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Studies have demonstrated that donkey milk (DM) displays anti-tumor activity. In this study, we investigated the role and underlying mechanism of DM in the progression of 4T1 breast tumors in mice. We found that DM significantly reduced tumor volumes and tumor weights in 4T1-treated mice. Simultaneously, DM ameliorated the pathological changes in spleen, liver and lung tissues of 4T1 tumor-bearing mice. WB results showed that DM inducing the expression of Bax and pyroptosis-related proteins, and inhibiting the expression of Bcl-2 in tumors. Besides, DM up-regulation of Th1 cytokines and down-regulation of Th2/Treg cytokines in the tumors and spleen. Moreover, DM significantly decreased the ratios of p-JAK2/JAK2, p-STAT3/STAT3, p-STAT5/STAT5, as well as up-regulation the ratio of p-STAT4/STAT4 in tumors and spleen. Our data suggest that DM inhibit the growth of mouse 4T1 tumors by inducing apoptosis and pyroptosis, as well as promoting Th1 cell activation and quelling immunosuppression from Tregs.

Lutein (Lut) and zeaxanthin (Zx) are promising healthy food ingredients; however, the low solubilities, stabilities, and bioavailabilities limit their applications in the food and beverage industries. A protein-based complex represents an efficient protective carrier for hydrophobic ligands, and its ligand-binding properties are influenced by the formulation conditions, particularly the pH level. This study explored the effects of various pH values (2.5–9.5) on the characteristics of whey protein isolate (WPI)–Lut/Zx complexes using multiple spectroscopic techniques, including ultraviolet–visible (UV–Vis), fluorescence, and Fourier transform infrared (FTIR) spectroscopies and dynamic light scattering (DLS). UV–Vis and DLS spectra revealed that Lut/Zx were present as H-aggregates in aqueous solutions, whereas WPI occurred as nanoparticles. The produced WPI–Lut/Zx complexes exhibited binding constants of 104–105 M−1, which gradually increased with increasing pH from 2.5 to 9.5. FTIR spectra demonstrated that pH variations and Lut/Zx addition caused detectable changes in the secondary WPI structure. Moreover, the WPI–Lut/Zx complexes effectively improved the physicochemical stabilities and antioxidant activities of Lut/Zx aggregates during long-term storage and achieved bioaccessibilities above 70% in a simulated gastrointestinal digestion process. The comprehensive data obtained in this study offer a basis for formulating strategies that can be potentially used in developing commercially available WPI complex-based xanthophyll-rich foods.

Seeking a low-cost, high-efficiency greenhouse mapping technology has immense significance. While greenhouse extraction methods using deep learning have been proposed, the challenge of extracting dense small objects remains an unresolved problem. The inherent downscaling strategy in general-purpose semantic segmentation (SS) models renders them unsuitable for such tasks. In contrast, the dramatically increasing computational complexity associated with this problem may result in an unaffordable cost for consumer-level applications. To address the aforementioned challenges, this study presents a novel greenhouse mapping model based on remote sensing (RS) images, which not only exhibits high precision and robust generalization capabilities but also offers significant lightweight advantages. To meet broader needs, we also provide corresponding customizable and scalable rules that allow for a trade-off between accuracy and speed. To evaluate the performance of our model, we select several representative works to conduct benchmark experiments on a self-annotated dataset. The results demonstrate that our method can provide more powerful visual representations for greenhouse segmentation with minimal cost. Compared to the control group, the proposed method achieves an mIoU improvement of 1.116 %-10.77 % using only 3.282 M parameters, while maintaining a considerable inference speed. Code will be available at: https://github.com/W-qp/EGENet.git

