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Chinese yam (Dioscorea opposita Thunb. cv. Tiegun), a type of homologous medicinal plant, mainly grows in sandy soil (SCY) and loessial soil (LCY). However, the effects of the soil on the metabolites in SCY and LCY remain unclear. Herein, this study aims to comprehensively elucidate the metabolites in SCY and LCY. A UPLC-MS/MS-based, widely targeted metabolomics approach was adapted to compare the chemical composition of SCY and LCY. A total of 988 metabolites were detected, including 443 primary metabolites, 510 secondary metabolites, and 35 other compounds. Notably, 177 differential metabolites (classified into 12 categories) were identified between SCY and LCY; among them, 85.9% (152 differential metabolites) were upregulated in LCY. LCY significantly increased the contents of primary metabolites such as 38 lipids and 6 nucleotides and derivatives, as well as some secondary metabolites such as 36 flavonoids, 28 phenolic acids, 13 alkaloids, and 6 tannins. The results indicate that loessial soil can improve the nutritional and medicinal value of D. opposita. [ABSTRACT FROM AUTHOR]

Dioscorea opposita Thunb., a traditional medicinal and food homologous plant, has been used for thousands of years in folk medicine and nutritious food, partially due to the metabolites. However, detailed information on the metabolites in Dioscorea opposita Thunb. peel is still scarce. Herein, an ultra‐high‐performance liquid chromatography‐quadrupole/orbitrap high‐resolution mass spectrometry‐based metabolomics approach was used to reveal the comprehensive metabolites in Dioscorea opposita Thunb. peel. The proposed method provided tentative identification of 307 metabolites. Among them, 286 metabolites are reported herein in Dioscorea opposita Thunb. peel for the first time, namely: 87 lipids, 49 phenolic acids, 34 flavonoids, 29 amino acids and derivatives, 28 organic acids, 14 alkaloids, 10 lignans, and coumarins, eight saccharides and vitamins, six nucleotides and derivatives, two quinones, and 19 others. The obtained results highlight the importance of Dioscorea opposita Thunb. peel as a promising source of bioactive ingredients, and form a basis for future quantitative and bioavailability studies. [ABSTRACT FROM AUTHOR]

Fig. 1. The Research Process and Technical Workflow Diagram Used in the Article. [Display omitted] • This study uses single-cell technology to analyze a publicly available dataset (GSE149614) through a series of analyses. • Reveal the changes in the composition of the tumor microenvironment and differences in immune cell communication at different stages of HCC. • We identified genes associated with the prognosis of HCC and predict drugs that related to these genes. • The findings may contribute to improving the immunosuppressive microenvironment and providing new therapeutic targets for HCC. Hepatocellular Carcinoma (HCC) is the most common type of primary liver cancer, accounting for the majority of liver cancer cases. Hepatocellular Carcinoma not only exhibits high heterogeneity but also possesses an immune-suppressive tumor microenvironment that promotes tumor evasion, posing substantial difficulties for efficient therapy. Our aim is to utilize single-cell RNA transcriptome data to investigate the dynamic changes in the tumor microenvironment during the malignant progression of HCC, the communication among immune cells, and the marker genes associated with patient prognosis. We constructed expression matrices from open single-cell RNA transcriptome data (GSE149614) of HCC patients (representing stages I–IV), establishing single-cell RNA transcriptional atlases for different stages of HCC progression. For each stage, we conducted cell subgroup analysis to identify cell types at each stage. Horizontally, we explored the dynamic changes of the same cell type across different stages, performing trajectory analysis and prognosis analysis. Vertically, we investigated pairwise comparisons of different stages of HCC progression, probing the dynamic alterations in tumor microenvironment immune cell signaling pathways. Finally, potential drugs for the treatment of HCC were predicted based on relevant genes. As the HCC advances towards increased malignancy, there is a shift in the predominant composition of the tumor microenvironment, with a decline in the dominance of hepatic cells. Tumor-infiltrating immune cells migrate and accumulate within the tumor microenvironment, where T cells and myeloid cells display distinct patterns of change. Genes associated with cancer-associated fibroblasts (CAFs) and T cells are correlated with adverse patient outcomes. In the late stages of HCC, the tumor microenvironment is infiltrated by more myeloid-derived suppressor cells (MDSCs), and a prognostic model constructed based on genes related to myeloid cells can predict patient outcomes. Additionally, in the analysis of transcription factors, YY1 and MYC are found to be highly expressed. Cell communication analysis among tumor-infiltrating immune cells reveals significant differences in the main signaling pathways at different stages of HCC progression. Finally, drug sensitivity analysis based on key genes identifies Acetalax, Allopurinol, and Amonafide as potential candidates for HCC treatment. [ABSTRACT FROM AUTHOR]

