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Abstract Background Resolvin D1 (RvD1), a specialized pro-resolving lipid mediator (SPM), is derived from docosahexaenoic acid (DHA). It plays a key role in actively resolving inflammatory responses, which further reduces small intestinal damage. However, its regulation of the apoptosis triggered by endoplasmic reticulum (ER) stress in intestinal epithelial cells is still poorly understood. The intestinal porcine epithelial cells (IPEC-J2) were stimulated with tunicamycin to screen an optimal stimulation time and concentration to establish an ER stress model. Meanwhile, RvD1 (0, 1, 10, 20, and 50 nM) cytotoxicity and its impact on cell viability and the effective concentration for reducing ER stress and apoptosis were determined. Finally, the effects of RvD1 on ER stress and associated apoptosis were furtherly explored by flow cytometry analysis, AO/EB staining, RT-qPCR, and western blotting. Results The ER stress model of IPEC-J2 cells was successfully built by stimulating the cells with 1 µg/mL tunicamycin for 9 h. Certainly, the increased apoptosis and cell viability inhibition also appeared under the ER stress condition. RvD1 had no cytotoxicity, and its concentration of 1 nM significantly decreased cell viability inhibition (p= 0.0154) and the total apoptosis rate of the cells from 14.13 to 10.00% (p= 0.0000). RvD1 at the concentration of 1 nM also significantly reduced the expression of glucose-regulated protein 78 (GRP-78, an ER stress marker gene) (p= 0.0000) and pro-apoptotic gene Caspase-3 (p= 0.0368) and promoted the expression of B cell lymphoma 2 (Bcl-2, an anti-apoptotic gene)(p= 0.0008). Conclusions Collectively, the results shed light on the potential of RvD1 for alleviating apoptosis triggered by ER stress, which may indicate an essential role of RvD1 in maintaining intestinal health and homeostasis.

Abstract Background Several studies have proposed grading systems for risk stratification of early‐stage lung adenocarcinoma based on histological patterns. However, the reproducibility of these systems is poor in clinical practice, indicating the need to develop a new grading system which is easy to apply and has high accuracy in prognostic stratification of patients. Methods Patients with stage I invasive nonmucinous lung adenocarcinoma were retrospectively collected from pathology archives between 2009 and 2016. The patients were divided into a training and validation set at a 6:4 ratio. Histological features associated with patient outcomes (overall survival [OS] and progression‐free survival [PFS]) identified in the training set were used to construct a new grading system. The newly proposed system was validated using the validation set. Survival differences between subgroups were assessed using the log‐rank test. The prognostic performance of the novel grading system was compared with two previously proposed systems using the concordance index. Results A total of 539 patients were included in this study. Using a multioutcome decision tree model, four pathological factors, including the presence of tumor spread through air space (STAS) and the percentage of lepidic, micropapillary and solid subtype components, were selected for the proposed grading system. Patients were accordingly classified into three groups: low, medium, and high risk. The high‐risk group showed a 5‐year OS of 52.4% compared to 89.9% and 97.5% in the medium and low‐risk groups, respectively. The 5‐year PFS of patients in the high‐risk group was 38.1% compared to 61.7% and 90.9% in the medium and low‐risk groups, respectively. Similar results were observed in the subgroup analysis. Additionally, our proposed grading system provided superior prognostic stratification compared to the other two systems with a higher concordance index. Conclusion The newly proposed grading system based on four pathological factors (presence of STAS, and percentage of lepidic, micropapillary, and solid subtypes) exhibits high accuracy and good reproducibility in the prognostic stratification of stage I lung adenocarcinoma patients.

ABSTRACT: This study investigated the effects of feeding paddy rice on the physiology, metabolism, and gut microbiota of ducks in a rice–duck–crayfish (RDC) system. A total of 540 ducks (20-days-old) were randomly divided into 3 groups with 3 replicates and 60 ducks per replicate. The 40-d experiment involved 3 diet treatments: a complete diet (CD), 50% paddy rice + 50% complete diet (RCD), and 100% paddy rice diet (RD). Results show that feeding paddy rice did not significantly affect duck growth, the final weight in the RD group was reduced by 5%, and the feed-to-gain ratio increased by 7% compared to the CD group. Additionally, compared with the CD group, the keel length, gizzard and proventriculus indices, and serum high-density lipoprotein levels increased (P < 0.05), and duodenal villus height and ileal crypt depth (P < 0.05) reduced in the RD group and ileal villus height decreased in the RCD group (P < 0.05). Compared with the CD group, the cecal abundance of Bacteroidota, Prevotellaceae_Ga6A1_group, and Prevotellaceae_NK3B31_group decreased in the RD group (P < 0.05) while the abundance of Firmicutes, Megamonas and Faecalibacterium increased (P < 0.05). Metabolome analysis revealed that serum citric acid increased (P < 0.05) in the RCD and RD groups, whereas cytidine, cytosine, and 4-aminobutyric acid decreased (P < 0.05) in the RD group. In conclusion, these preliminary results suggest that paddy rice supplementation under an RDC system had no significant effect on duck growth, but it did cause changes in intestinal morphology, microbiota, and serum metabolic profiles. However, it is important to note that the limited overall number of replicates in this study contributed to a certain degree of high variance. While the growth differences among groups were not statistically significant, the full replacement of paddy rice still poses potential performance losses. In practical applications, this finding provides a reference for the RDC system, but further validation through larger-scale trials is required.

ABSTRACT: Retinoic acid (RA) is an active derivative of vitamin A and is involved in a variety of physiological processes, including cell growth, antioxidant, and inflammation. However, the role of RA in intestinal oxidative stress injury in caged-stressed laying ducks is unknown. In this study, we analyzed the effect and underlying mechanism of RA supplementation on intestinal damage in cage-stressed young laying ducks. One hundred and sixty laying ducks were divided into 5 treatment groups, including a control group (CR) and 4 treatment groups exposed to different RA concentrations (2,500, 5,000, 7,500 and 10,000 IU/kg, TG1 to TG4). The experimental period comprised a 7-d prefeeding period and a 10-d experimental feeding period, for a total of 17 d. Phenotypic analysis revealed that compared with the control group, RA addition increased the intestinal villus height and the villus-to-crypt ratio; decreased the crypt depth (P < 0.01); decreased the serum diamine oxidase and D-lactate concentrations (P < 0.05); increased the serum antioxidant capacity and intestinal antioxidant gene expression levels (P < 0.05); and increased the expression levels of tight junction-related genes, with the greatest effect observed in TG2 group. Our further whole-transcriptome analysis of duodenum tissues from CR and TG2 ducks revealed 706 differentially expressed mRNAs (DEmRNAs), 357 differentially expressed lncRNAs (DElncRNAs), 14 differentially expressed circRNAs (DEcircRNAs), and 4 differentially expressed miRNAs (DEmiRNAs). These DEGs are involved in calcium signaling, NOD-like receptor signaling, pyruvate metabolism, Jak-STAT signaling, Wnt signaling, riboflavin metabolism, and the adherens junction and tight junction pathways. The results of omics and marker gene expression analysis suggested that RA treatment may play a role in endoplasmic reticulum stress (ERS) and apoptosis. In conclusion, the addition of RA to the diet improved intestinal injury by improving the redox homeostasis of intestinal cells associated with ERS, enhancing the intestinal tight junction structure and alleviating the apoptosis of intestinal epithelial cells; moreover, 5,000 IU/kg RA was determined to be the most appropriate concentration for supplementation.

ABSTRACT: Previously, we reported that glucagon-like peptide-1 (GLP-1) and its analog liraglutide could inhibit fat de novo synthesis in the liver and reduce abdominal fat accumulation in broiler chickens. Nevertheless, the impact of GLP-1 on adipocyte fat deposition remains enigmatic. This study aimed to investigate the effects of GLP-1, via its analog liraglutide, on chicken chicken adipocytes in vitro. Chemical assays, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot were employed to assess the proliferation, differentiation, and fat deposition of chicken adipocytes. Our findings indicated that liraglutide significantly suppressed cell proliferation and promoted preadipocyte differentiation in comparison to the control group. This was evidenced by elevated triglyceride (TG) content and upregulated mRNA expression of lipogenesis-related enzymes, such as acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), as well as regulators including peroxisome proliferator-activated receptor γ (PPARγ), sterol regulatory element binding protein-1 (SREBP1) and CCAAT/enhancer binding protein α (CEBPα). In mature adipocytes, liraglutide attenuated fat deposition by inhibiting fat de novo synthesis, evidenced by decreased mRNA expression of ACC, FAS, PPARγ, C/EBPα, and SREBP1, and concurrent upregulation of phosphorylated AMP-activated protein kinase (p-AMPK) and phosphorylated ACC (p-ACC). This resulted in reduced accumulation of lipid droplets and TG content in mature adipocytes. Collectively, our findings indicate that liraglutide suppresses the proliferation of preadipocytes, enhances their differentiation, and concurrently inhibits de novo lipogenesis in mature adipocytes. This observation offers profound insights into the mechanisms that underlie liraglutide's anti-adipogenic effects, which could have significant implications for the treatment of obesity in broiler chickens.

