ESM1 enhances fatty acid synthesis and vascular mimicry in ovarian cancer by utilizing the PKM2-dependent warburg effect within the hypoxic tumor microenvironment.

BACKGROUND: The hypoxic tumor microenvironment is a key factor that promotes metabolic reprogramming and vascular mimicry (VM) in ovarian cancer (OC) patients. ESM1, a secreted protein, plays an important role in promoting proliferation and angiogenesis in OC. However, the role of ESM1 in metabolic reprogramming and VM in the hypoxic microenvironment in OC patients has not been determined. METHODS: Liquid chromatography coupled with tandem MS was used to analyze CAOV3 and OV90 cells. Interactions between ESM1, PKM2, UBA2, and SUMO1 were detected by GST pull-down, Co-IP, and molecular docking. The effects of the ESM1-PKM2 axis on cell glucose metabolism were analyzed based on an ECAR experiment. The biological effects of the signaling axis on OC cells were detected by tubule formation, transwell assay, RT‒PCR, Western blot, immunofluorescence, and in vivo xenograft tumor experiments. RESULTS: Our findings demonstrated that hypoxia induces the upregulation of ESM1 expression through the transcription of HIF-1α. ESM1 serves as a crucial mediator of the interaction between PKM2 and UBA2, facilitating the SUMOylation of PKM2 and the subsequent formation of PKM2 dimers. This process promotes the Warburg effect and facilitates the nuclear translocation of PKM2, ultimately leading to the phosphorylation of STAT3. These molecular events contribute to the promotion of ovarian cancer glycolysis and vasculogenic mimicry. Furthermore, our study revealed that Shikonin effectively inhibits the molecular interaction between ESM1 and PKM2, consequently preventing the formation of PKM2 dimers and thereby inhibiting ovarian cancer glycolysis, fatty acid synthesis and vasculogenic mimicry. CONCLUSION: Our findings demonstrated that hypoxia increases ESM1 expression through the transcriptional regulation of HIF-1α to induce dimerization via PKM2 SUMOylation, which promotes the OC Warburg effect and VM.

Detoxification and underlying mechanisms towards toxic alkaloids by Traditional Chinese Medicine processing: A comprehensive review.

BACKGROUND: Alkaloids have attracted enduring interest worldwide due to their remarkable therapeutic effects, including analgesic, anti-inflammatory, and anti-tumor properties, thus offering a rich source for lead compound design and new drug discovery. However, some of these alkaloids possess intrinsic toxicity. Processing (Paozhi) is a pre-treatment step before the application of herbal medicines in traditional Chinese medicine (TCM) clinics, which has been employed for centuries to mitigate the toxicity of alkaloid-rich TCMs. PURPOSE: To explore the toxicity phenotypes, chemical basis, mode of action, detoxification processing methods, and underlying mechanisms, we can gain crucial insights into the safe and rational use of these toxic alkaloid-rich herbs. Such insights have the great potential to offer new strategies for drug discovery and development, ultimately improving the quality of life for millions of people. METHODS: Literatures published or early accessed until December 31, 2023, were retrieved from databases including PubMed, Web of Science, and CNKI. The following keywords, such as "toxicity", "alkaloid", "detoxification", "processing", "traditional Chinese medicine", "medicinal plant", and "plant", were used in combination or separately for screening. RESULTS: Toxicity of alkaloids in TCM includes hepatotoxicity, nephrotoxicity, neurotoxicity, cardiotoxicity, and other forms of toxicity, primarily induced by pyrrolizidines, quinolizidines, isoquinolines, indoles, pyridines, terpenoids, and amines. Factors such as whether the toxic-alkaloid enriched part is limited or heat-sensitive, and whether toxic alkaloids are also therapeutic components, are critical for choosing appropriate detoxification processing methods. Mechanisms of alkaloid detoxification includes physical removal, chemical decomposition or transformation, as well as biological modifications. CONCLUSION: Through this exploration, we review toxic alkaloids and the mechanisms underlying their toxicity, discuss methods to reduce toxicity, and unravel the intricate mechanisms behind detoxification. These offers insights into the quality control of herbs containing toxic alkaloids, safe and rational use of alkaloid-rich TCMs in clinics, new strategies for drug discovery and development, and ultimately helping improve the quality of life for millions of people.

Right ventricular volume and function by three-dimensional echocardiography: results of the echocardiographic measurements in normal Chinese adults (EMINCA) II.