Background: Delta‐like homologue 1 (DLK1), a transmembrane protein, is highly expressed in hepatocellular carcinoma (HCC). We explored whether DLK1‐directed chimeric antigen receptor (CAR) T cells can specifically eliminate DLK1‐positive HCC cells and serve as a therapeutic strategy for HCC immunotherapy. Methods: We first characterized a homemade anti‐human DLK1 monoclonal antibody, sequenced the single‐chain Fragment variable (scFv) and integrated it into the second‐generation CAR lentiviral vector, and then developed the DLK1‐directed CAR‐T cells. The cytotoxic activities of DLK1‐directed CAR‐T cells against different HCC cells were evaluated in vitro and in vivo. Results: The genetically modified human T cells with the DLK1‐directed CARs produced cytotoxic activity against DLK1‐positive HCC cells. Additionally, the DLK1‐directed CARs enhanced T cell proliferation and activation in a DLK1‐dependent manner. Interestingly, the DLK1‐targeted CAR‐T cells significantly inhibited both subcutaneous and peritoneal xenograft tumours derived from human liver cancer cell lines HepG2 or Huh‐7. Conclusion: DLK1‐directed CAR‐T cells specifically suppresses DLK1‐positive HCC cells in vitro and in vivo. This study provides a novel transmembrane antigen DLK1 as a potential therapeutic target appropriate for CAR‐T cell therapy, which may be further developed as a clinical therapeutic strategy for HCC immunotherapy. [ABSTRACT FROM AUTHOR]

Callicarpa kwangtungensis Chun is a traditional Chinese medicine that has various therapeutic effects. Despite its wide use in Chinese medicine, the study is still quite limited, especially its chemical compositions. In this research, an ultra‐high‐pressure liquid chromatography coupled with Q Exactive hybrid quadrupole‐orbitrap high‐resolution accurate mass spectrometry tandem mass spectrometry method was utilized to analyze its chemical compositions for the first time. As a result, a total of 124 compounds, including 20 phenylethanoid glycosides, 31 flavonoids, 36 organic acids, 26 terpenoids and 11 phenols, were identified or tentatively characterized in 30 min. Among them, 49 compounds, including 5 phenylethanoid glycosides, 12 flavonoids, 16 organic acids, 12 terpenoids, and 4 phenols, were identified in Callicarpa kwangtungensis Chun for the first time. Besides, the fragmentation pathways were also discussed. This research established a rapid and reliable method to analyze the chemical compositions of complicated herb without the process of isolation, and provide abundant information on the chemical material basis for further bioactivity and quality control studies. [ABSTRACT FROM AUTHOR]

A series of peptidomimetic aldehydes were designed, synthesized, and evaluated for their biochemical activity against 3C protease (3C pro ) and anti-enterovirus 71 (EV71) activity in vitro . Molecular docking revealed that 5s (IC 50 = 0.22 ± 0.07 μM, EC 50 = 0.18 ± 0.05 μM) could bind well to the active site of EV71 3C pro , which was consistent with the biological data compared to reference 5a (IC 50 = 0.54 ± 0.02 μM, EC 50 = 0.26 ± 0.07 μM). Structure and relationship study led to the discovery of aldehyde 5x (IC 50 = 0.10 ± 0.02 μM, EC 50 = 0.11 ± 0.07 μM), which exhibited the most potent 3C pro inhibitory and antiviral activity. [ABSTRACT FROM AUTHOR]

