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This study aimed to investigate the structure-function relationship of angiotensin-converting enzyme (ACE) inhibitory peptides and to elucidate the action mechanism of food-derived ACE inhibitory peptides. Based on the amino acid sequences of recently reported ACE inhibitory pentapeptides and their half-maximal inhibitory concentration (IC50) values, a library of ACE inhibitory pentapeptides was generated and the structures of the ACE inhibitory pentapeptides were characterized using three amino acid descriptors, Z-scales, VHSE and SVHEHS. A partial least square (PLS) model for describing the quantitative structure-activity relationship (QSAR) of the ACE inhibitory peptides with the hydrophobic properties, steric properties, and electrical properties of amino acids as the independent variables and the lg IC50 of the ACE inhibitory pentapeptides as the dependent variable was established using Matlab software. The results showed that the R2 and Q2 of the QSAR model based on Z-scales descriptor were 0.641 1 and 0.536 9, respectively, and Gln-Arg-Pro-Asn-Met showed higher ACE inhibitory activity as predicted by this model. The predicted and measured IC50 were 0.051 7 and (0.040 0 ± 0.008 3) μmol/L, respectively, and the error between them was 0.011 7 μmol/L. The R2 and Q2 of the QSAR model based on VHSE descriptor were 0.763 6 and 0.508 1, respectively, and Leu-Arg-Ala-Phe-Gln exhibited better ACE inhibitory activity as predicted by this model. The predicted and measured IC50 were 0.043 8 and (0.027 3 ± 0.005 3) μmol/L, respectively, and the error between them was 0.016 5 μmol/L. The R2 and Q2 of the QSAR model based on SVHEHS descriptor were 0.840 5 and 0.400 5, respectively, and Leu-Arg-Ala-Phe-Gln displayed better ACE inhibitory activity as predicted by this model. The predicted and measured IC50 were 0.005 5 and (0.031 2 ± 0.004 2) μmol/L, and the error between them was 0.025 7 μmol/L. Among the three QSAR models, the one based on SVHEHS descriptor had the strongest fitting capability but weak predictive capacity, while the models based on Z-scales and VHSE descriptors could allow good QSAR analysis of the pentapeptides. Our modeling analysis showed that the activity of the ACE inhibitory peptides was negatively correlated with the hydrophobic characteristics of amino acids and positively correlated with the steric characteristics of amino acids. Molecular docking of three ACE inhibitory peptides to ACE protein (2X8J) showed that all the ACE inhibitory peptides could bind to ACE protein. This study provides a new tool for developing ACE inhibitory peptides and a theoretical basis for the development and application of food-derived ACE inhibitory peptides.

In this experiment, HEK293 cells were induced by H2O2 to establish a cell model of oxidative damage, and the optimal H2O2 concentration and treatment time were determined. The effects of five antioxidant peptides (AFK, IEQI, FPFF, LPVPQ and RELEEL) derived from yak milk casein on the survival rate, malondialdehyde (MDA) content, antioxidant enzyme activities, reduced glutathione and oxidized glutathione contents of the damaged cells were studied, and the mechanism of action of the antioxidant peptides was explored to provide a theoretical basis for their development and application in high value-added biological products and functional foods. The results showed that these antioxidant peptides had different scavenging effects on different radical species, but they all showed a dose-effect relationship. After being treated with a final concentration of 400 μmol/L H2O2 for 12 h, the inhibitory rate of HEK293 cells was (46.21 ± 0.40)%. Cytotoxicity test showed that the five antioxidant peptides had no toxic or side effects on HEK-293 cells, and did not promote cell proliferation either. These antioxidant peptides could significantly reduce the contents of malondialdehyde (except LPVPQ) and oxidized glutathione in HEK293 cells damaged by oxidation, and enhance the activity of antioxidant enzymes. RELEEL at a concentration of 200 μg/mL significantly reduced MDA content to (0.062 ± 0.000) nmol/104 cells and increased glutathione content to (61.17 ± 2.48) μg/106 cells while maintaining high GSH/GSSG ratio of 64.93 ± 0.95. The antioxidant peptide LPVPQ at 200 μg/mL significantly reduced the content of oxidized glutathione to (0.74 ± 0.26) μg/106 cells and increased the activity of superoxide dismutase (SOD) to (1.17 ± 0.02) U/104 cells; the antioxidant peptide AFK at 200 μg/mL significantly enhanced catalase (CAT) activity to (0.60 ± 0.09) U/104 cells. These results indicate that the antioxidant peptides derived from yak milk casein have positive effects on cells damaged by oxidation, which can provide a reference for further development of relevant products.

Ghee is a traditional Tibetan dairy product with high-fat content, low yield, plasticity, caseation, and rich nutrition. In this study, we analyzed the diversity of microbial communities in yak milk and ghee samples at high and low altitudes, especially the Lactobacillus genus, and further used metabolomic techniques to compare the differences in metabolites in yak ghee at different altitudes. The results showed that the increase in altitude had a significant and generally inhibitory effect on the microbial community diversity in milk ghee, and yak milk at high altitude was abundant in nutrients, which could antagonize the negative impact of increased altitude. Using non-targeted metabolomics, we infer the composition of flavor compounds in ghee: nine kinds of carboxylic acids, 11 kinds of esters, six kinds of ketones, two kinds of alcohols, and four kinds of alkene compounds, among which the key flavor compounds are dl-2-(acetylamino)-3-phenylephrine acid, 1-(4-methoxyphenyl)-2-propanone, sebacic acid, Lysope 18:1, and uracil 1-beta-d-arabinofuranoside. These flavor substances are found in Lactococcus, Lactobacillus, and Streptococcus. With the participation of Lactobacillus, it is synthesized through biosynthesis of alkaloids derived from ornithine, lysine, and nicotine acid and glyoxylate and decarboxylate metabolism, among which Lactococcus plays a key role. In this study, a variety of lactic acid bacteria related to ghee fermentation were screened out, revealing the composition of volatile flavor compounds in Gannan yak milk ghee in the Qinghai–Tibet Plateau and providing a reference for further key volatile flavor compounds and the formation mechanism of flavor compounds.

