Betulinic acid inhibits glioma cell viability by downregulation of NF-κB and enhancement of apoptosis

Purpose: To determine the inhibitory potential of betulinic acid on pro-survival signaling pathway in glioblastoma.Methods: Changes in viabilities of glioma cells and primary astrocytes were measured using 3-(4, 5dimethylthiazol-2-yl)-2,  5-diphenyltetrazolium bromide (MTT) assay. Apoptotic changes were analyzed using Hoechst 33342 staining and Annexin V-FITC/PI kits. Western blotting was used for assaying the protein expressions of various pro-apoptotic and anti-apoptotic factors.Results: The proliferative potential of U87MG and A172 cells were significantly reduced on treatment with betulinic acid in a concentration- and time-dependent manner. Treatment with betulinic acid at a dose of 8.75 µg/mL increased apoptosis in U87MG and A172 cells to 41.8 ± 0.5 and 48.8 ± 0.5%, respectively (p < 0.05). Betulinic acid significantly decreased intracellular levels of NFκB p65 andsuppressed levels of survivin, XIAP and Bcl-2 in U87MG and A172 cells (p < 0.05). However, betulinic acid significantly increased the levels of Bax and activated caspase-9 and caspase-3 in U87MG and A172 cells (p < 0.05).Conclusion: Betulinic acid inhibited the proliferation of U87MG and A172 glioblastoma cells and mediated their apoptosis. There is need for in vivo studies for validation of the therapeutic potential of betulinic acid as an anti-glioblastoma drug. Keywords: Glioblastoma, Betulinic acid, Proliferation, Apoptosis, Chemotherapy, Intracranial malignanc

Assessment of Reclamation Treatments of Abandoned Farmland in an Arid Region of China

Reclamation of abandoned farmland is crucial to a sustainable agriculture in arid regions. This study aims to evaluate the impact of different reclamation treatments on abandoned salinized farmland. We investigated four artificial reclamation treatments, continuous cotton (CC), continuous alfalfa (CA), tree-wheat intercropping (TW) and trees (TS), which were conducted in 2011–2012 in the Manasi River Basin of Xinjiang Province, China. Soil nutrient, microorganism and enzyme activity were examined in comparison with natural succession (CK) in an integrated analysis on soil fertility improvement and soil salinization control with these reclamations. Results indicate that the four artificial reclamation treatments are more effective approaches than natural restoration to reclaim abandoned farmland. TW and CA significantly increased soil nutrient content compared to CK. CC reduced soil salinity to the lowest level among all treatments. TW significantly enhanced soil enzyme activity. All four artificial reclamations increased soil microbial populations and soil microbial biomass carbon. TW and CA had the greatest overall optimal effects among the four treatments in terms of the ecological outcomes. If both economic benefits and ecological effects are considered, TW would be the best reclamation mode. The findings from this study will assist in selecting a feasible method for reclamation of abandoned farmland for sustainable agriculture in arid regions.This research was supported by the Special Fund for Agro-scientific Research in the Public Interest (201503120); Science and Technology Research and Achievement Transformation Project of The Xinjiang Production and Construction Crops (2016AD022); and the National Key Technology Research and Development Program of the Ministry of Science and Technology of China (2014BAC14B03)

Monogenean fauna of alien tilapias (Cichlidae) in south China

Tilapias are important aquaculture fishes that have been introduced widely all over the world, often carrying their monogenean parasites with them. An extensive investigation on monogeneans of invasive tilapias was conducted in 19 natural water sources in south China between July 2015 and December 2017. We found nine known species of monogeneans, i.e., Enterogyrus coronatus, E. malmbergi, Cichlidogyrus cirratus, C. halli, C. sclerosus, C. thurstonae, C. tilapiae, Scutogyrus longicornis, Gyrodactylus cichlidarum, and one unknown Gyrodactylus species. In addition to reporting ten new hosts and four new geographical records, we observed new morphological characteristics of these species. Observation on living specimens of Enterogyrus spp. demonstrated that these two species have characteristic opisthaptoral retraction capacities, while the opisthaptor glands were not observed in our specimens of E. coronatus and E. malmbergi. The morphological differences of the accessory piece of the male copulatory complex between C. cirratus and C. mbirizei (character for species differentiation) could result from the observation at different perspectives, which indicates that C. mbirizei is likely a synonym of C. cirratus. A more detailed structure of the sclerotized parts of Cichlidogyrus spp. and S. longicornis were revealed by scanning electron microscopy. As was the case for the monogeneans found on alien tilapias from other geographic regions, the present study confirmed the high potential of these monogeneans to establish populations in new habitats