A Se site targeted-two circles antioxidant of polyphenols EGCG and genistein in glutathione peroxidase 4 (GPx4)–like catalytic peroxide H2O2 and cumene hydroperoxide degradation was demonstrated by surface-enhanced Raman scattering (SERS). Se atom's active center is presenting a ‘low-oxidation’ and a ‘high-oxidation’ catalytic cycle. The former is oxidized to selenenic acid (SeO−) with a Raman bond at 619/ 610 cm−1 assigned to the νO − Se by the hydroperoxide substrate at 544/ 551 cm−1 assigned to ωHSeC decreased. Under oxidative stress, the enzyme shifted to ‘high-oxidation’ catalytic cycle, in which GPx4 shuttles between R-SeO− and R-SeOO− with a Raman intensity of bond at 840/ 860 cm−1 assigned to νOSe. EGCG could act as a reducing agent both in H2O2 and Cu-OOH degradation, while, genistein can only reduce Cu-OOH, because it binds more readily to the selenium site in GPx4 than EGCG with a closer proximity, therefore may affect its simultaneous binding to coenzymes.

IntroductionAs a symbiotic probiotic for the host, Clostridium butyricum (CB) has the potential to strengthen the body’s immune system and improve intestinal health. However, the probiotic mechanism of CB is not completely understood. The Clostridium butyricum CBX 2021 strain isolated by our team from a health pig independently exhibits strong butyric acid production ability and stress resistance. Therefore, this study comprehensively investigated the efficacy of CBX 2021 in pigs and its mechanism of improving pig health.MethodsIn this study, we systematically revealed the probiotic effect and potential mechanism of the strain by using various methods such as microbiome, metabolites and transcriptome through animal experiments in vivo and cell experiments in vitro.ResultsOur in vivo study showed that CBX 2021 improved growth indicators such as daily weight gain in weaned piglets and also reduced diarrhea rates. Meanwhile, CBX 2021 significantly increased immunoglobulin levels in piglets, reduced contents of inflammatory factors and improved the intestinal barrier. Subsequently, 16S rRNA sequencing showed that CBX 2021 treatment implanted more butyric acid-producing bacteria (such as Faecalibacterium) in piglets and reduced the number of potentially pathogenic bacteria (like Rikenellaceae RC9_gut_group). With significant changes in the microbial community, CBX 2021 improved tryptophan metabolism and several alkaloids synthesis in piglets. Further in vitro experiments showed that CBX 2021 adhesion directly promoted the proliferation of a porcine intestinal epithelial cell line (IPEC-J2). Moreover, transcriptome analysis revealed that bacterial adhesion increased the expression of intracellular G protein-coupled receptors, inhibited the Notch signaling pathway, and led to a decrease in intracellular pro-inflammatory molecules.DiscussionThese results suggest that CBX 2021 may accelerate piglet growth by optimizing the intestinal microbiota, improving metabolic function and enhancing intestinal health.

This study investigated the batch stability of egg white peptides (EWPs) during the enzymatic hydrolysis process, and confirmed the potential application of four crucial four peptides inoxidative damage repair. The results revealed that different batches of EWPs had good stability relating to antioxidant activity. With a similar sequence to confirmed antioxidant peptides, four EWPs (QMDDFE, WDDDPTD, DEPDPL, and FKDEDTQ) were identified withhigh repetition rates, and their potential to repair oxidative damage was investigated. Network pharmacology results showed that these four peptides could regulate the targets related to oxidative damage. Enrichment results demonstrated that these four peptides could influence the targets and pathways related to glutathione transferase activity (enrichment score: 148.0) and glutathione metabolism (p value: 9.22 × 10−10). This study could provide evidence for the batch stability of hydrolyzed prepared EWPs, and offer theoretical support for the development of antioxidant damage ingredients derived from foods.

Aiming at the problem that the surface defects of blAister tablets are difficult to detect correctly, this paper proposes a detection method based on the improved U2Net. First, the features extracted from the RSU module of U2Net are enhanced and adjusted using the large kernel attention mechanism, so that the U2Net model strengthens its ability to extract defective features. Second, a loss function combining the Gaussian Laplace operator and the cross-entropy function is designed to make the model strengthen its ability to detect edge defects on the surface of blister tablets. Finally, thresholds are adaptively determined using the local mean and OTSU(an adaptive threshold segmentation method) method to improve accuracy. The experimental results show that the method proposed in this paper can reach an average accuracy of 99% and an average precision rate of 96.3%; the model test only takes 50 ms per image, which can meet the rapid detection requirements. Minor surface defects can also be accurately detected, which is better than other algorithmic models of the same type, proving the effectiveness of this method.

Nickel (Ni), an environmental health hazard, is nephrotoxic to humans, but the exact mechanism is unknown. This study aims to identify whether nephrotoxicity is associated with autophagy. Here, nickel chloride (NiCl2) increased autophagy in TCMK-1 cells. NiCl2 induces autophagy through Akt and AMPK/mTOR pathways. Next, oxidative stress was investigated in NiCl2-induced autophagy. The findings demonstrated that the antioxidant (NAC) or mitochondrial targeted antioxidant (Mito-TEMPO) attenuated NiCl2-induced autophagy, reversed the influence on AMPK-mTOR and Akt pathways. Additionally, our study examined the role of autophagy in NiCl2-induced nephrotoxicity. Autophagy inhibition with 3-MA could inhibit cell viability and increase apoptosis in the TCMK-1 cells, however, autophagy promotion with rapamycin relieved cytotoxicity and decreased apoptosis. Additionally, co-treatment with Z-VAD-FMK reduced cytotoxicity, but did not affect autophagy. Besides, NiCl2 can increase the level of mitophagy in vivo and vitro. Mitophagy inhibition could inhibit cell viability and increase apoptosis in the TCMK-1 cells, whereas, promotion of mitophagy could increase cell viability and decrease apoptosis. In summary, above-mentioned results showed that NiCl2 induces autophagy in TCMK-1 cells through oxidative stress-dependent AMPK/AKT-mTOR pathway, autophagy plays a role in reducing NiCl2-induced renal toxicity, and a major mechanism in autophagy's inhibitory effect on NiCl2-induced apoptosis may be mitophagy.

This study investigates the underlying causes of Variable Polarity Plasma Arc Welding (VPPAW) spatial positional instability and its adverse impact on weld seam quality. Microstructural analysis reveals that the primary cause of poor transverse mechanical properties is the asymmetric distribution of grains. Through the study of heat and mass transfer in the molten pool, it was found that the asymmetric flow of molten metal under the influence of gravity is the main factor leading to uneven temperature distribution and asymmetric grain distribution in the weld pool. A novel approach based on a predefined temperature field is proposed to regulate the weld pool's stability and welding quality. The implementation of the predefined temperature field effectively improves VPPAW weld pool flow, leading to enhanced temperature distribution and grain size and distribution. These findings provide a theoretical foundation and valuable engineering recommendations for achieving high-quality spatial position welding in VPPAW.

This study investigated the effects of ultrasound-assisted soybean lecithin (SL) on the rehydration behavior and physical properties of egg white protein powder (EWPP) and its ability to enhance the efficacy of EWPP instant solubility. The results of rehydration, including wettability and dispersibility, indicated that ultrasound (200 W)-assisted SL (5 g/L) addition had the shortest wetting time and dispersion time, which were 307.14 ± 7.00 s and 20.95 ± 2.27 s, respectively. In terms of powder properties, the EWPP with added SL had lower lightness, moisture content and bulk density. In addition, the increase in average particle size, net negative charge, free sulfhydryl group content and surface hydrophobicity indicated that ultrasound treatment facilitated the protein structures unfolding and promoted the formation of SL-EWP complexes. Overall, our study provided a new perspective for the food industry regarding using ultrasound technology to produce instant EWPP with higher biological activity and more complete nutritional value.