Multiple sclerosis (MS) is a chronic inflammatory and degenerative disease of central nervous system (CNS). Aging is the most significant risk factor for the progression of MS. Dietary modulation (such as ketogenic diet) and caloric restriction, can increase ketone bodies, especially β-hydroxybutyrate (BHB). Increased BHB has been reported to prevent or improve age-related disease. The present studies were performed to understand the therapeutic effect and potential mechanisms of exogenous BHB in cuprizone (CPZ)-induced demyelinating model. In this study, a continuous 35 days CPZ mouse model with or without BHB was established. The changes of behavior function, pathological hallmarks of CPZ, and intracellular signal pathways in mice were detected by Open feld test, Morris water maze, RT-PCR, immuno-histochemistry, and western blot. The results showed that BHB treatment improved behavioral performance, prevented myelin loss, decreased the activation of astrocyte as well as microglia, and up-regulated the neurotrophin brain-derived neurotrophic factor in both the corpus callosum and hippocampus. Meanwhile, BHB treatment increased the number of MCT1+ cells and APC+ oligodendrocytes. Furthermore, the treatment decreased the expression of HDAC3, PARP1, AIF and TRPA1 which is related to oligodendrocyte (OL) apoptosis in the corpus callosum, accompanied by increased expression of TrkB. This leads to an increased density of doublecortin (DCX)+ neuronal precursor cells and mature NeuN+ neuronal cells in the hippocampus. As a result, BHB treatment effectively promotes the generation of PDGF-Ra+ (oligodendrocyte precursor cells, OPCs), Sox2+ cells and GFAP+ (astrocytes), and decreased the production of GFAP+ TRAP1+ cells, and Oligo2+ TRAP1+ cells in the corpus callosum of mouse brain. Thus, our results demonstrate that BHB treatment efficiently supports OPC differentiation and decreases the OLs apoptosis in CPZ-intoxicated mice, partly by down-regulating the expression of TRPA1 and PARP, which is associated with the inhibition of the p38-MAPK/JNK/JUN pathway and the activation of ERK1/2, PI3K/AKT/mTOR signaling, supporting BHB treatment adjunctive nutritional therapy for the treatment of chronic demyelinating diseases, such as multiple sclerosis (MS).

Owing to the well-established application of prebiotics in human food products, there is a growing interest in their potential as dietary supplements for gut microbiota composition and improvement of the digestive health of dogs. However, targeted studies with dogs as research subjects are still limited. In the present study, an in vitro simulated gut microbiota fermentation system using canine feces from a healthy Border Collie breed was used to investigate the prebiotic effects of five different oligosaccharides and compare their regulatory effects on the gut microbiota structure and the resultant metabolites. Due to the addition of oligosaccharides, the fermented samples had lower pH and higher bacterial proliferation. The oligosaccharide-fermentation selectively boosted Lactobacillus spp., Streptococcus spp., Enterococcus spp., Bacteroides spp., and hindered Escherichia-Shigella spp., Paeniclostridium, spp., and Bacteroides spp. Each oligosaccharide showed distinct characteristics and preferences for regulating gut microbiota structure and abundance. Furthermore, the addition of oligosaccharides increased the production of short-chain fatty acids, particularly butyric acid. This study provides a preliminary basis for the rapid and rational selection of prebiotic oligosaccharides as canine dietary supplements and further explores the function of oligosaccharides and their combinations in canine health.

Plant fiber-reinforced polylactic acid (PLA) exhibits excellent mechanical properties and environmental friendliness and, therefore, has a wide range of applications. This study investigated the mechanical properties of three short plant fiber-reinforced PLA composites (flax, jute, and ramie) using mechanical testing and material characterization techniques (SEM, FTIR, and DSC). Additionally, we propose a methodology for predicting the mechanical properties of high-content short plant fiber-reinforced composite materials. Results indicate that flax fibers provide the optimal reinforcement effect due to differences in fiber composition and microstructure. Surface pretreatment of the fibers using alkali and silane coupling agents increases the fiber–matrix interface contact area, improves interface performance, and effectively enhances the mechanical properties of the composite. The mechanical properties of the composites increase with increasing fiber content, reaching the highest value at 40%, which is 38.79% higher than pure PLA. However, further increases in content lead to fiber agglomeration and decreased composite properties. When the content is relatively low (10%), the mechanical properties are degraded because of internal defects in the material, which is 40.42% lower than pure PLA. Through Micro-CT technology, the fiber was reconstructed, and it was found that the fiber was distributed mainly along the direction of injection molding, and the twin-screw process changes the shape and length of the fiber. By introducing the fiber agglomeration factor function and correcting the Halpin-Tsai criterion, the mechanical properties of composite materials with different contents were successfully predicted. Considering the complex stress state of composite materials in actual service processes, a numerical simulation method was established based on transversely isotropic material using the finite element method combined with theoretical analysis. The mechanical properties of high-content short plant fiber-reinforced composite materials were successfully predicted, and the simulation results showed strong agreement with the experimental results.