A series of polyamine conjugates of flavonoids with a naphthalene motif were synthesized and evaluated for their anti-hepatocellular carcinoma properties using in vitro and in vivo assays. Compound 8a displayed favorable selectivity between hepatocellular carcinoma cells and normal hepatocyte cells, and the combination of 8a with aspirin resulted in additive inhibition of in vitro tumor cell growth and migration. The 8a -aspirin combination also inhibited H22 liver tumor growth and pulmonary metastasis and improved body weight index in animal models. Preliminary mechanistic studies indicated that 8a increased the expression of apoptosis-related proteins such as p-p38, p-JNK, p53 and Bcl-2, an effect that was further amplified by aspirin. Therefore, a cocktail therapy of flavonoid-polyamine conjugates with aspirin has potential use as an antitumor therapy. [ABSTRACT FROM AUTHOR]

Enterovirus 71 (EV71) is one of the major etiological agents of human hand-foot-and-mouth disease (HFMD) worldwide. EV71 infection in young children and people with immunodeficiency causes severe symptoms with a high fatality rates. However, there is still no approved drugs to treat such infections. Based on our previous report of a peptide-aldehyde anti-EV71 protease, we present here a highly specific α-hydroxy-nitrile derivative NK-1.9k, which inhibited the proliferation of multiple EV71 strains and coxsackievirus A16 (CVA16) in various cells with EC 50 of 37.0 nM with low cytotoxicity (CC 50 > 200 μM). The hydroxy-nitrile covalent warhead conferred NK-1.9k high potency and selectivity to interact with the cysteine residue of the active site of the viral protease. We also documented the resistance to NK-1.9k with a N69S mutation in EV71 3C pro . The combination of NK-1.9k and EV71 polymerase or entry inhibitors produced strong synergistic antiviral effects. Collectively, our findings suggest our compounds can potentially be developed as drugs for the treatment of HFMD. [ABSTRACT FROM AUTHOR]

Preliminary investigations have demonstrated that the cysteines located at the C-terminus of HEV ORF2 protein exhibits disulfide bonding capability during virus-like particles (VLPs) assembly. However, the effect and mechanism underlying the pairing of disulfide bonds formed by C627, C630, and C638 remains unclear. The p222 protein encompasses C-terminus and serves as a representative of HEV ORF2 to investigate the specific impacts of C627, C630, and C638. The three cysteines were subjected to site-directed mutagenesis and expressed in prokaryotes; Both the mutated proteins and p222 underwent polymerization except for p222A; Surprisingly, only p222 was observed as abundant spherical particles under transmission electron microscope (TEM); Stability and immunogenicity of the p222 exhibited higher than other mutated proteins; LC/MS/MS analysis identified four disulfide bonds in the p222. The novel findings suggest that the three cysteines contribute to structural and functional properties of ORF2 protein, highlighting the indispensability of each cysteine. • Three cysteines (C627, C630, C638) in the C-terminus of ORF2 contribute to structural and functional properties of protein. • The indispensability of the C627, C630, andC638 is underscored. • LC/MS/MS analysis confirmed the presence of four disulfide bond pairs within the p222 protein. [ABSTRACT FROM AUTHOR]

Quadrotor AUV is a new and promising vehicle in applications due to its special advantages. However, the problem of dynamic modeling of quadrotor AUV has not been investigated yet. In this study, a new dynamic modeling method for a quadrotor AUV is proposed by using a novel CFD simulation to calculate the hydrodynamic coefficients. Star CCM + is used to simulate the uniform and variable motion of each degree of freedom of a quadrotor AUV to decouple original high coupling dynamic model. Through the simulation of the AUV and the propeller motion, the main hydrodynamic coefficients are calculated, while the mathematical relationship between the rotation velocity and the thrust/torque is concluded. Specifically, the static mesh and dynamic mesh models are used to simulate the uniform and variable motion of the quadrotor AUV respectively. The calculation of added mass and drag coefficient does not interfere with each other, leading to accurate results. A numerical method is also proposed to separate the linear and nonlinear parts of the total drag coefficients. Then a six DOF dynamic model of a quadrotor AUV is established. The proposed CFD simulation also provides a reliable, repeatable and low-cost method for dynamic modeling of underwater vehicles. • The hydrodynamic coefficients of a type of quadrotor AUV are calculated. • The mathematical relationship between the propeller speed and its thrust/torque is obtained. • A novel mesh configuration method for star CCM+ simulation is proposed. • A numerical method is proposed to separate the linear and nonlinear parts of the total drag coefficients. • The complete six degree of freedom dynamic model of the quadrotor AUV is obtained. [ABSTRACT FROM AUTHOR]