The search for new probiotics has been regarded as an important approach to improving intestinal health in animals. Bacillus has many advantages, such as strong resistance to harmful external factors, wide distribution, and easy colonization of the intestine. Hence, this study aims to screen for a probiotic Bacillus strain that improves animal intestinal health and to elucidate its probiotic mechanism so as to provide probiotic resources for the development of feed-using probiotic formulations. In this research, a strain of Bacillus was isolated from adult pig feces and named B. tequilensis YB-2. In vitro probiotic experiments showed that B. tequilensis YB-2 had strong acid and bile salt resistance, indicating that this strain can customize in the intestine. To further explore the effect of B. tequilensis YB-2 upon animal intestinal health, DSS-induced murine colitis models were established, and the body weight, colonic morphology, inflammatory cytokines level, and intestinal-barrier- and TLR4/NF-κB-pathway-related protein were determined. The results showed that mice receiving drinking water with 3% DSS were found to develop colitis symptoms, including body weight loss and increased disease activity index (DAI); colon length and microvilli shedding were shortened; tight junctions were disrupted; goblet cells decreased; anti-inflammatory cytokines were inhibited; and pro-inflammatory cytokines and the TLR4/NF-κB signaling pathway were activated. Notably, orally received B. tequilensis YB-2 alleviated symptoms of DSS-induced colitis in mice. The above results indicated that B. tequilensis YB-2 was capable of improving colitis in mice by weakening inflammation and intestinal barrier damage, and its mechanism may involve the TLR4/NF-κB pathway. Overall, this research suggests that B. tequilensis YB-2 has the potential to serve as an animal feed additive to prevent intestinal inflammation.

Abstract Ulcerative colitis (UC) threatens teenagers’ health as it can damage the immune system and intestinal flora. The impact of egg white peptides (EWPs) on dextran sulfate sodium‐induced young colitis mice models was investigated. Findings suggested that EWPs improved colitis symptoms and modulated inflammatory factors in mice. EWPs treatment could enhance the abundance ratio of Firmicutes to Bacteroidetes, the relative abundances of Lactobacillus, and the concentrations of short‐chain fatty acids (SCFAs). According to Pearson correlation analysis, Bacteroides was favorably connected with IL‐6 and negatively correlated with acetic acid and total SCFAs. In conclusion, EWPs relieved young mice's UC symptoms by inhibiting the progression of colitis, regulating the inflammation response, and improving the imbalance of intestinal flora. The current study also supports using EWPs as a practical dietary resource for ameliorating UC.

Abstract Background Fertility declines in high-parity sows. This study investigated whether parity-dependent declines in embryonic survival and reproductive performance could be restored by dietary coenzyme Q10 (CoQ10) supplementation. Methods Two experiments were performed. In Exp. 1, 30 young sows that had completed their 2nd parity and 30 high-parity sows that had completed their 10th parity, were fed either a control diet (CON) or a CON diet supplemented with 1 g/kg CoQ10 (+ CoQ10) from mating until slaughter at day 28 of gestation. In Exp. 2, a total of 314 post-weaning sows with two to nine parities were fed the CON or + CoQ10 diets from mating throughout gestation. Results In Exp. 1, both young and high-parity sows had a similar number of corpora lutea, but high-parity sows had lower plasma CoQ10 concentrations, down-regulated genes involved with de novo CoQ10 synthesis in the endometrium tissues, and greater levels of oxidative stress markers in plasma and endometrium tissues. High-parity sows had fewer total embryos and alive embryos, lower embryonic survival, and greater embryo mortality than young sows. Dietary CoQ10 supplementation increased the number of live embryos and the embryonic survival rate to levels similar to those of young sows, as well as lowering the levels of oxidative stress markers. In Exp. 2, sows showed a parity-dependent decline in plasma CoQ10 levels, and sows with more than four parities showed a progressive decline in the number of total births, live births, and piglets born effective. Dietary supplementation with CoQ10 increased the number of total births, live births, and born effective, and decreased the intra-litter covariation coefficients and the percentage of sows requiring farrowing assistance during parturition. Conclusions Dietary CoQ10 supplementation can improve the embryonic survival and reproductive performance of gestating sows with high parity, probably by improving the development of uterine function.

Abstract Introduction Stage IB (deep myometrial invasion) high‐grade endometrioid adenocarcinoma (EA), regardless of LVSI status, is classified into high‐intermediate risk groups, requiring surgical lymph node staging. Intraoperative frozen section (IFS) is commonly used, but its adequacy and reliability vary between reports. Hence, we determined the utility of IFS in identification of high‐risk factors, including deep myometrial invasion and high‐grade. Method We retrospectively analyzed 9,985 cases operated with hysterectomy and diagnosed with FIGO stage I/II EA in postoperative paraffin section (PS) results at 30 Chinese hospitals from 2000 to 2019. We determined diagnostic performance of IFS and investigated whether the addition of IFS to preoperative biopsy and imaging could improve identification of high‐risk factors. Results IFS and postoperative PS presented the highest concordance in assessing deep myometrial invasion (Kappa: 0.834), followed by intraoperative gross examination (IGE Kappa: 0.643), MRI (Kappa: 0.395), and CT (Kappa: 0.207). IFS and postoperative PS presented the highest concordance for high‐grade EA (Kappa: 0.585) compared to diagnostic curettage (D&C 0.226) and hysteroscope (Hys 0.180). Sensitivity and specificity for detecting deep myometrial invasion were 86.21 and 97.20% for IFS versus 51.72 and 88.81% for MRI, 68.97 and 94.41% for IGE. These figures for detecting high‐grade EA were 58.21 and 96.50% for IFS versus 16.42 and 98.83% for D&C, 13.43 and 98.64% for Hys. Parallel strategies, including MRI‐IFS (Kappa: 0.626), D&C‐IFS (Kappa: 0.595), and Hys‐IFS (Kappa: 0.578) improved the diagnostic efficiencies of individual preoperative examinations. Based on the high sensitivity of IFS, parallel strategies improved the sensitivities of preoperative examinations to 89.66% (MRI), 64.18% (D&C), 62.69% (Hys), respectively, and these differences were statistically significant (p = 0.000). Conclusion IFS presented reasonable agreement rates predicting postoperative PS results, including deep myometrial invasion and high‐grade. IFS helps identify high‐intermediate risk patients in preoperative biopsy and MRI and guides intraoperative lymphadenectomy decisions in EA.

Abstract Background Bisphosphonates (BPs) are widely used in clinical practice to prevent and treat bone metabolism-related diseases. Medication-related osteonecrosis of the jaw (MRONJ) is one of the major sequelae of BPs use. Early prediction and intervention of MRONJ are of great significance. Methods Ninety-seven patients currently on treatment with BPs or with a history of BPs usage and 45 healthy volunteers undergoing dentoalveolar surgery were included in this study. Participants' serum Semaphorin 4D (Sema4D) levels were measured and analyzed before participants underwent surgery (T0) and after a 12-month follow-up (T1). Kruskal–Wallis test and ROC analysis were used to examine the predictive effect of Sema4D on MRONJ. Results Sema4D levels in serum of patients corresponding to confirmed MRONJ were significantly lower at both T0 and T1 time points compared to non-MRONJ and healthy controls. Sema4D has a statistically predictive effect on the occurrence and diagnosis of MRONJ. Serum Sema4D levels were significantly reduced in MRONJ class 3 patients. MRONJ patients who received intravenous BPs had significantly lower Sema4D levels than those who received oral BPs. Conclusion Serum Sema4D level has predictive value for the onset of MRONJ in BPs users within 12 weeks after dentoalveolar surgery.

Under caged stress conditions, severe disruptions in duck intestinal barrier function, which adversely affect economic performance, have been observed. MiRNAs play a crucial role in cellular processes, but the mechanisms underlying their involvement in repairing oxidative stress-induced damage to duck intestinal barriers have not been elucidated. We performed miRNA-seq and protein tandem mass tagging (TMT) sequencing and identified differentially expressed miRNAs and proteins in oxidative stress-treated ducks. Dual-luciferase reporter vector experiments, RT-qPCR, and Western blotting revealed the regulatory role of apla-miR-106a-5p/MAP3K2 in intestinal barrier damage repair. The results showed that oxidative stress led to shortened villi and deepened crypts, impairing intestinal immune function. Significant downregulation of apla-miR-106a-5p was revealed by miRNA-seq, and the inhibition of its expression not only enhanced cell viability but also improved intestinal barrier function. TMT protein sequencing revealed MAP3K2 upregulation in caged-stressed duck intestines, and software analysis confirmed MAP3K2 as the target gene of apla-miR-106a-5p. Dual-fluorescence reporter gene experiments demonstrated direct targeting of MAP3K2 by apla-miR-106a-5p. RT-qPCR showed no effect on MAP3K2 expression, while Western blot analysis indicated that MAP3K2 protein expression was suppressed. In summary, apla-miR-106a-5p targets MAP3K2, regulating gene expression at the transcriptional level and facilitating effective repair of intestinal barrier damage. This discovery provides new insights into the molecular mechanisms of physiological damage in ducks under caged stress, offering valuable guidance for related research.

