Antagonistic RALF peptides control an intergeneric hybridization barrier on Brassicaceae stigmas.

Pollen-pistil interactions establish interspecific/intergeneric pre-zygotic hybridization barriers in plants. The rejection of undesired pollen at the stigma is crucial to avoid outcrossing but can be overcome with the support of mentor pollen. The mechanisms underlying this hybridization barrier are largely unknown. Here, in Arabidopsis, we demonstrate that receptor-like kinases FERONIA/CURVY1/ANJEA/HERCULES RECEPTOR KINASE 1 and cell wall proteins LRX3/4/5 interact on papilla cell surfaces with autocrine stigmatic RALF1/22/23/33 peptide ligands (sRALFs) to establish a lock that blocks the penetration of undesired pollen tubes. Compatible pollen-derived RALF10/11/12/13/25/26/30 peptides (pRALFs) act as a key, outcompeting sRALFs and enabling pollen tube penetration. By treating Arabidopsis stigmas with synthetic pRALFs, we unlock the barrier, facilitating pollen tube penetration from distantly related Brassicaceae species and resulting in interspecific/intergeneric hybrid embryo formation. Therefore, we uncover a "lock-and-key" system governing the hybridization breadth of interspecific/intergeneric crosses in Brassicaceae. Manipulating this system holds promise for facilitating broad hybridization in crops.

Melatonin partially rescues defects induced by tranexamic acid exposure during oocyte maturation in mice.

Tranexamic acid (TXA) is widely used among young women because of its ability to whiten skin and treat menorrhagia. Nevertheless, its potential effects on oocyte maturation and quality have not yet been clearly clarified. Melatonin (MT) is an endogenous hormone released by the pineal gland and believed to protect cells from oxidative stress injury. In the present study, we used an in vitro maturation model to investigate the toxicity of TXA and the protective role of MT in mouse oocytes. Compared with the control group, the TXA-exposed group had significantly lower nuclear maturation (57.72% vs. 94.08%, P < 0.001) and early embryo cleavage rates (38.18% vs. 87.66%, P < 0.001). Further study showed that spindle organization (52.56% vs. 18.77%, P < 0.01) and chromosome alignment (33.23% vs. 16.66%, P < 0.01) were also disrupted after TXA treatment. Mechanistically, we have demonstrated that TXA induced early apoptosis of oocytes (P < 0.001) by raising the level of reactive oxygen species (P < 0.001), which was consistent with an increase in mitochondrial damage (P < 0.01). Fortunately, all these effects except the spindle defect were successfully rescued by an appropriate level of MT. Collectively, our findings indicate that MT could partially reverse TXA-induced oocyte quality deterioration in mice by effectively improving mitochondrial function and reducing oxidative stress-mediated apoptosis.NEW & NOTEWORTHY Tranexamic acid is increasingly used to whiten skin, reverse dermal damages, and treat heavy menstrual bleeding in young women. However, its potential toxicity in mammalian oocytes is still unclear. Our study revealed that tranexamic acid exposure impaired the mouse oocyte quality and subsequent embryo development. Meanwhile, melatonin has been found to exert beneficial effects in reducing tranexamic acid-induced mitochondrial dysfunction and oxidative stress.

Mechanism underlying the rapid growth of Phalaenopsis equestris induced by 60Co-γ-ray irradiation.

