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Vascular endothelial growth factor B (VEGF-B) has been suggested to play a crucial role in regulating whole-body glucose homeostasis. However, the involved mechanisms are not fully understood. This study aimed to elucidate the regulatory effects and mechanisms of VEGF-B on glucose uptake in skeletal muscle, focusing on glucose uptake by skeletal muscle cells and vascular endothelial cells. Our results showed that a high-fat diet (HFD) induced significant increase in VEGF-B expression and decrease in glucose uptake by skeletal muscle, accompanied by elevated serum glucose levels. Interestingly, VEGF-B had no direct effect on glucose uptake by skeletal muscle cells (differentiated C2C12). Instead, VEGF-B inhibited glucose uptake of vascular endothelial cells bEnd.3 and subsequent trans-endothelial glucose transport, ultimately resulting in decreased glucose uptake by skeletal muscle cells. Furthermore, VEGF-B suppressed glucose uptake of vascular endothelial cells by downregulating the expression of glucose transporter 1 (GLUT1) through the VEGFR-PI3K/Akt signaling pathway. In vivo, knockdown of VEGF-B in skeletal muscle increased the HFD-impaired glucose uptake of skeletal muscle and improved the HFD-induced glucose intolerance and insulin resistance. This beneficial effect of VEGF-B knockdown was associated with the elevated expression of GLUT1 in the plasma membrane and the activation of the PI3K/Akt pathway in skeletal muscle. In conclusion, our findings demonstrated that knockdown of VEGF-B improved HFD-induced insulin resistance by enhancing glucose uptake in vascular endothelial cells via the PI3K/Akt pathway. These results highlighted the critical role of VEGF-B in regulating glucose uptake by vascular endothelial cells in skeletal muscle, providing a potential new target for improving obesity-induced glucose homeostasis imbalance., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Vascular endothelial growth factor B (VEGFB) has been well demonstrated to play a crucial role in regulating vascular function by binding to the VEGF receptors (VEGFRs). However, the specific role of VEGFB and VEGFRs in pubertal mammary gland development remains unclear. In this study, we observed that blocking the VEGF receptors with Axitinib suppressed the pubertal mammary gland development. Meanwhile, the proliferation of mammary epithelial cells (HC11) was repressed by blocking the VEGF receptors with Axitinib. Additionally, knockdown of VEGFR1 rather than VEGFR2 and NRP1 elicited the inhibition of HC11 proliferation, suggesting the essential role of VEGFR1 during this process. Furthermore, Axitinib or VEGFR1 knockdown led to the inhibition of the PI3K/Akt pathway. However, the inhibition of HC11 proliferation induced by Axitinib and or VEGFR1 knockdown was eliminated by the Akt activator SC79, indicating the involvement of the PI3K/Akt pathway. Finally, the knockdown of VEGFB and VEGFR1 suppressed the pubertal development of mice mammary gland with the inhibition of the PI3K/Akt pathway. In summary, the results showed that knockdown of the VEGFB/VEGFR1 signaling suppresses pubertal mammary gland development of mice via the inhibition of the PI3K/Akt pathway, which provides a new target for the regulation of pubertal mammary gland development., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Loach (Misgurnus anguillicaudatus) is a common freshwater commercial fish species in China. The meat of this fish is a good source of protein and other nutrients that are needed for human health. Aquaculture challenges such as diseases and pest susceptibility, excessive density, and nutritional deficiency result in low production of loach rather than increased demand. Due to a lack of knowledge about the immune system of loaches, we carried out this study to better understand its antibacterial molecular mechanism. Here, we performed RNA sequencing from liver tissue obtained from soya bean-fermented fed loach after subjecting it to the LPS challenge. The results revealed a total of 18,399 differentially expressed genes (DEGs) in the LPS-treated and control groups. There were 7482 DEGs that were upregulated and 10,917 DEGs were downregulated. The enrichment analysis of DEGs revealed that the majority of DEGs were found to be abundant in the pathways of DNA replication, spliceosome, nucleotide exception repair, cell cycle, and Herpes simplex virus 1 infection. Furthermore, qRT-PCR analysis of 21 selected DEGs demonstrated that the transcriptomic data is extremely reliable. Overall, this study provides insight into the molecular features and control mechanisms of genes that affect loach growth. The availability of this information will also contribute to the enhancement of the breeding and protection of loach resources., Competing Interests: Declaration of competing interest The authors have declared that no competing interests exist., (Copyright © 2024. Published by Elsevier B.V.)

