HF Group Research Articles

Effects of Dietary Energy Profiles on Energy Metabolic Partition and Excreta in Songliao Black Pigs Under Different Ambient Temperature.

In order to further reveal the special characteristics of energy metabolism and the characteristics of energy requirements of fattening pigs grown in low-temperature environments, this study used a 2 × 2 × 2 factorial array of treatments, which harnessed two temperatures (low-temperature, LT group: 10 °C; normal-temperature, NT group: 20 °C), two feed energy levels (normal-energy, NE group: 14.02 MJ/kg metabolic energy; high-energy, HE group: 15.14 MJ/kg metabolic energy), and two feed energy sources (LF group: low fat, HF group: high fat). Thirty-two Songliao black fattening pigs with an initial body weight of 85.48 ± 2.31 kg were completely randomized into eight treatment groups, with four replicates in each treatment group and one pig in each replicate. The pigs were placed in a respiratory metabolic chamber for a 6-day trial. There was one pig per respiratory metabolic chamber in a single cage. The results showed that the average daily weight gain in the normal-temperature, high-energy, and high-fat groups was higher than that of the low-temperature, normal-energy, and low-fat groups (p < 0.05). The fat deposition rate, protein oxidation, and fat oxidation of the high-fat group were higher than those of the low-fat group (p < 0.05). The energy digestibility, protein digestibility, and fat digestibility in the high-fat group were higher than those in the normal-energy group (p < 0.05). The fat digestibility and energy deposition rate in the high-fat group were higher than those in the low-fat group (p < 0.05). The respiratory quotient in the high-energy group was lower than that in the normal-energy group (p < 0.05), and the respiratory quotient in the high-fat group was lower than that in the low-fat group (p < 0.05). There was an interaction between temperature and energy sources in terms of the respiratory quotient, fat oxidation, blood urea nitrogen content, and glucose content (p < 0.05). Appropriately increasing the energy level of the diet and improving the energy structure of the feed (increasing the level of fats and oils) will benefit Songliao black fattening pigs by increasing their energy use efficiency and at the same time reducing greenhouse gas CO2 emissions, and these changes are more pronounced in cold environments.

Comparative Analysis of Shear Bond Strength in Orthodontic Brackets Between Milled and 3D-Printed Definitive CAD/CAM Restorations

Objective: The objective of this study was to evaluate the effect of different surface treatment methods on the shear bond strength (SBS) of metal brackets bonded to two types of CAD/CAM composite restorations: milled and 3D-printed. Materials and Methods: A total of 160 flat-shaped specimens (10 × 10 × 2 mm3) were prepared from four different CAD/CAM composites; two milled (Lava Ultimate™ [LU] and Grandio™ [GR]) and two 3D-printed (Crowntec™ [CT] and C&amp;B Permanent™ [CB]). These specimens underwent thermocycling (5000 cycles at 5–55 °C), then were categorized based on the surface treatment into four groups (n = 10): Group C (control, no surface treatment), Group HF (treated with 9.6% hydrofluoric acid), Group DB (mechanical roughening by a diamond bur), and Group SB (sandblasting using aluminum oxide). Metal brackets were bonded using Transbond XT Primer and universal adhesive, stored in artificial saliva for 24 h, then thermocycled again. Shear bond strength (SBS) was tested using a universal testing machine until bracket debonding occurred. The adhesive remnant index (ARI) was assessed using a stereomicroscope to quantify the residual adhesive following debonding. Result: Regarding material, GR and LU restorations had significantly higher SBS values compared to CT and CB, ranging from 13.90 MPa to 20.35 MPa. Regarding surface treatment, SB and HF groups showed significantly higher SBS values. The ARI scores showed different adhesive modes of failure, with higher instances of scores 0 and 1, which indicate no or minimal adhesive remaining. Conclusions: Both milled and 3D-printed materials had adequate SBS for clinical use, with milled materials showing superior results. Surface treatments like sandblasting and HF significantly improved bond strength, with adhesive failure being common.

Lipoprotein(a) and Other Risk Factors in Dyslipidemic Patients with and without Heart Failure.