Gamma (γ)-ray irradiation is one of the important modern breeding methods. Gamma-ray irradiation can affect the growth rate and other characteristics of plants. Plant growth rate is crucial for plants. In horticultural crops, the growth rate of plants is closely related to the growth of leaves and flowering time, both of which have important ornamental value. In this study, 60Co-γ-ray was used to treat P. equestris plants. After irradiation, the plant's leaf growth rate increased, and sugar content and antioxidant enzyme activity increased. Therefore, we used RNA-seq technology to analyze the differential gene expression and pathways of control leaves and irradiated leaves. Through transcriptome analysis, we investigated the reasons for the rapid growth of P. equestris leaves after irradiation. In the analysis, genes related to cell wall relaxation and glucose metabolism showed differential expression. In addition, the expression level of genes encoding ROS scavenging enzyme synthesis regulatory genes increased after irradiation. We identified two genes related to P. equestris leaf growth using VIGS technology: PeNGA and PeEXPA10. The expression of PeEXPA10, a gene related to cell wall expansion, was down-regulated, cell wall expansion ability decreased, cell size decreased, and leaf growth rate slowed down. The TCP-NGATHA (NGA) molecular regulatory module plays a crucial role in cell proliferation. When the expression of the PeNGA gene decreases, the leaf growth rate increases, and the number of cells increases. After irradiation, PeNGA and PeEXPA10 affect the growth of P. equestris leaves by influencing cell proliferation and cell expansion, respectively. In addition, many genes in the plant hormone signaling pathway show differential expression after irradiation, indicating the crucial role of plant hormones in plant leaf growth. This provides a theoretical basis for future research on leaf development and biological breeding.

Sustainable Sulfur-Carbon Hybrids for Efficient Sulfur Redox Conversions in Nanoconfined Spaces.

Nanoconfinement is a promising strategy in chemistry enabling increased reaction rates, enhanced selectivity, and stabilized reactive species. Sulfur's abundance and highly reversible two-electron transfer mechanism have fueled research on sulfur-based electrochemical energy storage. However, the formation of soluble polysulfides, poor reaction kinetics, and low sulfur utilization are current bottlenecks for broader practical application. Herein, a novel strategy is proposed to confine sulfur species in a nanostructured hybrid sulfur-carbon material. A microporous sulfur-rich carbon is produced from sustainable natural precursors via inverse vulcanization and condensation. The material exhibits a unique structure with sulfur anchored to the conductive carbon matrix and physically confined in ultra-micropores. The structure promotes Na+ ion transport through micropores and electron transport through the carbon matrix, while effectively immobilizing sulfur species in the nanoconfined environment, fostering a quasi-solid-state redox reaction with sodium. This translates to ≈99% utilization of the 2e- reduction of sulfur and the highest reported capacity for a room temperature Na-S electrochemical system, with high rate capability, coulombic efficiency, and long-term stability. This study offers an innovative approach toward understanding the key physicochemical properties of sulfurcarbon nanohybrid materials, enabling the development of high-performance cathode materials for room-temperature Na-S batteries with efficient sulfur utilization.

Radial basis function neural network optimization algorithm based on dynamic inertial weight particle swarm optimization for separating overlapping peaks in ion mobility spectrometry.

RATIONALE: Ion mobility spectrometry (IMS), as a promising analytical tool, has been widely employed in the structural characterization of biomolecules. Nevertheless, the inherent limitation in the structural resolution of IMS frequently results in peak overlap during the analysis of isomers exhibiting comparable structures. METHODS: The radial basis function (RBF) neural network optimization algorithm based on dynamic inertial weight particle swarm optimization (DIWPSO) was proposed for separating overlapping peaks in IMS. The RBF network structure and parameters were optimized using the DIWPSO algorithm. By extensively training using a large dataset, an adaptive model was developed to effectively separate overlapping peaks in IMS data. This approach successfully overcomes issues related to local optima, ensuring efficient and precise separation of overlapping peaks. RESULTS: The method's performance was evaluated using experimental validation and analysis of overlapping peaks in the IMS spectra of two sets of isomers: 3'/6'-sialyllactose; fructose-6-phosphate, glucose-1-phosphate, and glucose-6-phosphate. A comparative analysis was conducted using other algorithms, including the sparrow search algorithm, DIWPSO algorithm, and multi-objective dynamic teaching-learning-based optimization algorithm. The comparison results show that the DIWPSO-RBF algorithm achieved remarkably low maximum relative errors of only 0.42%, 0.092%, and 0.41% for ion height, mobility, and half peak width, respectively. These error rates are significantly lower than those obtained using the other three algorithms. CONCLUSIONS: The experimental results convincingly demonstrate that this method can adaptively, rapidly, and accurately separate overlapping peaks of multiple components, improving the structural resolution of IMS.

A Rapid Nanofocusing Method for a Deep-Sea Gene Sequencing Microscope Based on Critical Illumination.

