Circ_0012152 Accelerates Acute Myeloid Leukemia Progression through the miR-652-3p/SOX4 Axis.

OBJECTIVE: Acute myeloid leukemia (AML) is an aggressive hematological malignancy characterized by abnormal myeloid blast expansion. Recent studies have demonstrated that circular RNAs play a role in AML pathogenesis. In this study, we aimed to investigate the clinical significance of circ_0012152 in AML and elucidate its underlying molecular mechanism in the pathogenesis of this condition. METHODS: Circ_0012152 expression was detected by quantitative real-time polymerase chain reaction in samples obtained from 247 patients with AML and 40 healthy controls. A systematic analysis of clinical characteristics and prognostic factors was also conducted. Cell growth was assessed using the Cell Counting Kit-8 (CCK-8) assay, and apoptosis and cell cycle progression were evaluated by flow cytometry. Moreover, RNA pull-down was performed to identify target microRNAs, and transcriptome RNA sequencing and bioinformatics analyses were utilized to identify downstream mRNA targets. RESULTS: Circ_0012152 was significantly upregulated in samples from patients with AML and served as an independent adverse prognostic factor for overall survival (OS) (hazard ratio: 2.357; 95% confidence interval 1.258-4.415). The circ_0012152 knockdown reduced cell growth, increased apoptosis, and inhibited cell cycle progression in AML cell lines. RNA pull-down and sequencing identified miR-652-3p as a target microRNA of circ_0012152. Cell growth inhibition by circ_0012152 knockdown was significantly relieved by miR-652-3p inhibitors. We suggested that miR-652-3p targeted SOX4, as the decrease in SOX4 expression resulting from circ_0012152 knockdown was upregulated by miR-652-3p inhibitors in AML cells. CONCLUSION: Circ_0012152 is an independent poor prognostic factor for OS in AML, and it promotes AML cell growth by upregulating SOX4 through miR-652-3p.

Impacts of different slash disposals on soil and water erosion of high-intensity management Eucalyptus grandis × urophylla plantation.

Background: The slash disposal-burning forest-in high-intensity management Eucalyptus grandis × urophylla plantation has accelerated soil degradation. Statement of the problem: Slash disposals is a contributing factor, but its specific role in the correlation between rainfall-runoff and soil erosion remains elusive. Objectives: his study investigated the characteristics of rainfall-runoff and soil erosion resistance in different methods of slash disposals in plantation. Methods: Three methods of slash disposal, namely burning forest (BF), moving away (MA), and spreading evenly (SE), were established. A field simulation experiment of rainfall was conducted, and path analysis was used. Results: The findings revealed that the water holding, infiltrating properties and the time the rainfall-runoff generated of SE were increased by approximately 10∼20 %, 100 %, and 80 %, respectively, compared with BF and MA. Water loss, soil loss and nutrient loss were significantly reduced by 62.23 % and 61.56 %, 69.06 % and 49.55 %, and 58.8 % and 65.42 % in SE and BF compared to MA. Path analysis suggested that different from BF and MA, the correlation between soil water properties and rainfall-runoff factors in SE was weakened, simultaneously considering the result that SE had the lower proportions of silt for sediment component (75.31 %), it stabilized the soil structure. Conclusions and prospect: Consequently, SE mitigated the erosion force by reducing rainfall-runoff and enhancing the anti-erosion of soil through improved water properties, making it a viable slash disposal. This work provides a detailed description of the soil erosion characteristics of plantation, including water, soil, and nutrient losses caused by rainfall-runoff, as well as the soil anti-erosion due to different slash disposals. These findings offer valuable insights for the management of high-intensity Eucalyptus grandis × urophylla plantations.

Smoking-induced CCNA2 expression promotes lung adenocarcinoma tumorigenesis by boosting AT2/AT2-like cell differentiation.

