Search

Abstract Background Ovarian cancer (OC) has the highest fatality rate among all gynecological malignancies, necessitating the exploration of novel, efficient, and low-toxicity therapeutic strategies. Ferroptosis is a type of programmed cell death induced by iron-dependent lipid peroxidation and can potentially activate antitumor immunity. Developing highly effective ferroptosis inducers may improve OC prognosis. Results In this study, we developed an ultrasonically controllable two-dimensional (2D) piezoelectric nanoagonist (Bi2MoO6-MXene) to induce ferroptosis. A Schottky heterojunction between Bi2MoO6 (BMO) and MXene reduced the bandgap width by 0.44 eV, increased the carrier-separation efficiency, and decreased the recombination rate of electron–hole pairs under ultrasound stimulation. Therefore, the reactive oxygen species yield was enhanced. Under spatiotemporal ultrasound excitation, BMO-MXene effectively inhibited OC proliferation by more than 90%, induced lipid peroxidation, decreased mitochondrial-membrane potential, and inactivated the glutathione peroxidase and cystathionine transporter protein system, thereby causing ferroptosis in tumor cells. Ferroptosis in OC cells further activated immunogenic cell death, facilitating dendritic cell maturation and stimulating antitumor immunity. Conclusion We have succeeded in developing a highly potent ferroptosis inducer (BMO-MXene), capable of inhibiting OC progression through the sonodynamic-ferroptosis-immunogenic cell death pathway. Graphical Abstract

Estimation of crop residue cover is important for energy balance in agroecosystem and sustainable development of agriculture. We evaluated the dimidiate pixel model, widely used for estimating photosynthetic vegetation cover, for non-photosynthetic vegetation (such as winter wheat residue) cover estimation. In this study, based on spectral and cover data of winter wheat residue in dry and wet soil backgrounds, the spectral curves of winter wheat residue and soil were identified, the applicability of non-photosynthetic vegetation indices in dimidiate pixel model was analyzed, and the potential of dimidiate pixel model to estimate winter wheat residue cover was explored. In dry soil background, a lignocellulose absorption trough near 2100 nm in the spectral curve of residue-soil mixed scene was observed, and the absorption trough became deeper with increasing residue cover. The normalized difference tillage index (NDTI) had the best correlation with the measured cover of winter wheat residue, and the dimidiate pixel model constructed on the basis of this index was able to accurately estimate the winter wheat residue cover (R2=0.64, RMSE=0.16, RE=26.32 %). In wet soil background, the ability of non-photosynthetic vegetation index to distinguish between winter wheat residue and soil was reduced by soil moisture. The results of this study provide effective insights into the estimation of winter wheat residue cover under different soil moisture conditions, and provide a useful reference for the study of remote sensing estimation of crop residue cover in a large region. The dimidiate pixel model using NDTI can also be used to estimate non-photosynthetic vegetation cover of natural vegetation.

Accurately assessing grassland aboveground biomass (AGB) over large areas is essential for the conservation of grassland resource and the improvement of ecological environment. In this study, the models for estimating grassland AGB were structured using Google Earth Engine (GEE), based on the large-scale and long-term measurement data of grassland AGB in northern China, combined with remote sensing, topography and climate data. The distribution pattern of grassland AGB was produced, and the spatial–temporal evolution pattern and future change trend of grassland AGB were analyzed. The results show that: (1) the random forest (RF) model, incorporating topography, climate and remote sensing data, exhibited good simulation accuracy (training dataset: R2 = 0.73, RMSE = 44.85 g/m2, MAE = 30.92 g/m2; testing dataset: R2 = 0.64, RMSE = 57.54 g/m2, MAE = 44.74 g/m2). (2) the grassland AGB in northern China increased spatially from west to east, and the annual average was between 16.02–272.84 g/m2. The grassland AGB showed a fluctuating increasing trend at a rate of 0.59 g/m2/a from 2000 to 2020, and the coefficient of variation of the grassland AGB was small, ranging from 0.00 to 0.69, which was in a more stable state. (3) the grassland AGB in northern China generally exhibited an upward trend before 2020 (67.99 %). However, the upward trend may weaken after 2020 (38.95 %). The research results provide a quantitative perspective for studies on grassland livestock carrying capacity and climate change in northern China.