In the deep-sea environment, the volume available for an in-situ gene sequencer is severely limited. In addition, optical imaging systems are subject to real-time, large-scale defocusing problems caused by ambient temperature fluctuations and vibrational perturbations. To address these challenges, we propose an edge detection algorithm for defocused images based on grayscale gradients and establish a defocus state detection model with nanometer resolution capabilities by relying on the inherent critical illumination light field. The model has been applied to a prototype deep-sea gene sequencing microscope with a 20× objective. It has demonstrated the ability to focus within a dynamic range of ±40 µm with an accuracy of 200 nm by a single iteration within 160 ms. By increasing the number of iterations and exposures, the focusing accuracy can be refined to 78 nm within a dynamic range of ±100 µm within 1.2 s. Notably, unlike conventional photoelectric hill-climbing, this method requires no additional hardware and meets the wide dynamic range, speed, and high-accuracy autofocusing requirements of deep-sea gene sequencing in a compact form factor.

Simulation Guided Coaxial Electrospinning of Polyvinylidene Fluoride Hollow Fibers with Tailored Piezoelectric Performance.

Electrospun polyvinylidene fluoride (PVDF) piezoelectric fibers have high potential applicability in mechanical energy harvesting and self-powered sensing owing to their high electromechanical coupling capabilities. Strategies for tailoring fiber morphology have been the primary focus for realizing enhanced piezoelectric output. However, the relationship between piezoelectric performance and fiber structure remains unclear. This study fabricates PVDF hollow fibers through coaxial electrospinning, whose wall thickness can be tuned by changing the internal solution concentration. Simulation analysis demonstrates an increased effective deformation of the hollow fiber as enlarging inner diameter, resulting in enhanced piezoelectric output, which is in excellent agreement with the experimental results. This study is the first to unravel the influence mechanism of morphology regulation of a PVDF hollow fiber on its piezoelectric performance from both simulation and experimental aspects. The optimal PVDF hollow fiber piezoelectric energy harvester (PEH) delivers a piezoelectric output voltage of 32.6 V, ≈3 times that of the solid PVDF fiber PEH. Furthermore, the electrical output of hollow fiber PEH can be stably stored in secondary energy storage systems to power microelectronics. This study highlights an efficient approach for reconciling the simulation and tailoring the fiber PEH morphology for enhanced performances for future self-powered systems.

Probing Sodium Storage Mechanism in Hollow Carbon Nanospheres Using Liquid Phase Transmission Electron Microscopy.

Carbonaceous materials are promising sodium-ion battery anodes. Improving their performance requires a detailed understanding of the ion transport in these materials, some important aspects of which are still under debate. In this work, nitrogen-doped porous hollow carbon spheres (N-PHCSs) are employed as a model system for operando analysis of sodium storage behavior in a commercial liquid electrolyte at the nanoscale. By combining the ex situ characterization at different states of charge with operando transmission electron microscopy experiments, it is found that a solvated ionic layer forms on the surface of N-PHCSs at the beginning of sodiation, followed by the irreversible shell expansion due to the solid-electrolyte interphase (SEI) formation and subsequent storage of Na(0) within the porous carbon shell. This shows that binding between Na(0) and C creates a Schottky junction making Na deposition inside the spheres more energetically favorable at low current densities. During sodiation, the SEI fills the gap between N-PHCSs, binding spheres together and facilitating the sodium ions' transport toward the current collector and subsequent plating underneath the electrode. The N-PHCSs layer acts as a protective layer between the electrolyte and the current collector, suppressing the possible growth of dendrites at the anode.

ConGPS: A Smart Container Positioning System Using Inertial Sensor and Electronic Map with Infrequent GPS.

Real-time global positioning is important for container-based logistics. However, a challenge in real-time global positioning arises from the frequency of both global positioning system (GPS) calls and GPS-denied environments during transportation. This paper proposes a novel system named ConGPS that integrates both inertial sensor and electronic map data. ConGPS estimates the speed and heading direction of a moving container based on the inertial sensor data, the container trajectory, and the speed limit information provided by an electronic map. The directional information from magnetometers, coupled with map-matching algorithms, is employed to compute container trajectories and current positions. ConGPS significantly reduces the frequency of GPS calls required to maintain an accurate current position. To evaluate the accuracy of the system, 280 min of driving data, covering a distance of 360 km, are collected. The results demonstrate that ConGPS can maintain positioning accuracy within a GPS-call interval of 15 min, even if using low-cost inertial sensors in GPS-denied environments.