Lung adenocarcinoma (LUAD), a type of non-small cell lung cancer (NSCLC), originates from not only bronchial epithelial cells but also alveolar type 2 (AT2) cells, which could differentiate into AT2-like cells. AT2-like cells function as cancer stem cells (CSCs) of LUAD tumorigenesis to give rise to adenocarcinoma. However, the mechanism underlying AT2 cell differentiation into AT2-like cells in LUAD remains unknown. We analyze genes differentially expressed and genes with significantly different survival curves in LUAD, and the combination of these two analyses yields 147 differential genes, in which 14 differentially expressed genes were enriched in cell cycle pathway. We next analyze the protein levels of these genes in LUAD and find that Cyclin-A2 (CCNA2) is closely associated with LUAD tumorigenesis. Unexpectedly, high CCNA2 expression in LUAD is restrictedly associated with smoking and independent of other driver mutations. Single-cell sequencing analyses reveal that CCNA2 is predominantly involved in AT2-like cell differentiation, while inhibition of CCNA2 significantly reverses smoking-induced AT2-like cell differentiation. Mechanistically, CCNA2 binding to CDK2 phosphorylates the AXIN1 complex, which in turn induces ubiquitination-dependent degradation of ß-catenin and inhibits the WNT signaling pathway, thereby failing AT2 cell maintenance. These results uncover smoking-induced CCNA2 overexpression and subsequent WNT/ß-catenin signaling inactivation as a hitherto uncharacterized mechanism controlling AT2 cell differentiation and LUAD tumorigenesis.

Structural equation model was used to evaluate the effects of soil chemical environment, fertility and enzyme activity on eucalyptus biomass.

This paper aims to reveal the effects of multi-generational succession of eucalyptus on soil fertility, organic structure and biological properties. Soil samples were collected from eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) in a typical area in south Asia, soil organic fraction structure and content characteristics were investigated using Fourier transform infrared (FTIR), and structural equation modelling (SEM) was used to explore influences of soil fertility, enzyme activity and organic fraction on stand biomass. FTIR analysis showed that 11 infrared absorption peaks existed in the soils of this study area, attributed to silicates, aromatics, carbonate ions, sugars, esters, polysaccharides, aliphatic hydrocarbons and phenolic alcohols. Combined with the results of peak area integration, the content of esters, aromatics and phenolic alcohols was significantly higher in 17- and 21-year-old stand soils than in control soils. The results of SEM showed that organic components were negatively related (p < 0.01) to enzyme activity and biomass, with standardized coefficients of 0.53 and 0.49, respectively. In summary, multi-generation succession of eucalyptus trees can change the structure of soil organic functional group composition and promote the enrichment of aromatic and phenolic alcohol functional groups. Such changes can directly inhibit the increase in eucalyptus biomass and indirectly negatively affect biomass by inhibiting enzyme activity.

Short-term cultivation limiting soil aggregate stability and macronutrient accumulation associated with glomalin-related soil protein in Eucalyptus urophylla × Eucalyptus grandis plantations.

The relationship between glomalin-related soil protein (GRSP) and soil aggregation has been a hot topic of research for its close link to soil stability and quality. However, the short-term cultivation of Eucalyptus poses serious threats to soil stability and nutrient stocks, and the effects of GRSP on soil aggregate stability and macronutrient accumulation remain unclear. The aim is to clarify the potential mechanisms affecting soil aggregate stability and macronutrient accumulation in short-term Eucalyptus plantations. Five Eucalyptus urophylla × Eucalyptus grandis plantations with different cultivation periods (1-5 years) in this study were investigated, and a native evergreen broadleaf forest (0 year) was selected as control. The mean weight diameter index increased in the first 3 years and then significantly decreased during 5 years cultivation of Eucalyptus. Soil organic carbon (SOC) and total nitrogen also decreased after planting Eucalyptus for 3 years, but variation in total phosphorus was not obvious. The relative abundance of Glomeraceae and Claroideoglomeraceae decreased in the 5-year-old Eucalyptus plantations and was positively correlated with GRSP content. In pathway modeling, nutrient-acquisition enzyme activities positively affected GRSP and macronutrient content. Total GRSP (T-GRSP) had higher total effects than easily extractable GRSP on soil aggregate stability, and positively correlated with SOC in macroaggregates. Both T-GRSP and SOC had positive and direct effects on soil aggregate stability. Variance partitioning analysis further explained the contribution of GRSP and SOC to aggregate stability, particularly in >2 and 2-0.25 mm macroaggregates. Our results suggested that GRSP was directly associated with SOC content and soil aggregate stability, and was a potential key factor affecting soil aggregate stability in Eucalyptus plantations. Improving T-GRSP and SOC are efficient approaches for preventing the gradual deterioration of soil aggregate stability. Short-term cultivation should be carefully used in Eucalyptus plantations, and a new cultivation period is needed.

