajectory of mothers and infants. We explored mother-infant gut microbiome transmission via comparison with corresponding Finnish data. Results: Metagenomic analysis of gut microbiota profiles indicated that the communities of mothers and infants were distinct. The composition of the infant gut microbiome was highly variable but also followed predictable patterns in the early stages of life. Maternal communities were stable and mainly dominated by species from Bacteroidacea spp. We used PStrain to analyze and visualize strain transmission in each mother-infant pair. Excluding missing data, we included 32 mother-infant pairs for analysis of strain transmission. Most CS deliveries (65.6%, 21/32) did not demonstrate transmission of strains from mother to infant. To further explore the mother-infant strain transmission, we analyzed metagenomics data from Finnish mother-infant pairs. A total of 32 mother-infant pairs were included in the analysis, including 28 vaginal delivery (VD) infants and four CS infants. Strain transmission was observed in 30 infants, including 28 VD infants and two CS infants. All VD infants received transmitted stains from their mothers. Finally, a total of 193 strain transmission events were observed, comprising 131 strains and 45 species. Discussion: Taken together, our data suggested that delivery mode was an important factor influencing the mother-infant strain transmission.

The implementation and effect evaluation of AIDET standard communication health education mode under the King theory of goal attainment: A randomized control study.

BACKGROUND: This research addresses inadequate understanding of interventional prenatal diagnosis, preoperative anxiety psychological problems in pregnant women undergoing interventional prenatal diagnosis, proposing a health education mode combined AIDET standard communication and King's theory of goal attainment approach to potentially improve health education outcomes, anxiety psychological problems, and patient satisfaction. METHODS: A convenient sampling method was used to select a total of 300 pregnant women who were ready to undergo interventional prenatal diagnosis. They were randomly divided into a implementation group and a control group, with 150 pregnant women in each group. The control group used the communication mode of the traditional process of nurse-patient communication. The implementation group used the AIDET standard communication health education model under the King theory of goal attainment in the process of nurse-patient communication and the interventional prenatal diagnosis health education content questionnaire, the pregnant women's satisfaction questionnaire, state anxiety scale, and disease uncertainty scale were used for evaluation. RESULTS: The results of the interventional prenatal diagnosis health education questionnaire, the results of pregnant women's anxiety, the results of pregnant women's disease uncertainty, the results of pregnant women's satisfaction, the implementation group all were better than the control group (P < .05). CONCLUSION: Using the AIDET standard communication health education model under the King theory of goal attainment in nurse-patient communication is conducive to the rapid establishment of a harmonious and trusting nurse-patient relationship between pregnant women and nurses, helping pregnant women and nurses jointly promote the establishment and implementation of health education goals, helping to improve pregnant women's acceptance of information related to interventional prenatal diagnosis, health education and the procedure of walking on the day of surgery. It helps enhance the effectiveness of health education and satisfaction, reducing pregnant women's uncertainty about the disease, their unfamiliarity with the surgery environment and surgery procedure, and their preoperative anxiety.

Effects of music therapy on pain relief during fundus screening in infants: Randomized controlled clinical trial.

BACKGROUND: To determine the efficacy of music therapy on pain relief during fundus screening in infants. METHODS: The sample consisted of infants aged 0 to 3 months who required fundus screening. Infants were randomized to fast music, slow music, and control groups. All groups underwent fundus screening under topical anesthesia. Music therapy was provided to the music groups prior to, during, and after the operation. The patient's heart rate (HR), transcutaneous oxygen saturation, and crying decibel were measured. The Face, Legs, Activity, Cry, Consolability scale was used for pain measurement. RESULTS: A total of 300 subjects' data were collected. The quantitative analysis revealed that in both music groups, peripheral capillary oxygen saturation and satisfaction levels increased while pain scores decreased (P < .05). The slow music group's HR was shown to have significantly decreased (P < .05). CONCLUSION: Music therapy can effectively reduce pain and crying, and increase blood oxygen saturation during fundus examination of infants. Music with a rhythm of 60 to 80 beats per minute can decrease HR. Music therapy must be remembered to increase infants' comfort during fundus examination.