Carrying Position-Independent Ensemble Machine Learning Step-Counting Algorithm for Smartphones.

Current step-count estimation techniques use either an accelerometer or gyroscope sensors to calculate the number of steps. However, because of smartphones unfixed placement and direction, their accuracy is insufficient. It is necessary to consider the impact of the carrying position on the accuracy of the pedometer algorithm, because of people carry their smartphones in various positions. Therefore, this study proposes a carrying-position independent ensemble step-counting algorithm suitable for unconstrained smartphones in different carrying positions. The proposed ensemble algorithm comprises a classification algorithm that identifies the carrying position of the smartphone, and a regression algorithm that considers the identified carrying position and calculates the number of steps. Furthermore, a data acquisition system that collects (i) label data in the form of the number of steps estimated from the Force Sensitive Resistor (FSR) sensors, and (ii) input data in the form of the three-axis acceleration data obtained from the smartphones is also proposed. The obtained data were used to allow the machine learning algorithms to fit the signal features of the different carrying positions. The reliability of the proposed ensemble algorithms, comprising a random forest classifier and a regression model, was comparatively evaluated with a commercial pedometer application. The results indicated that the proposed ensemble algorithm provides higher accuracy, ranging from 98.1% to 98.8%, at self-paced walking speed than the commercial pedometer application, and the machine learning-based ensemble algorithms can effectively and accurately predict step counts under different smart phone carrying positions.

Efficient Degradation of Congo Red in Water by UV-Vis Driven CoMoO4/PDS Photo-Fenton System.

In order to improve the catalytic activity of cobalt molybdate (CoMoO4), a PDS-activated and UV-vis assisted system was constructed. CoMoO4 was prepared by coprecipitation and calcination, and characterized by XRD, FTIR, Raman, SEM, TEM, XPS, TGA Zeta potential, BET, and UV-Vis DRS. The results showed that the morphology of the CoMoO4 nanolumps consisted of stacked nanosheets. XRD indicated the monoclinic structures with C2/m (C32h, #12) space group, which belong to α-CoMoO4, and both Co2+ and Mo6+ ions occupy distorted octahedral sites. The pH of the isoelectric point (pHIEP) of CMO-8 at pH = 4.88 and the band gap of CoMoO4 was 1.92 eV. The catalytic activity of CoMoO4 was evaluated by photo-Fenton degradation of Congo red (CR). The catalytic performance was affected by calcination temperature, catalyst dosage, PDS dosage, and pH. Under the best conditions (0.8 g/L CMO-8, PDS 1 mL), the degradation efficiency of CR was 96.972%. The excellent catalytic activity of CoMoO4 was attributed to the synergistic effect of photo catalysis and CoMoO4-activated PDS degradation. The capture experiments and the ESR showed that superoxide radical (·O2-), singlet oxygen (1O2), hole (h+), sulfate (SO4-·), and hydroxyl (·OH-) were the main free radicals leading to the degradation of CR. The results can provide valuable information and support for the design and application of high-efficiency transition metal oxide catalysts.

The egg cell is preferentially fertilized in Arabidopsis double fertilization.

In flowering plants (angiosperms), fertilization of the egg cell by one sperm cell produces an embryo, whereas fusion of a second sperm cell with the central cell generates the endosperm. In most angiosperms like Arabidopsis, a pollen grain contains two isomorphic sperm cells required for this double fertilization process. A long-standing unsolved question is whether the two fertilization events have any preference. A tool to address this question is the usage of the cyclin-dependent kinase a1 (cdka;1) mutant pollen, which produces a single sperm-like cell (SLC). Here, we first adopt a complementation-based fluorescence-labeling method to successfully separate and collect cdka;1 mutant pollen containing a single SLC. Single-cell RNA-sequencing analysis revealed that cdka;1 SLCs show a gene expression profile highly similar to that of sperm cells and not to the generative cell, precursor of the two sperm cells. Pollination assays using a limited number of cdka;1 mutant pollen revealed that in 98.2% of the ovules, single fertilization of the egg cell occurred. Pollination of pistils with excessive cdka;1 mutant pollen allowed the delivery of a second SLC via fertilization recovery, which fertilized the central cell, resulting in 20.7% double-fertilized ovules. This indicates that cdka;1 SLCs are able to fertilize both the egg and the central cell. Taken together, our findings have answered a long-standing question and support that preferential fertilization of the egg cell is evident in Arabidopsis.