MicroRNAs (miRNAs) are a class of RNA macromolecules that play regulatory roles in follicle development by inhibiting protein translation through binding to the 3'UTR of its target genes. Granulosa cell (GC) proliferation, steroidogenesis, and lipid metabolism have indispensable effect during folliculogenesis. In this study, we found that miR-22-3p was highly expressed in the hierarchical follicles of the chickens, which indicated that it may be involved in follicle development. The results obtained suggested that miR-22-3p promoted proliferation, hormone secretion (progesterone and estrogen), and the content of lipid droplets (LDs) in the chicken primary GC. The results from the bioinformatics analysis, luciferase reporter assay, qRT-PCR, and Western blotting, confirmed that PTEN was directly targeted to miR-22-3p. Subsequently, it was revealed that PTEN inhibited proliferation, hormone secretion, and the content of LDs in GC. Therefore, this study showed that miR-22-3p could activate PI3K/Akt/mTOR pathway via targeting PTEN. Taken together, the findings from this study indicated that miR-22-3p was highly expressed in the hierarchical follicles of chickens, which promotes GC proliferation, steroidogenesis, and lipid metabolism by repressing PTEN to activate PI3K/AKT/mTOR pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Dihydromyricetin (DMY) is a natural dihydroflavonol compound known for its diverse pharmacological benefits. However, its limited stability and bioavailability posed significant challenges for further applications. To address these issues, in this study, an ion crosslinking method was utilized to prepare chitosan nanoparticles that were loaded with DMY. The synthesized chitosan nanoparticles (CS-DMY-NPs) were spherical in shape with particle size and ζ potential of 198.7 nm and 45.05 mV, respectively. Furthermore, in vitro release experiments demonstrated that CS-DMY-NPs had sustained release and protective effects in simulated gastric and intestinal fluids. CS-DMY-NPs exhibited better antioxidant activity by ABTS and DPPH radical scavenging activity than free DMY. In vivo study showed that CS-DMY-NPs alleviated cisplatin-induced kidney damage by inhibiting oxidative stress and proinflammatory cytokines, and had better activity compared to DMY (free). Immunofluorescence data showed that CS-DMY-NPs activated the Nrf2 signaling pathways in a dose-dependent manner to combat cisplatin-induced kidney damage. Our results demonstrate that CS-TPP has good compatibility with DMY, and CS-DMY-NPs exhibited better protective effects against cisplatin-induced acute kidney injury (AKI) than free DMY., Competing Interests: Declaration of competing interest The authors declare that they have no known economic interests or personal relationships that could have influenced the work reported in this article and potentially biased its findings., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Transarterial chemoembolization (TACE) is an important approach for the treatment of unresectable hepatocellular carcinoma (HCC). However, the lactic acid-induced acidic tumor microenvironment (TME) may reduce the therapeutic outcome of TACE. Herein, monodispersed gelatin microspheres loaded with calcium carbonate nanoparticles (CaNPs@Gel-MS) as novel embolic agents were prepared by a simplified microfluidic device. It was found that the particle size and homogeneity of as-prepared CaNPs@Gel-MS were strongly dependent on the flow rates of continuous and dispersed phases, and the inner diameter of syringe needle. The introduction of CaNPs provided the gelatin microspheres with an enhanced ability to encapsulate the chemotherapeutic drug of DOX, as well as a pH-responsive sustained drug release behavior. In vitro results revealed that CaNPs@Gel-MS could largely increase the cellular uptake and chemotoxicity of DOX by neutralizing the lactic acid in the culture medium. In addition, CaNPs@Gel-MS exhibited an excellent and persistent embolic efficiency in a rabbit renal model. Finally, we found that TACE treatment with DOX-loaded CaNPs@Gel-MS (DOX/CaNPs@Gel-MS) had a much stronger ability to inhibit tumor growth than the DOX-loaded gelatin microspheres without CaNPs (DOX@Gel-MS). Overall, CaNPs@Gel-MS could be a promising embolic microsphere that can significantly improve anti-HCC ability by reversing lactic acid-induced chemotherapy resistance during TACE treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Starch is a basic biomacromolecule, and an in-depth understanding of the process and mechanism of starch-lipid complexation has great significance for starch based food and pharmaceutical. In this study, molecular dynamics simulation was used to explore the complexation details between starch molecules and trilinolenin, such as complexation process, interaction forces, conformation changes and stability changes, which are difficult to be verified by using other characterization methods. The results show