Fall risk management in interventional prenatal diagnosis perioperative pregnant women based on tracking methodology and failure mode and effect analysis application.

The aim was to explore the effectiveness of a tracing methodology combined with failure mode and effect analysis (FMEA) for managing falls in pregnant women during the perioperative period of interventional prenatal diagnosis. Using the tracing methodology, the process was evaluated and analyzed using FMEA after reviewing data, on-site interview, case tracking and on-site inspection, and improvement measures were proposed for the existing risk factors, and the fall-related quality indicators, satisfaction with fall-related health education, and risk priority number were compared before and after implementation. Effectiveness analysis for interventional prenatal diagnosis of perioperative maternal falls risk management resulted in a significant decrease in risk priority number (P < .01), a significant increase in the rate of correct fall risk identification and assessment, correct handover rate of pregnant women at risk of falls, correct intervention rate of pregnant women at high risk of falls, and effective coverage of falls-related health education (P < .01), a significant increase in satisfaction with falls-related health education (P < .001), and the incidence of falls among pregnant women decreased from 0.12% to 0%. The use of tracking methodology combined with FMEA can reduce the risk of perioperative maternal falls in interventional prenatal diagnosis and improve the safety of maternal visits.

Design and practice of innovative practice workshop for new nurses based on creativity component theory and outcome based education(OBE) concept.

OBJECTIVE: To design a teaching model of innovative nursing practice workshop for new nurses based on creativity component theory and OBE concept, and to explore its implementation effect and application evaluation. METHODS: Using convenience sampling, 50 newly recruited nurses in 2021 from a tertiary hospital in Chengdu were selected as the study subjects and taught using the new nurses' innovative practice workshop based on creativity component theory and the OBE concept. RESULTS: Before and after the implementation of the teaching, the new nurses' creativity scale scores were significantly improved, and the effects of practice demonstration, teaching satisfaction results, and research output (one-year follow-up) were better. All 50 new nurses (100%) expressed willingness to participate in the course again. CONCLUSIONS: Based on creativity component theory and the OBE concept, the innovative practice workshop for new nurses integrates theory and practice, and fully mobilizes students' thinking, interest, and subjective initiative; during the teaching process, students' creative thinking and problem-solving skills are improved, in addition, teamwork, literature review, communication and other skills are improved to different degrees, which is conducive to the research results. In addition, students' abilities in teamwork, literature review, communication, and other aspects have been improved to different degrees, which is conducive to producing scientific research results and lays a good foundation for their future career development. NO PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution is involved in this study.

Prematurely delivering mothers show reductions of lachnospiraceae in their gut microbiomes.

BACKGROUND: Preterm birth is the leading cause of perinatal morbidity and mortality. Despite evidence shows that imbalances in the maternal microbiome associates to the risk of preterm birth, the mechanisms underlying the association between a perturbed microbiota and preterm birth remain poorly understood. METHOD: Applying shotgun metagenomic analysis on 80 gut microbiotas of 43 mothers, we analyzed the taxonomic composition and metabolic function in gut microbial communities between preterm and term mothers. RESULTS: Gut microbiome of mothers delivering prematurely showed decreased alpha diversity and underwent significant reorganization, especially during pregnancy. SFCA-producing microbiomes, particularly species of Lachnospiraceae, Ruminococcaceae, and Eubacteriaceae, were significantly depleted in preterm mothers. Lachnospiraceae and its species were the main bacteria contributing to species' differences and metabolic pathways. CONCLUSION: Gut microbiome of mothers delivering prematurely has altered and demonstrates the reduction of Lachnospiraceae.

Application of AtMYB75 as a reporter gene in the study of symbiosis between tomato and Funneliformis mosseae.