Three-dimensional (3D) echocardiography is an emerging technique for assessing right ventricular (RV) volume and function, but 3D-RV normal values from a large Chinese population are still lacking. The aim of the present study was to establish normal values of 3D-RV volume and function in healthy Chinese volunteers. A total of 1117 Han Chinese volunteers from 28 laboratories in 20 provinces of China were enrolled, and 3D-RV images of 747 volunteers with optimal image quality were ultimately analyzed by a core laboratory. Both vendor-dependent and vendor-independent software platforms were used to analyze the 3D-RV images. We found that men had larger RV volumes than women did in the whole population, even after indexing to body surface area, and older individuals had smaller RV volumes. The normal RV volume was significantly smaller than that recommended by the American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines in both sexes. There were significant differences in 3D-RV measurements between the two vendor ultrasound systems and the different software platforms. The echocardiographic measurements in normal Chinese adults II study revealed normal 3D-RV volume and function in a large Chinese population, and there were significant differences between the sexes, ages, races, and vendor groups. Thus, normal 3D-RV values should be stratified by sex, age, race, and vendor.

Ultralow Strain-Induced Emergent Polarization Structures in a Flexible Freestanding BaTiO3 Membrane.

The engineering of ferroic orders, which involves the evolution of atomic structure and local ferroic configuration in the development of next-generation electronic devices. Until now, diverse polarization structures and topological domains are obtained in ferroelectric thin films or heterostructures, and the polarization switching and subsequent domain nucleation are found to be more conducive to building energy-efficient and multifunctional polarization structures. In this work, a continuous and periodic strain in a flexible freestanding BaTiO3 membrane to achieve a zigzag morphology is introduced. The polar head/tail boundaries and vortex/anti-vortex domains are constructed by a compressive strain as low as ≈0.5%, which is extremely lower than that used in epitaxial rigid ferroelectrics. Overall, this study c efficient polarization structures, which is of both theoretical value and practical significance for the development of next-generation flexible multifunctional devices.

Enhancing pig growth and gut health with fermented Jatropha curcas cake: Impacts on microbiota, metabolites, and neurotransmitters.

Given the escalating global crisis in feed protein availability, Jatropha curcas L. cake has attracted significant interest as a viable alternative protein source in animal feed. This experiment was conducted to investigate the effects of fermented Jatropha curcas L. cake (FJCC) as a protein feed in the diet of pigs. A total of 96 growing pigs with an average weight of 27.60 ± 1.59 kg were divided into three dietary groups with varying FJCC inclusion levels (0, 2.5, and 5%) for a 28 d trial. Results showed that the diet with 5% FJCC (FJCC5) demonstrated significant improvements in average daily gain (p = 0.009), feed-to-gain ratio (p = 0.036), nutrient digestibility, and intestinal morphology. Furthermore, the FJCC5 diet resulted in a decrease in pH values in different gut sections (jejunum p = 0.045, cecum p = 0.001, colon p = 0.012), and favorably altered the profile of short-chain fatty acids (SCFAs) with increased butyric acid content (p = 0.005) and total SCFAs (p = 0.019). Additionally, this diet notably decreased IL-6 levels in the jejunum (p = 0.008) and colon (=0.047), significantly reduced IL-1 levels in the hypothalamus (p < 0.001), and lowered IL-1, IL-6, and IL-10 levels in plasma (p < 0.05). Microbiota and metabolite profile analysis revealed an elevated abundance of beneficial microbes (p < 0.05) and key metabolites such as 4-aminobutyric acid (GABA) (p = 0.003) and serotonin (5-HT) (p = 0.022), linked to neuroactive ligand-receptor interaction. Moreover, FJCC5 significantly boosted circulating neurotransmitter levels of 5-HT (p = 0.006) and GABA (p = 0.002) in plasma and hypothalamus, with corresponding increases in precursor amino acids (p < 0.05). These findings suggest that FJCC, particularly at a 5% inclusion rate, can be an effective substitute for traditional protein sources like soybean meal, offering benefits beyond growth enhancement to gut health and potentially impacting the gut-brain axis. This research underscores FJCC's potential as a valuable component in sustainable animal nutrition strategies.

Investigation into the impact of CeO2 morphology regulation on the oxidation process of dichloromethane.

Four distinct CeO2 catalysts featuring varied morphologies (nanorods, nanocubes, nanoparticles, and nano spindle-shaped) were synthesized through a hydrothermal process and subsequently employed in the oxidation of dichloromethane (DCM). The findings revealed that the nano spindle-shaped CeO2 exhibited exposure of crystal faces (111), demonstrating superior catalytic oxidation performance for DCM with a T90 of 337 °C and notably excellent low-temperature catalytic activity (T50 = 192 °C). The primary reaction products were identified as HCl and CO2. Through obvious characterizations, it showed that the excellent catalytic activity presented by CeO2-s catalyst might be related to the higher oxygen vacancy concentration, surface active oxygen content, and superior redox performance caused by specific exposed crystal planes. Meanwhile, CeO2-s catalyst owned outstanding stability, reusability, and water inactivation regeneration, which had tremendous potential in practical treatment.