Potential effects of soil chemical and biological properties on wood volume in Eucalyptus urophylla × Eucalyptus grandis hybrid plantations and their responses to different intensity applications of inorganic fertilizer.

Long-term and high-intensity application of inorganic fertilizer leads to a strong variation of soil characteristics. The changes in soil chemical and biological properties can significantly affect the yield of Eucalyptus plantation. However, the mechanism of soil chemical properties affecting wood volume mediated by biological factors is not clear. The purpose of this study was to identify which soil properties were affected by different fertilization intensities and to disentangle the dominant factors affecting Eucalyptus volume. After clear felling evergreen broad-leaved forest, a Eucalyptus plantation was established that was coppiced every 5 years and fertilized every year. Within this plantation, areas with different treatments were established. These treatments were a 5-year growth period (low); two times 5-year growth period (medium); and three times 5-year growth period (high). In each treatment area and in a nearby evergreen broad-leaved forest (EBLF Control), five sample plots per treatment were set up. Various biological and chemistry analyses (18 in total) were related to determining the most important path and index for optimizing Eucalyptus plantation. The analysis of variance of enzyme activity and microbial biomass showed that the soil biological characteristics decreased over 10 years of plantation, and the enzyme activity was close to the state of EBLF control in medium, while the microbial biomass failed to return to its original state during continuous planting. Redundancy analysis results show that there was a strong correlation in chemical indicators and biological characteristics. Partial least square structural equation model showed that total phosphorus, nitrate nitrogen, urease, catalase, and microbial biomass nitrogen and phosphorus were the most influential soil biochemical factors, and the indirect effect of chemical properties on volume was achieved by microorganisms through enzyme activity. Continuous planting and large-scale application of inorganic fertilizer would lead to a decrease in plantation yield and fertilizer utilization efficiency and would affect the microbial biomass and enzyme activity by destroying the stability of soil chemical properties.

Hyperthermia combined with immune checkpoint inhibitor therapy: Synergistic sensitization and clinical outcomes.

BACKGROUND: Within the field of oncotherapy, research interest regarding immunotherapy has risen to the point that it is now seen as a key application. However, inherent disadvantages of immune checkpoint inhibitors (ICIs), such as their low response rates and immune-related adverse events (irAEs), currently restrict their clinical application. Were these disadvantages to be overcome, more patients could derive prolonged benefits from ICIs. At present, many basic experiments and clinical studies using hyperthermia combined with ICI treatment (HIT) have been performed and shown the potential to address the above challenges. Therefore, this review extensively summarizes the knowledge and progress of HIT for analysis and discusses the effect and feasibility. METHODS: In this review, we explored the PubMed and clinicaltrials.gov databases, with regard to the searching terms "immune checkpoint inhibitor, immunotherapy, hyperthermia, ablation, photothermal therapy". RESULTS: By reviewing the literature, we analyzed how hyperthermia influences tumor immunology and improves the efficacy of ICI. Hyperthermia can trigger a series of multifactorial molecular cascade reactions between tumors and immunization and can significantly induce cytological modifications within the tumor microenvironment (TME). The pharmacological potency of ICIs can be enhanced greatly through the immunomodulatory amelioration of immunosuppression, and the activation of immunostimulation. Emerging clinical trials outcome regarding HIT have verified and enriched the theoretical foundation of synergistic sensitization. CONCLUSION: HIT research is now starting to transition from preclinical studies to clinical investigations. Several HIT sensitization mechanisms have been reflected and demonstrated as significant survival benefits for patients through pioneering clinical trials. Further studies into the theoretical basis and practical standards of HIT, combined with larger-scale clinical studies involving more cancer types, will be necessary for the future.

Soil qualities and change rules of Eucalyptus grandis × Eucalyptus urophylla plantation with different slash disposals.