Saving the Energy Loss in Lithium-Mediated Nitrogen Fixation by Using a Highly Reactive Li3 N Intermediate for C-N Coupling Reactions.

Direct synthesis of N-containing organic compounds from dinitrogen (N2 ) can make synthetic chemistry more sustainable. Previous bottlenecks in lithium-mediated N2 fixation were resolved by loading Li-metal anodes covered with the typical Li+ ion-conducting solid electrolyte interface, which are subsequently allowed to react with N2 . The developed strategy allowed us to reach high Faradaic efficiencies toward Li3 N. These reactive Li3 N were then contacted with acylchlorides. Surface nitride ions are more nucleophilic than amines which direct the two C-N coupling reactions toward formation of imides rather than amides, and an integrated current efficiency of 57-77 % could be realized. This study thereby not only provides a feasible electrochemical Li3 N synthesis, but also delineates an economical and green synthesis of highly valuable N-containing compounds from N2 under mild conditions, just using commercial spare parts and processes from the omnipresent Li battery technology.

N-myristoylation: from cell biology to translational medicine.

Various lipids and lipid metabolites are bound to and modify the proteins in eukaryotic cells, which are known as 'protein lipidation'. There are four major types of the protein lipidation, i.e. myristoylation, palmitoylation, prenylation, and glycosylphosphatidylinositol anchor. N-myristoylation refers to the attachment of 14-carbon fatty acid myristates to the N-terminal glycine of proteins by N-myristoyltransferases (NMT) and affects their physiology such as plasma targeting, subcellular tracking and localization, thereby influencing the function of proteins. With more novel pathogenic N-myristoylated proteins are identified, the N-myristoylation will attract great attentions in various human diseases including infectious diseases, parasitic diseases, and cancers. In this review, we summarize the current understanding of N-myristoylation in physiological processes and discuss the hitherto implication of crosstalk between N-myristoylation and other protein modification. Furthermore, we mention several well-studied NMT inhibitors mainly in infectious diseases and cancers and generalize the relation of NMT and cancer progression by browsing the clinic database. This review also aims to highlight the further investigation into the dynamic crosstalk of N-myristoylation in physiological processes as well as the potential application of protein N-myristoylation in translational medicine.

Mechanism of DNA-Induced Phase Separation for Transcriptional Repressor VRN1.

Phase separation of proteins/nucleic acids to form non-membrane organelles is crucial in cellular gene-expression regulation. However, little is known about transcriptional regulator phase separation and the underlying molecular mechanism. Vernalization 1 (VRN1) encodes a crucial transcriptional repressor involved in plant vernalization that contains two B3 DNA-binding domains connected by an intrinsic disorder region (IDR) and nonspecifically binds DNA. We found that the Arabidopsis VRN1 protein undergoes liquid-liquid phase separation (LLPS) with DNA that is driven by multivalent protein-DNA interactions (LLPS), and that both B3 domains are required. The distribution of charged residues in the VRN1 IDR modulates the interaction strength between VRN1 and DNA, and changes in the charge pattern lead to interconversion between different states (precipitates, liquid droplets, and no phase separation). We further showed that VRN1 forms puncta in plant cell nuclei, suggesting that it may stabilize the vernalized state by repressing gene expression through LLPS.

Advances in Molecular Pathology, Diagnosis and Treatment of Spinal Cord Astrocytomas.

