Is 3T MR nerve-bone fusion imaging a viable alternative to MRI-CBCT to identify the relationship between the inferior alveolar nerve and mandibular third molar.

OBJECTIVES: To investigate the feasibility of MRI nerve-bone fusion imaging in assessing the relationship between inferior alveolar nerve (IAN) / mandibular canal (MC) and mandibular third molar (MTM) compared with MRI-CBCT fusion. MATERIALS AND METHODS: The MRI nerve-bone fusion and MRI-CBCT fusion imaging were performed in 20 subjects with 37 MTMs. The Hausdorff distance (HD) value and dice similarity coefficient (DSC) was calculated. The relationship between IAN/MC and MTM roots, inflammatory, and fusion patterns were compared between these two fused images. The reliability was assessed using a weighted κ statistic. RESULTS: The mean HD and DSC ranged from 0.62 ~ 1.35 and 0.83 ~ 0.88 for MRI nerve-bone fusion, 0.98 ~ 1.50 and 0.76 ~ 0.83 for MRI-CBCT fusion. MR nerve-bone fusion had considerable reproducibility compared to MRI-CBCT fusion in relation classification (MR nerve-bone fusion κ = 0.694, MRI-CBCT fusion κ = 0.644), direct contact (MR nerve-bone fusion κ = 0.729, MRI-CBCT fusion κ = 0.720), and moderate to good agreement for inflammation detection (MR nerve-bone fusion κ = 0.603, MRI-CBCT fusion κ = 0.532, average). The MR nerve-bone fusion imaging showed a lower ratio of larger pattern compared to MR-CBCT fusion (16.2% VS 27.3% in the molar region, and 2.7% VS 5.4% in the retromolar region). And the average time spent on MR nerve-bone fusion and MRI-CBCT fusion was 1 min and 3 min, respectively. CONCLUSIONS: Both MR nerve-bone fusion and MRI-CBCT fusion exhibited good consistency in evaluating the spatial relationship between IAN/MC and MTM, fusion effect, and inflammation detection. CLINICAL RELEVANCE: MR nerve-bone fusion imaging can be a preoperative one-stop radiation-free examination for patients at high risk for MTM surgery.

Pathway analysis of spermidine anti-oxidative stress and inducing autophagy in granulosa cells of Sichuan white geese.

Spermidine, a natural polyamine, has been proven antioxidant function, but its pathway and mechanism of action remain unclear. Based on the oxidative stress model by 3-nitropropionic acid (3-NPA), the study explored the pathways by spermidine to rescue oxidative stress via autophagic process in goose granulosa cells by RNA-seq and RNA interference. In transcriptional regulation, in addition to KEGG pathways related to cell proliferation and differentiation, lots of KEGG pathways associated with inflammation, metabolism, and signaling were also significantly enriched in 3-NPA vs. 3-NPA + spermidine treatments. Six key genes (JUN, CD44, KITLG, RND2, BMP4 and KALRN) involved in spermidine-mediated anti-oxidative stress were screened. Furthermore, the experimental results showed that spermidine (80 µmol/L) significantly increased autophagic gene expression in goose granulosa cells, while EP300-siRNA or MAP1S-siRNA also significantly increased autophagic process. The autophagic gene expressions were no difference between EP300-siRNA and EP300-siRNA + spermidine treatments, although spermidine significantly increased autophagic process of granulosa cells compared to MAP1S-siRNA alone. In addition, inhibition of mTOR pathway significantly increased autophagic gene expression, which was further enhanced by spermidine in combined with mTOR inhibitor. These results suggest that spermidine can alleviate oxidative stress by inducing autophagy regulated by EP300, MAP1S and mTOR as well as regulating other independent gene expressions in goose granulosa cells.

Polyamines in Ovarian Aging and Disease.

Ovarian aging and disease-related decline in fertility are challenging medical and economic issues with an increasing prevalence. Polyamines are a class of polycationic alkylamines widely distributed in mammals. They are small molecules essential for cell growth and development. Polyamines alleviate ovarian aging through various biological processes, including reproductive hormone synthesis, cell metabolism, programmed cell death, etc. However, an abnormal increase in polyamine levels can lead to ovarian damage and promote the development of ovarian disease. Therefore, polyamines have long been considered potential therapeutic targets for aging and disease, but their regulatory roles in the ovary deserve further investigation. This review discusses the mechanisms by which polyamines ameliorate human ovarian aging and disease through different biological processes, such as autophagy and oxidative stress, to develop safe and effective polyamine targeted therapy strategies for ovarian aging and the diseases.

