Nano molybdenum trioxide-mediated enhancement of soybean yield through improvement of rhizosphere soil molybdenum bioavailability for nitrogen-fixing microbial recruitment.

Molybdenum (Mo) plays a pivotal role in the growth and nitrogen-fixing process of plants mediated by rhizobia. However, the influence of nano­molybdenum trioxide (MoO3NPs) on soybean growth, rhizosphere bioavailable Mo, and nitrogen-fixing microorganisms remains underexplored. Here, we report that compared with that of ionic Mo and bulk MoO3, the utilization of MoO3NPs (specifically NPs0.05 and NPs0.15) significantly boosted the available Mo content in the rhizosphere soil throughout the seedling (by 21.64 %-101.38 %), podding (by 54.44 %-68.89 %), and mature stage (by 34.41 %-to 45.71 %) of soybean growth. Furthermore, both NPs0.05 and NPs0.15 treatments maintained consistently higher levels of acid-extractable Mo, reducible Mo, and oxidizable Mo across these stages, which facilitated stable conversion and supply of bioavailable Mo. Within the rhizosphere soil, NPs0.05 and NPs0.15 treatments resulted in the highest relative abundance of Rhizobiales and Bradyrhizobium genera, and significantly promoted the colonization of nitrogen-fixing microorganisms, thereby increasing the content of nitrate nitrogen (NO3--N) by 8.69 % and 7.72 % and ammonium nitrogen (NH4+-N) by 44.75 % and 17.55 %, respectively. Ultimately, these effects together contributed to 107.17 % and 84.00 % increment in soybean yield by NPs0.05 and NPs0.15 treatments, respectively. In summary, our findings underscore the potential of employing MoO3NPs to promote plant growth and maintain soil nitrogen cycling, indicating distinct advantages of MoO3NPs over ionic Mo and bulk MoO3.

Anti-Inflammatory Activity of Peptides from Ruditapes philippinarum in Lipopolysaccharide-Induced RAW264.7 Cells and Mice.

In our previous study, two peptides with favorable anti-inflammatory effects, Asp-Gln-Thr-Phe (DQTF) and Gly-Tyr-Thr-Arg (GYTR), were screened from Ruditapes philippinarum using an in vitro-in silico strategy. The present study aims to investigate the ameliorative effect of Ruditapes philippinarum peptides (RPPs) on acute inflammation and clarify the potential mechanism through in vitro and in vivo experiments. The anti-inflammatory effects of DQTF and GYTR were verified with a lipopolysaccharide (LPS)-induced RAW264.7 cell acute inflammation model and the anti-inflammatory effect of the enzymatic hydrolysates of Ruditapes philippinarum was explored in vivo using an LPS-induced acute inflammatory injury model in mice. The results show that DQTF and GYTR improved the morphology of LPS-injured cells and decreased the concentrations of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in LPS-induced cells. Moreover, the antioxidant enzyme activity in cells was markedly increased with DQTF and GYTR. The enzymatic hydrolysates of Ruditapes philippinarum were obtained with hydrolysis using pepsin-chymotrypsin-trypsin (PeCTHC) and pepsin-trypsin (PeTHC), respectively. PeCTHC and PeTHC significantly reduced pro-inflammatory cytokines and nitric oxide (NO) in the serum. Additionally, the blood indices and levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and malondialdehyde (MDA) in the livers of mice were markedly improved with RPPs administration. In conclusion, RPPs have preventive and protective effects on acute inflammation, with significant prospects for development in the field of functional foods.

Purification, Characterization, cDNA Cloning, and Bioinformatic Analysis of Zinc-Binding Protein from Magallana hongkongensis.

