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Hyperuricemia is associated with poor clinical outcomes in several cardiovascular diseases, including heart failure (HF). However, whether lowering serum uric acid (SUA) levels improves the prognosis of HF remains insufficiently studied. To evaluate whether urate-lowering therapy (ULT) with febuxostat confers clinical benefits in patients with HF and concomitant hyperuricemia. Prospective, observational cohort study. Patients with chronic HF and hyperuricemia were enrolled and assigned either to a febuxostat group or to a non-ULT group and were followed prospectively for 5 years. The primary endpoint was all-cause mortality or rehospitalization for HF. Among 2005 patients, those with higher SUA levels experienced more endpoint events. After propensity score matching, we found that febuxostat therapy significantly reduced the incidence of primary endpoints in patients with HF with preserved ejection fraction (HFpEF) [ = 0.012; hazard ratios (HR), 0.744; 95% confidence intervals (CI), 0.589-0.939], but not in those with HF with reduced ejection fraction (HFrEF) or mildly reduced ejection fraction (HFmrEF) ( = 0.234; HR, 0.894; 95% CI, 0.742-1.077). The benefits of febuxostat in HFpEF were most evident in patients within the highest tertiles of B-type natriuretic peptide (BNP) ( = 0.021; HR, 0.647; 95% CI, 0.436-0.960) and SUA ( = 0.025; HR, 0.651; 95% CI, 0.441-0.963). High SUA levels are associated with increased all-cause mortality and rehospitalization for HF. Febuxostat-mediated SUA reduction significantly improved clinical outcomes in patients with HFpEF, particularly those with elevated SUA and BNP levels.

Arrhythmias and major adverse cardiac events remain significant complications following ST-segment elevation myocardial infarction (STEMI). Shenfu injection, a traditional Chinese medicine formulation, has shown cardioprotective effects in preclinical studies. This trial is aimed at investigating whether Shenfu injection as an adjunctive therapy to standard treatment could reduce arrhythmias and improve clinical outcomes in patients with STEMI undergoing percutaneous coronary intervention (PCI). A single-center, prospective, randomized, controlled trial was conducted at Shanghai Ninth People's Hospital among 245 patients with STEMI undergoing PCI. Participants were randomized to receive either standard therapy plus Shenfu injection (50 mL, administered intravenously twice daily for five consecutive days) ( = 123) or standard therapy alone ( = 122). The primary endpoint was the incidence of in-hospital arrhythmias. Secondary endpoints included major adverse cardiac events (MACEs) during the 12-month follow-up period and cardiac magnetic resonance imaging parameters. A total of 245 patients underwent randomization (123 assigned to Shenfu injection group and 122 assigned to control group). During hospitalization, patients assigned to Shenfu injection had a significantly lower incidence of arrhythmias compared with the control group (24.4% vs. 38.5%, = 0.017), with the most pronounced effect on frequent ventricular premature contractions (7.3% vs. 15.5%, = 0.042). After adjustment for key baseline covariates including age, coronary artery disease extent, myocardial injury markers (CK-MB max and TNI max), left ventricular ejection fraction, B-type natriuretic peptide, door-to-balloon time, hypertension, and diabetes mellitus, Shenfu injection remained independently associated with reduced risk of in-hospital arrhythmias (adjusted OR 0.454, 95% CI: 0.249-0.827, = 0.010). Cardiac magnetic resonance imaging performed in 174 patients revealed significantly smaller infarct size (16.1 ± 9.1 vs. 20.8 ± 13.1 g, = 0.007) and lower incidence of microvascular obstruction (45.0% vs. 65.0%, = 0.008) in the Shenfu group, with both parameters showing significant positive correlations with arrhythmia occurrence. During the 12-month follow-up, patients receiving Shenfu injection had a higher event-free rate from MACEs compared with the control group (12-month Kaplan-Meier event-free rate estimates, 84.6% vs. 73.0%, respectively; = 0.028). Treatment with Shenfu injection as an adjunctive therapy to standard treatment in patients with STEMI undergoing PCI significantly reduced in-hospital arrhythmias, infarct size, microvascular obstruction, and major adverse cardiac events during a 12-month follow-up period. The independent effect on arrhythmias after comprehensive statistical adjustment and the demonstrated correlation between reduced myocardial damage and arrhythmia prevention suggest the potential therapeutic value of Shenfu injection in improving both short-term and long-term outcomes in STEMI patients. Chinese Clinical Trial Registry Identifier: ChiCTR2200066918.