IntroductionWe aimed to assess the differences between patients with or without HF regarding lipid profile including Lp(a) as well as comorbidities and pharmacotherapy.Material and methodsWe included 510 consecutive patients from the PMMHRI-Lp(a) Registry.ResultsHF was diagnosed in 59 patients (11.57%). Higher Lp(a) levels were observed in HF group, but it was not statistically significant. The multivariable analysis revealed four significant HF, including higher category of Lp(a) (OR 2.00, 95%CI:1.19-3.35, p=0.009).ConclusionsLp(a) may play a more significant role than other lipid parameters in HF patients, warranting further investigation and emphasizing the need to measure Lp(a) in these patients.

Diet rich in soluble dietary fibres increases excretion of perfluorooctane sulfonic acid (PFOS) in male Sprague-Dawley rats

Perfluorooctane sulfonic acid (PFOS) belongs to a large group of anthropogenic compounds with high persistency named per- and polyfluorinated substances (PFAS). Widespread use from industry to household appliances and food-contact materials contributes to PFAS exposure with food as the primary source. Association studies suggest that vegetables and fibre rich diet may reduce PFOS levels in humans, but experimental data remain limited. Here, we investigated PFOS uptake and wash-out after seven days of PFOS (3 mg/kg/day) in two groups of rats (N = 12 per group) fed diets either high (HF) or low (LF) in soluble dietary fibres. Two control groups (N = 12/group) were fed the same diets without PFOS. Changes in pH and transit time were monitored alongside intestinal and faecal microbiota composition. We quantified systemic and excreted, linear and branched PFOS. Results revealed significantly lower pH and faster intestinal transit in the HF groups. Importantly, HF rats had lower serum PFOS concentrations and higher PFOS concentrations in caecal content and faeces, indicating a more efficient excretion on the fibre rich diet. In both dietary groups, PFOS affected the gut microbiota composition. Our results suggest that a diet rich in soluble dietary fibres accelerates excretion of PFOS and lowers PFOS concentration in serum.

Dissociation between liver fat content and fasting metabolic markers of selective hepatic insulin resistance in humans.

Fasting hyperglycemia and hypertriglyceridemia are characteristic of insulin resistance (IR) and rodent work has suggested this may be due to selective hepatic IR; defined by increased hepatic gluconeogenesis and de novo lipogenesis (DNL), but this has not been shown in humans. Cross-sectional study in men and women across a range of adiposity. Medication-free participants (n=177) were classified as normoinsulinemic (NI) or hyperinsulinemic (HI) and as having low (LF) or high (HF) liver fat content measured by magnetic resonance spectroscopy. Fractional gluconeogenesis (frGNG) and hepatic DNL were measured using stable isotope tracer methodology following an overnight fast. Although HI and HF groups had higher fasting plasma glucose and triglyceride concentrations when compared to NI and LF groups respectively, there was no difference in frGNG. However, HF participants tended to have lower frGNG than LF participants. HI participants had higher DNL compared to NI participants but there was no difference observed between liver fat groups. Taken together, we found no metabolic signature of selective hepatic IR in fasting humans. DNL may contribute to hypertriglyceridemia in individuals with HI but not those with HF. Glycogenolysis and systemic glucose clearance may have a larger contribution to fasting hyperglycemia than gluconeogenesis, especially in those with HF and these pathways should be considered for therapeutic targeting.

Influence of supplementation with probiotic bacteria Lactiplantibacillus plantarum and Latilactobacillus curvatus on selected parameters of duodenum iron metabolism in rats on a high-fat, iron-deficient diet

ObjectivesA high-fat, iron (Fe)-deficient Western diet induces obesity and dysregulates Fe metabolism. We compared the influence of Lactiplantibacillus plantarum and Latilactobacillus curvatus with and without Fe supplementation on duodenal Fe uptake under high-fat diet conditions. MethodsRats were fed a high-fat diet (HF group) or high-fat, Fe-deficient diet (HFDEF group) or control diet (C group) for 8 wk. For the next 8 wk, the rats in the C and HF groups continued on the same diet, whereas the rats in the HFDEF group were divided into six groups and fed high-fat, Fe-deficient diet combinations with L. plantarum (Lp), L. curvatus (Lc), and Fe supplementation (HFDEF, HFDEFFe, HFDEFLp, HFDEFLc, HFDEFFeLp, HFDEFFeLc). Duodenum and serum samples were collected for analysis. ResultsIn the duodenum, the Fe content was higher in the HFDEFFeLp and HFDEFFeLc groups; the ferroportin level was higher in the HFDEFFeLp and HFDEFFeLc groups versus the HF group; the divalent metal transporter 1 level was higher in the HFDEFFeLc group versus the C and HF groups; and duodenal cytochrome B was higher in the HFDEFLc versus all the other groups. In addition, duodenal expression of the solute carrier family 11 member 2 gene was higher in the HFDEF group versus the C, HF, HFDEFFe, HFDEFFeLp, and HFDEFFeLc groups; that of the TFRC gene was higher in the HFDEFFeLc group versus the C, HF, HFDEF, and HFDEFFe groups; and that of the HJV gene was higher in the HFDEFFeLp group versus the C, HF, HFDEF, HFDEFFe, and HFDEFLc groups. ConclusionsL. plantarum and L. curvatus supplementation shows some potential to enhance duodenal cellular Fe uptake in rats on a high-fat, Fe-deficient diet.