Abstract Histone lactylation has been reported to involve in tumorigenesis and development. However, its biological regulatory mechanism in endometrial carcinoma (EC) is yet to be reported in detail. In the present study, we evaluated the modification levels of global lactylation in EC tissues by immunohistochemistry and western blot, and it was elevated. The non-metabolizable glucose analog 2-deoxy-d-glucose (2-DG) and oxamate treatment could decrease the level of lactylation so as to inhibit the proliferation and migration ability, induce apoptosis significantly, and arrest the cell cycle of EC cells. Mechanically, histone lactylation stimulated USP39 expression to promote tumor progression. Moreover, USP39 activated PI3K/AKT/HIF-1α signaling pathway via interacting with and stabilizing PGK1 to stimulate glycolysis. The results of present study suggest that histone lactylation plays an important role in the progression of EC by promoting the malignant biological behavior of EC cells, thus providing insights into potential therapeutic strategies for endometrial cancer.

Abstract Background Metabolic reprogramming is one of hallmarks of cancer progression and is of great importance for the tumor microenvironment (TME). As an abundant metabolite, lactate has been found to play a critical role in cancer development and immunosuppression of TME. However, the potential role of lactate metabolism-related genes in endometrial cancer (EC) remains obscure. Methods RNA sequencing data and clinical information of EC were obtained from The Cancer Genome Atlas (TCGA) database. Lactate metabolism-related genes (LMRGs) WERE from Molecular Signature Database v7.4 and then compared the candidate genes from TCGA to obtain final genes. Univariate analysis and Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression were performed to screen prognostic genes. A lactate metabolism-related risk profile was constructed using multivariate Cox regression analysis. The signature was validated by time-dependent ROC curve analysis and Kaplan-Meier analysis. The relationship between the risk score and age, grade, stage, tumor microenvironmental characteristics, and drug sensitivity was as well explored by correlation analyses. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway functional analysis between the high and low-risk groups were performed. CCK8, EdU, and clone formation assays were applied to detect the proliferation ability of EC cells, Transwell assay was performed to detect the migration ability of EC cells, and intracellular lactate and glucose content was used to asses lactate metabolism. Results We constructed a risk signature based on 18 LMRGs. Kaplan-Meier curves confirmed that the high-risk group had poorer prognosis compared to the low-risk group. A nomogram was then constructed to predict the probability of EC survival. We also performed GO enrichment analysis and KEGG pathway functional analysis between the high and low-risk groups, and the outcome revealed that the features were significantly associated with energy metabolism. There was a significant correspondence between LMRGs and tumor mutational load, checkpoints and immune cell infiltration. C1, C2, and C4 were the most infiltrated in the high-risk group. The high-risk group showed increased dendritic cell activation, while the low-risk group showed increased plasma cells and Treg cells. Drug sensitivity analysis showed LMRGs risk was more resistant to Scr kinase inhibitors. We further proved that one of the lactate metabolism related genes, TIMM50 could promote EC cell proliferation, migration and lactate metabolism. Conclusion In conclusion, we have established an effective prognostic signature based on LMRG expression patterns, which may greatly facilitate the assessment of prognosis, molecular features and treatment modalities in EC patients and may be useful in the future translation to clinical applications. TIMM50 was identified as a novel molecule that mediates lactate metabolism in vitro and in vivo, maybe a promising target for EC prognosis.