Oysters contain significant amounts of the zinc element, which may also be found in their proteins. In this study, a novel zinc-binding protein was purified from the mantle of the oyster Magallana hongkongensis using two kinds of gel filtration chromatograms. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that its molecular weight was approximately 36 kDa. The protein identified by the Q-Exactive mass spectrometer shared the highest sequence identity with carbonic anhydrase derived from Crassostrea gigas concerning amino acid sequence similarity. Based on homologous cloning and RACE PCR, the full-length cDNA of carbonic anhydrase from Magallana hongkongensis (designated as MhCA) was cloned and sequenced. The cDNA of MhCA encodes a 315-amino-acid protein with 89.74% homology to carbonic anhydrase derived from Crassostrea gigas. Molecular docking revealed that the two zinc ions primarily form coordination bonds with histidine residues in the MhCA protein. These results strongly suggest that MhCA is a novel zinc-binding protein in Magallana hongkongensis.

Prognostic implications of systemic immune-inflammation index in myocardial infarction patients with and without diabetes: insights from the NOAFCAMI-SH registry.

BACKGROUND: It is well-known that systemic inflammation plays a crucial role in the pathogenesis and prognosis of acute myocardial infarction (AMI). The systemic immune-inflammation index (SII, platelet × neutrophil/lymphocyte ratio) is a novel index that is used for the characterization of the severity of systemic inflammation. Recent studies have identified the high SII level as an independent predictor of poor outcomes in patients with AMI. We aimed to investigate the prognostic implications of SII in AMI patients with and without diabetes mellitus (DM). METHODS: We included 2111 patients with AMI from February 2014 to March 2018. Multivariable Cox regression analyses were performed to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause death and cardiovascular (CV) death. Multiple imputation was used for missing covariates. RESULTS: Of 2111 patients (mean age: 65.2 ± 12.2 years, 77.5% were males) analyzed, 789 (37.4%) had DM. Generalized additive model analyses showed that as the SII increased, the C-reactive protein and peak TnT elevated while the LVEF declined, and these associations were similar in patients with and without DM. During a median of 2.5 years of follow-up, 210 all-cause deaths and 154 CV deaths occurred. When treating the SII as a continuous variable, a higher log-transformed SII was significantly associated with increased all-cause mortality (HR: 1.57, 95%CI: 1.02-2.43) and CV mortality (HR: 1.85, 95%CI 1.12-3.05), and such an association was also significant in the diabetics (HRs and 95%CIs for all-cause death and CV death were 2.90 [1.40-6.01] and 3.28 [1.43-7.57], respectively) while not significant in the nondiabetics (Pinteraction for all-cause death and CV death were 0.019 and 0.049, respectively). Additionally, compared to patients with the lowest tertiles of SII, those with the highest tertiles of SII possessed significantly higher all-cause mortality (HR: 1.82, 95%CI 1.19-2.79) and CV mortality (HR: 1.82, 95%CI 1.19-2.79) after multivariable adjustment, and this relationship remained pronounced in the diabetics (HRs and 95%CIs for all-cause death and CV death were 2.00 [1.13-3.55] and 2.09 [1.10-3.98], respectively) but was not observed in the nondiabetics (HRs and 95%CIs for all-cause death and CV death were 1.21 [0.75-1.97] and 1.60 [0.89-2.90], respectively). Our restricted cubic splines analyses indicated a pronounced linear association between SII and mortality only in diabetics. CONCLUSIONS: In AMI patients with DM, high SII is an independent predictor of poor survival and may be helpful for patient's risk stratification.

Carboxymethyl cellulose and carboxymethyl chitosan-based composite nanogel as a stable delivery vehicle for oyster peptides: Characterization, absorption and transport mechanism.

An oyster peptide (OPs)-loaded composite nanogel based on carboxymethyl cellulose and carboxymethyl chitosan (CMC@CMCS@OPs) was prepared, and the characterization, absorption and transport mechanism were further investigated. CMC@CMCS@OPs, a dense spherical microstructure with a diameter of ∼64 nm, which enhanced the thermal and digestive stabilities of individual OPs and improved its retention rate of hypoglycemic activity in vitro. The swelling response and in-vitro release profiles showed that CMC@CMCS@OPs could help OPs achieve targeted and controlled release in the intestine. In addition, CMC@CMCS@OPs had no cytotoxicity on Caco-2 cells, and its apparent permeability coefficients increased 4.70-7.45 times compared with OPs, with the absorption rate increased by 129.38 %. Moreover, the transcytosis of CMC@CMCS@OPs nanogel occurred primarily through the macropinocytosis pathway, endocytosis pathway and intestinal efflux transporter-mediated efflux. Altogether, these results suggested that CMC@CMCS@OPs nanogel could be as an effective OPs delivery device for enhancing its stability and absorption.