Interplay between fluorine and cadmium on intestinal accumulation, oxidative stress, permeability and inflammatory response in rats

Fluorine (F) and Cadmium (Cd) have given rise to public concern regarding their adverse impacts on the environment and human beings. Yet, the toxic interplay between F and Cd on the intestine is still vague. Aiming to investigate the role of F on Cd-damaged intestine, a total of five groups of 30 SD rats were picked at random to be gavaged for 90 days: Control group (Ultra-pure water), Cd (Cd 1 mg/kg), Cd+LF (Cd 1 mg/kg+F 15 mg/kg), Cd+MF (Cd 1 mg/kg+F 45 mg/kg), and Cd+HF (Cd 1 mg/kg+F 75 mg/kg). It demonstrated that Cd enriched in the intestine and disordered intestinal barrier of rats. Interestingly, two side effects of F were observed resisting to the Cd toxicity. The Cd levels in colon contents were attenuated by 45.45 %, 28.11 %, and 19.54 % by F supplement, respectively. In the Cd+LF group, SOD, GSH-Px, and CAT activities elevated by 0.93, 1.76, and 1.78 times, respectively, and the MDA content reduced 0.67 times; the expressions of NQO1, SOD2, and GSH-Px mRNA markedly enhanced, as well as the Keap1 mRNA significantly decreased. Nevertheless, all indexes above in the Cd+HF group showed the opposite trends. Furthermore, LPS levels decreased by 45.93 % for the Cd+LF group and increased by 12.70 % in that the Cd+HF group. The ZO-1 expression in the Cd+LF group increased, whereas the Cd+HF group's expressions of Claudin-1, Occludin, and ZO-1 were all diminished by 35.46 %, 27.23 %, and 16.32 %, respectively. Moreover, the levels of TNF-α, IL-1β and TLR-4 decreased and IL-10 level promoted, while all showed opposite trends in the Cd+HF group. Collectively, it indicated there is a twofold interplay between F and Cd on intestinal damage and mainly depends on F dosages.

Single-cell transcriptomics reveals writers of RNA modification-mediated immune microenvironment and cardiac resident Macro-MYL2 macrophages in heart failure

BackgroundHeart failure (HF), which is caused by cardiac overload and injury, is linked to significant mortality. Writers of RNA modification (WRMs) play a crucial role in the regulation of epigenetic processes involved in immune response and cardiovascular disease. However, the potential roles of these writers in the immunological milieu of HF remain unknown.MethodsWe comprehensively characterized the expressions of 28 WRMs using datasets GSE145154 and GSE141910 to map the cardiac immunological microenvironment in HF patients. Based on the expression of WRMs, the immunological cells in the datasets were scored.ResultsSingle-cell transcriptomics analysis (GSE145154) revealed immunological dysregulation in HF as well as differential expression of WRMs in immunological cells from HF and non-HF (NHF) samples. WRM-scored immunological cells were positively correlated with the immunological response, and the high WRM score group exhibited elevated immunological cell infiltration. WRMs are involved in the differentiation of T cells and myeloid cells. WRM scores of T cell and myeloid cell subtypes were significantly reduced in the HF group compared to the NHF group. We identified a myogenesis-related resident macrophage population in the heart, Macro-MYL2, that was characterized by an increased expression of cardiomyocyte structural genes (MYL2, TNNI3, TNNC1, TCAP, and TNNT2) and was regulated by TRMT10C. Based on the WRM expression pattern, the transcriptomics data (GSE141910) identified two distinct clusters of HF samples, each with distinct functional enrichments and immunological characteristics.ConclusionOur study demonstrated a significant relationship between the WRMs and immunological microenvironment in HF, as well as a novel resident macrophage population, Macro-MYL2, characterized by myogenesis. These results provide a novel perspective on the underlying mechanisms and therapeutic targets for HF. Further experiments are required to validate the regulation of WRMs and Macro-MYL2 macrophage subtype in the cardiac immunological milieu.