Abstract Introduction Myometrial invasion is a prognostic factor for lymph node metastases and decreased survival in non-endometrioid endometrial carcinoma patients. Herein, we explored the mode of myometrial invasion diagnosis in FIGO stage I non-endometrioid carcinoma and evaluated the differences in diagnostic efficiency among intraoperative frozen section (IFS), intraoperative gross examination (IGE), magnetic resonance imaging (MRI), and computed tomography (CT) in clinical practice. Finally, we suggested which test should be routinely performed. Method This was a historical cohort study nationwide with 30 centers in China between January 2000 and December 2019. Clinical data, including age, histology, method of myometrial invasion evaluation (MRI, CT, IGE, and IFS), and final diagnosis of postoperative paraffin sections, were collected from 490 non-endometrioid endometrial carcinoma (serous, clear cell, undifferentiated, mixed carcinoma, and carcinosarcoma) women in FIGO stage I. Results Among the 490 patients, 89.59% presented myometrial invasion. The methods reported for myometrial invasion assessment were IFS in 23.47%, IGE in 69.59%, MRI in 37.96%, and CT in 10.20% of cases. The highest concordance was detected between IFS and postoperative paraffin sections (Kappa = 0.631, accuracy = 93.04%), followed by IGE (Kappa = 0.303, accuracy = 82.40%), MRI (Kappa = 0.131, accuracy = 69.35%), and CT (Kappa = 0.118, accuracy = 50.00%). A stable diagnostic agreement between IFS and the final results was also found through the years (2000–2012: Kappa = 0.776; 2013–2014: Kappa = 0.625; 2015–2016: Kappa = 0.545; 2017–2019: Kappa = 0.652). Conclusion In China, the assessment of myometrial invasion in non-endometrioid endometrial carcinoma is often performed via IGE, but the reliability is relatively low in contrast to IFS. In clinical practice, IFS is a reliable method that can help accurately assess myometrial invasion and intraoperative decision-making (lymph node dissection or not). Hence, it should be routinely performed in non-endometrioid endometrial carcinoma patients.

Oncorhynchus mykiss is delicious and contains abundant flavor substances. However, few studies focused on umami peptides of O. mykiss. In the current work, umami peptides derived from O. mykiss were identified using virtual screening, molecular docking, and electronic tongue analysis. First, the O. mykiss protein was hydrolyzed using the PeptideCutter online enzymolysis program. Subsequently, water-soluble and toxicity screening were performed by Innovagen and ToxinPred software, respectively. The potential peptides were docked with umami receptor T1R1/T1R3. Furthermore, taste properties of potential peptides were validated by electronic tongue. Docking results suggested that the three tetrapeptide EANK, EEAK, and EMQK could enter the binding pocket in the T1R1 cavity, wherein Arg151, Asp147, Gln52, and Arg277 may play key roles in the production of umami taste. Electronic tongue results showed that the umami value of EANK, EEAK, and EMQK were stronger than monosodium glutamate. This work provides a new insight for the screening of umami peptides in O. mykiss.

As an important nutritional and functional base for food, protein powders are widely used in the food processing industry. However, the solubility of protein powders is reduced during the dissolution process due to lumping and agglomeration caused by interfacial effects, which severely limits the application and economic value of food proteins. Food surfactants can effectively bind protein powders and reduce the interfacial effects that occur during the dissolution process. Therefore, food surfactants can be more widely used to improve the solubility of protein powders. This paper reviews the main types of food surfactants, their mechanism of action on protein binding, and their effects on the various stages of protein powder solubilization, intending to provide a theoretical reference for the application of food surfactants in highly soluble protein powders.

The purpose of this study was to screen the xanthine oxidase (XO) inhibitory peptides from egg white proteins through virtual hydrolysis, in vitro activity validation, and molecular docking. The results demonstrated that tripeptide EEK from ovalbumin exhibited potent XO inhibitory activity with an IC50 value of 141 µmol/L. The molecular docking results showed that tripeptide EEK bound with the active center of XO via 3 carbon hydrogen bond interactions, 2 salt bridges, 5 conventional hydrogen bond interactions, and 4 attractive charge interactions. The residues Glu802, Phe1009, and Arg880 may play key roles in the XO catalytic reaction. Especially, the key intermolecular forces of inhibiting XO activity may be special type of hydrogen bonds including carbon hydrogen bond interactions and attraction charge interactions. The novel tripeptide EEK is potential candidates for controlling hyperuricemia.

The understanding of the structural requirements and the intermolecular-interaction mechanism are important for discovering potent angiotensin-converting enzyme (ACE) inhibitory peptides. In this study, we modified an egg-white derived peptide, LAPYK, using the amino acids with different properties to produce the LAPYK-modified peptides. The ACE inhibitory activities of the modified peptides were determined to explore the structural requirements of ACE inhibitory peptides (ACEIPs). Molecular simulation and isothermal titration calorimetry analysis were used to investigate interactions between the peptides and ACE. We found that hydrophobicity and the amino acids with ring structures were beneficial for the ACE inhibitory activities of the peptides. The results of the molecular mechanics poisson boltzmann surface area (MMPBSA) binding free energy calculations indicated that the polar solvation free energy (ΔGpolar) of the charged peptides (LAPYK, LAPYE) were unfavorable for binding to ACE. On the other hand, the results of isothermal titration calorimetry analyses suggested that the enthalpy-driven ACE-peptide interactions were more favorable than the entropy-driven ACE-peptide interaction counterparts.

Despite improvements in modern medical therapies, inflammatory diseases, such as atherosclerosis, diabetes, non-alcoholic fatty liver, chronic kidney diseases, and autoimmune diseases have high incidence rates, still threaten human health, and represent a huge financial burden. N6-methyladenosine (m6A) modification of RNA contributes to the pathogenesis of various diseases. As the most widely discussed m6A methyltransferase, the pathogenic role of METTL3 in inflammatory diseases has become a research hotspot, but there has been no comprehensive review of the topic. Here, we summarize the expression changes, modified target genes, and pathogenesis related to METTL3 in cardiovascular, metabolic, degenerative, immune, and infectious diseases, as well as tumors. In addition to epithelial cells, endothelial cells, and fibroblasts, METTL3 also regulates the function of inflammation-related immune cells, including macrophages, neutrophils, dendritic cells, Th17 cells, and NK cells. Regarding therapeutic applications, METTL3 serves as a target for the treatment of inflammatory diseases with natural plant drug components, such as emodin, cinnamaldehyde, total flavonoids of Abelmoschus manihot, and resveratrol. This review focuses on recent advances in the initiation, development, and therapeutic application of METTL3 in inflammatory diseases. Knowledge of the specific regulatory mechanisms involving METTL3 can help to deepen understanding of inflammatory diseases and lay the foundation for the development of precisely targeted drugs to address inflammatory processes.

BackgroundMyocardial fibrosis, as quantified by late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR), provides valuable prognostic information for patients with myocarditis. However, due to the low incidence rate of fulminant myocarditis (FM) and accordingly small sample size, the knowledge about the role of LGE to patients with FM is limited.Methods and resultsA total of 44 adults with viral-FM receiving the Chinese treating regimen were included in this retrospective study. They were divided into the low LGE group and the high LGE group according to the ratio of LGE to left ventricular mass (LGE mass%). CMR exams and LGE were performed after hemodynamic assistance at discharge in all patients with FM. Routine echocardiography parameters and global longitudinal strain (GLS) at discharge and at 2-year follow-up were obtained and then compared. Both left ventricular ejection fraction (LVEF) and GLS showed no significant difference in both groups at discharge, whereas significant differences were observed at 2-year follow-up between two groups. Moreover, there were significant improvements of LVEF and GLS in the low LGE group, but not in the high LGE group during the 2-year period. Furthermore, LGE mass% was negatively correlated with GLS and LVEF.ConclusionsThere were two distinct forms of LGE presentation in patients with FM. Moreover, the cardiac function of patients with low LGE was significantly better than those with high LGE at 2-year follow-up. LGE mass% at discharge provided significant prognosis information about cardiac function of patients with FM.