Association of stress hyperglycemia ratio with in-hospital new-onset atrial fibrillation and long-term outcomes in patients with acute myocardial infarction.

AIMS: To investigate the predictive value and prognostic impact of stress hyperglycemia ratio (SHR) for new-onset atrial fibrillation (NOAF) complicating acute myocardial infarction (AMI). MATERIALS AND METHODS: This retrospective study included 2145 AMI patients without AF history between February 2014 and March 2018. SHR was calculated using fasting blood glucose (mmol/L)/[1.59*HbA1c (%)-2.59]. The association between SHR and post-MI NOAF was assessed with multivariable logistic regression analyses. The primary outcome was a composite of cardiac death, heart failure hospitalisation, recurrent MI, and ischaemic stroke (MACE). Cox regression-adjusted hazard ratios with 95% confidence intervals (CI) were estimated for MACE. RESULTS: A total of 245 (11.4%) patients developed NOAF. In the multivariable logistic regression analyses, SHR (each 10% increase) was significantly associated with increased risks of NOAF in the whole population (OR: 1.05, 95% CI: 1.01-1.10), particularly in non-diabetic individuals (OR:1.08, 95% CI: 1.01-1.17). During a median follow-up of 2.7 years, 370 (18.5%) MACEs were recorded. The optimal cut-off value of SHR for MACE prediction was 1.119. Patients with both high SHR (≥1.119) and NOAF possessed the highest risk of MACE compared to those with neither high SHR nor NOAF after multivariable adjustment (HR: 2.18, 95% CI: 1.39-3.42), especially for diabetics (HR: 2.63, 95% CI: 1.41-4.91). Similar findings were observed using competing-risk models. CONCLUSIONS: SHR is an independent predictor of post-MI NOAF in non-diabetic individuals. Diabetic patients with both high SHR and NOAF had the highest risk of MACE, suggesting that therapies targeting SHR may be considered in these patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03533543.

Influences of two transport strategies on AMPK-mediated metabolism and flesh quality of shrimp (Litopenaeus vannamei).

BACKGROUND: Water-free transportation (WFT), as a novel strategy for express delivery of live shrimp (Litopenaeus vannamei), was developed recently. However, air exposure during this transportation arouses a series of abiotic stress to the shrimp. In the present study, the influences of WFT stress on glycolysis and lipolysis metabolism and meat quality (umami flavor and drip loss) were investigated in comparison with conventional water transportation (WT). RESULTS: The results showed that type II muscle fibers with the feature of anaerobic metabolism were dominated in shrimp flesh. In addition, the increments of intracellular Ca2+ was detected in WFT and WT, which then activated the AMP-activated protein kinase pathway and promoted the consumption of glycogen, as well as the accumulation of lactate and lipolysis, under the enzymolysis of hexokinase, pyruvate kinase, lactate dehydrogenase and adipose triglyceride lipase. Glycogen glycolyzed to latate. Meanwhile, ATP degraded along with glycolysis resulting in the generation of ATP-related adenosine phosphates such as inosine monophosphate with umami flavor and phosphoric acid. More remarkable (P < 0.05) physiological changes (except lactate dehydrogenase and lactate) were observed in WFT compared to WT. Additionally, the fatty acid profile also slightly changed. CONCLUSION: The transport stress induced significant energy metabolism changes of shrimp flesh and therefore effected the flesh quality. The intensifications of freshness (K-value) of shrimp flesh were detected as a result of ATP degradation, which were more pronounced after WFT. However, the drip loss of shrimp flesh was more significantly increased (P < 0.05) after WFT compared to WT. © 2023 Society of Chemical Industry.

Purification and characterization of a novel immunoregulatory peptide from Sipunculus nudus L. protein.