This paper focuses on the impact of return decisions on the bullwhip effect in the online closed-loop supply chain. We investigate the optimal return modes when the inspection system is undertaken by the logistics centre or the remanufacturer. Then, we optimise the online retailers' return decisions of minimising the inventory cost and bullwhip effect under different supply chain circumstances. Distinctive from previous conclusion that the inspection operation is usually undertaken by the remanufacturer to sort the returned products, the analysis results reveal that the optimal decision of mitigating the bullwhip effect in most cases is to set the inspection system on logistics centre. Besides, consumers' return and exchange behaviours in e-commerce have different impacts on the supply chain efficiency. The product return can not necessarily mitigate the information distortion in online closed-loop supply chain. The research provides insights for managers to strategise about return policies and resource allocation in different e-commerce contexts. [ABSTRACT FROM AUTHOR]

Radiation-induced intestinal injury is one of the most common intestinal complications caused by pelvic and abdominal tumor radiotherapy, severely impacting patients' quality of life. Ionizing radiation, while killing tumor cells, inevitably damages healthy tissue. Radiation-induced enteropathy results from radiation therapy-induced intestinal tissue damage and inflammatory responses. This damage involves various complex molecular mechanisms, including cell apoptosis, oxidative stress, release of inflammatory mediators, disruption of immune responses, and imbalance of intestinal microbiota. A thorough understanding of these molecular mechanisms is crucial for developing effective prevention and treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Subarachnoid hemorrhage (SAH) is a severe cerebrovascular disorder primarily caused by the rupture of aneurysm, which results in a high mortality rate and consequently imposes a significant burden on society. The occurrence of SAH initiates an immune response that further exacerbates brain damage. The acute inflammatory reaction subsequent to SAH plays a crucial role in determining the prognosis. Th17 cells, a subset of T cells, are related to the brain injury following SAH, and it is unclear how Th17 cells are cleared in the brain. Meningeal lymphatic vessels are a newly discovered intracranial fluid transport system that has been shown to drain large molecules and immune cells to deep cervical lymph nodes. There is limited understanding of the role of the meningeal lymphatic system in SAH. The objective of this research is to explore the impact and underlying mechanism of drainage Th17 cells by meningeal lymphatics on SAH. Methods: Treatments to manipulate meningeal lymphatic function and the CCR7-CCL21 pathway were administered, including laser ablation, injection of VEGF-C geneknockout, and protein injection. Mouse behavior was assessed using the balance beam experiment and the modified Garcia scoring system. Flow cytometry, enzyme-linked immunosorbent assays (ELISA), and immunofluorescence staining were used to study the impact of meningeal lymphatic on SAH drainage. Select patients with unruptured and ruptured aneurysms in our hospital as the control group and the SAH group, with 7 cases in each group. Peripheral blood and cerebrospinal fluid (CSF) samples were assessed by ELISA and flow cytometry. Results: Mice with SAH showed substantial behavioral abnormalities and brain damage in which immune cells accumulated in the brain. Laser ablation of the meningeal lymphatic system or knockout of the CCR7 gene leads to Th17 cell aggregation in the meninges, resulting in a decreased neurological function score and increased levels of inflammatory factors. Injection of VEGF-C or CCL21 protein promotes Th17 cell drainage to lymph nodes, an increased neurological function score, and decreased levels of inflammatory factors. Clinical blood and CSF results showed that inflammatory factors in SAH group were significantly increased. The number of Th17 cells in the SAH group was significantly higher than the control group. Clinical results confirmed Th17 cells aggravated the level of neuroinflammation after SAH. Conclusion: This study shows that improving the drainage of Th17 cells by meningeal lymphatics via the CCR7-CCL21 pathway can reduce brain damage and improve behavior in the SAH mouse model. This could lead to new treatment options for SAH. [ABSTRACT FROM AUTHOR]

Defect engineering is a key chemical tool to modulate the electronic structure and reactivity of nanostructured catalysts. Here, it is reported how targeted introduction of defect sites in a 2D palladium metallene nanostructure results in a highly active catalyst for the alkaline oxygen reduction reaction (ORR). A defect‐rich WOx and MoOx modified Pd metallene (denoted: D‐Pd M) is synthesized by a facile and scalable approach. Detailed structural analyses reveal the presence of three distinct atomic‐level defects, that are pores, concave surfaces, and surface‐anchored individual WOx and MoOx sites. Mechanistic studies reveal that these defects result in excellent catalytic ORR activity (half‐wave potential 0.93 V vs. RHE, mass activity 1.3 A mgPd−1 at 0.9 V vs. RHE), outperforming the commercial references Pt/C and Pd/C by factors of ≈7 and ≈4, respectively. The practical usage of the compound is demonstrated by integration into a custom‐built Zn‐air battery. At low D‐Pd M loading (26 µgPd cm−2), the system achieves high specific capacity (809 mAh gZn−1) and shows excellent discharge potential stability. This study therefore provides a blueprint for the molecular design of defect sites in 2D metallene nanostructures for advanced energy technology applications. [ABSTRACT FROM AUTHOR]