A comparative analysis of precipitation estimationmethods for streamflow prediction

Surface hydrologic models are widely used for streamflow prediction, forecasting and for understanding hydrologic processes. They are also an important tool for contributing to the resolution of wider resource and environmental issues, providing information to support policies and decisions for water resource management. Precipitation is a key input to hydrologic models and is however also the major source of predictive uncertainty. Whilst station-based observed precipitation data can be adequate for hydrologic modelling in small catchments, they may not be sufficient for large catchments, in particular for large catchments with a mountainous terrain. Areal estimation of precipitation is a potential option to provide more precise precipitation input to models for large catchments. Conventionally, for areal precipitation estimation, station-based precipitation data are interpolated across the model domain using various methods, including Spline fitting, Inverse Distance Weighting (IDW) and the classical Thiessen Polygon, which are among the more popular and commonly used methods. Different precipitation interpolation methods will affect the spatial and temporal variability of areal precipitation inputs, resulting in different uncertainties when used to help calibrate a surface hydrologic model. This paper investigates the effect of the above three types of precipitation interpolation methods (ANUSPLIN surface, IDW surface and Thiessen polygon) on streamflow predictions. The Chaohe basin located in northern China is selected as the study area. It is an important headwater of the Miyun Reservoir which provides drinking water to Beijing and surrounding townships. Three lumped, surface hydrologic models (GR4J, IHACRES and Sacramento) are selected to study the accuracy and predictive uncertainty of these three types of precipitation interpolation on daily streamflow. The models were calibrated separately using discharge observations from three gauges in the basin. The results show that the ANUSPLIN surface interpolation performs the best overall under various combinations of conditions. The IDW surface also performs well in the upper and middle basin but the Thiessen polygon is inferior to the other two methods. The comparison of the three hydrologic models shows that IHACRES and Sacramento perform better than GR4J. The best combination is areal rainfall estimated using the ANUSPLIN derived surface with the IHACRES model in the case study catchments, though the Sacramento model is a close second.This work was supported by the National Natural Science Foundation of China (No. 41271004)

Applicability assessment and uncertainty analysis of multi-precipitation datasets for the simulation of hydrologic models

Hydrologic models are essential tools for understanding hydrologic processes, such as precipitation, which is a fundamental component of the water cycle. For an improved understanding and the evaluation of different precipitation datasets, especially their applicability for hydrologic modelling, three kinds of precipitation products, CMADS, TMPA-3B42V7 and gauge-interpolated datasets, are compared. Two hydrologic models (IHACRES and Sacramento) are applied to study the accuracy of the three types of precipitation products on the daily streamflow of the Lijiang River, which is located in southern China. The models are calibrated separately with different precipitation products, with the results showing that the CMADS product performs best based on the Nash-Sutcliffe efficiency, including a much better accuracy and better skill in capturing the streamflow peaks than the other precipitation products. The TMPA-3B42V7 product shows a small improvement on the gauge-interpolated product. Compared to TMPA-3B42V7, CMADS shows better agreement with the ground-observation data through a pixel-to-point comparison. The comparison of the two hydrologic models shows that both the IHACRES and Sacramento models perform well. The IHACRES model however displays less uncertainty and a higher applicability than the Sacramento model in the Lijiang River basin

Predicting intraoperative major blood loss in microsurgery for brain arteriovenous malformations