Bisphenol S exposure induces cardiac remodeling and aggravates high-fat diet-induced cardiac hypertrophy in mice

Bisphenol S (BPS) is widely used in the manufacture products and increase the risk of cardiovascular diseases. The effect of the association between obesity and BPS on cardiac outcomes is still unknown. Male C57BL/6 mice were divided into standard chow diet (SC; 15 kJ/g), standard chow diet + BPS (SCB), high-fat diet (HF; 21 kJ/g), and high-fat diet + BPS (HFB). Over 12 weeks, the groups were exposed to BPS through drinking water (dose: 25 μg/kg/day) and/or a HF diet. We evaluated: body mass (BM), total cholesterol, systolic blood pressure (SBP), left ventricle (LV) mass, and cardiac remodeling. In the SCB group, BM, total cholesterol, and SBP increase were augmented in relation to the SC group. In the HF and HFB groups, these parameters were higher than in the SC and SCB groups. Cardiac hypertrophy was evidenced by augmented LV mass and wall thickness, and ANP protein expression in all groups in comparison to the SC group. Only the HFB group had a thicker LV wall than SCB and HF groups, and increased cardiomyocyte area when compared with SC and SCB groups. Concerning cardiac fibrosis, SCB, HF, and HFB groups presented higher interstitial collagen area, TGFβ, and α-SMA protein expression than the SC group. Perivascular collagen area was increased only in the HF and HFB groups than SC group. Higher IL-6, TNFα, and CD11c protein expression in all groups than the SC group evidenced inflammation. All groups had elevated CD36 and PPARα protein expression in relation to the SC group, but only HF and HFB groups promoted cardiac steatosis with increased perilipin 5 protein expression than the SC group. BPS exposure alone promoted cardiac remodeling with pathological concentric hypertrophy, fibrosis, and inflammation. Diet-induced remodeling is aggravated when associated with BPS, with marked hypertrophy, alongside fibrosis, inflammation, and lipid accumulation.

Effects of cardiac rehabilitation on in vivo nailfold microcirculation in patients with cardiovascular disease.

This study aimed to explore the impact of cardiac rehabilitation (CR) on in vivo and ex vivo microcirculation, exercise capacity, and oxidative stress in patients with cardiovascular disease (CVD). The study included patients with acute coronary syndrome (ACS; n = 45; age, 69.0 ± 14.1 years) and heart failure (HF; n = 66; age, 77.3 ± 10.7 years) who underwent supervised CR during hospitalization. The control group comprised patients without CVD (NCVD; n = 20; age, 75.9 ± 11.2 years). In vivo microcirculatory observations using nailfold video capillary endoscopy at rest and during hyperemia, exercise capacity, and oxidative stress were assessed at baseline and 12 weeks after discharge. Baseline capillary densities were significantly lower in the ACS (5.0 ± 1.7 capillaries/mm2) and HF (4.9 ± 1.7 capillaries/mm2) groups than in the NCVD group (6.5 ± 1.1 capillaries/mm2, p < 0.01). Similarly, capillary density during reactive hyperemia was significantly lower in the ACS (5.8 ± 1.7 capillaries/mm2) and HF (5.4 ± 1.8 capillaries/mm2) groups than in the NCVD group (7.3 ± 1.4 capillaries/mm2, p < 0.01). Patients with ACS and HF had increased capillary densities at 12 weeks compared with at baseline (p < 0.05). This improvement was particularly pronounced among post-discharge outpatient CR participants (n = 20). Grip strength, exercise capacity, and oxidative stress improved at 12 weeks. Baseline capillary density changes were positively correlated with grip strength changes (r = 0.45, p < 0.001). CR significantly improved nailfold capillary density in patients with ACS and HF 12 weeks after discharge.

Masseteric-facial anastomosis and hypoglossal-facial anastomosis after lateral skull base and middle ear surgery.

