Analysis of the Mechanism of RAD18 in Glioma.

INTRODUCTION: This study aimed to evaluate the regulatory mechanism of RAD18 in glioma development. METHODS: RAD18 expression was compared in glioma tumors and normal samples. Furthermore, we investigated the association between gene transcription and clinical factors in glioma samples, followed by functional enrichment analysis, screening for key Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, immune infiltration analysis of high and low RAD18 expression groups, and correlation analysis of quantified KEGG signaling pathways and immune cell types. RESULTS: The expression of RAD18 was upregulated in gliomas. Moreover, RAD18 expression was significantly correlated with age, tumor grade, and histological subtype. Notably, patients with gliomas with high RAD18 expression levels had worse overall survival. Functional enrichment analysis showed that RAD18 was significantly related to biological processes, such as cell division, chemical synaptic transmission, and mitotic nuclear division, and KEGG pathways such as cell cycle, oxidative phosphorylation, and extracellular matrix (ECM)-receptor interaction. The infiltration of five immune cells (plasma B cells, naive B cells, resting CD4+ memory T cells, monocytes, and M1 macrophages) was significantly different between the high and low RAD18 expression groups, and this difference was significantly related to key KEGG pathways, such as neuroactive ligand-receptor interaction and ECM-receptor interaction. CONCLUSION: RAD18 may serve as a target for glioma treatment and as a key regulator of glioma development.

Identification and characterization of three novel antimicrobial peptides from Acipenser dabryanus.

Antimicrobial peptides (AMPs) play essential roles in the innate immune system to protect against a wide variety of pathogens in aquatic environments. In this study, three very important AMPs, cathelicidin, hepcidin and defensin, were identified in the critically endangered Acipenser dabryanus. The full-length cDNA sequences of these three AMPs were identified from transcriptome sequencing and the rapid amplification of cDNA ends (RACE) technique. Phylogenetic analysis showed that cathelicidin formed a clade with the other members of the cathelicidin family, and similar results were obtained for hepcidin. The A. dabryanus ß-defensin belonged to the fish class 2 ß-defensins. A tissue distribution study showed that the three AMP transcripts could be detected constitutively in various tissues. The highest expression levels of cathelicidin and hepcidin were found in the liver, while defensin was primarily expressed in the skin. Bacterial challenge in vivo revealed significant changes in the gene expression of the three AMPs at both mucosal sites and systemic sites. Striking upregulation of cathelicidin and hepcidin was observed in the skin at 12 h post-challenge, with increases of more than 7000-fold and 1000-fold, respectively, compared to the control, and the expression of defensin mRNA was remarkably elevated in the hindgut (by 230-fold at 6 h post-challenge). Moreover, according to the expression profiles of the AMPs post-challenge, we found that the mucosal immune response occurred earlier than the systemic immune response following bacterial infection. Our results suggest that these three novel AMPs may play important roles in the innate immune system of A. dabryanus to protect against invading pathogens, especially during the mucosal immune response.

Protective effect of anisodamine in rats with glycerol-induced acute kidney injury.

BACKGROUND: Anisodamine is used for the treatment of reperfusion injury in various organs. In this study, we investigated the effectiveness and mechanisms of action of anisodamine in promoting recovery from glycerol-induced acute kidney injury (AKI). METHODS: We compared the protective effects of atropine and anisodamine in the rat model of glycerol-induced AKI. We examined signaling pathways involved in oxidative stress, inflammation and apoptosis, as well as expression of kidney injury molecule-1 (KIM-1). Renal injury was assessed by measuring serum creatinine and urea, and by histologic analysis. Rhabdomyolysis was evaluated by measuring creatine kinase levels, and oxidative stress was assessed by measuring malondialdehyde (MDA) and superoxide dismutase (SOD) levels in kidney tissues. Inflammation was assessed by quantifying interleukin 6 (IL-6) and CD45 expression. Apoptosis and necrosis were evaluated by measuring caspase-3 (including cleaved caspase 3) and RIP3 levels, respectively. RESULTS: Glycerol administration resulted in a higher mean histologic damage score, as well as increases in serum creatinine, urea, creatine kinase, reactive oxygen species (ROS), MDA, IL-6, caspase-3 and KIM-1 levels. Furthermore, glycerol reduced kidney tissue SOD activity. All of these markers were significantly improved by anisodamine and atropine. However, the mean histologic damage score and levels of urea, serum creatinine, creatine kinase, ROS and IL-6 were lower in the anisodamine treatment group compared with the atropine treatment group. CONCLUSION: Pretreatment with anisodamine ameliorates renal dysfunction in the rat model of glycerol-induced rhabdomyolytic kidney injury by reducing oxidative stress, the inflammatory response and cell death.