Slash disposal changes soil quality by affecting soil properties and nutrient cycling, and the appropriate disposal approaches remain controversial. This work aimed to explore the impact of different slash disposal methods on soil qualities. For this purpose, a Eucalyptus grandis × Eucalyptus urophylla plantation that had been cultivated in 2002 and felled for the third time in 2016 was established in Hezhou City, China. Burning forest (BF, for moderate intensity fire) and no-burning forest (NF) were set in the plantation, and the native evergreen broadleaf forest near the plantation was used as the control (CK). Soils were sampled quarterly in 2017, and 27 indicators that represent soil physical, chemical, and biological properties were analyzed and compared through the analysis of the sustainability index (SI), which adopts five indices to calculate soil quality. The obtained data showed that the indicators of BF and NF, except for the total potassium content, were much lower than those of CK. The physical properties (Max-WHC, CWHC, Min-WHC, MMC, CPD, TPD) of NF were significantly better (29.07%, 30.98%, 29.61%, 52.08%, 21.89%, 19.76%) than those of BF, unlike the chemical properties of BF (SOM, TN, ACa, AFe, AMn, ACu, AZn) were significantly better than those of NF (45.61%, 81.33%, 12.78%, 23.18%, 96.13%, 144.30%, 114.04%). The enzymatic activities of NF (URE, APHO) were significantly better (43.33%, 156.58%)than those of BF, except the activities of INV (- 25.21%). Results of SI showed that the soil quality of CK was much better than that of BF, and NF the worst. But it exhibited the most unevenness of CK, followed by NF, and BF the best. The change rules of BF and NF were contrasting, and soil quality reached the same level after half a year. In summary, the soil qualities, either BF or CK, were not comparable to that of CK. BF increased the soil quality fleetly and transiently, and NF was sustainable for the eucalyptus plantation.

Correlations between forest soil quality and aboveground vegetation characteristics in Hunan Province, China.

As a key component of terrestrial ecosystems, soil interacts directly with aboveground vegetation. Evaluating soil quality is therefore of great significance to comprehensively explore the interaction mechanism of this association. The purpose of this study was to fully understand the characteristics of aboveground vegetation, soil quality, and their potential coupling relationship among different forest types in Hunan Province, and to provide a theoretical basis for further exploring the mechanisms underlying soil-vegetation interactions in central China. We have set up sample plots of five kinds of forests (namely broad-leaved forest, coniferous forest, coniferous broad-leaved mixed forest, bamboo forest, and shrub forest) in Hunan Province. To explore the differences of vegetation characteristics and soil physical and chemical properties among the five stand types, variance analysis, principal component analysis, and regression analysis were used. Finally, we explored the coupling relationship between soil quality and aboveground vegetation characteristics of each forest. We found that there were significant differences in soil quality among the forest types, ranked as follows: shrub forest > bamboo forest > broad-leaved forest > mixed coniferous and broad-leaved forest > coniferous forest. In general, there was a negative correlation between vegetation richness and soil quality in the broad-leaved forest and the shrub forest, but they showed a positive correlation in the coniferous forest, the mixed coniferous and broad-leaved forest, and the bamboo forest. As a necessary habitat condition for aboveground vegetation, soil directly determines the survival and prosperity of plant species. These results indicated that for vegetation-soil dynamics in a strong competitive environment, as one aspect wanes the other waxes. However, in a weak competitive environment, the adverse relationship between vegetation and soil is less pronounced and their aspects can promote.

Network Pharmacology, Molecular Docking, and Experimental Validation to Unveil the Molecular Targets and Mechanisms of Compound Fuling Granule to Treat Ovarian Cancer.