Influence of Gadoxetate disodium to the hepatic proton density fat fraction quantified with the Dixon sequences in a rabbit model.

OBJECTIVE: To study the impact of Gx on quantification of hepatic fat contents under metabolic dysfunction-associated steatotic liver disease (MASLD) imaged on VIBE Dixon in hepatobiliary specific phase. METHODS: Forty-two rabbits were randomly divided into control group (n = 10) and high-fat diet group (n = 32). Imaging was performed before enhancement (Pre-Gx) and at the 13th (Post-Gx13) and 17th (Post-Gx17) min after Gx enhancement with 2E- and 6E-VIBE Dixon to determine hepatic proton density fat fractions (PDFF). PDFFs were compared with vacuole percentage (VP) measured under histopathology. RESULTS: 33 animals were evaluated and including control group (n = 11) and MASLD group (n = 22). Pre-Gx, Post-Gx13, Post-Gx17 PDFFs under 6E-VIBE Dixon had strong correlations with VPs (r2 = 0.8208-0.8536). PDFFs under 2E-VIBE Dixon were reduced significantly (P < 0.001) after enhancement (r2 = 0.7991/0.8014) compared with that before enhancement (r2 = 0.7643). There was no significant difference between PDFFs of Post-Gx13 and Post-Gx17 (P = 0.123) for which the highest consistency being found with 6E-VIBE Dixon before enhancement (r2 = 0.8536). The signal intensity of the precontrast compared with the postcontrast, water image under 2E-VIBE Dixon increased significantly (P < 0.001), fat image showed no significant difference (P = 0.754). CONCLUSION: 2E- and 6E-VIBE Dixon can obtain accurate PDFFs in the hepatobiliary specific phase from 13 to 17th min after Gx enhancement. On 2E-VIBE Dixon (FA = 10°), effective minimization of T1 Bias by the Gx administration markedly improved the accuracy of the hepatic PDFF quantification.

Advanced Nanoencapsulation-Enabled Ultrasensitive Analysis: Unraveling Tumor Extracellular Vesicle Subpopulations for Differential Diagnosis of Hepatocellular Carcinoma via DNA Cascade Reactions.

Tumor-derived extracellular vesicles (tEVs) hold immense promise as potential biomarkers for the precise diagnosis of hepatocellular carcinoma (HCC). However, their clinical translation is hampered by their inherent characteristics, such as small size and high heterogeneity and complex environment, including non-EV particles and normal cell-derived EVs, which prolong separation procedures and compromise detection accuracy. In this study, we devised a DNA cascade reaction-triggered individual EV nanoencapsulation (DCR-IEVN) strategy to achieve the ultrasensitive and specific detection of tEV subpopulations via routine flow cytometry in a one-pot, one-step fashion. DCR-IEVN enables the direct and selective packaging of multiple tEV subpopulations in clinical serum samples into flower-like particles exceeding 600 nm. This approach bypasses the need for EV isolation, effectively reducing interference from non-EV particles and nontumor EVs. Compared with conventional analytical technologies, DCR-IEVN exhibits superior efficacy in diagnosing HCC owing to its high selectivity for tEVs. Integration of machine learning algorithms with DCR-IEVN resulted in differential diagnosis accuracy of 96.7% for the training cohort (n = 120) and 93.3% for the validation cohort (n = 30), effectively distinguishing HCC, cirrhosis, and healthy donors. This strategy offers a streamlined workflow and rapid assay completion and requires only small-volume serum samples and routine clinical devices, facilitating the clinical translation of tEV-based tumor diagnosis.

A photoelectrochemical sensor based on In2O3/In2S3/ZnIn2S4 ternary Z-scheme heterojunction for ultrasensitive detection of dopamine in sweat.