Spinal cord astrocytoma (SCA) is a rare subtype of astrocytoma, posing challenges in diagnosis and treatment. Low-grade SCA can achieve long-term survival solely through surgery, while high-grade has a disappointing prognosis even with comprehensive treatment. Diagnostic criteria and standard treatment of intracranial astrocytoma have shown obvious limitations in SCA. Research on the molecular mechanism in SCA is lagging far behind that on intracranial astrocytoma. In recent years, huge breakthroughs have been made in molecular pathology of astrocytoma, and novel techniques have emerged, including DNA methylation analysis and radiomics. These advances are now making it possible to provide a precise diagnosis and develop corresponding treatment strategies in SCA. Our aim is to review the current status of diagnosis and treatment of SCA, and summarize the latest research advancement, including tumor subtype, molecular characteristics, diagnostic technology, and potential therapy strategies, thus deepening our understanding of this uncommon tumor type and providing guidance for accurate diagnosis and treatment.

Integrating Network Pharmacology and Experimental Verification to Explore the Pharmacological Mechanisms of Radix Paeoniae Rubra Against Glioma.

Glioma has a high mortality and can hardly be completely cured. Radix Paeoniae Rubra (RPR) is a prevalent component in traditional Chinese medicine used for tumor treatments. We explored the mechanism of RPR in treating glioma using network pharmacology and experiments. A network pharmacology approach was used to screen active ingredients, targets of RPR and glioma. We then constructed a herb-active ingredient-target-pathway network and conducted protein-protein interaction (PPI) network analysis, as well as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecular docking was also performed. Using CCK-8, colony formation, and xenograft experiments, we evaluated the effect of RPR on glioma. The involved pathway and proteins were identified by Western blot. From public databases, we identified nine active RPR ingredients and 40 overlapping targets among 109 RPR targets and 1360 glioma-associated targets. The PPI analysis revealed ten targets, such as AKT1, TP53, and VEGFA, which were identified as hub genes. The results from GO and KEGG analysis highlighted the involvement of the PI3K/AKT pathway. A herb-active ingredient-target-pathway network was constructed. By docking molecular structures, six suitable conformations have been identified. The RPR extract demonstrated anti-tumor properties by inhibiting glioma cell proliferation in vitro and in vivo, likely achieved by suppressing the phosphorylation of the PI3K/AKT signaling pathway. RPR concurrently downregulated the phosphorylation level of AKT1 and the protein expression level of VEGFA, while upregulating the expression of P53 in the U251 cell line. Utilizing network pharmacology and molecular docking, our study not only predicted the impact of RPR on glioma but also delineated the herb-active ingredient-target-pathway network. Experimentally, we confirmed that RPR may exert its anti-tumor properties by inhibiting the phosphorylation of the PI3K/AKT pathway, including AKT1, and by regulating the expression levels of VEGFA and P53.

Chemical characteristics, distribution patterns, and source apportionment of particulate elements and inorganic ions in snowpack in Harbin, China.

Snowpack, which serves as a natural archive of atmospheric deposition of multiple pollutants, is a practical environmental media that can be used for assessing atmospheric records and input of the pollutants to the surface environments and ecosystems. A total of 29 snowpack samples were collected at 20 sampling sites covering three different functional areas of a major city (Harbin) in Northeast China. Two samples at the "snow layer" and one or two samples at the "particulate layer" were collected at each sampling site in the industrial areas characterized by multi-layer snowpack, and only one sample at the "snow layer" was collected at each sampling site in the cultural and recreational as well as agricultural areas. The snow contents of 31 elements (Na, Mg, Al, K, Ca, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Y, Cd, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, and Pb) and six major water-soluble inorganic ions (WSIIs, NH4+, K+, Ca2+, NO2-, NO3-, and SO42-) were analyzed. The total mass of the measured elements is dominated (95.8%-99.2%) by crustal elements. Heavy metals only account for 0.77%-4.07% of the total mass of the elements, but are occasionally close to or even above the standard limit in the "Environmental Quality Standards for Surface Water" of China (GB3838-2002). SO42- and Ca2+ are the main anion and cation, accounting for 34.9%-81.1% and 1.43%-29.9%, respectively, of the measured total ions. Total atmospheric deposition of crustal elements and heavy metals is dominated by wet deposition in areas near the petrochemical plant and by dry deposition in areas near the cement plant. Coal combustion, industrial emissions, and traffic-related activities lead to the enrichment of heavy metals in the snowpacks of urban and suburban areas, while coal combustion and biomass burning contribute to pollution in rural areas. The cities and regions situated in the western, northwestern, northern, and northeastern directions from Harbin are potential source regions of these pollutant species.