Background: Vaccination is the most effective way to prevent coronavirus disease 2019 (COVID-19). However, it is often less protective and does not significantly increase antibody levels, especially in individuals with impaired immune systems. Nevertheless, the immunocompetence can be enhanced using a natural immunomodulator, such as Dendrobium officinale aqueous extract (DoAE). Methods: To determine whether DoAE promotes antibody production, we treated healthy volunteers with DoAE during COVID-19 vaccination. Meanwhile, the control volunteers were given a placebo (cornstarch) during the vaccination. Antibody levels were measured at three-week intervals in the DoAE and control groups. Results: DoAE enhanced immunity and preserved immune cell homeostasis. However, the neutralizing antibody (nAb) levels in the DoAE group were lower than those in the control group. Analysis of the gut microbiota revealed that the abundance of anti-inflammatory flora was increased, while the pro-inflammatory flora was reduced in the DoAE group. Conclusion: DoAE has immunomodulatory and anti-inflammatory properties. Therefore, DoAE has the potential for COVID-19 prophylaxis, treatment, and recovery from the adverse effects of COVID-19. However, its anti-inflammatory activity affects the production of nAbs. Thus, DoAE may not be recommended for consumption during COVID-19 vaccination.

Puerarin is an isoflavone extracted from Pueraria mirifica, a wildlife leguminous plant. It has been reported to possess antioxidant, anti-inflammatory, and anti-bacterial properties. However, the effects of directly adding puerarin to the diets of sows, in terms of reproductive performance and antioxidant properties, have not been reported. For this study, 240 sows with varying parities were selected and randomly divided into six treatment groups using a two × three experimental design. The six treatment groups consisted of two diets (control and puerarin) and three parities (zero, one, and two parities or more). The puerarin group was supplemented with 1 g/kg of puerarin. The experiment commenced with mating and continued until 21 days post-delivery. The sow reproductive performance was not affected by supplementing their diets with puerarin (p > 0.05). Dietary supplementation with puerarin significantly increased the daily body weight (BW) gain of piglets and their mean BW at weaning (p < 0.05). Compared with the control group, sows in the puerarin group had significantly higher glutathione peroxidase activity in serum and also significantly increased immunoglobulin A and G levels in serum, colostrum, and milk, but significantly lower malondialdehyde concentration in serum (p < 0.05). Thus, puerarin improved the immune response and antioxidant capacity of sows and increased the daily BW gain of their offspring.

Egg white proteins pose notable limitations in emulsion applications due to their inadequate wettability and interfacial instability. Polyphenol-driven alterations in proteins serve as an effective strategy for optimizing their properties. Herein, covalent and non-covalent complexes of egg white proteins-proanthocyanins were synthesized. The analysis of structural alterations, amino acid side chains and wettability was performed. The superior wettability (80.00° ± 2.23°) and rigid structure (2.95 GPa) of covalent complexes established favorable conditions for their utilization in emulsions. Furthermore, stability evaluation, digestion kinetics, free fatty acid (FFA) release kinetics, and correlation analysis were explored to unravel the impact of covalent and non-covalent modification on emulsion stability, dynamic digestion process, and interlinkages. Emulsion stabilized by covalent complex exhibited exceptional stabilization properties, and FFA release kinetics followed both first-order and Korsmeyer–Peppas models. This study offers valuable insights into the application of complexes of proteins-polyphenols in emulsion systems and introduces an innovative approach for analyzing the dynamics of the emulsion digestion process.

Phosphorus (P) is an essential nutrient for diverse biological processes, which aggregate to the animal's requirement for P, and nutritionists strive to meet this requirement accurately. The P demand for a growing pig comprises requirements for maintenance and tissue deposition. The P in feed ingredients, however, must be digested and absorbed before its ultimate partition between the 2 aforementioned requirement components. Phosphorus from various sources could behave differently during digestion and absorption, which results in their disparate bioavailability for pigs. The system of standardized total tract digestibility reflects true total tract digestibility of P and feed ingredient effects on specific endogenous P loss with relative ease of implementation, and this system guarantees satisfactory additivity in digestible P among the ingredients in a diet—the foundation for diet formulation. The basal endogenous P loss, which is much easier to measure than the specific endogenous P loss, is considered as part of the pig's maintenance requirement. With this arrangement, a digestibility framework is established both for measuring the P-providing capacity of various feed ingredients and for describing the pig's P requirement. This framework entails basic understanding of the function, digestion, absorption, excretion, and homeostasis of P as support pillars. Understanding the workings of this framework enables potential integration of factors such as environment conditions and disease status in future P requirement models. The current review discusses dietary sources, digestion, absorption, bioavailability and requirement of P for growing pigs to understand the status quo, revealing the points of consensus as well as those of debate, and to encourage further investigation to provide more clarity.

Multidrug resistance (MDR) promotes tumor recurrence and metastasis and heavily reduces anticancer efficiency, which has become a primary reason for the failure of clinical chemotherapy. The mechanisms of MDR are so complex that conventional chemotherapy usually fails to achieve an ideal therapeutic effect and even accelerates the occurrence of MDR. In contrast, the combination of chemotherapy with dual-drug has significant advantages in tumor therapy. A novel dual-drug codelivery nanosystem, which combines dual-drug administration with nanotechnology, can overcome the application limitation of free drugs. Both the characteristics of nanoparticles and the synergistic effect of dual drugs contribute to circumventing various drug-resistant mechanisms in tumor cells. Therefore, developing dual-drug codelivery nanosystems with different multidrug-resistant mechanisms has an important reference value for reversing MDR and enhancing the clinical antitumor effect. In this review, the advantages, principles, and common codelivery nanocarriers in the application of dual-drug codelivery systems are summarized. The molecular mechanisms of MDR and the dual-drug codelivery nanosystems designed based on different mechanisms are mainly introduced. Meanwhile, the development prospects and challenges of codelivery nanosystems are also discussed, which provide guidelines to exploit optimized combined chemotherapy strategies in the future.

Background Mismatch repair deficiency (dMMR) is a well-recognized biomarker for response to immune checkpoint blockade (ICB). Strategies to convert MMR-proficient (pMMR) to dMMR phenotype with the goal of sensitizing tumors to ICB are highly sought. The combination of bromodomain containing 4 (BRD4) inhibition and ICB provides a promising antitumor effect. However, the mechanisms underlying remain unknown. Here, we identify that BRD4 inhibition induces a persistent dMMR phenotype in cancers.Methods We confirmed the correlation between BRD4 and mismatch repair (MMR) by the bioinformatic analysis on The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium data, and the statistical analysis on immunohistochemistry (IHC) scores of ovarian cancer specimens. The MMR genes (MLH1,MSH2,MSH6,PMS2) were measured by quantitative reverse transcription PCR, western blot, and IHC. The MMR status was confirmed by whole exome sequencing, RNA sequencing, MMR assay and hypoxanthine-guanine phosphoribosyl transferase gene mutation assay. The BRD4i AZD5153 resistant models were induced both in vitro and in vivo. The transcriptional effects of BRD4 on MMR genes were investigated by chromatin immunoprecipitation among cell lines and data from the Cistrome Data Browser. The therapeutic response to ICB was testified in vivo. The tumor immune microenvironment markers, such as CD4, CD8, TIM-3, FOXP3, were measured by flow cytometry.Results We identified the positive correlation between BRD4 and MMR genes in transcriptional and translational aspects. Also, the inhibition of BRD4 transcriptionally reduced MMR genes expression, resulting in dMMR status and elevated mutation loads. Furthermore, prolonged exposure to AZD5153 promoted a persistent dMMR signature both in vitro and in vivo, enhancing tumor immunogenicity, and increased sensitivity to α-programmed death ligand-1 therapy despite the acquired drug resistance.Conclusions We demonstrated that BRD4 inhibition suppressed expression of genes critical to MMR, dampened MMR, and increased dMMR mutation signatures both in vitro and in vivo, sensitizing pMMR tumors to ICB. Importantly, even in BRD4 inhibitors (BRD4i)-resistant tumor models, the effects of BRD4i on MMR function were maintained rendering tumors sensitive to ICB. Together, these data identified a strategy to induce dMMR in pMMR tumors and further, indicated that BRD4i sensitive and resistant tumors could benefit from immunotherapy.