A novel ternary heterojunction material In2O3/In2S3/ZnIn2S4 was synthesized, and a photoelectrochemical sensor was fabricated for the non-invasive test of dopamine (DA) in sweat. In2O3 multihollow microtubules were synthesized and then In2S3 was formed on their surface to construct a type-I heterojunction between In2S3 and In2O3. ZnIn2S4 was further introduced to form a Z-scheme heterojunction between In2S3/ZnIn2S4. Under photoexcitation, the photogenerated holes of In2O3 transferred to the valence band of In2S3, superimposed with the holes produced by In2S3, leads to a significantly higher photocatalytic oxidation capacity of In2O3/In2S3/ZnIn2S4 ternary composites than that of In2O3/In2S3. The Z-scheme heterojunction accelerates the transfer of photogenerated electrons accumulated on the type-I heterojunction. In the presence of DA, it is rapidly oxidized into polydopamine (PDA) by In2O3/In2S3, and the benzoquinone groups of PDA compete for the photogenerated electrons to reduce the current in the external circuit, whereby DA determination is achieved. Owing to the combination of type-I and Z-scheme heterojunction, the sensor showed extremely high sensitivity, with a detection limit of 3.94 × 10-12 mol/L. It is one of the most sensitive methods for DA detection reported and has been applied to the determination of DA in human sweat.

Dietary ethylenediamine dihydroiodide mitigated Escherichia coli O78-induced immune and intestinal damage of ducks via suppression of NF-κB signal.

This study investigated the effect of Ethylenediamine dihydroiodide (EDDI) on growth performance, immune function and intestinal health of meat ducks challenged with Avian pathogenic Escherichia coli (APEC). A total of 360 one-day-old Cherry Valley ducks with similar body weight were randomly allocated to 6 treatments (6 floor cages, 10 birds/cage). A 3 × 2 factor design was used with 3 dietary iodine levels (0, 8, 16 mg/kg in the form EDDI and whether APEC was challenged or not at 7-day-old ducks. The feeding period lasted for 20 d. The results showed that the addition of EDDI reduced APEC-induced decrease of the 20-d weight loss of meat ducks (P < 0.05), and alleviated the inflammatory response of liver tissue induced by APEC challenge in meat ducks. In terms of immune function, EDDI supplementation reduced the immune organ index and increased the immune cell count of meat ducks, reduced the level of endotoxins in the serum of meat ducks (P < 0.05), as well as inhibited the expression levels of liver and spleen inflammatory factors and TLR signaling pathway related genes induced by APEC (P < 0.05). In terms of intestinal health, EDDI inhibited APEC-induced decreases in ZO-3 genes expression and increases in IL-1ß and TNF-α expression, increased relative abundance of beneficial bacteria in the cecum and content of metabolites. Pearson correlation analysis showed that there was a significant correlation between liver inflammatory factors and TLR4 signaling pathway genes, and there might be a significant correlation between intestinal microbial flora and other physiological indexes of meat ducks, which indicated that EDDI could reduce the damage to immune function and intestinal health caused by APEC challenge through regulating the structure of intestinal flora. Collectively, our findings suggest that the EDDI can promote growth performance, improve immune function and the intestinal barrier in APEC-challenged meat ducks, which may be related to the suppression of NF-κB signal.

Effects of Ninjurin 2 polymorphisms on susceptibility to coronary heart disease.

OBJECTIVE: The aim of this study was to explore the effects of Ninjurin 2 (NINJ2) polymorphisms on susceptibility to coronary heart disease (CHD). METHODS: We conducted a case-control study with 499 CHD cases and 505 age and gender-matched controls. Five single nucleotide polymorphisms (SNPs) in NINJ2 (rs118050317, rs75750647, rs7307242, rs10849390, and rs11610368) were genotyped by the Agena MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression analysis to assess the association of NINJ2 polymorphisms and CHD risk-adjusted for age and gender. What's more, risk genes and molecular functions were screened via protein-protein interaction (PPI) network and functional enrichment analysis. RESULTS: Rs118050317 in NINJ2 significantly increased CHD risk in people aged more than 60 years and women. Rs118050317 and rs7307242 had strong relationships with hypertension risk in CHD patients. Additionally, rs75750647 exceedingly raised diabetes risk in cases under multiple models, whereas rs10849390 could protect CHD patients from diabetes in allele, homozygote, and additive models. We also observed two blocks in NINJ2. Further interaction network and enrichment analysis showed that NINJ2 played a greater role in the pathogenesis and progression of CHD. CONCLUSION: Our results suggest that NINJ2 polymorphisms are associated with CHD risk.

Post-secondary classroom teaching quality evaluation using small object detection model.

The classroom video has a complex background and dense targets. This study utilizes small object detection technology to analyze and evaluate students' behavior in the classroom, aiming to objectively and accurately assess classroom quality. Firstly, noise is removed from the images using a median filter, and the contrast of the images is enhanced through histogram equalization. Label smoothing is applied to reduce the model's sensitivity to labels. Then, features are extracted from the preprocessed images, and multi-scale feature fusion is employed to enhance semantic expression across multiple scales. Finally, a combination loss function is utilized to improve the accuracy of multi-object recognition tasks. Real-time detection of students' behaviors in the classroom is performed based on the small object detection model. The average head-up rate in the classroom is calculated, and the quality of teaching is evaluated and analyzed. This study explores the methods and applications of small object detection technology based on actual teaching cases and analyzes and evaluates its effectiveness in evaluating the quality of higher education classroom teaching. The research findings demonstrate the significant importance of small object detection technology in effectively evaluating students' learning conditions in higher education classrooms, leading to improved teaching quality and personalized education.