Years of outbreaks of woody canker (Cryptosphaeria pullmanensis) in the United States, Iran, and China have resulted in massive economic losses to biological forests and fruit trees. However, only limited information is available on their distribution, and their habitat requirements have not been well evaluated due to a lack of research. In recent years, scientists have utilized the MaxEnt model to estimate the effect of global temperature and specific environmental conditions on species distribution. Using occurrence and high resolution ecological data, we predicted the spatiotemporal distribution of C. pullmanensis under twelve climate change scenarios by applying the MaxEnt model. We identified climatic factors, geography, soil, and land cover that shape their distribution range and determined shifts in their habitat range. Then, we measured the suitable habitat area, the ratio of change in the area of suitable habitat, the expansion and shrinkage of maps under climate change, the direction and distance of range changes from the present to the end of the twenty-first century, and the effect of environmental variables. C. pullmanensis is mostly widespread in high-suitability regions in northwestern China, the majority of Iran, Afghanistan, and Turkey, northern Chile, southwestern Argentina, and the west coast of California in the United States. Under future climatic conditions, climate changes of varied intensities favored the expansion of suitable habitats for C. pullmanensis in China. However, appropriate land areas are diminishing globally. The trend in migration is toward latitudes and elevations that are higher. The estimated area of possible suitability shifted eastward in China. The results of the present study are valuable not only for countries such as Morocco, Spain, Chile, Turkey, Kazakhstan, etc., where the infection has not yet fully spread or been established, but also for nations where the species has been discovered. Authorities should take steps to reduce greenhouse gas emissions in order to restrict the spread of C. pullmanensis. Countries with highly appropriate locations should increase their surveillance, risk assessment, and response capabilities.

IntroductionThis study was to determine whether coronary artery bypass grafting without cardiopulmonary bypass (off-pump CABG, OPCAB) could reduce early postoperative mortality and major complications compared with conventional coronary artery bypass grafting with cardiopulmonary bypass (on-pump CABG, ONCAB) by experienced surgeons.Material and methodsFrom January 2016 to June 2020, isolated CABG was performed in 1200 patients (ONCAB 429, OPCAB 771) in Wuhan Union Hospital. The propensity score matching was used to adjust for differences in baseline characteristics between the ONCABG and OPCABG groups. After 1:1 matching, 404 pairs for each group were selected to compare outcomes within 30 days after surgery. All the operations were completed by experienced surgeons that had completed more than 500 on-pump and 200 off-pump CABG, respectively.ResultsAfter propensity matching, the two groups were comparable in terms of preoperative characteristics. The OPCAB group had less vein graft (2.5 ± 1.0 vs. 2.7 ± 0.9; P < 0.001) and a higher rate of incomplete revascularization (12.4 vs. 8.2%; P < 0.049) than the ONCAB group. There was no significant difference in early postoperative mortality between ONCAB and OPCAB groups (2.2 vs. 2.2%; P = 1.00). However, patients in the OPCAB group had a lower risk of postoperative stroke (1.5 vs. 4.7%; P = 0.008), new-onset renal insufficiency (8.9 vs. 18.8%; P < 0.001), respiratory failure (2.2 vs. 7.2%; P = 0.001), reoperation for bleeding (0.5 vs. 2.7%; P = 0.001), and required less ventilator assistance time (33.4 ± 37.9 h vs. 51.0 ± 66.1 h; P < 0.001) and intensive care unit (ICU) time (3.7 ± 2.7 days vs. 4.8 ± 4.3 days; P < 0.001).ConclusionsIn our study, patients undergoing OPCAB had fewer postoperative complications and a faster recovery. It is a feasible and safe surgical approach to achieve revascularization when performed by experienced surgeons.