Zea mays cultivation, biochar, and arbuscular mycorrhizal fungal inoculation influenced lead immobilization.

Plant cultivation can influence the immobilization of heavy metals in soil. However, the roles of soil amendments and microorganisms in crop-based phytoremediation require further exploration. In this study, we evaluated the impact of Zea mays L. cultivation, biochar application, and arbuscular mycorrhizal fungi (AMF) inoculation on soil lead (Pb) immobilization. Our results indicated that biochar addition resulted in a significant, 42.00%, reduction in AMF colonization. Plant cultivation, AMF inoculation, and biochar addition all contributed to enhanced Pb immobilization, as evidenced by decreased levels of diethylenetriaminepentaacetic acid- and CaCl2-extractable Pb in the soil. Furthermore, soil subjected to plant cultivation with AMF and biochar displayed reduced concentrations of bioavailable Pb. Biochar addition altered the distribution of Pb fractions in the soil, transforming the acid-soluble form into the relatively inert reducible and oxidizable forms. Additionally, biochar, AMF, and their combined use promoted maize growth parameters, including height, stem diameter, shoot and root biomass, and phosphorus uptake, while simultaneously reducing the shoot Pb concentration. These findings suggest a synergistic effect in Pb phytostabilization. In summary, despite the adverse impact of biochar on mycorrhizal growth, cultivating maize with the concurrent use of biochar and AMF emerges as a recommended and effective strategy for Pb phytoremediation.IMPORTANCEHeavy metal contamination in soil is a pressing environmental issue, and phytoremediation has emerged as a sustainable approach for mitigating this problem. This study sheds light on the potential of maize cultivation, biochar application, and arbuscular mycorrhizal fungi (AMF) inoculation to enhance the immobilization of Pb in contaminated soil. The findings demonstrate that the combined use of biochar and AMF during maize cultivation can significantly improve Pb immobilization and simultaneously enhance maize growth, offering a promising strategy for sustainable and effective Pb phytoremediation practices. This research contributes valuable insights into the field of phytoremediation and its potential to address heavy metal pollution in agricultural soils.

Multifunctionalized alginate/polydopamine cryogel for hemostasis, antibacteria and promotion of wound healing.

Hemostasis and anti-infection are crucial for emergency treatment of severe trauma. Developing functional biomaterial with efficient hemostasis, antibacterial activity and wound healing is of great social significance and clinical value to fast stop bleeding and save lives, but it is still challenged. Here we designed a series of multifunctionalized SA/PDA cryogels by using two-step cross-linking of dopamine and sodium alginate. The resulting interpenetrating network structure had good swelling ratio, excellent mechanical and shape memory properties. Compared with cotton gauze and gelatin sponge, the cryogels exhibited excellent activation of coagulation cascade, more blood cells and platelet adhesion. Due to the action of polydopamine, the cryogel also showed good antioxidant activity and photothermal antibacterial ability assisted by near-infrared radiation, as well as better wound healing performance than gelatin sponge and Tegaderm™ film. Moreover, in the tests of mouse tail docking model, rat femoral artery hemostasis model and non-compressible rabbit liver defect model, the treatment by SA/PDA cryogels presented less blood loss and shorter hemostasis time than cotton gauze and gelatin sponge. Therefore, SA/PDA cryogels with simple preparation process, low cost, and good biocompatibility would be applied in the variety of great clinical applications in bleeding control, anti-infection and wound healing, etc.

CircTTLL13 Promotes TMZ Resistance in Glioma via Modulating OLR1-Mediated Activation of the Wnt/ß-Catenin Pathway.

Glioma, originating from neuroglial progenitor cells, is a type of intrinsic brain tumor with poor prognosis. temozolomide (TMZ) is the first-line chemotherapeutic agent for glioma. Exploring the mechanisms of circTTLL13 underlying TMZ resistance in glioma is of great significance to improve glioma treatment. Bioinformatics was adopted to identify target genes. The circular structure of circTTLL13 and its high expression in glioma cells were disclosed by quantitative real time-PCR (qRT-PCR) and PCR-agarose gel electrophoresis. Functional experiments proved that oxidized LDL receptor 1 (OLR1) promotes TMZ resistance of glioma cells. CircTTLL13 enhances TMZ resistance of glioma cells via modulating OLR1. Luciferase reporter, RNA-binding protein immunoprecipitation (RIP), RNA pulldown, mRNA stability, N6-methyladenosine (m6A) dot blot and RNA total m6A quantification assays were implemented, indicating that circTTLL13 stabilizes OLR1 mRNA via recruiting YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) and promotes m6A methylation of OLR1 pre-mRNA through recruiting methyltransferase-like 3 (METTL3). TOP/FOP-flash reporter assay and western blot verified that circTTLL13 activates Wnt/ß-catenin signaling pathway by regulating OLR1. CircTTLL13 promotes TMZ resistance in glioma through regulating OLR1-mediated Wnt/ß-catenin pathway activation. This study offers an insight into the efficacy improvement of TMZ for glioma treatment.