The global increase in the elderly population has heightened the need to address nutritional risks in this vulnerable group. However, the relationship between overall dietary antioxidant intake and nutritional risk in the elderly remains unclear. This study aimed to investigate this association using the composite dietary antioxidant index (CDAI) and the geriatric nutritional risk index (GNRI). We analyzed data from the National Health and Nutrition Examination Survey (2010-2018), focusing on 4,208 participants aged ≥65 years. CDAI was calculated based on the intake of vitamins A, C, E, selenium, zinc, and carotenoids, while GNRI was derived from serum albumin and body weight. Multivariate regression models were employed to assess associations between CDAI, individual dietary antioxidants, and GNRI. Smooth curve fitting and two-piecewise linear regression were further performed to identify the non-linear relationships and determine the corresponding inflection points. A statistically significant positive correlation was observed between the CDAI and GNRI, indicating that increased dietary antioxidant intake is linked to reduced nutritional risk. Vitamin C, selenium, zinc, and carotenoids were strongly associated with higher GNRI scores, with vitamin C and zinc showing the most robust effects. Subgroup analyses further revealed that men, diabetic individuals, and those without cancer exhibited greater improvements in nutritional risk with higher CDAI levels. Threshold effect analysis identified an optimal range for CDAI, beyond which the nutritional benefits diminished. Our findings highlight the critical role of dietary antioxidants, especially vitamin C and zinc, in mitigating nutritional risk among the elderly. These results support the importance of balanced dietary intake of antioxidants to optimize nutritional health in aging populations.

Heterochromatin is a tightly packed form of chromatin that is associated with DNA methylation and histone 3 lysine 9 methylation (H3K9me). Here, we identify an H3K9me2-binding protein, Agenet domain (AGD)-containing p1 (AGDP1), in Arabidopsis thaliana . Here we find that AGDP1 can specifically recognize the H3K9me2 mark by its three pairs of tandem AGDs. We determine the crystal structure of the Agenet domain 1 and 2 cassette (AGD12) of Raphanus sativus AGDP1 in complex with an H3K9me2 peptide. In the complex, the histone peptide adopts a unique helical conformation. AGD12 specifically recognizes the H3K4me0 and H3K9me2 marks by hydrogen bonding and hydrophobic interactions. In addition, we find that AGDP1 is required for transcriptional silencing, non-CG DNA methylation, and H3K9 dimethylation at some loci. ChIP-seq data show that AGDP1 preferentially occupies long transposons and is associated with heterochromatin marks. Our findings suggest that, as a heterochromatin-binding protein, AGDP1 links H3K9me2 to DNA methylation in heterochromatin regions. DNA methylation and H3K9 dimethylation are two linked epigenetic marks of silenced chromatin in plants that depend on the activity of CMT3/2 and SUVH4/5/6. Here the authors identify AGDP1 as an H3K9me2-binding protein required for heterochromatic non-CG DNA methylation, H3K9 dimethylation, and transcriptional silencing.

Kalanchoe daigremontiana reproduces asexually by producing plantlets along the leaf margin. The aim of this study was to identify the function of the SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 gene in Kalanchoe daigremontiana ( KdSOC1 ) during plantlet morphogenesis. In this study, KdSOC1 gene expression was detected at stem cell niche during in vitro somatic embryogenesis and plantlet morphogenesis. Disrupting endogenous auxin transportation suppressed the KdSOC1 gene response. Knockdown of the KdSOC1 gene caused a defect in cotyledon formation during the early heart stage of somatic embryogenesis. Over-expression (OE) of the KdSOC1 gene resulted in asymmetric plantlet distribution, a reduced number of plantlets, thicker leaves, and thicker vascular fibers. Higher KdPIN1 gene expression and auxin content were found in OE plant compared to those of wild-type plant leaves, which indicated possible KdSOC1 gene role in affecting auxin distribution and accumulation. KdSOC1 gene OE in DR5-GUS Arabidopsis reporting lines resulted in an abnormal auxin response pattern during different stages of somatic embryogenesis. In summary, the KdSOC1 gene OE might alter auxin distribution and accumulation along leaf margin to initiate plantlet formation and distribution, which is crucial for plasticity during plantlet formation under various environmental conditions.

Yellow-seed trait is a desirable breeding characteristic of rapeseed ( Brassica napus ) that could greatly improve seed oil yield and quality. However, the underlying mechanisms controlling this phenotype in B. napus plants are difficult to discern because of their complexity. Here, we assemble high-quality genomes of yellow-seeded (GH06) and black-seeded (ZY821). Combining in-depth fine mapping of a quantitative trait locus (QTL) for seed color with other omics data reveal BnA09MYB47a , encoding an R2R3-MYB-type transcription factor, as the causal gene of a major QTL controlling the yellow-seed trait. Functional studies show that sequence variation of BnA09MYB47a underlies the functional divergence between the yellow- and black-seeded B. napus . The black-seed allele BnA09MYB47a ZY821 , but not the yellow-seed allele BnA09MYB47a GH06 , promotes flavonoid biosynthesis by directly activating the expression of BnTT18 . Our discovery suggests a possible approach to breeding B. napus for improved commercial value and facilitates flavonoid biosynthesis studies in Brassica crops. Yellow-seed trait is preferred in rapeseed breeding as it can greatly improve seed oil yield and quality. Here, the authors assemble the genome of two rapeseed lines with yellow-seed and black-seed phenotypes, and clone an R2R3-MYB-type transcription factor encoding gene as a key regulator of seed color.

Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disorder of the colon, and it has become one of the world-recognized medical problems as it is recurrent and refractory. Berberine (BBR) is an effective drug for UC treatment. However, the underlying mechanism and targets remain obscure. In this study, we systematically investigated the therapeutic effect and its mechanism of BBR in ameliorating DSS-induced mouse colitis. Expectedly, the colon inflammation was significantly relieved by BBR, and microbiota depletion by antibiotic cocktail significantly reversed the therapeutic effect. Further studies showed that BBR can regulate the abundance and component of bacteria, reestablish the broken chemical and epithelial barriers. Meanwhile, BBR administration dramatically decreased ILC1 and Th17 cells, and increased Tregs as well as ILC3 in colonic tissue of DSS-induced mice, and it was able to regulate the expression of various immune factors at the mRNA level. Moreover, a proteomic study revealed that Wnt/β-catenin pathway was remarkably enhanced in colonic tissue of BBR-treated mice, and the therapeutic effect of BBR was disappeared after the intervention of Wnt pathway inhibitor FH535. These results substantially revealed that BBR restores DSS-induced colon inflammation in a microbiota-dependent manner, and BBR performs its protective roles in colon by maintaining the structure and function of the intestinal mucosal barrier, regulating the intestinal mucosal immune homeostasis and it works through the Wnt/β-catenin pathway. Importantly, these findings also provided the proof that BBR serves as a potential gut microbiota modulator and mucosal barrier protector for UC prevention and therapy.

Aims To explore the knowledge, attitudes and practice status of the intrahospital transport (IHT) of critically ill patients among clinical nurses and their influencing factors. Design Cross‐sectional study. Methods A questionnaire determined the nurses' knowledge, attitudes and practice scores. The questionnaire was used for data collection in a tertiary hospital from 10 January to 17 January 2023. Multivariate regression analysis was also used to evaluate the related factors of IHT of critically ill patients in different dimensions. Results Out of 670 distributed questionnaires, 612 nurses returned the completed questionnaire. The scores of KAP were (9.72 ± 1.61), (42.91 ± 4.58) and (82.84 ± 1.61), respectively. Pearson's correlation analysis showed that knowledge, attitude and behaviour scores were positively correlated. Variables that were associated with the scores of transfer knowledge were the scores of transfer practice, different departments and the scores of transfer attitude. The score of practice, number of IHT and received hospital‐level training had statistical significance on the nurses' attitude scores. Furthermore, the score of the attitude and transport knowledge had statistical significance on the nurses' practice. Conclusion The findings indicate a clear need for clinical nurses' knowledge of IHT of critically ill patients, especially in the emergency department (ED) and ICU. In addition, nurses need to be more active in transporting critically ill patients. Managers should enhance nurses' confidence in the IHT of critically ill patients and promote clinical nurses to establish a correct and positive attitude. Impact The findings of this study benefit nursing managers in understanding the current situation of IHT of critically ill patients. Managers should apply new training methods to nursing education and develop a multi‐level training program that is systematic, comprehensive and demand‐oriented. Patient or Public Contribution The participants of this study were nurses and this contribution has been explained in the Data collection section. There was no patient contribution in this study.

Background Hypercholesterolemia and gut microbiota dysbiosis are associated with the risk of cardiovascular diseases. Hawthorn fruits has shown to be cardioprotective and hypocholesterolemic. However, no studies to date have studied the biological activity of hawthorn seed oil (HSO). The present study was to investigate if HSO could favourably reduce plasma cholesterol and modulate gut microbiota in hypercholesterolemia hamsters. Methods Golden Syrian hamsters (age, 8 weeks) were randomly divided into five groups ( n  = 8, each) and fed one of the following five diets, namely a non-cholesterol diet, a high cholesterol diet containing 0.15% cholesterol (HCD); a HCD diet with addition of 4.75% HSO (LHSO), a HCD diet with addition of 9.5% HSO (HHSO), a HCD diet with addition of 0.50% cholestyramine as positive control diet. After 6-week dietary intervention, plasma lipids, inflammatory markers, atherosclerosis plaque, hepatic and fecal lipids were quantified. Microbiota in fresh feces were analysed by sequencing 16S rRNA genes, while RT-PCR and Western blot analyses were employed to quantify the expression of genes involved in cholesterol homeostasis. Results HSO at a dose of 9.5% HSO could decrease plasma cholesterol and non-HDL-cholesterol by 15%. Additionally, both HSO experimental groups also suppressed mRNA of 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMG-CoA-R). Supplementation of HSO at 4.75% could significantly increase the excretion of fecal acidic sterols, accompanied by elevation of short-chain fatty acid levels in feces. The analyses of gut microbiome indicated that HSO supplementation could selectively alter the genera abundance of gut bacteria that were correlated with cholesterol metabolism including unclassified_f__Christensenellaceae, Ruminococcaceae_NK4A214_ group, norank_o_Gastranaerophilales, Faecalibaculum, Peptococcus, norank_f__Clostridiales_vadinBB60_group and Ruminococcus_2. Conclusions HSO supplementation was able to decrease plasma cholesterol by favourably modulating gut microbiota composition and gut-derived metabolites associated with cholesterol regulation. Graphical Abstract