Confinement inside MOFs Enables Guest-Modulated Spin Crossover of Otherwise Low-Spin Coordination Cages.

Confinement of discrete coordination cages within nanoporous lattices is an intriguing strategy to gain unusual properties and functions. We demonstrate here that the confinement of coordination cages within metal-organic frameworks (MOFs) allows the spin state of the cages to be regulated through multilevel host-guest interactions. In particular, the confined in situ self-assembly of an anionic FeII4L6 nanocage within the mesoporous cationic framework of MIL-101 leads to the ionic MOF with an unusual hierarchical host-guest structure. While the nanocage in solution and in the solid state has been known to be invariantly diamagnetic with low-spin FeII, FeII4L6@MIL-101 exhibits spin-crossover (SCO) behavior in response to temperature and release/uptake of water guest within the MOF. The distinct color change concomitant with water-induced SCO enables the use of the material for highly selective colorimetric sensing of humidity. Moreover, the spin state and the SCO behavior can be modulated also by inclusion of a guest into the hydrophobic cavity of the confined cage. This is an essential demonstration of the phenomenon that the confinement within porous solids enables an SCO-inactive cage to show modulable SCO behaviors, opening perspectives for developing functional supramolecular materials through hierarchical host-guest structures.

Spermidine suppresses oxidative stress and ferroptosis by Nrf2/HO-1/GPX4 and Akt/FHC/ACSL4 pathway to alleviate ovarian damage.

AIMS: Oxidative stress is considered to be one of the culprits of ovarian dysfunction. Spermidine (SPD) is a natural aliphatic polyamine that is widely present in living organisms and has been shown to exert preventive effects on various ageing-related diseases. This study seeks to investigate the potential preventive and protective effects of SPD on ovarian oxidative damage. MAIN METHODS: Ovarian oxidative stress model in C57BL/6 mice was established by 3-nitropropionic acid. Female mice were administrated 10 mg/kg or 15 mg/kg SPD. The estrous cycle, serum hormone levels and mating test were measured to evaluate ovarian function. Follicle counts and AMH levels to assess ovarian reserve. Masson's trichrome to assess ovarian fibrosis. TUNEL analysis to evaluate follicular granulosa cells (GCs) apoptosis. Oxidative stress and autophagy indicators (Nrf2, HO-1, GPX4, LC3B, P62) were measured in vivo and in vitro. RNA-sequencing was performed on SPD-treated GC to study the effects of SPD on Akt and FHC/ACSL4 signaling. KEY FINDINGS: SPD supplementation improved ovarian endocrine function and reproductive capacity in oxidative stress mice. SPD regularized the estrous cycle and alleviated oxidative stress. Furthermore, SPD increased the ovarian reserve, reducing GC apoptosis by activating the Nrf2/HO-1/GPX4 pathway. RNA-sequencing showed that SPD induced 230 genes changes in porcine GC, which were mainly involved in oocyte meiosis, arginine biosynthesis and glutathione metabolism pathways. SPD attenuated H2O2-induced ferroptosis by regulating Akt/FHC/ACSL4 signaling. SIGNIFICANCE: SPD alleviates oxidative stress and ferroptosis by regulating the Nrf2/HO-1/GPX4 and Akt/FHC/ACSL4 pathway, which may be a novel potential strategy to protect ovarian oxidative damage.

Effects of exogenous spermidine on autophagy and antioxidant capacity in ovaries and granulosa cells of Sichuan white geese.