This study aimed to purify and characterize immunoregulatory peptides from Sipunculus nudus L. and to explore the underlying mechanisms. Ultrafiltration, gel filtration chromatography, and reverse phase high-performance liquid chromatography (RP-HPLC) were used to purify the peptide following enzymatic hydrolysis. Rates of lymphocyte proliferation and phagocytosis as well as nitric oxide (NO) production levels were used as indicators of immunoregulatory activity to screen the fractions. The amino acid sequence of the peptide, designated as SNLP, was identified as Arg-Val-Lys-Gly-Lys-Ile-Leu-Ala-Lys-Arg-Leu-Asn (RVKGKILAKRLN) by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Treatment with the synthetic SNLP increased the proliferation and phagocytosis of RAW 264.7 macrophages and promoted the secretion of tumor necrosis factor-ɑ (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and NO levels. The mRNA levels of these cytokines and iNOS were also increased by SNLP. Our results provide preliminary evidence suggesting that SNLP acts as a dual immunomodulatory peptide with immunostimulatory and anti-inflammatory activities. In summary, SNLP derived from Sipunculus nudus L. is a potent immunoregulatory peptide and represents a potential functional food or immunoregulatory drug.

Optimization of a Novel Tyrosinase Inhibitory Peptide from Atrina pectinata Mantle and Its Molecular Inhibitory Mechanism.

In order to realize the multi-level utilization of marine shellfish resources and to develop the potential biological activity of processing by-products of Atrina pectinata, gelatin was extracted from the mantle and the potential whitening effect of its enzymatic peptides was explored. Taking tyrosinase inhibitory activity as the evaluation index, the enzyme hydrolysate process was optimized by response-surface methodology, and the optimal enzyme hydrolysate conditions were as follows: pH 5.82, 238 min enzyme hydrolysate time, and temperature of 54.5 °C. Under these conditions, the tyrosinase inhibition activity of Atrina pectinata mantle gelatin peptide (APGP) was 88.6% (IC50 of 3.268 ± 0.048 mg/mL). The peptides obtained from the identification were separated by ultrafiltration and LC-MS/MS, and then four new peptides were screened by molecular docking, among which the peptide Tyr-Tyr-Pro (YYP) had the strongest inhibitory effect on tyrosinase with an IC50 value of 1.764 ± 0.025 mM. The molecular-docking results indicated that hydrogen bonding is the main driving force for the interaction of the peptide YYP with tyrosinase. From the Lineweaver-Burk analysis, it could be concluded that YYP is inhibitory to tyrosinase and exhibits a mixed mechanism of inhibition. These results suggest that YYP could be widely used as a tyrosinase inhibitor in whitening foods and pharmaceuticals.

Effects of molybdenum supply on microbial diversity and mineral nutrient availability in the rhizosphere soil of broad bean (Vicia Faba L.).

Molybdenum application holds the potential to enhance agricultural productivity. However, the precise impact on soil microbial diversity and mineral nutrient availability remains uncertain. In this study, we collected rhizosphere soil samples from different growth stages of broad beans. By analyzing mineral element contents, soil phosphorus and zinc fractions, as well as fungal and bacterial diversity, we observed that Mo application resulted in a reduction of soil Citrate‒P and HCl‒P content. This reduction led to an increase in available P content at different stages. Moreover, Mo application elevated root P concentration, but concurrently impeded the translocation of P to the shoots. Mo application also decreased the soil Exc‒Zn (exchangeable Zn) content while increasing the Res‒Zn (residual Zn) content, ultimately causing a decrease in available Zn content at different stages. Consequently, the Zn concentration within broad beans correspondingly decreased. Mo application fostered an augmentation in fungal richness and Shannon indices at the branching and podding stages. The analysis of microbial co-occurrence networks indicated that Mo application bolstered positive connectivity among fungal taxa. Remarkably, Mo significantly increased the abundance of Chaetomium, Leucosporidium, and Thielavia fungi. Spearman correlation analysis demonstrated a significant positive correlation between fungal diversity and soil available P content, as well as a notable negative correlation with soil available Zn content. These findings suggest that Mo application may modify the availability of soil P and Zn by influencing fungal diversity in the rhizosphere of crop soil, ultimately impacting nutrient accumulation within the grains.