Composite plants containing transgenic hairy roots produced with Agrobacterium rhizogenes-mediated transformation have become an important method to study the interaction between plants and arbuscular mycorrhizal fungi (AMF). Not all hairy roots induced by A. rhizogenes are transgenic, however, which leads to requirement of a binary vector to carry a reporter gene to distinguish transgenic roots from non-transformed hairy roots. The beta-glucuronidase gene (GUS) and fluorescent protein gene often are used as reporter markers in the process of hairy root transformation, but they require expensive chemical reagents or imaging equipment. Alternatively, AtMYB75, an R2R3 MYB transcription factor from Arabidopsis thaliana, recently has been used as a reporter gene in hairy root transformation in some leguminous plants and can cause anthocyanin accumulation in transgenic hairy roots. Whether AtMYB75 can be used as a reporter gene in the hairy roots of tomato and if the anthocyanins accumulating in the roots will affect AMF colonization, however, are still unknown. In this study, the one-step cutting method was used for tomato hairy root transformation by A.rhizogenes. It is faster and has a higher transformation efficiency than the conventional method. AtMYB75 was used as a reporter gene in tomato hairy root transformation. The results showed that the overexpression of AtMYB75 caused anthocyanin accumulation in the transformed hairy roots. Anthocyanin accumulation in the transgenic hairy roots did not affect their colonization by the arbuscular mycorrhizal fungus, Funneliformis mosseae strain BGC NM04A, and there was no difference in the expression of the AMF colonization marker gene SlPT4 in AtMYB75 transgenic roots and wild-type roots. Hence, AtMYB75 can be used as a reporter gene in tomato hairy root transformation and in the study of symbiosis between tomato and AMF.

Effect of hypertension on the long-term prognosis of children with primary focal segmental glomerulosclerosis-a retrospective cohort study.

Background: Primary focal segmental glomerulosclerosis is a common clinicopathologic syndrome. More than 50% of the patients may have hypertension, which can further deteriorate the renal function of patients. However, the impact of hypertension on the development of end-stage renal disease in children with primary focal segmental glomerulosclerosis is still unclear. The end-stage renal disease greatly increases medical costs and mortality. Studying the related factors of end-stage renal disease is helpful to prevent and treat end-stage renal disease. This study aimed to explore the impact of hypertension on the long-term prognosis of children with primary focal segmental glomerulosclerosis. Methods: The data of 118 children with primary focal segmental glomerulosclerosis admitted to the Nursing Department of West China Second Hospital from January 2012 to January 2017 were retrospectively collected. The children were divided into a hypertension group (n=48) and a control group (n=70) according to whether they had hypertension. The children were followed up (by clinic visit and telephone interviews) for 5 years to compare the differences in the incidence of end-stage renal disease between the two groups. Results: Compared with the control group, the proportion of patients with severe renal tubulointerstitial damage in the hypertension group was significantly higher (18.75% vs. 5.71%, P=0.026). Moreover, the incidence of end-stage renal disease was markedly higher (33.33% vs. 5.71%, P<0.001). Both systolic and diastolic blood pressure had a certain value in predicting the development of end-stage renal disease in children with primary focal segmental glomerulosclerosis (P<0.001 and P=0.025, respectively), and the predictive value of systolic blood pressure was relatively higher. Multivariate logistic regression analysis showed that hypertension was risk factors for end-stage renal disease in children with primary focal segmental glomerulosclerosis (P=0.009, relative risk: 17.022, 95% CI: 2.045-141.723). Conclusions: Hypertension was a risk factor for poor long-term prognosis in children with primary focal segmental glomerulosclerosis. For primary focal segmental glomerulosclerosis children with hypertension, blood pressure should be actively controlled to prevent the development of end-stage renal disease. Moreover, due to the high incidence of end-stage renal disease, we should monitor the end-stage renal disease during follow-up.

An Oxalate Transporter Gene, AtOT, Enhances Aluminum Tolerance in Arabidopsis thaliana by Regulating Oxalate Efflux.

Secretion and efflux of oxalic acid from roots is an important aluminum detoxification mechanism for various plants; however, how this process is completed remains unclear. In this study, the candidate oxalate transporter gene AtOT, encoding 287 amino acids, was cloned and identified from Arabidopsis thaliana. AtOT was upregulated in response to aluminum stress at the transcriptional level, which was closely related to aluminum treatment concentration and time. The root growth of Arabidopsis was inhibited after knocking out AtOT, and this effect was amplified by aluminum stress. Yeast cells expressing AtOT enhanced oxalic acid resistance and aluminum tolerance, which was closely correlated with the secretion of oxalic acid by membrane vesicle transport. Collectively, these results underline an external exclusion mechanism of oxalate involving AtOT to enhance oxalic acid resistance and aluminum tolerance.