Autophagy can inhibit ovarian senescence induced by oxidative stress and regulate follicle development and atresia, but its mechanism is still unclear. Exogenous spermidine can induce autophagy and scavenge reactive oxygen species (ROS). In this experiment, oxidative stress in Sichuan white geese ovaries and follicular granulosa cells (GCs) was caused by 3-nitropropionic acid (3-NPA) and spermidine was added to explore the effect of exogenous spermidine inducing autophagy and inhibiting oxidative stress in vivo and in vitro. Research results showed that putrescine, spermidine and spermine contents in goose ovaries in the group treated with spermidine combined with 3-NPA were 2.70, 1.94, and 1.70 times higher than those in the group treated with 3-NPA, respectively (P < 0.05). The contents of spermidine and spermine in GCs were 1.37 and 0.89 times higher in the spermidine in combination with the 3-NPA group than in the 3-NPA group, respectively (P < 0.05). LC3 and p62 were mainly expressed in the follicular granulosa layer. The LC3-II/I ratio and p62 level in GCs in the spermidine combined with 3-NPA treatment group were 1.37 and 0.77 times higher than that of the 3-NPA treatment group, respectively (P < 0.05). 3-NPA treatment significantly increased ROS level and the apoptosis rate in GCs, while the combined treatment of spermidine and 3-NPA reversed this change (P < 0.05). In conclusion, spermidine alleviated the oxidative damage induced by 3-NPA by improving the antioxidant capacity of ovaries and follicular GCs of Sichuan white geese and may be alleviated by inducing autophagy in GCs.

This study investigated the effects of exogenous spermidine on oxidative stress induced by 3-nitropropionic acid (3-NPA) in ovaries and granulosa cells of Sichuan white geese. In ovarian tissue, spermidine can reduce malondialdehyde accumulation induced by 3-NPA by increasing antioxidant enzyme activity, thus alleviating the oxidative damage induced by 3-NPA. In addition, spermidine can also improve the morphological structure of follicles and alleviate the structural damage caused by 3-NPA. Our results showed that autophagy-associated proteins are mainly concentrated in the granulosa layer of follicles and spermidine can alter their expression. Subsequently, we found that spermidine could induce autophagy and reduce the accumulation of reactive oxygen species and apoptosis rate induced by 3-NPA in granulosa cells. Therefore, we speculate that spermidine can alleviate oxidative stress induced by 3-NPA by inducing autophagy in granulosa cells. In conclusion, spermidine can relieve oxidative stress induced by 3-NPA by increasing the activity of antioxidant enzymes, and may also relieve oxidative stress by inducing autophagy.

Correlation analysis of polyamine metabolism and reproductive hormone levels in goose ovarian follicles.

To investigate the relationship between polyamine metabolism and reproductive hormones in ovarian follicles of Sichuan white geese, follicle polyamine content and reproductive hormone levels and gene expressions related to polyamine metabolism, steroidogenesis and steroid hormone receptors were detected by HPLC, ELISA and RT-qPCR. The results showed that the overall trend of spermidine and spermine levels increased first and then decreased as increasing follicle size, with the highest level in F3 and F5 follicles (P < 0.05). Putrescine and 17ß-estradiol (E2) levels in hierarchical follicles were significantly lower than those in prehierarchical follicles (P < 0.05). Progesterone (P4) first increased and then decreased, with the highest level in the F5 follicle (P < 0.05). The expression levels of estrogen receptor 1 (ER1) showed an overall increase as increasing follicle size (except in F3 follicles), while estrogen receptor 2 (ER2) in hierarchical follicles was significantly lower than that in the prehierarchical follicles (P < 0.05). In addition, the overall expression level of progesterone receptor (PR) decreased, with no significant differences among F1, F2 and F3 follicles (P > 0.05). Yolk putrescine contents were positively correlated with yolk E2 concentrations and PR expression levels (P < 0.05), A significant positive correlation of spermidine levels with yolk P4 concentrations and PR expressions was also observed, as well as the spermine levels with yolk P4 concentrations (P < 0.05). In summary, polyamines were involved in the regulation of follicular development in geese, and this regulation played a role in affecting steroidogenesis and the expression of genes related to hormone receptors.

Catalytic reactions of oxalic acid degradation with Pt/SiO2 as a catalyst in nitric acid solutions.