that, firstly, starch residues of one turn helix (8 residues) are enough to bind a trilinolenin molecule firmly. Secondly, the complex is maintained by Van der Waals and electrostatic interaction. Thirdly, the residues complexed with trilinolenin become more stable than the former or the free residues. In brief, the complexation process, interaction forces, conformation changes and stability changes of the starch-trilinolenin complex were clarified in this study. The results may create new insights for the research about the interaction of starch and lipid, then provide theoretical guidance for the research on starch based food and pharmaceutical., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, this manuscript., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Novel porous nitrogen-doped carbon supported Pd (Pd@N-C) catalytic composites were prepared by one-pot thermal carbonization of chitosan/poly(ethylene glycol)‑block‑poly(propylene glycol)‑block‑poly(ethylene glycol)/PdCl 2 (CS/P123/PdCl 2 ) blend hydrogel membranes at different temperature in N 2 atmosphere. The porous structure of the Pd@N-C catalytic composite was governed by both the addition of P123 and the carbonization temperature. At highest carbonization temperature of 900 °C, the prepared Pd@N-C catalytic composite from CS/P123/PdCl 2 blend membrane showed the highest specific area (S BET ) of 293.7 m 2 /g and total volume of pores (V tot ) of 0.79 cm 3 /g. The chemical state of the elements of C, N, O, Pd within the Pd@N-C catalytic composites were confirmed with X-ray photoelectron spectroscopy (XPS) measurements. Raman spectrum results showed that the prepared Pd@N-C catalytic composite contained mainly disordered carbon together with some graphite carbon. Pd nanoparticles sized in 5-20 nm dispersed well on the porous matrix of the carbon. The Pd@N-C catalytic composites showed excellent activities for the Ullmann homo-coupling reactions of aromatic halides, and can be recycled for 10 times. In such one-pot carbonization process, the polymer porogen is simultaneously decomposed without further etching and removal steps, which simplifies the preparation process and is beneficial to obtain Pd@N-C catalytic composites with desirable Pd loading., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In this study, chemical properties of polysaccharides from rhizomes of Panax japonicus C. A. Mey (PSPJ) were investigated and the antitumor immunostimulatory activity of PSPJ was assessed in mice bearing H22 hepatoma cells. Chemical properties of PSPJ were determined by GC, FT-IR, 1 H NMR and 13 C NMR analysis. Furthermore, we showed that PSPJ repressed H22 tumor growth in vivo with undetectable toxic effects on tumor-bearing mice. PSPJ upregulated host thymus/spleen indexes and ConA/LPS-induced splenocyte proliferation. Cytotoxic activities of natural killer and CD8+ T cells against H22 hepatoma cells were also elevated. Tumor transplantation led to substantial apoptosis of CD4+ T cells and dysregulation of the cytokine profile secreted by CD4+ T cells. These abnormalities were alleviated by PSPJ in a dose-dependent manner. In tumor-associated macrophages (TAMs), PSPJ reduced the production of immunosuppressive factors such as TGF-β, IL-10 and PEG2. In addition, M2-like polarization of TAMs was also considerably declined in response to PSPJ. Our findings clearly demonstrated the antitumor immunostimulatory activity of PSPJ and supported considering PSPJ as an adjuvant reagent in clinical treatment of malignant diseases., (Copyright © 2018. Published by Elsevier B.V.)

Roots of Astragalus membranaceus (Fish.) Bge. var. mongholicus (Bge.) Hsiao (A. membranaceus) have been long used as an auxiliary reagent supporting cancer treatment. Here, we compared the chemical composition and antitumor immunomodulating activity of polysaccharides from roots of A. membranaceus (PAMs) from five major habitats in Inner Mongolia, PR China. We revealed that compositions of monosaccharides and amino acids were comparable among PAMs from different habitats. However, amounts of selenium varied widely in roots of A. membranaceus and PAMs. PAMs selenium-dependently repressed the in vivo proliferation of transplanted H22 ascitic hepatoma and S180 sarcoma cells with low toxic impacts on tumor-bearing mice. Selenium-containing PAMs ameliorated host CD4+ T cell apoptosis and serum cytokine dysregulation induced by tumor transplantation, leading to the enhancement of cytotoxic activities of natural killer and CD8+ T cells. Moreover, PAMs also selenium-dependently improved the phagocytotic function of intra-abdominal macrophages and suppressed M2-like polarization of tumor-associated macrophages. These data suggested that the selenium content varies in the roots of A. membranaceus and PAMs from different geographical origins dramatically and selenium is an important contributor to the antitumor immunomodulation activities of PAMs., (Copyright © 2014 Elsevier B.V. All rights reserved.)