Revealing the Mechanistic Basis of Regulation of Phosphorus Uptake in Soybean (Glycine max) Roots by Molybdenum: An Integrated Omics Approach.

While molybdenum (Mo) application can improve phosphorus (P) availability to plants by changing P speciation in the rhizosphere, the mechanistic basis of this process remains unclear. This work investigated the impact of various combinations of Mo and P treatments on root morphology, P and Mo uptake, and root transcriptome and metabolome. Mo application significantly increased soybean biomass and the number of lateral roots at both low (5 µmol) or normal (500 µmol) P levels and significantly improved P concentration and accumulation in Normal P treatment. Compared with the Normal P treatment, Low P significantly increased the number of roots, root surface area, and root acid phosphatase secretion. A total of 6811 Mo-responsive differentially expressed genes and 135 differential metabolites were identified at two P levels. At Low P, transcriptional changes significantly increased root synthesis and secretion of succinic acid, methylmalonic acid, and other organic acids as well as acid phosphatase, thereby increasing the conversion of soil aluminum-bound P and organic P into available P. At Normal P, Mo application increased P uptake mainly by increasing the number of lateral roots. Thus, Mo helps crops adapt to different P levels by regulating root anatomy and transcriptional and metabolic profiles of their roots.

Extract of Pfaffia glomerata Ameliorates Paroxetine-Induced Sexual Dysfunction in Male Mice and the Characterization of Its Phytoconstituents by UPLC-MS.

Pfaffia glomerata extract (PGE) has a variety of biological activities. However, its ameliorative effect on and exact working mechanism in male sexual dysfunction are still poorly understood. This study aims to evaluate the ameliorative effect of PGE on paroxetine (PRX)-induced sexual dysfunction in male mice and uses molecular docking technology to investigate its underlying mechanism. In this work, PRX-induced sexual dysfunction was caused and PGE was gavaged in mice for 28 days. The results show that PGE significantly improved the sexual performance of mice and reduced the damage to testicular tissues. Further studies showed that PGE restored serum sex hormones to normal levels and increased nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) levels as well as nitric oxide synthase (NOS) activity in penile tissues, while also decreasing phosphodiesterase-5 (PDE-5) activity, thereby maintaining normal penile erection in mice. In addition, PGE improved the activities of enzymes (LDH, ACP, and ALP) related to energy metabolism in the testis and significantly increased sperm count and viability in mice. Furthermore, the molecular docking results show that all eight compounds in PGE could form a stable complex with PDE-5 and inhibit the activity of PDE-5. In conclusion, PGE had an ameliorative effect on PRX-induced sexual dysfunction, suggesting that PGE has a potential protective effect on male sexual health.

Functional, physicochemical, and structural properties of the hydrolysates derived from the abalone (Haliotis discus subsp hannai Ino) foot muscle proteins.

This study was conducted to investigate functional, physicochemical, and structural properties of abalone foot muscle proteins (AFPs) and their hydrolysates (HAFPs) obtained using animal protease (HA), papain (HPP), and Protamex® (HP) at different time points. The HA-hydrolysate obtained after 0.5 h of treatment demonstrated the highest solubility at pH 7.0 (84.19%); the HPP-hydrolysate at 4 h exhibited the highest degree of hydrolysis (11.4%); the HPP-hydrolysate at 0.5 h had the highest oil holding capacity (2.62 g/g) and emulsion stability index (39.73 min), and the HP-hydrolysate at 4 h had the highest emulsifying activity index (93.23 m2/g) and foaming stability (91.45%); Regarding the physicochemical properties, the HPP-hydrolysates revealed the largest particle size, higher absolute zeta potential, and superior interfacial activity. Structural characterization demonstrated the enzymolysis-based changes in the composition and the secondary structure of the AFPs. These results provide practical support for the theoretical basis of the use of AFPs as a source of nutritive proteins in the food industry.

Study on the Regulation Mechanism of Quality Deterioration Due to Chilling Stress and Dry Exposure during Anhydrous Storage and Transportation of Yesso Scallop Patinopecten yessoensis.