Huntington's disease (HD) represents an important model for neurodegenerative disorders and proteinopathies. It is mainly caused by cytotoxicity of the mutant huntingtin protein (Htt) with an expanded polyQ stretch. While Htt is ubiquitously expressed, HD is characterized by selective neurodegeneration of the striatum. Here we report a striatal-enriched orphan G protein-coupled receptor(GPCR) Gpr52 as a stabilizer of Htt in vitro and in vivo. Gpr52 modulates Htt via cAMP-dependent but PKA independent mechanisms. Gpr52 is located within an intron of Rabgap1l, which exhibits epistatic effects on Gpr52-mediated modulation of Htt levels by inhibiting its substrate Rab39B, which co-localizes with Htt and translocates Htt to the endoplasmic reticulum. Finally, reducing Gpr52 suppresses HD phenotypes in both patient iPS-derived neurons and in vivo Drosophila HD models. Thus, our discovery reveals modulation of Htt levels by a striatal-enriched GPCR via its GPCR function, providing insights into the selective neurodegeneration and potential treatment strategies.

Currently, it is believed that toad oocyte maturation is dependent on the physiological conditions of winter hibernation. Previous antibody-blocking experiments have demonstrated that toad ubiquitin carboxyl-terminal hydrolase L1 (tUCHL1) is necessary for germinal vesicle breakdown during toad oocyte maturation. In this paper, we first supply evidence that tUCHL1 is highly evolutionarily conserved. Then, we exclude protein availability and ubiquitin carboxyl-terminal hydrolase enzyme activity as factors in the response of oocytes to winter hibernation. In the context of MPF (maturation promoting factor) controlling oocyte maturation and to further understand the role of UCHL1 in oocyte maturation, we performed adsorption and co-immunoprecipitation experiments using toad oocyte protein extracts and determined that tUCHL1 is associated with MPF in toad oocytes. Recombinant tUCHL1 absorbed p34(cdc2), a component of MPF, in obviously larger quantities from mature oocytes than from immature oocytes, and p13(suc1) was isolated from tUCHL1 with a dependence on the ATP regeneration system, suggesting that still other functions may be involved in their association that require phosphorylation. In oocytes from hibernation-interrupted toads, the p34(cdc2) protein level was significantly lower than in oocytes from toads in artificial hibernation, providing an explanation for the different quantities isolated by recombinant tUCHL1 pull-down and, more importantly, identifying a mechanism involved in the toad oocyte's dependence on a low environmental temperature during winter hibernation. Therefore, in toads, tUCHL1 binds p34(cdc2) and plays a role in oocyte maturation. However, neither tUCHL1 nor cyclin B1 respond to low temperatures to facilitate oocyte maturation competence during winter hibernation.

Currently, research on the dynamic damage characteristics of sintered NdFeB is still in its early stages. Previous dynamic mechanical experiments on sintered NdFeB have shown that it is a strain rate-sensitive material. So, it is necessary to establish an appropriate damage constitutive model to describe the dynamic mechanical behavior of sintered NdFeB, with the aim of expanding its practical application range. This paper first establishes a damage evolution model by combining the Weibull distribution with a wing crack propagation model that considers crack spacing. Then, the damage model is integrated with the Zhu-Wang-Tang (ZWT) constitutive model to create the ZWT damage constitutive model. The model is fitted against previous experimental data to determine the specific parameters. Finally, to verify the accuracy of the newly established damage constitutive model, it is compared with the damage constitutive model proposed by Li. The comparison results fully affirmed the accuracy of the newly established ZWT damage constitutive model. [ABSTRACT FROM AUTHOR]

The article discusses a report about the striatal enriched G protein coupled receptor (GPCR) to act as a stabilizer of huntington's disease (HD) which is a neuro-degenerative disorder. It also focuses on the causes of HD which is cytotoxicity of mutant Htt (huntington) protein (mHtt) in the brain & peripheral tissues. In addition a selective vulnerability of the striatal neurons was found for the striatal enriched modulation of the Htt protein levels.