Cloning, Expression Analysis, and Functional Characterization of Candidate Oxalate Transporter Genes of HbOT1 and HbOT2 from Rubber Tree (Hevea brasiliensis).

Secretion of oxalic acid from roots is an important aluminum detoxification mechanism for many plants such as Hevea brasiliensis (rubber tree). However, the underlying molecular mechanism and oxalate transporter genes in plants have not yet been reported. In this study, the oxalate transporter candidate genes HbOT1 and HbOT2 from the rubber tree were cloned and preliminarily identified. It was found that HbOT1 had a full length of 1163 bp with CDS size of 792 bp, encoding 263 amino acids, and HbOT2 had a full length of 1647 bp with a CDS region length of 840 bp, encoding 279 amino acid residues. HbOT1 and HbOT2 were both stable hydrophobic proteins with transmembrane structure and SNARE_assoc domains, possibly belonging to the SNARE_assoc subfamily proteins of the SNARE superfamily. qRT-PCR assays revealed that HbOT1 and HbOT2 were constitutively expressed in different tissues, with HbOT1 highly expressed in roots, stems, barks, and latex, while HbOT2 was highly expressed in latex. In addition, the expressions of HbOT1 and HbOT2 were up-regulated in response to aluminum stress, and they were inducible by metals, such as copper and manganese. Heterologous expression of HbOT1 and HbOT2 in the yeast mutant AD12345678 enhanced the tolerance to oxalic acid and high concentration aluminum stress, which was closely correlated with the secretion of oxalic acid. This study is the first report on oxalate transporter genes in plants, which provides a theoretical reference for the study on the molecular mechanism of oxalic acid secretion to relieve aluminum toxicity and on aluminum-tolerance genetic engineering breeding.

[Cross-Sectional Study of Nutritional Status and Dietary Nutrient Intake in Children with Duchenne Muscular Dystrophy (DMD) in China].

Objective: To investigate the dietary nutrient intake and the nutritional status of children with Duchenne muscular dystrophy (DMD), and to explore the correlation between them, so as to provide theoretical basis for the formulation of proper nutritional treatment for children with DMD. Methods: A total of 223 children aged 2 to 14 years who came to West China Second University Hospital, Sichuan University from July 2017 to April 2021, and who were diagnosed with DMD by genetic testing were enrolled as the subjects of the study. Dietary assessment was conducted with a 3-day 24-hour dietary recall, and serum vitamin D level was measured by chemiluminescence method. Results: Only 33.2% of the children with DMD were found to be of normal nutritional status. The incidences of stunted growth, underweight, overweight and obesity were 13.5%, 14.4%, 14.3% and 8.1%, respectively. Among the children with DMD, those with serum vitamin D deficiency and insufficiency accounted for 9.0% and 89.7%, respectively. According to the dietary recall of the children with MDM, the daily energy ratio of carbohydrate, protein and fat were (47.40±6.64)%, (14.46±2.22)%, and (38.17±5.30)%, respectively. The daily intake of dietary calcium and vitamin D were (433.32±164.39) mg per day and (155.73±89.30) IU per day, respectively. The ratio of daily protein intake to the estimated average requirement for protein ( P=0.003) and ratio of daily energy intake to the estimated energy requirement ( P=0.007) were lower in children with stunted growth than those of DMD children of normal nutritional status. Conclusion: The dietary structure of children with DMD is obviously not suited to their condition and nutritional deficiency coexists with overnutrition among them. Further research needs to be done for developing appropriate nutritional guidance programs and standardized nutritional management measures for children with DMD.

AtGCS promoter-driven clustered regularly interspaced short palindromic repeats/Cas9 highly efficiently generates homozygous/biallelic mutations in the transformed roots by Agrobacterium rhizogenes-mediated transformation.