Ketogenic diet (KD) has increasingly captured the attention of researchers due to its anti-tumor activity. Here, we found that KD treatment significantly enhanced tumor-reactive immune responses, including increased intratumoral CD8+ and CD4+ T cells and decreased FOXP3+/CD4+ Treg cells. Moreover, KD administration increased the Th1-related cytokines IL-2, IFN-γ, IL-1α and IL-12, while decreased Th2-related cytokines IL-4, IL-13 and COX-2, as well as reduced the expression of PD-L1 and CTLA4. Further evaluation revealed that tumor vascularization decreased dramatically after KD treatment. Furthermore, KD reversed the epithelial-mesenchymal transition (EMT) in microenvironmental by up-regulation of E-cadherin, down-regulation of N-cadherin and vimentin. Additionally, KD decrease the expression of phosphorylated STAT1/STAT1, while promoting the expression of P53, Bax/Bcl-2 and caspase-3 in tumor tissues. Thus, our findings indicate that KD treatment can enhance the anti-tumor immunity and mitigate the tumor immunosuppression in the tumor microenvironment, as well as decrease the tumor vascularization.

Abstract Background Walnut anthracnose caused by Colletotrichum gloeosporioides (Penz.) Penz. and Sacc. is an important walnut production problem in China. Although the long non-coding RNAs (lncRNAs) are important for plant disease resistance, the molecular mechanisms underlying resistance to C. gloeosporioides in walnut remain poorly understood. Results The anthracnose-resistant F26 fruits from the B26 clone and the anthracnose-susceptible F423 fruits from the 4–23 clone of walnut were used as the test materials. Specifically, we performed a comparative transcriptome analysis of F26 and F423 fruit bracts to identify differentially expressed LncRNAs (DELs) at five time-points (tissues at 0 hpi, pathological tissues at 24 hpi, 48 hpi, 72 hpi, and distal uninoculated tissues at 120 hpi). Compared with F423, a total of 14,525 DELs were identified, including 10,645 upregulated lncRNAs and 3846 downregulated lncRNAs in F26. The number of upregulated lncRNAs in F26 compared to in F423 was significantly higher at the early stages of C. gloeosporioides infection. A total of 5 modules related to disease resistance were screened by WGCNA and the target genes of lncRNAs were obtained. Bioinformatic analysis showed that the target genes of upregulated lncRNAs were enriched in immune-related processes during the infection of C. gloeosporioides, such as activation of innate immune response, defense response to bacterium, incompatible interaction and immune system process, and enriched in plant hormone signal transduction, phenylpropanoid biosynthesis and other pathways. And 124 known target genes for 96 hub lncRNAs were predicted, including 10 known resistance genes. The expression of 5 lncRNAs and 5 target genes was confirmed by qPCR, which was consistent with the RNA-seq data. Conclusions The results of this study provide the basis for future functional characterizations of lncRNAs regarding the C. gloeosporioides resistance of walnut fruit bracts.

Combinatorial chemo-photodynamic therapy is regared as effective cancer therapy strategy, which could be realized via multiple nano-drug delivery system. Herein, novel high payload nanoparticles stabilized by amphiphilic block polymer cholesterol-b-poly(ethylene glycol) (PEG)2000 (Chol-PEG2000) were fabricated for loading chemotherapeutic drug 10-hydroxycamptothecin (HCPT) and photosensitizer chlorin e6 (Ce6). The obtained HCPT/Ce6 NPs showed uniform rod-like morphology with a hydration diameter of 178.9 ± 4.0 nm and excellent stability in aqueous solution. HCPT and Ce6 in the NPs displayed differential release profile, which was benefit for preferentially exerting the photodynamic effect and subsequently enhancing the sensitivity of the cells to HCPT. Under laser irradiation, the NPs demonstrated fantastic in vitro and in vivo anticancer efficiency due to combinational chemo-photodynamic therapy, enhanced cellular uptake effectiveness, and superb intracellular ROS productivity. Besides, the NPs were proved as absent of systemic toxicity. In summary, this nanoparticle delivery system could be hopefully utilized as effective cancer therapy strategy for synergistically exerting combined chemo-photodynamic therapy in clinic.