Lateral skull base (LSB) and middle ear pathologies often involve the facial nerve (FN), and their treatment may require FN sacrifice. Cases with unidentifiable proximal stump or intact FN with complete FN palsy, necessitate FN anastomosis with another motor nerve in order to restore innervation to the mimicking musculature. The results of hypoglossal-to-facial nerve anastomosis (HFA) and masseteric-facial nerve anastomosis in patients with facial paralysis after middle ear and LSB surgeries, are presented and compared. Adult patients with total definitive facial paralysis after middle ear or LSB surgery undergoing facial nerve reanimation through hypoglossal or masseteric transfer anastomosis were enrolled. The facial nerve function was graded according to the House Brackmann grading system (HB). The facial function results at 3months, 6months, 12months, 18months and at the last follow up (more than 18months) are compared. 153 cases of LSB and middle ear surgery presented postoperative facial palsy and underwent facial nerve reanimation surgery with HF in 85 patients (55.5%) and MF in 68 patients (44.5%). The duration of the FN palsy before reconstructive surgery was inversely associated to better FN results, in particular with having a grade III HB (p = 0.003). Both techniques had significantly lower HB scores when an interval between palsy onset and reanimation surgery was 6months or less (MF p = 0.0401; HF p = 0.0022). Patients who underwent a MF presented significant improvement of the FN function at 3months from surgery (p = 0.0078). At the last follow-up, 63.6% recovered to a grade III HB and 22.7% to a grade IV. On the other hand, the first significant results obtained in the HF group were at 6months from surgery (p < 0.0001). 67.8% of patients had a grade III HB after a HF at the last follow-up, 28.8% a grade IV. FN grading at 6months from surgery was significantly lower in the MF group compared to the HF (p = 0.0351). The two techniques had statistically similar results at later follow-up evaluations. MF was associated to initial superior results, presenting significant facial recovery at 3months, and significantly better functional outcomes at 6months from surgery compared to HF. Although later results were not significantly different in this study, earlier results have an important role in order to limit the duration of risk of corneal exposure.

Antrodia camphorata Supplementation during Early Life Alters Gut Microbiota and Inhibits Young-Onset Intestinal Tumorigenesis in APC1638N Mice Later in Life.

Young-onset colorectal cancer is an increasing concern worldwide due to the growing prevalence of Westernized lifestyles in childhood and adolescence. Environmental factors during early life, particularly early-life nutrition, significantly contribute to the increasing incidence. Recently, there have been reports of beneficial effects, including anti-inflammation and anti-cancer, of a unique fungus (Antrodia camphorate, AC) native to Taiwan. The objective of this study is to investigate the impact of AC supplementation in early life on the development of young-onset intestinal tumorigenesis. APC1638N mice were fed with a high-fat diet (HF) at 4-12 weeks of age, which is equivalent to human childhood/adolescence, before switching to a normal maintenance diet for an additional 12 weeks up to 24 weeks of age, which is equivalent to young to middle adulthood in humans. Our results showed that the body weight in the HF groups significantly increased after 8 weeks of feeding (p < 0.05). Following a switch to a normal maintenance diet, the change in body weight persisted. AC supplementation significantly suppressed tumor incidence and multiplicity in females (p < 0.05) and reduced IGF-1 and Wnt/β-catenin signaling (p < 0.05). Moreover, it altered the gut microbiota, suppressed inflammatory responses, and created a microenvironment towards suppressing tumorigenesis later in life.

Dietary Anthocyanins Mitigate High-Fat Diet-Induced Hippocampal Inflammation in Mice