The effect of 25-hydroxyvitamin D (25OHD) on the immune response of laying hens is not well elucidated. This study investigated the effects of 25OHD on egg production, egg quality, immune response, and intestinal health of laying hens challenged with Escherichia coli lipopolysaccharide (LPS). One hundred and sixty laying hens at 45 wk of age were randomly divided into 4 dietary treatments with 10 replicates of 4 birds. Hens were fed the corn-soybean based diets contained either 0 or 80 µg/kg 25OHD for 8 wks. At wk of 53 wk, birds of each dietary treatment were injected into the abdomen with 1.5 mg/kg body weight of either LPS or saline a day at 24-h intervals for continuous 7 d. LPS injection significantly decreased (PLPS < 0.05) egg laying rate, feed intake and feed efficiency; while the supplementation of 25OHD increased (PInteraction < 0.05) egg laying rate, feed efficiency and decreased (PInteraction < 0.05) the broken egg rate in layers under LPS injection. LPS challenge decreased (PLPS < 0.05) eggshell strength, eggshell thickness, albumen height and Haugh unit, while dietary 25OHD supplementation increased eggshell strength and eggshell thickness (P25OHD < 0.05). The serum proinflammatory factors [tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6)], endotoxin and diamine oxidase (DAO) levels were higher in layers under LPS challenge (PLPS < 0.05); whereas the dietary addition of 25OHD were shown to decrease (P25OHD < 0.05) serum IL-1β and IL-6 concentration irrespective of LPS challenge and led to a higher serum 25OHD level and a reduction in endotoxin concentration in layers under LPS challenge (PInteraction < 0.05). The layers under LPS challenge had higher crypt depth and lower villus height/crypt depth (V/C) ratio in duodenum and jejunum (PLPS < 0.05), while feeding 25OHD were shown to have decreasing effect on crypt depth and increasing effect V/C ratio in layers under LPS challenge (PInteraction < 0.05). Layers under LPS challenge had lower mRNA expression of intestinal barrier associated proteins (claudin-1 and mucin-1) (PLPS < 0.05), while the addition of 25OHD up-regulated claudin-1 and mucin-1 expression (Pinteraction < 0.05). Lower antioxidant enzymes activities, including superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (T-AOC), glutathione peroxidase (GPx) and higher malondialdehyde (MDA) content in jejunum were found in layers challenged with LPS (P25OHD < 0.05). The effect of 25OHD reversed the effect of LPS on SOD, T-AOC, and MDA content (PInteraction< 0.05). These results suggest that supplementing 80 µg/kg 25OHD in diets may elevate laying performance and egg quality through the improvement of intestinal barrier function, antioxidant capacity, and decreased the proinflammatory cytokines levels in laying hens with Escherichia coli LPS challenge.

Inflammatory bowel disease (IBD) results from a complex interplay between genetic predisposition, environmental factors, and gut microbes. The role of N6-methyladenosine (m6A) methylation in the pathogenesis of IBD has attracted increasing attention. m6A modification not only regulates intestinal mucosal immunity and intestinal barrier function, but also affects apoptosis and autophagy in intestinal epithelial cells. Additionally, m6A modification participated in the interaction between gut microbes and the host, providing a novel direction to explore the molecular mechanisms of IBD and the theoretical basis for specific microorganism-oriented prevention and treatment measures. m6A regulators are expected to be biomarkers for predicting the prognosis of IBD patients. m6A methylation may be utilized as a novel target in the management of IBD. This review focused on the recent advances in how m6A modification causes the initiation and development of IBD, and provided new insights into optimal prevention and treatment measures for IBD.

ABSTRACT: The underlying mechanism between the gut microbiota and reproductive function is not yet well-known. This study was conducted to investigate the effect of the administration of fecal microbiota transplantation (FMT) from highly laying rate donors on the cecal microbiota, intestinal health and ovarian function in broiler breeders. A total of 60 broiler breeders (53 wk of age) were selected by their laying rate [high (HP, 90.67 ± 0.69%; n = 10) and low (LP, 70.23 ± 0.87%; n = 20)]. The LP breeders were then be transplanted with fecal microbiota from HP hens (FMTHP; n = 10) or the same dosage of PBS (FMTCON; n = 10) for 28 d. The results revealed that FMT from HP donors increased egg-laying rate and serum hormone levels [17β-estradiol (E2), anti-Müller hormone], also decreased proinflammatory cytokine levels (interleukin-6, interleukin-8, tumor necrosis factor-α) of LP breeders (P < 0.05). The FMTHP group breeders had higher villus height, villus height/crypt depth ratio, and upregulated mRNA expression of jejunum barrier-related gene (ZO-2 and mucin-2) and estrogen, follicle-stimulating hormone (FSH) and anti-Müller hormone (AMH) receptor genes (ESR1, ESR2, FSHR, AMHR) (P < 0.05) than FMTCON group. FMT from HP donors led to higher mRNA expression of Bcl2 and sirtuin1 (SIRT1), while it downregulated the proapoptotic genes (Bax, caspase-3, caspase-8, and caspase-9) mRNA expressions in ovary compared with the FMTCON breeders (P < 0.05), and this pattern was also observed in HP donors. Also, HP breeder had higher observed_species and alpha-diversity indexes (Chao1 and ACE) than FMTCON group, while FMTHP can increase observed_species and alpha-diversity indexes (Chao1 and ACE) than FMTCON group (P < 0.05). The bacteria enrichment of Firmicutes (phylum), Bacteroidetes (phylum), Lactobacillus (genus), Enterococcus (genus), and Bacteroides (genus) were increased by FMTHP treatment. The genera Butyricicoccus, Enterococcus, and Lactobacillus were positively correlated with egg-laying rate. Therefore, cecal microbiomes of breeders with high egg-laying performance have more diverse activities, which may be related to the metabolism and health of the host; and FMT from high-yield donors can increase the hormone secretion, intestinal health, and ovarian function to improve egg-laying performance and the SIRT1-related apoptosis and cytokine signaling pathway were involved in this process.

Long noncoding RNAs (lncRNAs) play crucial roles in cardiovascular diseases. To date, only limited studies have reported the role of mitochondria-derived lncRNAs in heart failure (HF). In the current study, recombinant adeno-associated virus 9 was used to manipulate lncRNA cytb (lnccytb) expression in vivo. Fluorescence in situ hybridization (FISH) assay was used to determine the location of lnccytb, while microRNA (miRNA) sequencing and bioinformatics analyses were applied to identify the downstream targets. The competitive endogenous RNA (ceRNA) function of lnccytb was evaluated by biotin-coupled miRNA pull-down assays and luciferase reporter assays. Results showed that lnccytb expression was decreased in the heart of mice with transverse aortic constriction (TAC), as well as in the heart and plasma of patients with HF. FISH assay and absolute RNA quantification via real-time reverse transcription PCR suggested that the reduction of the lnccytb transcripts mainly occurred in the cytosol. Upregulation of cytosolic lnccytb attenuated cardiac dysfunction in TAC mice. Moreover, overexpression of cytosolic lnccytb in cardiomyocytes alleviated isoprenaline-induced reactive oxidative species (ROS) production and hypertrophy. Mechanistically, lnccytb acted as a ceRNA via sponging miR-103-3p, ultimately mitigating the suppression of PTEN by miR-103-3p. In summary, we demonstrated that the overexpression of cytosolic lnccytb could ameliorate HF.

One hundred and twenty-eight boars and gilts of the Duroc × Landrace × Yorkshire variety with an initial body weight (BW) of 52.49 ± 0.48 kg were used in a randomized complete block design for a 63-day experiment. The four treatment groups were: control diet (CON), CON + 0.2% soybean oligosaccharides (SBOS), CON + 0.4% SBOS, and CON + 0.8% SBOS. The results showed that the average daily weight gain (ADG) was significantly higher in the 0.8% SBOS group than in the CON group on days 0–63 (p < 0.05). Compared with the CON group, adding 0.8% SBOS to the diet significantly increased the carcass weight, dressing percentage, and carcass lean percentage, but decreased the average backfat depth of growing–finishing pigs (p < 0.05). Adding different concentrations (0.2%, 0.4%, and 0.8%) of SBOS to the diet can significantly increase the concentrations of acetate, propionate, and butyrate in feces (p < 0.05). The activities of malic enzyme and fatty acid synthase in the 0.8% group were significantly lower than those in the 0.2% and CON groups (p < 0.05). In summary, 0.8% SBOS supplementation to growing–finishing pigs’ diets can reduce lipid deposition and increase ADG.