In this paper, the quality change of Yesso scallop (Patinopecten yessoensis) in the process of anhydrous storage and transportation after cold acclimation and induced dormancy was studied, and the regulation mechanism of quality degradation during storage and transportation in the process of gradient chilling stress and drying exposure was further explored. The results show that, when transferred from hydrous to anhydrous states, the breathing pattern of the scallops changed from aerobic to anaerobic. Their gill filaments were altered and their apparent vitality constantly declined, which was reflected by the edge shrinkage of the pallium and the direct proportions of the edge reduction rate and the stimulus response period. After being in the anhydrous state for 4 d, the AEC value dropped to 67.59%. At this time, if they were placed under hydration again, the scallops resumed a good growth state. By proteomics analysis, it was revealed that cold acclimation and dry exposure mainly led to changes in biological functions and pathways, such as mitochondrial inner membrane and ATP hydrolysis activity. In addition, it can be seen from the functional annotation and enrichment analysis of the metabolite KEGG that cold acclimation promoted the purine metabolism of scallops, while dry exposure inhibited the metabolism of saturated fatty acids. In this study, the infrared sensing mode was used for the first time, too, in order to record the heart-rate changes of the scallops during circulation, which shows that non-destructive vitality monitoring of Lamellibranchia is feasible.

Effect of Drying Process on the Formation of the Characteristic Flavor of Oyster (Crassostrea hongkongensis).

Oysters are nutritious and tasty but difficult to store. Drying can extend the storage period of oysters and give them a unique flavor. In this study, the effects of four drying procedures, namely, vacuum freeze drying (VFD), vacuum drying (VD), natural sun-drying (NSD), and hot air drying (HAD), on the flavor characteristics of oysters (Crassostrea hongkongensis) were investigated using blanched oysters as a control (CK). Results showed that HAD produced more free amino acids than the other methods, but VFD retained the most flavor nucleotides. Compared with cold drying (VFD), hot drying (VD, NSD, and HAD) increased the abundance of organic acids, betaine, and aroma substances. Glutamic acid, alanine, AMP, hexanal, octanal, heptanal, (E, E)-2,4-heptadienal, (E)-2-decenal, nonanal, etc., are defined as the characteristic flavor compounds of dried oysters, with umami, sweet, green, fatty, and fruity aromas being the main organoleptic attributes of dried oysters. Glutamic acid, glycine, betaine, IMP, pentanal, ethyl heptanoate, (E, Z)-2,4-nonadienal, 1-octen-3-one, 2-hexenal, 2-octenal, hexanal, decanal were defined as markers to distinguish different drying methods. Overall, HAD showed improved flavor qualities and characteristics and was better suited for the highly commercialized production of dried oysters.

Maternal Western diet mediates susceptibility of offspring to Crohn's-like colitis by deoxycholate generation.

BACKGROUND: The Western dietary pattern, characterized by high consumption of fats and sugars, has been strongly associated with an increased risk of developing Crohn's disease (CD). However, the potential impact of maternal obesity or prenatal exposure to a Western diet on offspring's susceptibility to CD remains unclear. Herein, we investigated the effects and underlying mechanisms of a maternal high-fat/high-sugar Western-style diet (WD) on offspring's susceptibility to 2,4,6-Trinitrobenzenesulfonic acid (TNBS)-induced Crohn's-like colitis. METHODS: Maternal dams were fed either a WD or a normal control diet (ND) for eight weeks prior to mating and continued throughout gestation and lactation. Post-weaning, the offspring were subjected to WD and ND to create four groups: ND-born offspring fed a normal diet (N-N) or Western diet (N-W), and WD-born offspring fed a normal (W-N) or Western diet (W-W). At eight weeks of age, they were administered TNBS to induce a CD model. RESULTS: Our findings revealed that the W-N group exhibited more severe intestinal inflammation than the N-N group, as demonstrated by a lower survival rate, increased weight loss, and a shorter colon length. The W-N group displayed a significant increase in Bacteroidetes, which was accompanied by an accumulation of deoxycholic acid (DCA). Further experimentation confirmed an increased generation of DCA in mice colonized with gut microbes from the W-N group. Moreover, DCA administration aggravated TNBS-induced colitis by promoting Gasdermin D (GSDMD)-mediated pyroptosis and IL-1beta (IL-1ß) production in macrophages. Importantly, the deletion of GSDMD effectively restrains the effect of DCA on TNBS-induced colitis. CONCLUSIONS: Our study demonstrates that a maternal Western-style diet can alter gut microbiota composition and bile acid metabolism in mouse offspring, leading to an increased susceptibility to CD-like colitis. These findings highlight the importance of understanding the long-term consequences of maternal diet on offspring health and may have implications for the prevention and management of Crohn's disease. Video Abstract.