Effect of Arbuscular Mycorrhiza Fungus Diversispora eburnea Inoculation on Lolium perenne and Amorpha fruticosa Growth, Cadmium Uptake, and Soil Cadmium Speciation in Cadmium-Contaminated Soil.

Cadmium (Cd) pollution has become aggravated during the past decades of industrialization, severely endangering human health through its entry into the food chain. While it is well understood that arbuscular mycorrhizal fungi (AMF) have a strong ability to regulate plant growth and Cd uptake, studies investigating how they affect soil Cd speciation and influence Cd uptake are limited. We designed a pot experiment comprising two AMF-inoculant groups (inoculation with Diversispora eburnea or no inoculation), three Cd concentration levels (0, 5, and 15 mg/kg), and two plant species (Lolium perenne and Amorpha fruticosa) to study the effect of AMF Diversispora eburnea on plant growth, Cd uptake, and Cd speciation in the soil. The results revealed that L. perenne exhibited higher productivity and greater Cd uptake than A. fruticosa, regardless of AMF D. eburnea inoculation. However, AMF D. eburnea significantly altered soil Cd speciation by increasing the proportion of exchangeable Cd and decreasing residual Cd, resulting in Cd enrichment in the plant root organs and the elimination of Cd from the polluted soils. Our experiments demonstrate that inoculating plants with AMF D. eburnea is an effective alternative strategy for remediating Cd-contaminated soil.

Effects of Arbuscular Mycorrhizal Fungi and Biochar on Growth, Nutrient Absorption, and Physiological Properties of Maize (Zea mays L.).

Arbuscular mycorrhizal fungi (AMFs) and biochar are two common alternatives to chemical fertilizers applied to soil to improve crop growth. However, their interactive effects on maize (Zea mays L.) growth, nutrient absorption, and physiological properties remain poorly understood. In this study, maize plants were grown in pots treated with biochar and AMFs Diversispora eburnea, alone or in combination. The results showed that the individual application of AMFs or biochar increased maize growth and mineral contents in shoots and roots (including P, K, Ca, Na, Mg, Fe, Mn, and Zn). The chlorophyll a, chlorophyll b, and total chlorophyll contents in AMF-treated leaves were significantly higher than those in the control treatment group. However, AMFs had no synergistic effects with biochar on maize growth, nutrient absorption, nor photosynthetic pigments. The application of biochar to the soil significantly reduced mycorrhizal colonization by 40.58% in the root tissues, accompanied by a significant decline in mycorrhizal dependency from 80.57% to -28.67%. We conclude that the application of biochar and AMFs can affect maize growth, nutrient uptake, and physiological properties. Our study can provide vital information for further resource use optimization in agroecosystems.

WITHDRAWN: Circ-LAMP2 regulates aortic smooth muscle cell proliferation and apoptosis in thoracic aortic aneurysm via modulation of autophagy and NF-κB pathway.

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Arcuate Fasciculus Subsegment Impairments Distinctly Associated with Memory and Language Deficits in Acute Mild Traumatic Brain Injury Patients.

In acute mild traumatic brain injury (mTBI), the injury-related axonal swelling leads to white matter fiber bundle impairments, closely related to the memory and language deficits commonly shown in the patients. The arcuate fasciculus (AF) plays a central role in verbal learning and language function but could be functionally heterogeneous along the fiber tract. In this study, 25 patients with acute mTBI (<48 h after trauma) and 33 age- and sex-matched healthy controls (HCs) were included. Impaired verbal memory and language functions were shown in the patient group compared with the HCs. Combined diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) were applied to investigate the altered diffusion measure profiles of the AF tracts and the associated functional features. The fractional anisotropy (FA) in the right AF temporal subsegment of the mTBI group was negatively associated with the patient verbal memory function, whereas a positive correlation was found in the HC group. On the other hand, the correlation between the FA in the right AF frontal subsegment and the language function in HCs diminished in the patient group. Moreover, the functional connectivity between the inferior frontal gyrus and the middle occipital gyrus decreased, and its correlation with language function in HCs was absent in the patients with mTBI. Our work provides new insights into the understanding of the structural and functional heterogeneity of the AF tracts as well as the distinct associations of its subsegment impairments with verbal memory and language function deficits in patients with acute mTBI.