Betaine addition to the diet alleviates intestinal injury in growing rabbits during the summer heat through the AAT/mTOR pathway.

BACKGROUND: The aim of this experiment was to investigate the effect of different levels of betaine (Bet) inclusion in the diet on the intestinal health of growing rabbits under summer heat. A total of 100 weaned Qixing meat rabbits aged 35 d with body weight of 748.61 ± 38.59 g were randomly divided into 5 treatment groups: control group (basal diet) and Bet groups (basal diet + 0.75, 1.0, 1.5 or 2.0 g/kg Bet). The average daily temperature in the rabbitry during the experiment was 30.48 °C and the relative humidity was 69.44%. RESULTS: Dietary addition of Bet had no significant effect on growth performance and health status of growing rabbits (P > 0.05), but it increased ileal secretory immunoglobulin A content compared to the control under summer heat (P < 0.05). Addition of 0.75 g/kg Bet up-regulated jejunal IL-4, down-regulated ileal TNF-α expression (P < 0.05). The addition of 1.0 g/kg Bet increased the villi height (VH) in the jejunum (P < 0.05). Serum glucose levels were reduced, and the expression of SLC6A20 was up-regulated in jejunum and ileum of rabbits fed with 1.5 g/kg Bet (P < 0.05). When added at 2.0 g/kg, Bet reduced serum HSP70 content, increased jejunal VH, and up-regulated duodenal SLC7A6, SLC38A2, mTOR and 4EBP-2 expression (P < 0.05). Correlation analysis revealed that intestinal mTOR expression was significantly and positively correlated with SLC7A6, SLC38A2, SLC36A1 and IL-4 expression (P < 0.05). CONCLUSIONS: Dietary addition of Bet can up-regulate the expression of anti-inflammatory factors through the AAT/mTOR pathway, improve the intestinal immune function, alleviate intestinal damage in growing rabbits caused by summer heat, and improve intestinal health.

Dynamic changes and clinical value of Sirt6 in acute coronary syndrome (ACS) patients.

This study aimed to investigate the role of Sirt6 and inflammatory cytokines in blood samples of patients with ACS. This is a retrospective randomized controlled clinical trial, a total of 30 patients from our hospital are included and divided into following two groups: control group and experimental group, and experimental group consists of 15 patients with ACS and control group consists of 15 patients with non-acute coronary syndrome. Sirt6 protein is detected by western blotting and Sirt6 mRNA is detected by real-time PCR, then inflammatory cytokines such as IL-1ß, IL-18, TnI, and CK-MB are measured by ELISA and cytokines NT-proBNP are monitored by immunofluorescence. Our outcomes show that Sirt6 protein and Sirt6 mRNA in experimental group are remarkably lower than those in control group, and IL-1ß, IL-18, TnI, CK-MB, and NT-proBNP in the experimental group are remarkably higher than those in control group. We can conclude that Sirt6 can prevent or inhibit the development of ACS and IL-1ß, IL-18, TnI, CK-MB, and NT-proBNP can accelerate the development of ACS.

A green extraction process for the selective recovery of Sc(iii) based on hydrophobic betaine derivative ionic liquids.

The efficient extraction recovery of scandium (Sc(iii)) is crucial for its application in high-end technology. Two novel hydrophobic carboxylic acid ionic liquids (ILs), namely, [lauryl betaine][bis(trifluoromethanesulphonyl)imide] ([Laur][Tf2N]) and [cocamidopropyl betaine][bis(trifluoromethanesulphonyl)imide] ([Coca][Tf2N]), were synthesized using two inexpensive amphoteric surfactants as cation sources. [Laur][Tf2N] (257 °C) and [Coca][Tf2N] (251 °C) exhibited good thermal stability and strong hydrophobicity. The viscosity of [Coca][Tf2N] (4.29 × 103 mP s) was higher than that of [Laur][Tf2N] (2.55 × 103 mPa s) at 25 °C. The optimal extraction conditions were an extraction equilibrium time of 40 min, an initial Sc(iii) concentration of 0.001 mol L-1, a sodium nitrate concentration of 0.5 mol L-1, and a pH of 3. The extraction efficiency of [Laur][Tf2N] and [Coca][Tf2N] could even exceed 98.7% and 96.0%, respectively. The cation exchange extraction mechanism was studied by slope analysis, IR spectroscopy and 13C NMR spectroscopy. Sc(iii) extracted using [Laur][Tf2N] and [Coca][Tf2N] could be completely stripped with 0.1 mol L-1 and 0.2 mol L-1 HNO3 once, respectively. The structure of the ILs was not broken after stripping, and the extraction efficiency of the ILs remained almost unchanged after five cycles. In addition, the extraction differences at different pH levels made it possible to separate Sc(iii) from other rare earths using ionic liquids [Laur][Tf2N] and [Coca][Tf2N].