Large quantities of solutions containing oxalic acid and nitric acid are produced from nuclear fuel reprocessing, but oxalic acid must be removed before nitric acid and plutonium ions can be recovered in these solutions. The degradation of oxalic acid with Pt/SiO2 as a catalyst in nitric acid solutions has the characteristics of a fast and stable reaction, recyclable catalyst, and no introduction of impurity ions into the system. This method is one of the preferred alternatives to the currently used reaction of KMnO4 with oxalic acid but lacks theoretical support. Therefore, this study attempts to clarify the reaction mechanism of the method. First, there was no induction period for this catalytic reaction, and no evidence was found that the nitrous acid produced in the solution could have an effect on oxalic acid degradation. Furthermore, oxidation intermediates (structures of Pt-O) were formed through this reaction between NO3- adsorbed on the active sites and Pt on the catalyst surface, but H+ greatly promoted the reaction. Additionally, oxalic acid degradation through the oxidative dehydrogenation reaction occurred between oxalic acid molecules (HOOC-COOH) and Pt-O, with ·OOC-COOH, which is easily self-decomposable especially in acidic solution, generated simultaneously, and finally CO2 was produced.

Effect of Slightly Acidic Electrolyzed Water on Growth, Diarrhea and Intestinal Bacteria of Newly Weaned Piglets.

As an environmentally-friendly agent, slightly acidic electrolyzed water (SAEW) was introduced in drinking water of newly weaned piglets for diarrhea prevention. In total, 72 piglets were employed and 3% SAEW was added into the normal temperature and warm (30 °C) tap water, respectively, for this 33-day feeding experiment. It was found that the total bacteria and coliforms in the drinking water were reduced by 70% and 100%, respectively, with the addition of 3% SAEW. After SAEW treatment, the average daily water and feed intakes of piglets were increased during the first 16 days, and the diarrhea rate was reduced by 100%, with not one case of diarrhea recorded at the end of the experiment. The microbiome results demonstrated that SAEW decreased the diversity of caecum bacteria with normal tap water supplied, and increased the richness of the caecum bacteria with warm tap water supplied. SAEW also increased the abundance of potentially beneficial genera Sutterella and Ruminococcaceae_UCG-005 and reduced the abundance of pathogenic Faecalibacterium. Moreover, twelve metabolic functions belonging to the cluster of metabolism and organismal functions, including digestion and the endocrine and excretory systems, were greatly enhanced. Correlation analysis indicated that the influence of intestinal pathogens on water and feed intakes and the diarrhea of piglets were decreased by SAEW. The results suggest that SAEW can be used as an antibiotic substitute to prevent diarrhea in newly weaned piglets.

Spermidine alleviating oxidative stress and apoptosis by inducing autophagy of granulosa cells in Sichuan white geese.

Spermidine have been reported a role in antioxidative, antiaging, and antiinflammatory. Oxidative stress causes granulosa cell (GC) apoptosis, follicular atresia, and impairs poultry reproductive functions. Studies have found that autophagy is the protective mechanism against antioxidant stress and apoptosis in cells. However, the relationship between spermidine-induced autophagy, oxidative stress, and apoptosis in goose GCs remains unclear. In this study, we investigated the autophagy mechanism to mediate spermidine effects on the alleviation of oxidative stress and apoptosis in goose GCs. Follicular GCs were treated with spermidine combination with 3-Nitropropanoic acid (3-NPA), rapamycin (RAPA), and chloroquine (CQ) or with hydrogen peroxide, RAPA, and CQ. Spermidine upregulated the ratio of LC3-II/I, inhibited the accumulation of p62 protein, and induced autophagy. 3-NPA treatment significantly increased ROS production, MDA content, SOD activity, cleaved CASPASE-3 protein expression, and decreased BCL-2 protein expression in follicular GCs. Spermidine inhibited oxidative stress and apoptosis induced by 3-NPA. In addition, hydrogen peroxide-induced oxidative stress was inhibited by spermidine. However, the inhibitory effect of spermidine was eliminated under chloroquine. Our results demonstrated that spermidine relieved oxidative stress and apoptosis of GCs by inducing autophagy, indicating that spermidine has a great potential to maintain proteostasis and sustain granulosa cell viability in geese.

Combined metabolome and transcriptome analysis reveal the mechanism of eugenol inhibition of Aspergillus carbonarius growth in table grapes (Vitis vinifera L.).