Background: Compound fuling granule (CFG) is a traditional Chinese medicine formula that is used for more than twenty years to treat ovarian cancer (OC) in China. However, the underlying processes have yet to be completely understood. This research is aimed at uncovering its molecular mechanism and identifying possible therapeutic targets. Methods: Significant genes were collected from Therapeutic Target Database and Database of Gene-Disease Associations. The components of CFG were analyzed by LC-MS/MS, and the active components of CFG were screened according to their oral bioavailability and drug-likeness index. The validated targets were extracted from PharmMapper and PubChem databases. Venn diagram and STRING website diagrams were used to identify intersection targets, and a protein-protein interaction network was prepared using STRING. The ingredient-target network was established using Cytoscape. Molecular docking was performed to visualize the molecule-protein interactions using PyMOL 2.3. Enrichment and pathway analyses were performed using FunRich software and Reactome pathway, respectively. Experimental validations, including CCK-8 assay, wound-scratch assay, flow cytometry, western blot assay, histopathological examination, and immunohistochemistry, were conducted to verify the effects of CFG on OC cells. Results: A total of 56 bioactive ingredients of CFG and 185 CFG-OC-related targets were screened by network pharmacology analysis. The potential therapeutic targets included moesin, glutathione S-transferase kappa 1, ribonuclease III (DICER1), mucin1 (MUC1), cyclin-dependent kinase 2 (CDK2), E1A binding protein p300, and transcription activator BRG1. Reactome analysis showed 51 signaling pathways (P < 0.05), and FunRich revealed 44 signaling pathways that might play an important role in CFG against OC. Molecular docking of CDK2 and five active compounds (baicalin, ignavine, lactiflorin, neokadsuranic acid B, and deoxyaconitine) showed that baicalin had the highest affinity to CDK2. Experimental approaches confirmed that CFG could apparently inhibit OC cell proliferation and migration in vitro; increase apoptosis; decrease the protein expression of MUC1, DICER1, and CDK2; and suppress the progression and distant metastasis of OC in vivo. DICER1, a tumor suppressor, is essential for microRNA synthesis. Our findings suggest that CFG may impair the production of miRNAs in OC cells. Conclusion: Based on network pharmacology, molecular docking, and experimental validation, the potential mechanism underlying the function of CFG in OC was explored, which supplies the theoretical groundwork for additional pharmacological investigation.

Hyperspectral band selection and modeling of soil organic matter content in a forest using the Ranger algorithm.

Effective soil spectral band selection and modeling methods can improve modeling accuracy. To establish a hyperspectral prediction model of soil organic matter (SOM) content, this study investigated a forested Eucalyptus plantation in Huangmian Forest Farm, Guangxi, China. The Ranger and Lasso algorithms were used to screen spectral bands. Subsequently, models were established using four algorithms: partial least squares regression, random forest (RF), a support vector machine, and an artificial neural network (ANN). The optimal model was then selected. The results showed that the modeling accuracy was higher when band selection was based on the Ranger algorithm than when it was based on the Lasso algorithm. ANN modeling had the best goodness of fit, and the model established by RF had the most stable modeling results. Based on the above results, a new method is proposed in this study for band selection in the early phase of soil hyperspectral modeling. The Ranger algorithm can be applied to screen the spectral bands, and ANN or RF can then be selected to construct the prediction model based on different datasets, which is applicable to establish the prediction model of SOM content in red soil plantations. This study provides a reference for the remote sensing of soil fertility in forests of different soil types and a theoretical basis for developing portable equipment for the hyperspectral measurement of SOM content in forest habitats.

Creation of Hollow Calcite Single Crystals with CQDs: Synthesis, Characterization, and Fast and Efficient Decontamination of Cd(II).

In this work, carbon quantum dots were first prepared through one-pot hydrothermal route of the propyl aldehyde and sodium hydroxide via an aldol condensation reaction, and a novel solid-phase extraction adsorbent of hollow calcite single crystals was prepared via the precipitation of metal nitrates by the CO2 diffusion method in the presence of CQDs and further applied for excessive Cd(II) ions removal from water. The spectra and morphologies of the etched calcite were investigated by X-ray diffraction, Fourier transform infrared spectrometry, Scanning electron microscope, and Transmission electron microscopy. The results show that the CQDs etching technique successfully furnish a strategy for manufacturing interface defects onto the calcite crystal. Bath studies were done to evaluate the effects of the major parameters onto Cd(II) adsorption by the etched calcite, such as pH, contact time, and initial Cd(II) concentration. The Cd(II) adsorption onto the new adsorbent could reach a maximum adsorption amount of 66.68 mg/g at 120 min due to the abundant exterior adsorption sites on the adsorbent. The adsorption kinetics and adsorption isotherms of Cd(II) on the etched calcite were also investigated. The experimental datum showed that the adsorption kinetics and isotherms of Cd(II) on the etched calcite were well-fitted by the pseudo-second-order kinetic model and the Freundlich isotherm model respectively. The adsorption mechanisms could be primarily explained as the formation of Cd(OH)2 and CaxCd1-xCO3 solid solution on the adsorbent surface with the help of X-ray photoelectron spectroscopy.