All-trans retinoic acid alleviates transmissible gastroenteritis virus-induced intestinal inflammation and barrier dysfunction in weaned piglets.

BACKGROUND: Transmissible gastroenteritis virus (TGEV) is one of the main pathogens causing severe diarrhea of piglets. The pathogenesis of TGEV is closely related to intestinal inflammation. All-trans retinoic acid (ATRA) is the main active metabolite of vitamin A, which has immunomodulatory and anti-inflammatory properties. However, it is unclear whether ATRA can alleviate TGEV-induced intestinal inflammation and barrier dysfunction in piglets. This study aimed to investigate the effects of ATRA on growth performance, diarrhea, intestinal inflammation and intestinal barrier integrity of TGEV-challenged piglets. METHODS: In a 19-d study, 32 weaned piglets were randomly divided into 4 treatments: Control group (basal diet), TGEV group (basal diet + TGEV challenge), TGEV + ATRA5 group (basal diet + 5 mg/d ATRA + TGEV challenge) and TGEV + ATRA15 group (basal diet + 15 mg/d ATRA + TGEV challenge). On d 14, piglets were orally administered TGEV or the sterile medium. RESULTS: Feeding piglets with 5 and 15 mg/d ATRA alleviated the growth inhibition and diarrhea induced by TGEV (P < 0.05). Feeding piglets with 5 and 15 mg/d ATRA also inhibited the increase of serum diamine oxidase (DAO) activity and the decrease of occludin and claudin-1 protein levels in jejunal mucosa induced by TGEV, and maintained intestinal barrier integrity (P < 0.05). Meanwhile, 5 mg/d ATRA feeding increased the sucrase activity and the expressions of nutrient transporter related genes (GLUT2 and SLC7A1) in jejunal mucosa of TGEV-challenged piglets (P < 0.05). Furthermore, 5 mg/d ATRA feeding attenuated TGEV-induced intestinal inflammatory response by inhibiting the release of interleukin (IL)-1ß, IL-8 and tumor necrosis factor-α (TNF-α), and promoting the secretion of IL-10 and secretory immunoglobulin A (sIgA) (P < 0.05). Feeding 5 mg/d ATRA also down-regulated the expressions of Toll-like receptors and RIG-I like receptors signaling pathway related genes (TLR3, TLR4, RIG-I, MyD88, TRIF and MAVS) and the phosphorylation level of nuclear factor-κB-p65 (NF-κB p65), and up-regulated the inhibitor kappa B alpha (IκBα) protein level in jejunal mucosa of TGEV-challenged piglets (P < 0.05). CONCLUSIONS: ATRA alleviated TGEV-induced intestinal barrier damage by inhibiting inflammatory response, thus improving the growth performance and inhibiting diarrhea of piglets. The mechanism was associated with the inhibition of NF-κB signaling pathway mediated by TLR3, TLR4 and RIG-I.

Targeting iron-metabolism:a potential therapeutic strategy for pulmonary fibrosis.

Iron homeostasisis is integral to normal physiological and biochemical processes of lungs. The maintenance of iron homeostasis involves the process of intake, storage and output, dependening on iron-regulated protein/iron response element system to operate tightly metabolism-related genes, including TFR1, DMT1, Fth, and FPN. Dysregulation of iron can lead to iron overload, which increases the virulence of microbial colonisers and the occurrence of oxidative stress, causing alveolar epithelial cells to undergo necrosis and apoptosis, and form extracellular matrix. Accumulated iron drive iron-dependent ferroptosis to exacerbated pulmonary fibrosis. Notably, the iron chelator deferoxamine and the lipophilic antioxidant ferritin-1 have been shown to attenuate ferroptosis and inhibit lipid peroxidation in pulmonary fibrosis. The paper summarises the regulatory mechanisms of dysregulated iron metabolism and ferroptosis in the development of pulmonary fibrosis. Targeting iron metabolism may be a potential therapeutic strategy for the prevention and treatment of pulmonary fibrosis.