Postharvest Dehydration Temperature Modulates the Transcriptomic Programme and Flavonoid Profile of Grape Berries.

Raisins are a popular and nutritious snack that is produced through the dehydration of postharvest grape berries under high temperature (HT). However, the response of the endogenous metabolism of white grape varieties to postharvest dehydration under different temperature have not been fully elucidated to date. In this study, the white grape cultivar 'Xiangfei' was chosen to investigate the effect of dehydration at 50 °C, 40 °C, and 30 °C on the transcriptomic programme and metabolite profiles of grape berries. Postharvest dehydration promoted the accumulation of soluble sugar components and organic acids in berries. The content of gallic acid and its derivatives increased during the dehydration process and the temperature of 40 °C was the optimal for flavonoids and proanthocyanidins accumulation. High-temperature dehydration stress might promote the accumulation of gallic acid by increasing the expression levels of their biosynthesis related genes and regulating the production of NADP+ and NADPH. Compared with that at 30 °C, dehydration at 40 °C accelerated the transcription programme of 7654 genes and induced the continuous upregulation of genes related to the heat stress response and redox homeostasis in each stage. The results of this study indicate that an appropriate dehydration temperature should be selected and applied when producing polyphenols-rich raisins.

Molecular polymorphism and expression of MHC I α, II α, II ß and II invariant chain in the critically endangered Dabry's sturgeon (Acipenser dabryanus).

The major histocompatibility complex (MHC) is a key player in the regulation of immune responses through presenting foreign antigens to T lymphocytes. In this study, three MHC genes, namely, MHC I α, II α, II ß and the II invariant chain (Ii), were identified and characterized in the critically endangered Dabry's sturgeon (Acipenser dabryanus). A tissue distribution study showed that the MHC and Ii transcripts were widely expressed in various tissues. The highest expression levels of MHC I α, II α and Ii were found in the gill, while MHC II ß was primarily expressed in the spleen. Challenge of A. dabryanus with a pathogenic bacterium in vivo resulted in significant upregulation of both MHC and Ii expression, indicating potential roles of these genes in immune response. Phylogenetic analysis showed that A. dabryanus MHC grouped with other teleost MHC genes and sequences from Polyodon spathula and A. dabryanus had an intermingling of alleles. According to the split time between paddlefishes and sturgeons, this result indicated that trans-species MHC lineages in Chondrostei were much older than those in tetrapods. The molecular polymorphisms of the complete open reading frame regions of the MHC genes were analysed in several A. dabryanus individuals. MHC II α and II ß were highly polymorphic in different individuals, while MHC I α was more conserved. The ratio of non-synonymous substitution occurred at a significantly higher frequency than synonymous substitution in peptide-binding regions (PBR) of MHC II α and II ß, demonstrating the existence of positive selection at peptide-binding sites. Our study suggested potential roles of the MHC chains in immune response to pathogen microbial infection, and the numerous alleles identified in this study will help further genetic management and molecular marker-assisted selective breeding programmes in A. dabryanus.

Application of pulsed arterial resuscitation in a rabbit model of hemorrhagic shock.

BACKGROUND: Hemorrhagic shock is characterized by tissue hypoperfusion caused by a sharp reduction in the effective circulating volume of blood. The key to successful resuscitation lies in eliminating the shock as soon as possible while simultaneously restoring blood perfusion to vital organs. We present the applicability of pulsed arterial blood reinfusion for resuscitation of hemorrhagic shock. METHODS: Sixty rabbits were randomly assigned to resuscitation and control groups. A rabbit hemorrhagic shock model was developed by bloodletting from the carotid artery. The dynamic changes in blood pressure, urine output, blood lactate, and other indicators were measured. RESULTS: Compared with the control group, the mean arterial pressure (MAP), pulse pressure, and urine output were significantly higher in the resuscitation group at 60 min (MAP: 83.67±3.90 vs. 38.19±3.50 mmHg, p<0.001; pulse difference: 16.46±2.21 vs. 10.27±2.99 mmHg, p<0.001; urine output: 3.68±0.74 vs. 0.10±0.05 mL·kg-1·min-1, p<0.001), whereas the serum lactate level was significantly lower (3.82±0.50 vs. 6.49±0.61 mmol/L, p<0.001). In addition, the resuscitation group had a significantly higher lactate clearance rate (30 min: 0.26%±0.11% vs. 0.25%±0.14%, p<0.001; 60 min: 0.30%±0.09% vs. 0.67%±0.26%, p<0.001) than the control group. CONCLUSION: Pulsed arterial resuscitation might be useful for emergency treatment of hemorrhagic shock.