During storage, Aspergillus carbonarius (A. carbonarius) can easily infect grape berries, resulting in a pronounced decline in nutritional value and substantial economic loss for the grape industry. Characterised by broad-spectrum antibacterial activity, eugenol is proven to significantly inhibit A. carbonarius and ochratoxin A (OTA) in vitro. In this study, the potential mechanism of eugenol against A. carbonarius in grapes ('Kyoho') was evaluated using integrative transcriptomic and metabolomics analyses. After eugenol treatment at 50 mM, the inhibition of OTA was reduced by 100%, despite a 56.2% inhibition of A. carbonarius. In the meantime, mycelial growth was completely inhibited by 100 mM eugenol in grape berries. The application of eugenol to grapes stimulated the activity of several enzymes involved in disease resistance, namely catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), chitinase (CHI), ß-1,3-glucanase (GLU), cinnamate-4-hydroxylase (C4H), phenylalanine ammonia-lyase (PAL), 4-coumarate-CoA ligase (4CL) and glutathione (GSH) content. In addition, the contents of abscisic acid (ABA), jasmonic acid (JA) and salicylic acid (SA) in eugenol-treated grapes were higher after A. carbonarius inoculation. Combined transcriptomic and metabolomic analysis revealed that in phenylpropane biosynthesis, there were a variety of differentially expressed metabolites (DEMs) and differentially expressed genes (DEGs), and the plant hormone signalling pathway changed significantly. Among these, the levels of 47 polyphenol metabolites significantly increased in eugenol-treated grape berries compared to noneugenol-treated berries. Meanwhile, we investigated the transcript levels of 39 genes in 6 phytohormones signalling in response to eugenol-treated grape berries followed by A. carbonarius inoculation. These results suggest that eugenol positively improved the disease resistance of grapes and might be potentially beneficial for the prevention and treatment of A. carbonarius-caused disease.

Mixed legume-grass seeding and nitrogen fertilizer input enhance forage yield and nutritional quality by improving the soil enzyme activities in Sichuan, China.

Information regarding relationships between forage yield and soil enzymes of legume-grass mixtures under nitrogen (N) fertilization can guide the decision-making during sustainable forage production. The objective was to evaluate the responses of forage yield, nutritional quality, soil nutrients, and soil enzyme activities of different cropping systems under various N inputs. Alfalfa (Medicago sativa L.), white clover (Trifolium repens L.), orchardgrass (Dactylis glomerata L.), and tall fescue (Festuca arundinacea Schreb.) were grown in monocultures and mixtures (A1: alfalfa, orchardgrass, and tall fescue; A2: alfalfa, white clover, orchardgrass, and tall fescue) under three N inputs (N1: 150 kg ha-1; N2, 300 kg ha-1; and N3: 450 kg ha-1) in a split plot arrangement. The results highlight that A1 mixture under N2 input had a greater forage yield of 13.88 t ha-1 year-1 than the other N inputs, whereas A2 mixture under N3 input had a greater forage of 14.39 t ha-1 year-1 than N1 input, but it was not substantially greater than N2 input (13.80 t ha-1 year-1). The crude protein (CP) content of grass monocultures and mixtures significantly (P < 0.05) increased with an increase in the rate of N input, and A1 and A2 mixtures under N3 input had a greater CP content of 18.91% and 18.94% dry matter, respectively, than those of grass monocultures under various N inputs. The A1 mixture under N2 and N3 inputs had a substantially greater (P < 0.05) ammonium N content of 16.01 and 16.75 mg kg-1, respectively, whereas A2 mixture under N3 had a greater nitrate N content of 4.20 mg kg-1 than the other cropping systems under various N inputs. The A1 and A2 mixtures under N2 input had a substantial higher (P < 0.05) urease enzyme activity of 0.39 and 0.39 mg g-1 24 h-1 and hydroxylamine oxidoreductase enzyme activity of 0.45 and 0.46 mg g-1 5 h-1, respectively, than the other cropping systems under various N inputs. Taken together, growing legume-grass mixtures under N2 input is cost-effective, sustainable, and eco-friendly, which provide greater forage yield and improved nutritional quality by the better utilization of resources.

tsRNA Landscape and Potential Function Network in Subcutaneous and Visceral Pig Adipose Tissue.