Introduction: No previous studies comparing the outcomes between off-pump coronary artery bypass grafting (off-pump CABG, OPCAB) and on-pump CABG (ONCAB) have been performed in patients with severe left ventricular dysfunction (LVD) and a giant left ventricle. We aimed to investigate whether such patients could benefit from OPCAB. Methods: From January 2011 to January 2021, a total of 98 patients with severe LVD and a giant left ventricle underwent isolated CABG (ONCAB 46, OPCAB 52) in Wuhan Union Hospital. The clinical data were collected retrospectively and propensity score matching was performed to adjust baseline characteristics. Results: After propensity matching, the two groups were comparable in baseline variables. The OPCAB group had a higher rate of incomplete revascularization than the ONCAB group (25.0% vs. 9.1%; p = 0.047). The 30-day mortality was similar between the matched groups (4.5% vs. 4.5%; p = 1.000) but the OPCAB group had a lower risk of postoperative IABP usage (9.1% vs. 25.0%; p = 0.047) and renal insufficiency (11.4% vs. 29.5%; p = 0.034). The long-term probability of survival (log-rank test, p = 0.450) was similar between the two groups but the OPCAB group had a lower probability of major adverse cardiovascular events (log-rank test, p = 0.038). Conclusions: For patients with severe LVD and a giant left ventricle, OPCAB reduced early postoperative complications while sacrificing long-term quality of life compared to those having ONCAB.

Objective: The aim of this study is to assess the association between epicardial adipose tissue (EAT) and coronary artery disease (CAD) via meta−analysis. Methods: Specific searches of online databases from January 2000 to May 2022 were conducted. All observational studies evaluating the association between EAT and CAD in PubMed, Web of Science, and the Cochrane Library databases were screened. A meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta−Analyses guidelines (PRISMA). In total, 21 studies encompassing 4975 subjects met the inclusion criteria, including 2377 diagnosed and assigned as the CAD group, while the other 2598 were assigned as the non−CAD group. Subjects in the CAD group were further divided into the severe stenosis group (stenosis ≥ 50%, n = 846) and the mild/moderate stenosis group (stenosis < 50%, n = 577). Results: Both the volume and thickness of EAT in the CAD group were larger compared to the non−CAD group (p < 0.00001). In a subgroup analysis within the CAD group, the severe stenosis group had a larger volume and thickness with respect to EAT when compared to the mild/moderate group (p < 0.001). Conclusions: The enlargement of EAT presented in CAD patients with an association with CAD severity. Although limited by different CAD types and measuring methods for EAT, as well as a smaller sample size, our results suggest that EAT is a novel predictor and a potential therapeutic target for CAD.

Abstract Background The purpose of this study was to investigate the therapeutic effects and mechanisms of hyperbaric oxygen (HBO) treatment on rats following spinal cord injury (SCI). Methods A total of 45 Sprague-Dawley (SD) rats were randomly divided into three groups. Sham-SCI group was surgically exposed but not subjected to the SCI procedure. SCI-control group was administered SCI and treated with regular air. SCI-HBO group was administered SCI and HBO treatment. Neuromotor functions were examined using the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and the inclined plane assessment at before SCI (baseline) and after SCI. Superoxide dismutase (SOD) activities and malondialdehyde (MDA) levels were measured. Results Starting from Day 1 after SCI but except Day 2, the SCI-HBO group has significantly higher BBB scores than the SCI-control group. After SCI, the maximum inclination angles at which rats could maintain were significantly lower in both SCI groups. But the maximum angles were significantly bigger for the rats in the SCI-HBO group than those on the SCI-control group at 5, 10 and 20 days after SCI. SOD activities in SCI-HBO rats were significantly higher and MDA levels were significantly lower than in SCI-control rats, at two and five days after SCI. There was also less cystic degeneration of spinal cord in SCI-HBO rats, compared to SCI-control rats. Conclusions These results suggest that HBO treatment has a therapeutic value in treating SCI. Increased oxygen free radical scavenging and reduced lipid oxidation may be one of the mechanisms.