ObjectiveIntraoperative blood loss poses a great challenge for brain arteriovenous malformation (AVM) microsurgery, although systematic researches are still lacking. This study aimed to identify factors predicting intraoperative major blood loss in brain AVM microsurgery and to investigate its impact on patient outcome. To deal with the fierce bleeding, we introduced a modified hemostatic method, bone-wax (BW) coated bipolar electrocoagulation.MethodsThe authors retrospectively analyzed the clinical data of 131 patients (50/81 in intraoperative major/non-major blood loss cohort) with brain AVMs who underwent microsurgery in our center during the period between January 2018 and April 2023. According to previous studies, major blood loss was defined as blood loss of at least 1,000 mL. The accuracy and objectivity of our grouping methodology were validated by comparing the hemoglobin mass loss, hematocrit loss and factors associated with intraoperative bleeding. Potential clinical and radiological predictors for intraoperative major blood loss were evaluated using a multivariate stepwise logistic regression. And outcomes of patients in the two cohorts were also compared. At last, the performance of BW coated bipolar electrocoagulation in brain AVM microsurgery was illustrated by the case presentation, histological staining and transmission electron microscopy of the coagulated nidus vessels.ResultsHemoglobin mass loss, hematocrit loss and factors associated with intraoperative bleeding were significant different between the two cohorts. five independent factors predicting intraoperative major blood loss were identified: (1) clinical manifestations; (2,3) location and size of the nidus; (4) deep venous drainage; and (5) the number of draining veins. And the intraoperative major blood loss can not only adversely affect the surgical progression, but also predict poor perioperative outcomes for patients. Regarding the application of BW coated bipolar electrocoagulation, we found the novel hemostatic method exerted efficient hemostatic effect and reduced the damage to the vascular structure in brain AVM microsurgery.ConclusionThis study proposed a nomogram for neurosurgeons to predict intraoperative major blood loss in brain AVM microsurgery preoperatively. And intraoperative major blood loss is associated with poor patient outcomes. In addition, BW coated bipolar electrocoagulation, can be applied to control ferocious bleeding during brain AVM microsurgery, which still remains further researches

Visualization balloon occlusion-assisted technique in the treatment of large or giant paraclinoid aneurysms: A study of 17 cases series

ObjectiveAlthough balloon-assisted techniques are valuable in aneurysm clipping, repeated angiography and fluoroscopy are required to understand the location and shape of the balloon. This study investigated the value of visualization balloon occlusion-assisted techniques in aneurysm hybridization procedures.MethodsWe propose a visualization balloon technique that injects methylene blue into the balloon, allowing it to be well visualized under a microscope without repeated angiography. This study retrospects the medical records of 17 large or giant paraclinoid aneurysms treated by a visualization balloon occlusion-assisted technique in a hybrid operating room. Intraoperative surgical techniques, postoperative complications, and immediate and long-term angiographic findings are highlighted.ResultsAll 17 patients had safe and successful aneurysm clipping surgery with complete angiographic occlusion. Under the microscope, the balloon injected with methylene blue is visible through the arterial wall. The position and shape of the balloon can be monitored in real time without repeated angiography and fluoroscopic guidance. Two cases of intraoperative visualization balloon shift and slip into the aneurysm cavity were detected in time, and there were no cases of balloon misclipping or difficult removal. Of 17 patients, four patients (23.5%) experienced short-term complications, including pulmonary infection (11.8%), abducens nerve paralysis (5.9%), and thalamus hemorrhage (5.9%). The rate of vision recovery among patients with previous visual deficits was 70% (7 of 10 patients). The mean follow-up duration was 32.76 months. No aneurysms or neurological deficits recurred among all patients who completed the follow-up.ConclusionOur study indicates that microsurgical clipping with the visualization balloon occlusion-assisted technique seems to be a safe and effective method for patients with large or giant paraclinoid aneurysms to reduce the surgical difficulty and simplify the operation process of microsurgical treatment alone

Identification of Diagnostic Genes and Effective Drugs Associated with Osteoporosis Treatment by Single-Cell RNA-Seq Analysis and Network Pharmacology