BackgroundObesity and consumption of high-fat diets (HFD) are associated with intestinal permeabilization and increased paracellular transport of endotoxins, which can promote neuroinflammation. Inflammation can affect the hypothalamic pituitary adrenal (HPA) axis, which controls responses to stress and downregulates the brain-derived neurotrophic factor (BDNF), which can promote anxiety and depression, conditions frequently found in obesity. We previously showed that consumption of anthocyanins (AC) mitigate HFD-induced insulin resistance, intestinal permeability, and inflammation. ObjectivesThis study investigated if a dietary supplementation with a cyanidin- and delphinidin-rich extract (CDRE) could counteract HFD/obesity-induced hippocampal inflammation in mice. MethodsC57BL/6J male mice were fed for 14 wk on one of the following diets: 1) a control diet containing 10% total calories from fat (C), 2) a control diet supplemented with 40 mg AC/kg body weight (BW) (CAC), 3) a HFD containing 60% total calories from fat (lard) (HF), or 4) the HFD supplemented with 2, 20, or 40 mg AC/kg BW (HFA2, HFA20, and HFA40, respectively). In plasma and in the hippocampus, parameters of neuroinflammation and the underlying cause (endotoxemia) and consequences (alterations to the HPA and BDNF downregulation) were measured. ResultsConsumption of the HFD caused endotoxemia. Accordingly, hippocampal Tlr4 mRNA levels were 110% higher in the HF group, which were both prevented by CDRE supplementation. Consumption of the HFD also caused: 1) microgliosis and increased expression of genes involved in neuroinflammation, that is, Iba-1, Nox4, Tnfα, and Il-1β, 2) alterations of HPA axis regulation, that is, with low expression of mineralocorticoid (MR) and glucocorticoid (GR) receptors; and 3) decreased Bdnf expression. Supplementation of HFD-fed mice with CDRE mitigated neuroinflammation, microgliosis, and MR and BDNF decreases. ConclusionsCDRE supplementation mitigates the negative effects associated with HFD consumption and obesity in mouse hippocampus, in part by decreasing inflammation, improving glucocorticoid metabolism, and upregulating BDNF.

Alisma Orientalis Extract Ameliorates Hepatic Iron Deregulation in MAFLD Mice via FXR-Mediated Gene Repression.

Iron is a vital trace element for our bodies and its imbalance can lead to various diseases. The progression of metabolic-associated fatty liver disease (MAFLD) is often accompanied by disturbances in iron metabolism. Alisma orientale extract (AOE) has been reported to alleviate MAFLD. However, research on its specific lipid metabolism targets and its potential impact on iron metabolism during the progression of MAFLD remains limited. To establish a model of MAFLD, mice were fed either a standard diet (CON) or a high-fat diet (HFD) for 9 weeks. The mice nourished on the HFD were then randomly assigned to the HF group and the HFA group, with the HFA group receiving AOE by gavage on a daily basis for 13 weeks. Supplementation with AOE remarkably reduced overabundant lipid accumulation in the liver and restored the iron content of the liver. AOE partially but significantly reversed dysregulated lipid metabolizing genes (SCD1, PPAR γ, and CD36) and iron metabolism genes (TFR1, FPN, and HAMP) induced by HFD. Chromatin immunoprecipitation assays indicated that the reduced enrichment of FXR on the promoters of SCD1 and FPN genes induced by HFD was significantly reversed by AOE. These findings suggest that AOE may alleviate HFD-induced disturbances in liver lipid and iron metabolism through FXR-mediated gene repression.

Recast frequency and the acquisition of English articles in a computer-mediated context

This study examines the role of recast frequency and its effectiveness in the acquisition of English articles in a computer-mediated context. Sixty-one pre-intermediate university language learners in Turkey were randomly divided into four main groups: high frequency recast (HF), low frequency recast (LF), test control, and task control groups. The learners in the HF and LF recast groups completed five and two tasks, respectively, in a video-conferencing environment and received oral recasts on their incorrect use of English articles. Learners in the test control group only took the pre and posttests, and learners in the task control group completed five tasks without receiving feedback on the target structure. The outcome was measured through online picture description and error correction tasks. Findings showed that in the picture description task, learners in the HF group performed significantly better than those in the LF recast group and the control groups. In the error correction task, the results revealed a short-term advantage for learners in the HF group, which faded away in the delayed posttest. Significant correlations were also found between the recast frequency and learners’ score improvement in the immediate and delayed picture description tasks but not in the error correction tasks. These results suggest that recast quantity may play an important role in improving learners’ accuracy of their oral production.

Reparative effects after low-dose radiation exposure: Inhibition of atherosclerosis by reducing NETs release

ObjectiveThe cardiovascular system effects of environmental low-dose radiation exposure on radiation practitioners remain uncertain and require further investigation. The aim of this study was to initially investigate and explore the mechanisms by which low-dose radiation may contribute to atherosclerosis through a multi-omics joint comprehensive basic experiment. MethodsWe used WGCNA and differential analyses to identify shared genes and potential pathways between radiation injury and atherosclerosis sequencing datasets, as well as tissue transcriptome immune infiltration level extrapolation and single-cell transcriptome data correction using the CIBERSORT deconvolution algorithm. Animal models were constructed by combining a high-fat diet with 5 Gy γ-ray whole-body low-dose ionizing radiation. The detection of NETs release was validated by enzyme-linked immunosorbent assay. ResultsAnalysis reveals shared genes in both datasets of post-irradiation and atherosclerosis, suggesting that immune system neutrophils may be a key node connecting radiation to atherosclerosis. NETs released by neutrophil death can influence the development of atherosclerosis. Animal experiments showed that the number of neutrophils decreased (P < 0.05) and the concentration of NETs reduced after low-dose radiation compared with the control group, and the concentration of NETs significantly increased (P < 0.05) in the HF group. Endothelial plaques were significantly increased in the high-fat feed group and significantly decreased in the low-dose radiation group compared with the control group. ConclusionsLong-term low-dose ionizing radiation exposure stimulates neutrophils and inhibits their production of NETs, resulting in inhibition of atherosclerosis.