Retinol dehydrogenase 10 promotes epithelial-mesenchymal transition in spinal cord gliomas via PI3K/AKT pathway.

Background: Spinal cord glioma (SCG), a rare subset of central nervous system (CNS) glioma, represents a complex challenge in neuro-oncology. There has been research showing that Retinol Dehydrogenase 10 (RDH10) may be a tumor promoting factor in brain glioma, but the biological effects of RDH10 remain undefined in SCG. Methods: We performed gene set enrichment analysis (GSEA) and unsupervised clustering analysis to investigate the roles of EMT (epithelial-mesenchymal transition) in glioma. DEG (differently expressed gene) screening and correlation analysis were conducted to filter the candidate genes which were closely associated with EMT process in SCG. Enrichment analysis and GSVA (Gene Set Variation Analysis) were conducted to investigate the potential mechanism of RDH10 for SCG. Trans-well and healing assay were performed to explore the role of RDH10 in the invasion of SCG. Western blotting was performed to evaluate the levels of markers in PI3K-AKT and EMT pathway. In vivo tests were conducted to verify the role of RDH10 in EMT process. Results: Bioinformatic analysis demonstrated the EMT pathway was associated with dismal prognosis of glioma. Further analysis demonstrated that RDH10 showed the strongest correlation with the EMT process. Retinol Dehydrogenase 10 expression was significantly increased in SCG tissues, correlating with advanced tumor grade and unfavorable prognosis. Functional analysis indicated that decreasing RDH10 levels impeded the invasive and migratory abilities of SCG cells, whereas increasing RDH10 levels augmented them. Enrichment analysis and western blot revealed that RDH10 regulated EMT process of SCG by PI3K-AKT pathway. We observed that the enhanced invasion ability and increased EMT-related protein induced by RDH10 overexpression can be suppressed by PI3K-AKT pathway inhibitor (LY294002). Conclusion: Our research found that RDH10 was an effective biomarker associated with tumor grade and prognosis of SCG. RDH10 could regulate EMT process of SCG through PI3K-AKT pathway.

PSMC2 promotes glioma progression by regulating immune microenvironment and PI3K/AKT/mTOR pathway.

BACKGROUND: Glioma, the most frequent and malignant central nervous system (CNS) cancer, has a bad outcome. Proteasome 26S subunit ATPase 2 (PSMC2) is an essential part of the 26S proteasome and promotes the development of several tumors. However, the pathway and function of PSMC2 in glioma have not been unelucidated. METHODS: This study analyzed PSMC2 expression in glioma tissues and its predictive significance for patients. We examined the link between PSMC2 and DNA methylation, immune cell infiltration, tumor immune cycle, immune cell homeostasis, and immune checkpoints. Subsequently, immunohistochemistry and in vitro trials were employed to validate the expression, prognostic potential, and function of PSMC2 in glioma. The mechanisms of PSMC2 in glioma were further explored. RESULTS: Our study revealed that PSMC2 expression increased in glioma tissues contrasted with healthy tissues, and patients with high PSMC2 glioma exhibited poor overall survival (OS) compared to the low-PSMC2 group. Immune profile analysis revealed that PSMC2 was positively related to immunosuppressive cell infiltration and immune checkpoints and adversely related to the cancer immune cycle and immune cell homeostasis. In cell-based investigations, the inhibition of PSMC2 was found to effectively suppress the aggressiveness and proliferation of glioma cell lines while also enhancing cell cycle arrest and promoting cell death. Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA), and in vitro experiments showed that PSMC2 promoted glioma development through the PI3K/AKT/mTOR pathway. CONCLUSIONS: PSMC2 was upregulated in glioma and promoted cancer progression by modulating the tumor immune microenvironment, cancer cell biological behavior, immune cell homeostasis, and the PI3K/AKT/mTOR pathway, providing a new option to treat glioma.