Agrobacterium rhizogenes-mediated (ARM) transformation is an efficient and powerful tool to generate transgenic roots to study root-related biology. For loss-of-function studies, transgenic-root-induced indel mutations by CRISPR/Cas9 only with homozygous/biallelic mutagenesis can exhibit mutant phenotype(s) (excluding recessive traits). However, a low frequency of homozygous mutants was produced by a constitutive promoter to drive Cas9 expression. Here, we identified a highly efficient Arabidopsis thaliana gamma-glutamylcysteine synthetase promoter, termed AtGCSpro, with strong activity in the region where the root meristem will initiate and in the whole roots in broad eudicots species. AtGCSpro achieved higher homozygous/biallelic mutation efficiency than the most widely used CaMV 35S promoter in driving Cas9 expression in soybean, Lotus japonicus, and tomato roots. Using the pAtGCSpro-Cas9 system, the average homozygous/biallelic mutation frequency is 1.7-fold and 8.3-fold higher than the p2 × 35Spro-Cas9 system for single and two target site(s) in the genome, respectively. Our results demonstrate the advantage of the pAtGCSpro-Cas9 system used in ARM transformation, especially its great potential in diploids with multiple-copy genes targeted mutations and polyploid plants with multiplex genome editing. AtGCSpro is conservatively active in various eudicots species, suggesting that AtGCSpro might be applied in a wide range of dicots species.

Gold nanoparticle ring arrays from core-satellite nanostructures made to order by hydrogen bond interactions.

Polyethylene glycol-grafted gold nanoparticles are attached to silica nanoparticle cores via hydrogen bonding in a controlled fashion, forming well-defined core-satellite structures in colloidal solution. For separating these complex structures effectively from the parental nanoparticles, a straightforward and easy protocol using glass beads has been developed. The attached gold nanoparticles show unique surface mobility on the silica core surface, which allows for nanoparticle rearrangement into a 2D ring pattern surrounding the silica nanoparticle template when the core-satellite structures are cast to a planar surface. When etching away the silica core under conditions in which the polymer shell fixes the satellites to the substrate, highly ordered ring-shaped patterns of gold nanoparticles are formed. By variation of the size of the parental particles - 13 to 28 nm for gold nanoparticles and 39 to 62 nm for silica nanoparticles - a great library of different ring-structures regarding size and particle number is accessible with relative ease. The proposed protocol is low-cost and can easily be scaled up. It moreover demonstrates the power of hydrogen bonds in polymers as a dynamic anchoring tool for creating nanoclusters with rearrangement ability. We believe that this concept constitutes a powerful strategy for the development of new and innovative nanostructures.

FoxO3 restricts liver regeneration by suppressing the proliferation of hepatocytes.

Upon injury, the liver is capable of substantial regeneration from the original tissue until an appropriate functional size. The underlying mechanisms controlling the liver regeneration processes are not well elucidated. Previous studies have proposed that the transcription factor FoxO3 is involved in various liver diseases, but its exact role in the regulation of liver regeneration remains largely unclear. To directly test the detailed role of FoxO3 in liver regeneration, both a constitutive Albumin-Cre driver line and adeno-associated virus serotype 8 (AAV8)-Tbg-Cre (AAV-Cre)-injected adult FoxO3fl/fl mice were subjected to 70% partial hepatectomy (PH). Our data demonstrate that FoxO3 deletion accelerates liver regeneration primarily by limiting polyploidization and promoting the proliferation of hepatocytes during liver regeneration. RNA-seq analysis indicates that FoxO3 deficiency greatly alters the expression of gene sets associated with cell proliferation and apoptosis during liver regeneration. Chromatin immunoprecipitation-PCR (ChIP-PCR) and luciferase reporter assays reveal that FoxO3 promotes the expression of Nox4 but suppresses the expression of Nr4a1 in hepatocytes. AAV8 virus-mediated overexpression of Nox4 and knockdown of Nr4a1 significantly suppressed hepatocyte proliferation and liver regeneration in FoxO3-deficient mice. We demonstrate that FoxO3 negatively controls hepatocyte proliferation through Nox4 upregulation and Nr4a1 downregulation, thereby ensuring appropriate functional regeneration of the liver. Our findings provide novel mechanistic insight into the therapeutic mechanisms of FoxO3 in liver damage and repair.