LC-MS based metabolomics identification of natural metabolites against Fusarium oxysporum.

Fusarium is a soil-borne pathogen that poses a serious threat to the quality and yield of hundreds of crops worldwide, particularly tobacco production. Using metabolomics technology, we investigated natural metabolites from disease-conducting soil (DCS) and disease-suppressing soil (DSS) of tobacco rhizosphere as fungicides to control tobacco Fusarium wilt (TFW), which is mainly caused by Fusarium oxysporum. Furthermore, the antifungal mechanisms of these natural metabolites were preliminarily elucidated through various assessments, including antifungal activity determination, chemotaxis effect tests, PI staining experiments, and measurements of extracellular conductivity and protein content. Metabolomics results showed that the DCS with three different disease grades (G1, G5 and G9 groups) had significantly higher levels of 15, 14 and 233 differential rhizosphere metabolites (DRMs) and significantly lower levels of 72, 152 and 170 DRMs compared to the DSS (G0 group). According to KEGG pathway analysis, these DRMs were found to be enriched in the caffeine metabolism, biosynthesis of phenylpropanoids, galactose metabolism and tyrosine metabolism, etc. Linustatin, scopoletin and phenylpropiolic acid were picked out from these DRMs and found to have suppressive activity against F. oxysporum through correlation analysis and antifungal experiments. The three DRMs showed strong inhibitory effects on the growth and spore germination of F. oxysporum at concentrations of 0.5 mM or higher in each test period. Furthermore, F. oxysporum showed a phobotaxis effect against these three DRMs at concentrations as low as 0.25 mM. Finally, we found that the three DRMs had an inhibitory effect on F. oxysporum by destroying the integrity of the cell membrane and increasing the membrane permeability of F. oxysporum. This study firstly reports the inhibition activity of phenylpropiolic acid and linustatin on F. oxysporum, providing a practical and environmentally friendly method for biocontrol of TFW by using natural fungicides.

Cancer cell membrane-coated nanoparticles: a promising anti-tumor bionic platform.

Nanoparticle (NP) drug delivery systems have shown promise in tumor therapy. However, limitations such as susceptibility to immune clearance and poor targeting in a complex intercellular environment still exist. Recently, cancer cell membrane-encapsulated nanoparticles (CCM-NPs) constructed using biomimetic nanotechnology have been developed to overcome these problems. Proteins on the membrane surface of cancer cells can provide a wide range of activities for CCM-NPs, including immune escape and homologous cell recognition properties. Meanwhile, the surface of the cancer cell membrane exhibits obvious antigen enrichment, so that CCM-NPs can transmit tumor-specific antigen, activate a downstream immune response, and produce an effective anti-tumor effect. In this review, we first provided an overview of the functions of cancer cell membranes and summarized the preparation techniques and characterization methods of CCM-NPs. Then, we focused on the application of CCM-NPs in tumor therapy. In addition, we summarized the functional modifications of cancer cell membranes and compiled the patent applications related to CCM-NPs in recent years. Finally, we proposed the future challenges and directions of this technology in order to provide guidance for researchers in this field.

Combination of ferroptosis and pyroptosis dual induction by triptolide nano-MOFs for immunotherapy of Melanoma.

Immunotherapy has good potential to eradicate tumors in the long term. However, due to the low immunogenicity of tumor cells, current cancer immunotherapies are not effective. To address this limitation, we constructed a BSA-FA functionalized iron-containing metal-organic framework (TPL@TFBF) that triggers a potent systemic anti-tumor immune response by inducing ferroptosis and pyroptosis in tumor cells and releasing large quantities of damage-associated molecular patterns (DAMPs) to induce immunogenicity, and showing excellent efficacy against melanoma lung metastases in vivo. This nanoplatform forms a metal-organic framework through the coordination between tannic acid (TA) and Fe3+ and is then loaded with triptolide (TPL), which is coated with FA-modified BSA. The nanoparticles target melanoma cells by FA modification, releasing TPL, Fe3+ and TA. Fe3+ is reduced to Fe2+ by TA, triggering the Fenton reaction and resulting in ROS production. Moreover, TPL increases the production of intracellular ROS by inhibiting the expression of nuclear factor erythroid-2 related factor (Nrf2). Such simultaneous amplification of intracellular ROS induces the cells to undergo ferroptosis and pyroptosis, releasing large amounts of DAMPs, which stimulate antigen presentation of dendritic cells (DCs) and the proliferation of cytotoxic T lymphocytes (CD4+/CD8 + T cells) to inhibit tumor and lung metastasis. In addition, combining nanoparticle treatment with immune checkpoint blockade (ICB) further inhibits melanoma growth. This work provides a new strategy for tumor immunotherapy based on various combinations of cell death mechanisms.

Molecular identification and lipid mobilization role of adipokinetic hormone receptor in Spodoptera litura (F.).

Energy homeostasis is essential for organisms to maintain fluctuation in energy accumulation, mobilization. Lipids as the main energy reserve in insects, their metabolism is under the control of many physiological program. This study aimed to determine whether the adipokinetic hormone receptor (AKHR) was involved in the lipid mobilization in the Spodoptera litura. A full-length cDNA encoding AKHR was isolated from S. litura. The SlAKHR protein has a conserved seven-transmembrane domain which is the character of a putative G protein receptor. Expression profile investigation revealed that SlAKHR mRNA was highly expressed in immatural stage and abundant in fat body in newly emerged female adults. Knockdown of SlAKHR expression was achieved through RNAi by injecting double-stranded RNA (dsRNA) into the 6th instar larvae. The content of triacylgycerol (TAG) in the fat body increased significantly after the SlAKHR gene was knockdown. And decrease of TAG releasing to hemolymph with increase of free fatty acid (FFA) in hemolymph were observed when the SlAKHR gene was knowned-down. In addition, lipid droplets increased in fat body was also found. These results suggested that SlAKHR is critical for insects to regulate lipids metabolism.

Development of an MR safe reach and grasp movement evaluation system to study brain activation patterns after stroke.

An MR safe apparatus is important for the for monitoring of tasks in the magnetic resonance (MR) environment. This paper describes the development of an MR safe movement evaluation system to measure the hand grasp and elbow flexion/extension movements. The system will be used to monitor motor performance in the fMRI environment and assess functional and motor impairment level pre and post robot-assisted therapy.