This study aimed to investigate the effects and mechanisms of retinol and retinoic acid on primary duck intestinal epithelial cells under oxidative stress induced by H2O2. Different ratios of retinol and retinoic acid were used for treatment. The study evaluated the cell morphology, viability, antioxidative capacity, and barrier function of cells. The expression of genes related to oxidative stress and the intestinal barrier was analyzed. The main findings demonstrated that the treated duck intestinal epithelial cells exhibited increased viability, increased antioxidative capacity, and improved intestinal barrier function compared to the control group. High retinoic acid treatment improved viability and gene expression, while high retinol increased antioxidative indicators and promoted intestinal barrier repair. Transcriptome analysis revealed the effects of treatments on cytokine interactions, retinol metabolism, PPAR signaling, and cell adhesion. In conclusion, this study highlights the potential of retinol and retinoic acid in protecting and improving intestinal cell health under oxidative stress, providing valuable insights for future research.

This article comprehensively explores the cross-scale effects of gravity on macroscopic flow formation and weld bead formation in variable polarity plasma arc welding. Gravity-induced changes in welding direction were achieved through welding at different spatial positions. The properties of the weld bead were investigated at various spatial locations. Additionally, an elemental tracing technique was employed to study the internal flow behavior of molten metal. In the flat welding position, there is an observable trend of increasing grain size in the welded bead, accompanied by a significant expansion of the coarse grain zone. Consequently, the properties of the weld bead in the flat position are inferior to those achieved in the vertical welding position. This phenomenon can be attributed to the accumulation of molten metal at the exit side of the keyhole, resulting in temperature accumulation. Research indicates that the internal flow within the weld pool plays a critical role in causing this phenomenon. The study’s findings reveal the presence of two distinct vortex flow patterns within the weld pool: one aligned with the welding direction and the other directed towards the interior of the weld pool. Particularly noteworthy is the substantial expansion of the flow channel area in the flat welding position, which significantly amplifies the impact of internal flow. This enhanced flow intensity inevitably leads to the increased buildup of molten metal at the keyhole exit side. These studies lay the groundwork for achieving high-quality and controllable spatial-position welding.

Abstract Objective Small cell lung cancer (SCLC) is one of the most aggressive malignancies characterized by neuroendocrine (NE) differentiation. The Delta‐like protein 3 (DLL3), as a direct downstream target of ASCL1, is involved in NE differentiation and carcinogenesis of SCLC. This study aims to investigate the relationship between ASCL1 and DLL3 expressions and their clinicopathological implications in SCLC. Methods A total of 247 surgically resected pure SCLC samples with limited clinical stage and follow‐up data were retrieved in this retrospective study. ASCL1 and DLL3 protein expression was detected by immunohistochemistry staining. The correlations between ASCL1 and DLL3 expressions, as well as their clinicopathological features, were analyzed by χ2 tests. Disease‐free survival (DFS) and overall survival (OS) in SCLC patients with ASCL1/DLL3 low and high expressions were compared by the Kaplan‐Meier method and log‐rank tests. Results ASCL1 high expression was detected in 105 (42.5%) patients. Its expression was positively correlated with the clinical stage (p = 0.02) and nerve invasion (p = 0.03). DLL3 high expression was observed in 188 (72.8%) patients and was correlated with vascular invasion (p = 0.04). ASCL1 expression was positively associated with DLL3 expression (p = 0.03). In addition, DLL3 expression has a strong correlation with the expression of thyroid transcription factor‐1 (TTF1) and conventional NE markers. Conclusion ASCL1 and DLL3 were highly expressed in SCLC tumor samples, and a positive correlation between these two markers was observed. Co‐analysis of ASCL1 and DLL3 may identify a distinct SCLC subgroup benefit from targeted therapy. Therefore, ASCL1 and DLL3 could be potential biomarkers served for the selection of related patients.

Abstract Background Understanding dental students’ future career choice and motivation could provide beneficial references for both educators and students, but there were few studies on students in a Chinese dental school. The study aimed to investigate Chinese final year dental students’ the short-term and long-term plans, motivations, and identify the influence of gender on the future plans. Methods A total of 265 final year dental school students of the School of Stomatology, China Medical University from 2016 through 2020 were invited to complete an anonymous, 27-item questionnaire. Moreover, almost all of questions were in multiple-choice formats. Data were categorized and analysed using chi-square comparative analyses. Results 88.3% of respondents decided to pursue a graduate degree after graduating from dental school. Moreover, the single most important reason influencing their plans was “eligible for better jobs” (42.8%). More females than males studied dentistry (222 vs 111), and gender had an influence on the choice of specialty. Conclusions This study listed the selection tendency and influencing factors of students in a Chinese dental school for the reference of educators and students. And the results could raise some useful influence and feedback effect on current health and education policy, and on the career development of practicing dentists or dental students.

Sonic hedgehog (Shh)‐driven medulloblastoma (Shh MB) cells are dependent on constitutive Shh signaling, but targeted treatment of Shh MB has been ineffective due to drug resistance. The purpose of this study was to address the critical role of signal transducer and activator of transcription 3 (STAT3) in Shh signaling and drug resistance in Shh MB cells. Herein, we show that STAT3 is required for Smoothened (Smo)‐dependent Shh signaling and, in turn, is reciprocally regulated by Shh signaling, and demonstrate that STAT3 activity is critical for expression of HCK proto‐oncogene, Src family tyrosine kinase (Hck) in Shh MB. We also demonstrate that maintained STAT3 activity suppresses p21 expression and promotes colony formation of Shh MB cells, whereas dual treatment with inhibitors of both Smo and STAT3 results in marked synergistic killing and overcomes drug resistance in vitro of Smo antagonist‐resistant Shh MB cells. Finally, STAT3 inhibitor treatment significantly prevents in vivo tumor formation in genetically engineered Shh MB mice. Collectively, we show that STAT3 is necessary to maintain Shh signaling and thus is a potential therapeutic target to treat Shh MB and overcome anti‐Smo drug resistance.

Comparative analyses of a shield building subjected to a large commercial aircraft impact between decoupling method and coupling method are performed in this paper. The decoupling method is applying impact force time-history curves on impact area of the shield building to study impact damage effects on structure. The coupling method is using a model including aircraft and shield building to perform simulation of the entire impact process. Impact force time-history curves of the fuselage, wing and engine and their total impact force time-history curve are obtained by the entire aircraft normally impacting the rigid wall. Taking aircraft structure and impact progress into account some loading areas are determined to perform some comparative analyses between decoupling method and coupling method, the calculation results including displacement, plastic strain of concrete and stress of steel plate in impact area are given. If the loading area is determined unreasonably, it will be difficult to assess impact damage of impact area even though the accurate impact force of each part of aircraft obtained already. The coupling method presented at last in this paper can more reasonably evaluate the dynamic response of the shield building than the decoupling methods used in the current nuclear engineering design.

IntroductionFermented egg-milk peptides (FEMPs) could enhance the colon-intestinal barrier and upgrade the expression of zonula occludens-1 and mucin 2. Besides, the underlying biological mechanism and the targets FEMPs could regulate were analyzed in our study.MethodsHerein, the immunofluorescence technique and western blot were utilized to evaluate the repair of the intestinal barrier. Network pharmacology analysis and bioinformatics methods were performed to investigate the targets and pathways affected by FEMPs.Results and discussionAnimal experiments showed that FEMPs could restore intestinal damage and enhance the expression of two key proteins. The pharmacological results revealed that FEMPs could regulate targets related to kinase activity, such as AKT, CASP, RAF, and GSK. The above targets could interact with each other. GO analysis indicated that the targets regulated by FEMPs could participate in the kinase activity of the metabolic process. KEGG enrichment revealed that the core targets were enriched in pathways related to cell apoptosis and other important procedures. Molecular docking demonstrated that FEMPs could bind to the key target AKT via hydrogen bond interactions. Our study combined the experiment in vivo with the method in silico and investigated the interaction between peptides and targets in a pattern of multi-targets and multi-pathways, which offered a new perspective on the functional validation and potential application of bioactive peptides.