Selenomethionine alleviates chronic heat stress-induced breast muscle injury and poor meat quality in broilers via relieving mitochondrial dysfunction and endoplasmic reticulum stress.

In the present study, the chronic heat stress (CHS) broiler model was developed to investigate the potential protection mechanism of organic selenium (selenomethionine, SeMet) on CHS-induced skeletal muscle growth retardation and poor meat quality. Four hundred Arbor Acres male broilers (680 ± 70 g, 21 d old) were grouped into 5 treatments with 8 replicates of 10 broilers per replicate. Broilers in the control group were raised in a thermoneutral environment (22 ± 2 °C) and fed with a basal diet. The other four treatments were exposed to hyperthermic conditions (33 ± 2 °C, 24 h in each day) and fed on the basal diet supplied with SeMet at 0.0, 0.2, 0.4, and 0.6 mg Se/kg, respectively, for 21 d. Results showed that CHS reduced (P < 0.05) the growth performance, decreased (P < 0.05) the breast muscle weight and impaired the meat quality of breast muscle in broilers. CHS induced protein metabolic disorder in breast muscle, which increased (P < 0.05) the expression of caspase 3, caspase 8, caspase 9 and ubiquitin proteasome system related genes, while decreased the protein expression of P-4EBP1. CHS also decreased the antioxidant capacity and induced mitochondrial stress and endoplasmic reticulum (ER) stress in breast muscle, which increased (P < 0.05) the ROS levels, decreased the concentration of ATP, increased the protein expression of HSP60 and CLPX, and increased (P < 0.05) the expression of ER stress biomarkers. Dietary SeMet supplementation linearly increased (P < 0.05) breast muscle Se concentration and exhibited protective effects via up-regulating the expression of the selenotranscriptome and several key selenoproteins, which increased (P < 0.05) body weight, improved meat quality, enhanced antioxidant capacity and mitigated mitochondrial stress and ER stress. What's more, SeMet suppressed protein degradation and improved protein biosynthesis though inhibiting the caspase and ubiquitin proteasome system and promoting the mTOR-4EBP1 pathway. In conclusion, dietary SeMet supplementation increases the expression of several key selenoproteins, alleviates mitochondrial dysfunction and ER stress, improves protein biosynthesis, suppresses protein degradation, thus increases the body weight and improves meat quality of broilers exposed to CHS.

Synbiotics improve growth performance and nutrient digestibility, inhibit PEDV infection, and prevent intestinal barrier dysfunction by mediating innate antivirus immune response in weaned piglets.

This experiment was conducted to explore the effects of dietary synbiotics (SYB) supplementation on growth performance, immune function, and intestinal barrier function in piglets challenged with porcine epidemic diarrhea virus (PEDV). Forty crossbred (Duroc × Landrace × Yorkshire) weaned piglets (26 ±â€…1 d old) with a mean body weight (BW) of 6.62 ±â€…0.36 kg were randomly allotted to five groups: control (CON) I and CONII group, both fed basal diet; 0.1% SYB group, 0.2% SYB group, and 0.2% yeast culture (YC) group, fed basal diet supplemented with 0.1%, 0.2% SYB, and 0.2% YC, respectively. On day 22, all piglets were orally administrated with 40 mL PEDV (5.6 × 103 TCID50/mL) except piglets in CONI group, which were administrated with the same volume of sterile saline. The trial lasted for 26 d. Before PEDV challenge, dietary 0.1% SYB supplementation increased final BW, average daily gain (ADG), and decreased the ratio of feed to gain during 0 to 21 d (P < 0.05), as well as improved the apparent nutrient digestibility of dry matter (DM), organic matter (OM), crude protein, ether extract (EE), and gross energy (GE). At the same time, 0.2% YC also improved the apparent nutrient digestibility of DM, OM, EE, and GE (P < 0.05). PEDV challenge increased diarrhea rate and diarrhea indexes while decreased ADG (P < 0.05) from days 22 to 26, and induced systemic and intestinal mucosa innate immune and proinflammatory responses, destroyed intestinal barrier integrity. The decrease in average daily feed intake and ADG induced by PEDV challenge was suppressed by dietary SYB and YC supplementation, and 0.1% SYB had the best-alleviating effect. Dietary 0.1% SYB supplementation also increased serum interleukin (IL)-10, immunoglobulin M, complement component 4, and jejunal mucosal IL-4 levels, while decreased serum diamine oxidase activity compared with CONII group (P < 0.05). Furthermore, 0.1% SYB improved mRNA expressions of claudin-1, zonula occludens protein-1, mucin 2, interferon-γ, interferon regulatory factor-3, signal transducers and activators of transcription (P < 0.05), and protein expression of occludin, and downregulated mRNA expressions of toll-like receptor 3 and tumor necrosis factor-α (P < 0.05) in jejunal mucosa. Supplementing 0.2% SYB or 0.2% YC also had a positive effect on piglets, but the effect was not as good as 0.1% SYB. These results indicated that dietary 0.1% SYB supplementation improved growth performance under normal conditions, and alleviated the inflammatory response and the damage of intestinal barrier via improving innate immune function and decreasing PEDV genomic copies, showed optimal protective effects against PEDV infection.