Noncoding RNAs (ncRNAs) called tsRNAs (tRNA-derived short RNAs) have the ability to regulate gene expression. The information on tsRNAs in fat tissue is, however, limited. By sequencing, identifying, and analyzing tsRNAs using pigs as animal models, this research reports for the first time the characteristics of tsRNAs in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). A total of 474 tsRNAs, 20 and 21 of which were particularly expressed in VAT and SAT, respectively, were found in WAT. According to the analysis of the tsRNA/miRNA/mRNA co-expression network, the tsRNAs with differential expression were primarily engaged in the endocrine and immune systems, which fall under the classification of organic systems, as well as the global and overview maps and lipid metropolis, which fall under the category of metabolism. This research also discovered a connection between the activity of the host tRNA engaged in translation and the production of tsRNAs. This research also discovered that tRF-Gly-GCC-037/tRF-Gly-GCC-042/tRF-Gly-CCC-016 and miR-218a/miR281b may be involved in the regulation of fatty acid metabolism in adipose tissue through SCD based on the tsRNA/miRNA/mRNA/fatty acid network. In conclusion, our findings enrich the understanding of ncRNAs in WAT metabolism and health regulation, as well as reveal the differences between SAT and VAT at the level of tsRNAs.

Exploration of the Antioxidant Effect of Spermidine on the Ovary and Screening and Identification of Differentially Expressed Proteins.

Spermidine is a naturally occurring polyamine compound that has many biological functions, such as inducing autophagy and anti-inflammatory and anti-aging effects. Spermidine can affect follicular development and thus protect ovarian function. In this study, ICR mice were fed exogenous spermidine drinking water for three months to explore the regulation of ovarian function by spermidine. The results showed that the number of atretic follicles in the ovaries of spermidine-treated mice was significantly lower than that in the control group. Antioxidant enzyme activities (SOD, CAT, T-AOC) significantly increased, and MDA levels significantly decreased. The expression of autophagy protein (Beclin 1 and microtubule-associated protein 1 light chain 3 LC3 II/I) significantly increased, and the expression of the polyubiquitin-binding protein p62/SQSTM 1 significantly decreased. Moreover, we found 424 differentially expressed proteins (DEPs) were upregulated, and 257 were downregulated using proteomic sequencing. Gene Ontology and KEGG analyses showed that these DEPs were mainly involved in lipid metabolism, oxidative metabolism and hormone production pathways. In conclusion, spermidine protects ovarian function by reducing the number of atresia follicles and regulating the level of autophagy protein, antioxidant enzyme activity, and polyamine metabolism in mice.

Stabilizing High-Frequency Magnetic Properties of Stretchable CoFeB Films by Ribbon-Patterned Periodic Wrinkles.

The intrinsic nonstretchable feature of magnetic films has significantly limited its applications on wearable high-frequency devices. Recent studies have proved that the wrinkling surface structure based on the growth on polydimethylsiloxane (PDMS) is an effective route to obtain stretchable magnetic films. However, it is still a great challenge to simultaneously achieve a desired stretchability and stretching-insensitive high-frequency properties of magnetic films. Herein, we reported a convenient method to stabilize the high-frequency properties of stretchable magnetic films by depositing magnetic ribbon-patterned films on prestrain PDMS membranes. The ribbon-patterned wrinkling CoFeB films have far fewer cracks than the continuous film, which indicates a nice strain-relief effect and thus confers the stability of high-frequency properties for the films under stretching. However, the wrinkle bifurcation and the uneven thickness at the ribbon edge could adversely affect the stability of its high-frequency properties. The 200 µm wide ribbon-patterned film shows the best stretching-insensitive behaviors and maintains a constant resonance frequency of 3.17 GHz at strain from 10% to 25%. Moreover, a good repeatability has been demonstrated by performing thousands of stretch-release cycles, which did not significantly deteriorate its performances. The ribbon-patterned wrinkling CoFeB films with excellent stretching-insensitive high-frequency properties are promising for application in flexible microwave devices.

Ferritin heavy chain participated in ameliorating 3-nitropropionic acid-induced oxidative stress and apoptosis of goose follicular granulosa cells.