Abstract Ulcerative Colitis (UC) has been reported to be related to Porphyromonas gingivalis (P. gingivalis). Porphyromonas gingivalis peptidylarginine deiminase (PPAD), a virulence factor released by P. gingivalis, is known to induce inflammatory responses. To explore the pathological relationships between PPAD and UC, we used homologous recombination technology to construct a P. gingivalis strain in which the PPAD gene was deleted (Δppad) and a Δppad strain in which the PPAD gene was restored (comΔppad). C57BL/6 mice were orally gavaged with saline, P. gingivalis, Δppad, or comΔppad twice a week for the entire 40 days (days 0−40), and then, UC was induced by dextran sodium sulfate (DSS) solution for 10 days (days 31−40). P. gingivalis and comΔppad exacerbated DDS-induced colitis, which was determined by assessing the parameters of colon length, disease activity index, and histological activity index, but Δppad failed to exacerbate DDS-induced colitis. Flow cytometry and ELISA revealed that compared with Δppad, P. gingivalis, and comΔppad increased T helper 17 (Th17) cell numbers and interleukin (IL)-17 production but decreased regulatory T cells (Tregs) numbers and IL-10 production in the spleens of mice with UC. We also cocultured P. gingivalis, Δppad, or comΔppad with T lymphocytes in vitro and found that P. gingivalis and comΔppad significantly increased Th17 cell numbers and decreased Treg cell numbers. Immunofluorescence staining of colon tissue paraffin sections also confirmed these results. The results suggested that P. gingivalis exacerbated the severity of UC in part via PPAD.

In this study, A time-domain seismic response analysis method and a calculation model of the underground structure that can realize the input of seismic P, SV and Rayleigh waves are established, based on the viscoelastic artificial boundary elements and the boundary substructure method for seismic wave input. After verifying the calculation accuracy, a comparative study on seismic response of a shallow-buried, double-deck, double-span subway station structure under incident P, SV and Rayleigh waves is conducted. The research results show that there are certain differences in the cross-sectional internal force distribution characteristics of underground structures under different types of seismic waves. The research results show that there are certain differences in the internal force distribution characteristics of underground structures under different types of seismic waves. At the bottom of the side wall, the top and bottom of the center pillar of the underground structure, the section bending moments of the underground structure under the incidences of SV wave and Rayleigh wave are relatively close, and are significantly larger than the calculation result under the incidence of P wave. At the center of the side wall and the top floor of the structure, the peak value of the cross-sectional internal force under the incident Rayleigh wave is larger than the calculation result under SV wave. In addition, the floor of the underground structure under Rayleigh waves vibrates in both the horizontal and vertical directions, and the magnification effect in the vertical direction is more significant. Considering that the current seismic research of underground structures mainly considers the effect of body waves such as the shear waves, sufficient attention should be paid to the incidence of Rayleigh waves in the future seismic design of shallow underground structures.

Abstract Targeting the G2/M checkpoint mediator WEE1 has been explored as a novel treatment strategy in ovarian cancer, but mechanisms underlying its efficacy and resistance remains to be understood. Here, it is demonstrated that the WEE1 inhibitor AZD1775 induces endoplasmic reticulum stress and activates the protein kinase RNA‐like ER kinase (PERK) and inositol‐required enzyme 1α (IRE1α) branches of the unfolded protein response (UPR) in TP53 mutant (mtTP53) ovarian cancer models. This is facilitated through NF‐κB mediated senescence‐associated secretory phenotype. Upon AZD1775 treatment, activated PERK promotes apoptotic signaling via C/EBP‐homologous protein (CHOP), while IRE1α‐induced splicing of XBP1 (XBP1s) maintains cell survival by repressing apoptosis. This leads to an encouraging synergistic antitumor effect of combining AZD1775 and an IRE1α inhibitor MKC8866 in multiple cell lines and preclinical models of ovarian cancers. Taken together, the data reveal an important dual role of the UPR signaling network in mtTP53 ovarian cancer models in response to AZD1775 and suggest that inhibition of the IRE1α‐XBP1s pathway may enhance the efficacy of AZD1775 in the clinics.

Expanded vermiculite (EV) is an innovative alternative to conventional fire-resistance material due to exceptional thermal performance and non-combustible property. In this study, the effect of elevated temperatures on microstructure, mechanical and physical properties of foam concrete containing EV as lightweight aggregates (LWA) was investigated. Foam concrete samples with 10%, 15% and 20% EV as sand replacement were developed and exposed to 300 ℃, 600 ℃, and 900 ℃. Scanning electron microscopy (SEM) test was conducted to identify microstructure changes in the cement matrix and fine aggregates after elevated-temperature exposure. The enhanced close-fitted bond in the interfacial transition zone (ITZ) of EV-based foam concrete was observed in SEM, which might be due to the higher water absorption of EV granules. Residual compressive and flexural strength, relative porosity and water sorptivity coefficient of foam concrete were also obtained. The 15% EV reduced compressive strength loss of samples by 1.84%, 11.68% and 69.1% at 300 ℃, 600 ℃ and 900 ℃, respectively, compared with that of the reference as 9.81%, 33.7%, and 72.28%, respectively. Enhanced sorptivity-related durability and lower residual porosity were also obtained at elevated temperatures when 15% EV was added.

We investigated the effects of dietary supplementation of lactic acid bacteria on the immune and antioxidant performance of weaned pigs. A total of 128 Duroc × Landrace × Yorkshire piglets weaned on day 28 with an average body weight of 8.95 ± 1.15 kg were selected and randomly divided into four treatment groups according to body weight and sex for a 28-day study. The four dietary treatments were basal diet (CON), and CON with 0.05% (LJ0.05), 0.1% (LJ0.1), and 0.2% (LJ0.2) Lactobacillus johnsonii RS-7, respectively. The lowest feed-to-gain ratio (F:G) was found when LJ0.1 was added to the diet. The addition of compound lactic acid bacteria to the diet increased the concentrations of TP, ALB, IgA, and IgM on day 14 and IgG, IgA, and IgM on day 28 (p < 0.05) in the blood, with trait values greater for pigs fed LJ0.1 than CON pigs (p < 0.05). Concentrations of antioxidants (CAT, T-AOC, MDA, T-SOD, and GSH) in serum, intestinal mucosa, spleen, liver, and pancreas improved. In summary, dietary supplementation of Lactobacillus johnsonii RS-7 improved the antioxidant and immune function of weaned piglets.

Animals with intrauterine growth retardation (IUGR) usually undergo injured postnatal growth and development during the early period after birth. Equol (Eq), an isoflavan produced by gut bacteria in response to daidzein intake, has various health benefits. Therefore, the objective of this study was to evaluate whether Eq supplementation can influence the growth performance, redox status, intestinal health and skeletal muscle development of weanling piglets with IUGR. A total of 10 normal-birth-weight (NBW) newborn female piglets and 20 newborn female piglets with IUGR were selected. After weaning at the age of 21 d, 10 NBW piglets and 10 IUGR piglets were allocated to the NBW group and IUGR group, respectively, and offered a basal diet. The other 10 IUGR piglets were allocated to the IUGR + Eq group and offered a basal diet with 50 mg of Eq per kg of diet. The whole trial lasted for 21 d. At the end of the feeding trial, all piglets were sacrificed for the collection of serum, intestinal tissues and skeletal muscles. Supplementation with Eq increased the average daily gain (ADG), average daily feed intake (ADFI), duodenal villus height to crypt depth ratio (V/C), jejunal villus height and V/C, but reduced the duodenal crypt depth in neonatal piglets with IUGR. Meanwhile, Eq supplementation elevated the activities of superoxide dismutase (SOD) and catalase (CAT) in the serum and duodenum and the activity of SOD in the jejunum, but lowered malondialdehyde (MDA) content in the serum, jejunum and ileum of piglets with IUGR. In addition, supplementation with Eq reduced diamine oxidase (DAO) activity and the levels of D-lactate and endotoxin in serum, and the tumor necrosis factor-α (TNF-α) level in jejunum and ileum, whereas the concentration of serum immunoglobulin G (IgG) and the mRNA levels of intestinal barrier-related markers in jejunum and ileum of IUGR piglets were increased. Furthermore, supplementation with Eq elevated the percentage of fast-fibers and was accompanied with higher mRNA expression of myosin heavy chain IIb (MyHC IIb) and lower mRNA levels in MyHC I in the longissimus thoracis (LT) muscle of IUGR piglets. In summary, Eq supplementation can promote antioxidant capacity, maintain intestinal health and facilitate skeletal muscle development, thus resulting in the higher growth performance of IUGR piglets.