Porcine epidemic diarrhea virus (PEDV) infection causes watery diarrhea, vomiting, anorexia, and high mortality in piglets, which leads to serious economic losses in many pig-producing countries. Vaccination is commonly used for the prevention of PEDV infection. However, current vaccines are ineffective in preventing infections because of genetic variants of PEDV. Therefore, developing new and efficient strategies to reduce porcine epidemic diarrhea outbreaks for piglets is desirable. Synbiotics (SYB) refer to the biological mixture of probiotics and prebiotics, which combines the advantages of both. At present, the application of probiotics or prebiotics has been widely reported in piglets feeds, which improves growth performance, immune function, microbiota community, intestinal structure, and resistance to bacterial infection. However, there was little report on whether SYB can protect piglets against PEDV infection. Therefore, this study was conducted to investigate the effects of SYB on growth performance, intestinal barrier function, and immune function in PEDV-infected weaned piglets. Results indicated that dietary SYB supplementation improved growth performance, decreased the inflammatory response, and alleviated the damage of intestinal barrier by improving innate antiviral immunity and reducing PEDV genomic copies, ultimately offering optimal protective effects against PEDV infection.

Effects of betaine on growth performance and intestinal health of rabbits fed different digestible energy diets.

An experiment was conducted to determine the effects of betaine on growth performance and intestinal health in rabbits fed diets with different levels of digestible energy. During a 36-d experiment, a total of 144 healthy 35-d-old weaned New Zealand white rabbits with a similar initial body weight (771.05 ±â€…41.79 g) were randomly distributed to a 2 × 3 factorial arrangement. Experimental treatments consisted of two levels of digestible energy (normal: 10.20 and low: 9.60 MJ/kg) and three levels of betaine (0, 500, and 1,000 mg/kg). Results indicated that rabbits fed the diet with low digestible energy (LDE) had reduced body gain/feed intake on days 1 to 14 and 1 to 36 (P < 0.05), increased the apparent total tract digestibility (ATTD) of neutral detergent fiber, acid detergent fiber (ADF), and n-free extract, and decreased the ATTD of gross energy (GE), crude fiber, and organic matter (OM; P < 0.05). The LDE diet upregulated the gene abundance levels of duodenum junctional adhesion molecule-3 (JAM-3) and downregulated the ileum toll-like receptor 4, myeloid differentiation factor 88, and interleukin-6 (IL-6; P < 0.05). Activities of amylase, lipase, trypsin, and the immunoglobulin M content in the jejunum were decreased in the LDE treatment group (P < 0.05). Dietary betaine supplementation increased the ATTD of GE, dry matter (DM), ADF, and n-free extract by LDE (P < 0.05). The villus height, crypt depth, and goblet cell numbers were decreased, and the villus-crypt ratio was increased in the duodenum (P < 0.05). The gene abundance levels of duodenum IL-2 were downregulated, and the duodenum JAM-2 and JAM-3 were upregulated (P < 0.05). Furthermore, the addition of betaine to the LDE diet increased the ATTD of GE, DM, and OM in rabbits (P < 0.05). Gene abundance levels of ileum IL-6 and duodenum JAM-3 were upregulated (P < 0.05). In summary, LDE diets can reduce the activity of intestinal digestive enzymes and decrease the ATTD of nutrients. However, the addition of betaine to LDE diets improved the intestinal barrier structure and nutrient ATTD in rabbits, with better results when betaine was added at an additive level of 500 mg/kg.

Insufficient dietary energy can cause many negative effects on animal production and cause intestinal diseases, which are one of the main causes of morbidity and mortality in rabbits. Results of some experiments demonstrated that betaine has various physiological functions such as improving energy utilization and intestinal health. Therefore, the aim of this study was to evaluate the effects of betaine supplementation on growth performance, intestinal function, and health in rabbits fed diets with different levels of digestible energy. The results showed that the addition of betaine to a low-digestible energy diet improved the gut barrier structure and nutrient digestibility in rabbits.