Oxidative stress is the major culprits responsible for ovarian dysfunction by damaging granulosa cells (GCs). Ferritin heavy chain (FHC) may participate in the regulation of ovarian function by mediating GCs apoptosis. However, the specific regulatory function of FHC in follicular GCs remains unclear. Here, 3-nitropropionic acid (3-NPA) was utilized to establish an oxidative stress model of follicular GCs of Sichuan white geese. To explore the regulatory effects of FHC on oxidative stress and apoptosis of primary GCs in geese by interfering or overexpressing FHC gene. After transfection of siRNA-FHC to GCs for 60 h, the expressions of FHC gene and protein decreased significantly (P < 0.05). After FHC overexpression for 72 h, the expressions of FHC mRNA and protein upregulated considerably (P < 0.05). The activity of GCs was impaired after interfering with FHC and 3-NPA coincubated (P < 0.05). When overexpression of FHC combined with 3-NPA treatment, the activity of GCs was remarkably enhanced (P < 0.05). After interference FHC and 3-NPA treatment, NF-κB and NRF2 gene expression decreased (P < 0.05), the intracellular reactive oxygen species (ROS) level increased greatly (P < 0.05), BCL-2 expression reduced, BAX/BCL-2 ratio intensified (P < 0.05), the mitochondrial membrane potential decreased notably (P < 0.05), and the apoptosis rate of GCs aggravated (P < 0.05). While overexpression of FHC combined with 3-NPA treatment could promote BCL-2 protein expression and reduce BAX/BCL-2 ratio, indicating that FHC regulated the mitochondrial membrane potential and apoptosis of GCs by mediating the expression of BCL-2. Taken together, our research manifested that FHC alleviated the inhibitory effect of 3-NPA on the activity of GCs. FHC knockdown could suppress the expression of NRF2 and NF-κB genes, reduce BCL-2 expression and augment BAX/BCL-2 ratio, contributing to the accumulation of ROS and jeopardizing mitochondrial membrane potential, as well as exacerbating GCs apoptosis.

His bundle pacing versus left bundle branch pacing on ventricular function in atrial fibrillation patients referred for pacing: a prospective crossover comparison.

BACKGROUND: His bundle pacing (HBP) and left bundle branch pacing (LBBP) both provide physiologic pacing which maintain left ventricular synchrony. They both improve heart failure (HF) symptoms in atrial fibrillation (AF) patients. We aimed to assess the intra-patient comparison of ventricular function and remodeling as well as leads parameters corresponding to two pacing modalities in AF patients referred for pacing in intermediate term. METHODS: Uncontrolled tachycardia AF patients with both leads implantation successfully were randomized to either modality. Echocardiographic measurements, New York Heart Association (NYHA) classification, quality-of-life assessments and leads parameters were obtained at baseline and at each 6-month follow up. Left ventricular function including the left ventricular endo-systolic volume (LVESV), left ventricular ejection fraction (LVEF) and right ventricular (RV) function quantified by tricuspid annular plane systolic excursion (TAPSE) were all assessed. RESULTS: Consecutively twenty-eight patients implanted with both HBP and LBBP leads successfully were enrolled (69.1 ± 8.1 years, 53.6% male, LVEF 59.2% ± 13.7%). The LVESV was improved by both pacing modalities in all patients (n = 23) and the LVEF was improved in patients with baseline LVEF at less than 50% (n = 6). The TAPSE was improved by HBP but not LBBP (n = 23). CONCLUSION: In this crossover comparison between HBP and LBBP, LBBP was found to have an equivalent effect on LV function and remodeling but better and more stable parameters in AF patients with uncontrolled ventricular rates referred for atrioventricular node (AVN) ablation. HBP could be preferred in patients with reduced TAPSE at baseline rather than LBBP.

Comprehensive analysis of the biological functions of endoplasmic reticulum stress in prostate cancer.