Prognostic implications of the 4S-AF scheme to characterize new-onset atrial fibrillation after myocardial infarction.

AIMS: The 4S-AF scheme (Stroke risk [St], Symptom severity [Sy], Severity of atrial fibrillation burden [Sb], Substrate [Su]) is a novel approach for the holistic characterization of AF. We aimed to investigate the prognostic implications of the 4S-AF scheme score in acute myocardial infarction (AMI) patients with new-onset atrial fibrillation (NOAF). METHODS: We included 262 patients with post-MI NOAF who had complete data for the 4S-AF scheme evaluation between February 2014 and March 2018. The 4S-AF scheme score was calculated as a sum of each domain with a maximum of 9. The primary outcome was all-cause death. RESULTS: Of 262 patients (66.0% males, mean age 74.5 ± 10.4 years) were analyzed. The mean 4S-AF scheme score was 5.0 ± 1.6. There were 62 (27.3%) all-cause deaths within a median follow-up of 2.6 years. According to multivariable Cox regression models, each 1-point increase in the 4S-AF scheme score was significantly associated with 39% increased all-cause mortality (HR: 1.39, 95% CI: 1.16-1.67, P<0.001), which was mainly driven by the Sb (HR: 1.43, 95%CI: 1.05-1.95, P = 0.025) and Su (HR: 1.53, 95%CI: 1.17-2.02, P = 0.002) domains. Adding the 4S-AF scheme score on top of the Global Registry of Acute Coronary Events score could significantly improve its discriminative capability (C-index from 0.713 to 0.761, P = 0.039) and reclassification performance (continuous net reclassification improvement: 41.0% [95%CI: 12.5-69.6]; integrated discrimination improvement: 5.1% [95%CI: 2.2-8.1]) for all-cause mortality. CONCLUSIONS: Characterization of NOAF using the 4S-AF scheme aids in the risk stratification of AMI patients with NOAF.

TRIM21 deficiency protects against atrial inflammation and remodeling post myocardial infarction by attenuating oxidative stress.

Atrial remodeling is a major contributor to the onset of atrial fibrillation (AF) after myocardial infarction (MI). Tripartite motif-containing protein 21 (TRIM21), an E3 ubiquitin protein ligase, is associated with pathological cardiac remodeling and dysfunction. However, the role of TRIM21 in postmyocardial infarction atrial remodeling and subsequent AF remains unclear. This study investigated the role of TRIM21 in post myocardial infarction atrial remodeling using TRIM21 knockout mice and explored the underlying mechanisms by overexpressing TRIM21 in HL-1 atrial myocytes using a lentiviral vector. The expression of TRIM21 in the left atrium of the mouse MI model was significantly elevated. TRIM21 deficiency alleviated MI-induced atrial oxidative damage, Cx43 downregulation, atrial fibrosis and enlargement, and abnormalities in electrocardiogram parameters (prolongation of the P-wave and PR interval). TRIM21 overexpression in atrial myocyte HL-1 cells further enhanced oxidative damage and Cx43 downregulation, whereas these effects were reversed by the reactive oxygen species scavenger N-acetylcysteine. The findings suggest that TRIM21 likely induces Nox2 expression mechanistically by activating the NF-κB pathway, which in turn leads to myocardial oxidative damage, inflammation, and atrial remodeling.