Mir155hg Accelerates Hippocampal Neuron Injury in Convulsive Status Epilepticus by Inhibiting Microglial Phagocytosis.

Convulsive status epilepticus (CSE) is a common critical neurological condition that can lead to irreversible hippocampal neuron damage and cognitive dysfunction. Multiple studies have demonstrated the critical roles that long non-coding RNA Mir155hg plays in a variety of diseases. However, less is known about the function and mechanism of Mir155hg in CSE. Here we investigate and elucidate the mechanism underlying the contribution of Mir155hg to CSE-induced hippocampal neuron injury. By applying high-throughput sequencing, we examined the expression of differentially expressed genes in normal and CSE rats. Subsequent RT-qPCR enabled us to measure the level of Mir155hg in rat hippocampal tissue. Targeted knockdown of Mir155hg was achieved by the AAV9 virus. Additionally, we utilized HE and Tunel staining to evaluate neuronal injury. Immunofluorescence (IF), Golgi staining, and brain path clamping were also used to detect the synaptic plasticity of hippocampal neurons. Finally, through IF staining and Sholl analysis, we assessed the degree of microglial phagocytic function. It was found that the expression of Mir155hg was elevated in CSE rats. HE and Tunel staining results showed that Mir155hg knockdown suppressed the hippocampal neuron loss and apoptosis followed CSE. IF, Golgi staining and brain path clamp data found that Mir155hg knockdown enhanced neuronal synaptic plasticity. The results from IF staining and Sholl analysis showed that Mir155hg knockdown enhanced microglial phagocytosis. Our findings suggest that Mir155hg promotes CSE-induced hippocampal neuron injury by inhibiting microglial phagocytosis.

Improved weed mapping in corn fields by combining UAV-based spectral, textural, structural, and thermal measurements.

BACKGROUND: Spatial-explicit weed information is critical for controlling weed infestation and reducing corn yield losses. The development of unmanned aerial vehicle (UAV)-based remote sensing presents an unprecedented opportunity for efficient, timely weed mapping. Spectral, textural, and structural measurements have been used for weed mapping, whereas thermal measurements-for example, canopy temperature (CT)-were seldom considered and used. In this study, we quantified the optimal combination of spectral, textural, structural, and CT measurements based on different machine-learning algorithms for weed mapping. RESULTS: CT improved weed-mapping accuracies as complementary information for spectral, textural, and structural features (up to 5% and 0.051 improvements in overall accuracy [OA] and Marco-F1, respectively). The fusion of textural, structural, and thermal features achieved the best performance in weed mapping (OA = 96.4%, Marco-F1 = 0.964), followed by the fusion of structural and thermal features (OA = 93.6%, Marco-F1 = 0.936). The Support Vector Machine-based model achieved the best performance in weed mapping, with 3.5% and 7.1% improvements in OA and 0.036 and 0.071 in Marco-F1 respectively, compared with the best models of Random Forest and Naïve Bayes Classifier. CONCLUSION: Thermal measurement can complement other types of remote-sensing measurements and improve the weed-mapping accuracy within the data-fusion framework. Importantly, integrating textural, structural, and thermal features achieved the best performance for weed mapping. Our study provides a novel method for weed mapping using UAV-based multisource remote sensing measurements, which is critical for ensuring crop production in precision agriculture. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Ferroptosis Activation Scoring Model Assists in Chemotherapeutic Agents' Selection and Mediates Cross-Talk With Immunocytes in Malignant Glioblastoma.

Gliomas are aggressive tumors in the central nervous system and glioblastoma is the most malignant type. Ferroptosis is a programmed cell death that can modulate tumor resistance to therapy and the components of tumor microenvironment. However, the relationship between ferroptosis, tumor immune landscape, and glioblastoma progression is still elusive. In this work, data from bulk RNA-seq analysis, single cell RNA-seq analysis, and our own data (the Xiangya cohort) are integrated to reveal their relationships. A scoring system is constructed according to ferroptosis related gene expression, and high scoring samples resistant to ferroptosis and show worse survival outcome than low scoring samples. Notably, most of the high scoring samples are aggressive glioblastoma subtype, mesenchymal, and classical, by calculating RNA velocity. Cross-talk between high scoring glioblastoma cells and immunocytes are explored by R package 'celltalker'. Ligand-receptor pairs like the TRAIL or TWEAK signaling pathway are identified as novel bridges implying how ferroptosis modulate immunocytes' function and shape tumor microenvironment. Critically, potential drugs target to high scoring samples are predicted, namely, SNX2112, AZ628, and bortezomib and five compounds from the CellMiner database. Taken together, ferroptosis associates with glioblastoma aggressiveness, cross-talk with immunocytes and offer novel chemotherapy strategy.

The antimetastatic effect and underlying mechanisms of thioredoxin reductase inhibitor ethaselen.

Treating cancer metastasis is of vital importance to prolong patients' survival. Thioredoxin reductase (TrxR) is overexpressed in many cancer types and has been recognized as an anti-cancer target. The organoselenium compound ethaselen (BBSKE) has been proved to be a TrxR inhibitor and inhibit various types of tumor growth. However, whether BBSKE could inhibit tumor metastasis remains unclear. In this study, we aim to explore the antimetastatic effect of BBSKE and underlying mechanisms. BBSKE was found to dose-dependently suppress migration and invasion of MCF-7 and LoVo cells in vitro. The underlying mechanisms may include inhibition of TrxR activity, elevation of reactive oxygen species (ROS), decrease of EGFR activation and HER2 expression. Besides, the epithelial to mesenchymal transition process and expression of CD44, MMP-9, VEGFR2 and PD-L1 were also abrogated. Decreased migration and invasion, lower expression levels of EGFR, HER2, N-cadherin, CD44, MMP-9, VEGFR2 and PD-L1 were also observed in TrxR1-knockdown MCF-7 and LoVo cells. In the mouse breast cancer 4T1 model, BBSKE not only inhibited progression of primary tumor, but also suppressed formation of metastatic lung nodules and liver micro-metastases, indicating that BBSKE could effectively abolish tumor metastasis. In conclusion, our findings show that BBSKE is able to inhibit migration and invasion of cancer cells in vitro and in vivo, and may be used to prevent and treat metastasis.

Novel thioredoxin reductase inhibitor butaselen inhibits tumorigenesis by down-regulating programmed death-ligand 1 expression.

The thioredoxin system plays a role in a variety of physiological functions, including cell growth, differentiation, apoptosis, tumorigenesis, and immunity. We previously confirmed that butaselen (BS), a novel thioredoxin reductase inhibitor, can inhibit the growth of various human cancer cell lines, yet the underlying mechanism remains elusive. In this study, we investigated the anti-tumor effect of BS in vivo through regulating the immune system of KM mice. We found that BS inhibits tumor proliferation by promoting the activation of splenic lymphocytes in mice. BS can elevate the percentage of CD4-CD8+ T lymphocytes and the secretion of downstream cytokines in mice via down-regulating the expression of programmed death-ligand 1 (PD-L1) on the tumor cells' surface in vivo. Further study in HepG2 and BEL-7402 cells showed that decrease of PD-L1 level after BS treatment was achieved by inhibiting signal transducer and activator of transcription 3 (STAT3) phosphorylation. Taken together, our results suggest that BS has a role in promoting the immune response by reducing PD-L1 expression via the STAT3 pathway, and subsequently suppresses tumorigenesis.