Introduction: Endoplasmic reticulum stress (ERS) has sizeable affect on cancer proliferation, metastasis, immunotherapy and chemoradiotherapy resistance. However, the effect of ERS on the biochemical recurrence (BCR) of prostate cancer patients remains elusive. Here, we generated an ERS-related genes risk signature to evaluate the physiological function of ERS in PCa with BCR. Methods: We collected the ERS-related genes from the GeneCards. The edgeR package was used to screen the differential ERS-related genes in PCa from TCGA datasets. ERS-related gene risk signature was then established using LASSO and multivariate Cox regression models and validated by GEO data sets. Nomogram was developed to assess BCR-free survival possibility. Meanwhile, the correlations between ERS-related signature, gene mutations, drug sensitivity and tumor microenvironment were also investigated. Results: We obtained an ERS risk signature consisting of five genes (AFP, COL10A1, DNAJB1, EGF and PTGS2). Kaplan Meier survival analysis and ROC Curve analysis indicated that the high risk score of ERS-related gene signature was associated with poor BCR-free prognosis in PCa patients. Besides, immune cell infiltration and immune checkpoint expression levels differed between high- and low-risk scoring subgroups. Moreover, drug sensitivity analyzed indicated that high-risk score group may be involved in apoptosis pathway. Discussion: This study comprehensively analyzed the characteristics of ERS related genes in PCa, and created a five-gene signature, which could effectively predict the BCR time of PCa patients. Targeting ERS related genes and pathways may provide potential guidance for the treatment of PCa.

Grading meningiomas with diffusion metrics: a comparison between diffusion kurtosis, mean apparent propagator, neurite orientation dispersion and density, and diffusion tensor imaging.

OBJECTIVES: To compare the histogram features of multiple diffusion metrics in predicting the grade and cellular proliferation of meningiomas. METHODS: Diffusion spectrum imaging was performed in 122 meningiomas (30 males, 13-84 years), which were divided into 31 high-grade meningiomas (HGMs, grades 2 and 3) and 91 low-grade meningiomas (LGMs, grade 1). The histogram features of multiple diffusion metrics obtained from diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), mean apparent propagator (MAP), and neurite orientation dispersion and density imaging (NODDI) in the solid tumours were analysed. All values between the two groups were compared with the Man-Whitney U test. Logistic regression analysis was applied to predict meningioma grade. The correlation between diffusion metrics and Ki-67 index was analysed. RESULTS: The DKI_AK (axial kurtosis) maximum, DKI_AK range, MAP_RTPP (return-to-plane probability) maximum, MAP_RTPP range, NODDI_ICVF (intracellular volume fraction) range, and NODDI_ICVF maximum values were lower (p < 0.0001), whilst the DTI_MD (mean diffusivity) minimum values were higher in LGMs than those in HGMs (p < 0.001). Amongst the DTI, DKI, MAP, NODDI, and combined diffusion models, no significant differences were found in areas under the receiver operating characteristic curves (AUCs) for grading meningiomas (AUCs, 0.75, 0.75, 0.80, 0.79, and 0.86, respectively; all corrected p > 0.05, Bonferroni correction). Significant but weak positive correlations were found between the Ki-67 index and DKI, MAP, and NODDI metrics (r = 0.26-0.34, all p < 0.05). CONCLUSIONS: Whole tumour histogram analyses of the multiple diffusion metrics from four diffusion models are promising methods in grading meningiomas. The DTI model has similar diagnostic performance compared with advanced diffusion models. KEY POINTS: • Whole tumour histogram analyses of multiple diffusion models are feasible for grading meningiomas. • The DKI, MAP, and NODDI metrics are weakly associated with the Ki-67 proliferation status. • DTI has similar diagnostic performance compared with DKI, MAP, and NODDI in grading meningiomas.

Effects of Spermidine on Mouse Gut Morphology, Metabolites, and Microbial Diversity.

Spermidine is a class of biologically active organic small molecules that play an important role in maintaining intestinal homeostasis. The specific objective of this study was to explore the effects of spermidine on intestinal morphology, metabolites, and microbial diversity in mice. We showed that 0.3 mmol/L of spermidine significantly promoted the growth of ileal villi (p < 0.05), and 3.0 mmol/L of spermidine significantly increased the body weight of mice and promoted the growth of jejunum villi (p < 0.05). The 16S rDNA sequencing results indicated that 3.0 mmol/L of spermidine affected the balance of the intestinal flora by increasing the abundance of intestinal Lactic acid bacteria and reducing the abundance of harmful bacteria (Turicibacter and Alistipes). Additionally, spermidine affects the levels of microbial metabolites such as succinic acid and Pantetheine. In summary, spermidine affects intestinal morphology and regulates intestinal flora and metabolites, and this study has provided a new understanding of spermidine's effects on the intestinal tract.