Background. Osteoporosis is a common bone metabolic disease with increased bone fragility and fracture rate. Effective diagnosis and treatment of osteoporosis still need to be explored due to the increasing incidence of disease. Methods. Single-cell RNA-seq was acquired from GSE147287 dataset. Osteoporosis-related genes were obtained from chEMBL. Cell subpopulations were identified and characterized by scRNA-seq, t-SNE, clusterProfiler, and other computational methods. “limma” R packages were used to identify all differentially expressed genes. A diagnosis model was build using rms R packages. Key drugs were determined by proteins-proteins interaction and molecular docking. Results. Firstly, 15,577 cells were obtained, and 12 cell subpopulations were identified by clustering, among which 6 cell subpopulations belong to CD45+ BM-MSCs and the other subpopulations were CD45-BM-MSCs. CD45- BM-MSCs_6 and CD45+ BM-MSCs_5 were consider as key subpopulations. Furthermore, we found 7 genes were correlated with above two subpopulations, and F9 gene had highest AUC. Finally, five compounds were identified, among which DB03742 bound well to F9 protein. Conclusions. This work discovered that 7 genes were correlated with CD45-BM-MSCs_6 and CD45+ BM-MSCs_5 subpopulations in osteoporosis, among which F9 gene had better research value. Moreover, compound DB03742 was a potential inhibitor of F9 protein

Assessment of multiple precipitation interpolation methods and uncertainty analysis of hydrological models in Chaohe River basin, China

Precipitation interpolation is widely used to generate continuous rainfall surfaces for hydrological simulations. However, increasing the precision of values at the unknown points generated by different spatial interpolation methods is challenging. This study used the Chaohe River Basin, which is an important source of Beijing’s drinking water, as a research area to comprehensively evaluate several precipitation interpolation methods (Thiessen polygon, inverse distance weighting, ordinary kriging and ANUSPLIN) for inputs in hydrological simulations. This research showed that the precipitation time-series surface generated using the ANUSPLIN interpolation method had higher accuracy and reliability. Using this precipitation input to drive the hydrological models, we explored the parameter uncertainties of four typical hydrological models (GR4J, IHACRES, Sacramento and MIKE SHE) based on the multi-objective generalized likelihood uncertainty estimation (GLUE) method. The GLUE method was used to study the parameter sensitivity and uncertainty of the model. Results showed that the ANUSPLIN precipitation interpolation surface combined with the Sacramento model performed best. The multi-objective GLUE method had obvious advantages in parameter uncertainty analysis in hydrological models. Simultaneously exploring the convex line and point density distributions of the behavioural parameters with multi-objective functions determined their distribution and sensitivity more effectively

Identification of an Immune-Related Prognostic Signature for Glioblastoma by Comprehensive Bioinformatics and Experimental Analyses

Background: Glioblastoma (GBM), which has a poor prognosis, accounts for 31% of all cancers in the brain and central nervous system. There is a paucity of research on prognostic indicators associated with the tumor immune microenvironment in GBM patients. Accurate tools for risk assessment of GBM patients are urgently needed. Methods: In this study, we used weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) methods to screen out GBM-related genes among immune-related genes (IRGs). Then, we used survival analysis and Cox regression analysis to identify prognostic genes among the GBM-related genes to further establish a risk signature, which was validated using methods including ROC analysis, stratification analysis, protein expression level validation (HPA), gene expression level validation based on public cohorts, and RT-qPCR. In order to provide clinicians with a useful tool to predict survival, a nomogram based on an assessment of IRGs and clinicopathological features was constructed and further validated using DCA, time-dependent ROC curve, etc. Results: Three immune-related genes were found: PPP4C (p < 0.001, HR = 0.514), C5AR1 (p < 0.001, HR = 1.215), and IL-10 (p < 0.001, HR = 1.047). An immune-related prognostic signature (IPS) was built to calculate risk scores for GBM patients; patients classified into different risk groups had significant differences in survival (p = 0.006). Then, we constructed a nomogram based on an assessment of the IRG-based signature, which was validated as a potential prediction tool for GBM survival rates, showing greater accuracy than the nomogram without the IPS when predicting 1-year (0.35 < Pt < 0.50), 3-year (0.65 < Pt < 0.80), and 5-year (0.65 < Pt < 0.80) survival. Conclusions: In conclusion, we integrated bioinformatics and experimental approaches to construct an IPS and a nomogram based on IPS for predicting GBM prognosis. The signature showed strong potential for prognostic prediction and could help in developing more precise diagnostic approaches and treatments for GBM