P-638 Paternal Consumption of Caloric and Non-Caloric Sweeteners is Associated with Sex-Specific Differences in Reproductive outcomes in offspring

Abstract Study question Does paternal pre-conception consumption of caloric or non-caloric sweeteners (NCS) coupled with high fat diets (HFD) predispose offspring to early puberty onset in mice? Summary answer Paternal prenatal consumption of the NCS Rebaudioside A(RebA) resulted in early puberty onset in female offspring only compared to water and caloric sweetener groups. What is known already A growing body of evidence suggests that the paternal diet also influences health and disease onset in offspring. Early puberty onset is associated with metabolic syndrome, type 2 diabetes, and cardiovascular disease later in adulthood. NCS are often promoted as heathier alternatives to caloric sweeteners. Evidence examining the impact of NCS on male reproductive function and offspring health outcomes, including pubertal timing are lacking. Few studies have shown maternal HFD can contribute to early puberty onset in female offspring however to our knowledge this is the first study to investigate paternal diet and offspring reproductive outcomes. Study design, size, duration 32 6-week-old C57/BL6 male mice were randomly assigned to receive a control diet (CD) or HF plus water (Con), fructose (Fr), Acesulfame K (Ak) or RebA). After 8 weeks, mice were mated. Litters were standardised to 2 males and 2 females per group and fed a standard laboratory diet. Participants/materials, setting, methods Puberty onset was measured in females by vaginal opening (from postnatal day (PN28) and in males by preputial separation (from PN35). Oral glucose tolerance tests were carried out at PN70. Mice were culled from PN80. Data were analysed by repeated measures or 2-way ANOVA. Main results and the role of chance There were no significant differences in birth weight, sex ratio or organ weights across groups. There was an overall effect of paternal NCS on male but not female offspring weight[CR1] at cull(p &amp;lt; 0.05), with male CDRebA offspring having increased BW (29.52g±1.5) compared with CDAk at PN80 (26.4g±3; p &amp;lt; 0.05). Females from paternal HF and CD RebA group [CR2] entered puberty significantly earlier (31.8d±1) than Fr (34d±1;p&amp;lt;0.01) and Con (34±1;p&amp;lt;0.05) groups. Male offspring from HFAk had lower glucose AUC (913±31) compared with CDCon (1289±48;p&amp;lt;0.001). Female offspring from CDRebA (1263±84) and CDFr (1273±67) groups had lower glucose AUC compared with CDCon group (1445±56;p&amp;lt;0.05). Limitations, reasons for caution This study was carried out on mice therefore direct translatability to humans is limited. examining the impact of paternal NCS intakes on molecular pathways in the ovary and testes to assess offspring reproductive health later in life and to evaluate pregnancy success following mating would essential for providing further insight. Wider implications of the findings The present study adds to the experimental evidence to date suggesting that NCS may not be beneficial alternatives to sugar-sweetened products consumed preconceptionally on the health of the offspring. This study also highlights the importance of including paternal diet in research when looking at transgenerational effects. Trial registration number not applicable

Clinical segmentation in 22q11.2 deletion syndrome: Cognitive impairments and additional genetic load

The 22q11.2 deletion syndrome (22q11.2DS) is associated with high psychiatric morbidity. However, large phenotypic heterogeneity hampers early detection of 22q11.2DS individuals at highest risk. Here, we investigated whether individuals with 22q11.2DS can be subdivided into clinically relevant subgroups based on their severity of cognitive impairments and whether such subgroups differ in polygenic risk. Using a cross-sectional design, we examined the number of lifetime psychiatric diagnoses and polygenic risk scores for schizophrenia in an unselected nationwide biobank cohort of individuals with 22q11.2DS (n = 183). Approximately 35% of this sample, aged 10–30 years, had a history with one or more psychiatric diagnosis. In a representative nested subgroup of 28 children and youth, we performed additional comprehensive cognitive evaluation and assessed psychiatric symptoms. Unsupervised hierarchical cluster analysis was performed to divide the subgroup of 22q11.2DS individuals, based on their performance on the cognitive testing battery. This produced two groups that did not differ in mean age or gender composition, but were characterized by low cognitive (LF) and high cognitive (HF) functional levels. The LF group, which had significantly lower global cognitive functioning scores, also displayed higher negative symptom scores; whereas, the HF group displayed lower rate of current psychiatric disorders than the LF group and the reminder of the biobank cohort. The polygenic risk score for schizophrenia was insignificantly lower for the low functioning group than for the high functioning group, after adjustment. Cognitive functioning may provide useful information on psychiatric risk.

Sodium-glucose cotransporter-2 inhibitor (SGLT2i) plus glucagon-like peptide type 1 receptor combination is more effective than SGLT2i plus dipeptidyl peptidase-4 inhibitor combination in treating obese mice metabolic dysfunction-associated steatotic liver disease (MASLD).

Monotherapy to treat obesity-associated liver insult is limited. In diet-induced obese mice showing metabolic dysfunction-associated steatotic liver disease (MASLD), we aimed to compare the combinations of sodium-glucose cotransporter-2 inhibitor (SGLT2i, empagliflozin, E), dipeptidyl peptidase-4 inhibitor (DPP4i, linagliptin, L), and glucagon-like peptide type 1 receptor agonist (GLP1RA, dulaglutide, D). Male 3-month-old C57BL/6J mice were fed for 12 weeks in a control (C, n= 10) or high-fat (HF, n= 30) diet. Then, mice were followed for three additional weeks: C, HF, HF E + L, and HF E + D (n= 10/group). HF versus C showed higher hepatic triacylglycerol (TAG, +82%), steatosis (+850%), glucose intolerance (+71%), insulin (+98%), and insulin resistance (+68%). Compared to the HF group, HF E + L showed lower glucose intolerance (-60%), insulin (-61%), insulin resistance (-46%), TAG (-61%), and steatosis (-58%), and HF E + D showed lower glucose intolerance (-71%), insulin (-58%), insulin resistance (-62%), TAG (-61%), and steatosis (-82%). The principal component analysis (PCA) placed the HF group and the HF E + D group on opposite sides, while the HF E + L group was placed between C and HF E + D. PCA separated the groups considering the metabolism-related genes (glucose and lipid), mitochondrial biogenesis, and steatosis. The two pharmacological combinations showed beneficial effects in treating obesity and MASLD. However, the combination of SGLT2i and GLP1RA showed more potent beneficial effects on MASLD than SGLT2i and DPP4i and, therefore, should be the recommended combination.

Clinical Impact of Preoperative Symptoms of Aortic Stenosis on Prognosis After Transcatheter Aortic Valve Replacement.

Background: The prognostic significance of different presentations of aortic stenosis (AS) remains unclear. Our aim was to analyze outcomes after transcatheter aortic valve replacement (TAVR) according to preoperative AS symptoms. Methods and Results: We retrospectively enrolled 369 consecutive patients (age 84.3±5.0 years, and 64% females) who underwent TAVR from 2014 to 2021. We divided them into 4 groups by the main preoperative symptom: asymptomatic (n=50), chest pain (n=46), heart failure (HF; n=240), and syncope (n=33). Post-TAVR rates of HF readmission, all-cause death and cardiac death were compared among the 4 groups. The 4 groups showed no significant trends in age, sex, stroke volume index, or echocardiography indices of AS severity. During a follow-up, the overall survival rate at 1 and 5 years after TAVR was 97% and 90% in the asymptomatic group, 96% and 69% in the chest pain group, 93% and 69% in the HF group, and 90% and 72% in the syncope group, respectively. HF and syncope symptom had significantly lower HF readmission or cardiac death-free survival at 5 years after TAVR (log-rank test P=0.038). In the Cox hazard multivariate analysis, preoperative syncope was an independent predictor of future HF readmission or cardiac death after TAVR (HR=9.87; 95% CI 1.67-97.2; P=0.035). Conclusions: AS patients with preoperative syncope or HF had worse outcomes after TAVR than those with angina or no symptoms.