Vitamin D3 eradicates Helicobacter pylori by inducing VDR-CAMP signaling

BackgroundVitamin D3 [VitD3, 1,25 (OH)2D3] is known to have immunomodulatory and anti-microbial properties; however, its activity against Helicobacter pylori is unclear. In this study, we established H. pylori infection models in wild-type and VitD3 receptor (VDR) knockdown mice and analyzed the effects of VitD3 and their underlying mechanisms.MethodsVDR+/+ and VDR+/– mice were intragastrically infected with the H. pylori SS1 strain. After confirmation of H. pylori infection, mice were treated with different doses of VitD3. The infection levels in stomach tissues were quantified using the colony-forming assay, and the expression levels of the VDR and cathelicidin antimicrobial peptide (CAMP) in the gastric mucosa were analyzed by immunohistochemistry and western blotting.ResultsThe gastric mucosa of VDR+/– mice was more susceptible to H. pylori colonization and had lower levels of VDR and CAMP expression than that of VDR+/+ mice. H. pylori infection upregulated VDR and CAMP expression in the stomach of both wild-type and mutant mice, and VitD3 treatment resulted in further increase of VDR and CAMP levels, while significantly and dose-dependently decreasing the H. pylori colonization rate in both mouse groups, without affecting blood calcium or phosphorus levels.ConclusionOur data indicate that oral administration of VitD3 reduces the H. pylori colonization rate and upregulates VDR and CAMP expression in the gastric mucosa, suggesting a role for VitD3/VDR/CAMP signaling in the eradication of H. pylori in the stomach. These findings provide important insights into the mechanism underlying the anti-H. pylori activity of VitD3 and should be useful in the development of measures to eradicate H. pylori

The application and research progress of anti-angiogenesis therapy in tumor immunotherapy

Tumor immunotherapy, as the focus of scientific research and clinical tumor treatment in recent years, has received extensive attention. Due to its remarkable curative effect and fewer side effects than traditional treatments, it has significant clinical benefits for the treatment of various advanced cancers and can improve cancer patient survival in the long term. Currently, most patients cannot benefit from immunotherapy, and some patients may experience tumor recurrence and drug resistance even if they achieve remission overcome. Numerous studies have shown that the abnormal angiogenesis state of tumors can lead to immunosuppressive tumor microenvironment, which affects the efficacy of immunotherapy. Actually, to improve the efficacy of immunotherapy, the application of anti-angiogenesis drugs to normalize abnormal tumor vessel has been widely confirmed in basic and clinical research. This review not only discusses the risk factors, mechanisms, and effects of abnormal and normalized tumor angiogenesis state on the immune environment, but summarizes the latest progress of immunotherapy combined with anti-angiogenic therapy. We hope this review provides an applied reference for anti-angiogenesis drugs and synergistic immunotherapy therapy

Operation parameters multi-objective optimization method of large vertical mill based on CFD-DPM

The association mechanism between the main operation parameters and multi-physical fields of the large-scale vertical mill system is unclear, which leads to the difficulty in optimizing operation parameters to improve the performance of large vertical mill systems. To investigate the mechanism of multi-physical field coupling in the operation of the large vertical mill, the numerical simulation method is constructed by coupled CFD-DPM model to calculate the finished product quality, the simulation results were in good agreement with the actual operation results. Based on the Kriging surrogate model, a multi-objective optimization framework for large vertical mills is proposed. Finally, the multi-objective optimization design of LGM large vertical mills is carried out. Combined with CFD-DPM coupling method is developed, design variables and output responses are determined. The Kriging method is used for correlation analysis. The multi-objective optimization function was established. The NSGA-II. optimization algorithm was used to update the surrogate model and obtain the optimal solution, and the optimized operating parameters increased the vertical mill yield by 5.34% and the specific surface area by 9.07%. The maximum relative error between the simulated value and the optimized value is 2.02% through numerical calculation, which verifies the superiority of the optimization method of large vertical mill for performance improvement

Hydrofoil optimization of underwater glider using Free-Form Deformation and surrogate-based optimization

Hydrofoil is the direct component to generate thrust for underwater glider. It is significant to improve propulsion efficiency of hydrofoil. This study optimizes the shape of a hydrofoil using Free-Form Deformation (FFD) parametric approach and Surrogate-based Optimization (SBO) algorithm. FFD approach performs a volume outside the hydrofoil and the position changes of control points in the volume parameterize hydrofoil's geometric shape. SBO with adaptive parallel sampling method is regarded as a promising approach for CFD-based optimization. Combination of existing sampling methods is being widely used recently. This paper chooses several well-known methods for combination. Investigations are implemented to figure out how many and which methods should be included and the best combination strategy is provided. As the hydrofoil can be stretched from airfoil, the optimizations are carried out on a 2D airfoil and a 3D hydrofoil, respectively. The lift-drag ratios are compared among optimized and original hydrofoils. Results show that both lift-drag-ratios of optimized hydrofoils improve more than 90%. Besides, this paper preliminarily explores the optimization of hydrofoil with root-tip-ratio. Results show that optimizing 3D hydrofoil directly achieves slightly better results than 2D airfoil. Keywords: Underwater glider, Hydrofoil, Surrogate-based optimization, Adaptive parallel sampling approac

Shape optimization of blended-wing-body underwater glider by using gliding range as the optimization target

Blended-Wing-Body Underwater Glider (BWBUG), which has excellent hydrodynamic performance, is a new kind of underwater glider in recent years. In the shape optimization of BWBUG, the lift to drag ratio is often used as the optimization target. However this results in lose of internal space. In this paper, the energy reserve is defined as the direct proportional function of the internal space of BWBUG. A motion model, which relates gliding range to steady gliding motion parameters as well as energy consumption, is established by analyzing the steady-state gliding motion. The maximum gliding range is used as the optimization target instead of the lift to drag ratio to optimizing the shape of BWBUG. The result of optimization shows that the maximum gliding range of initial design is increased by 32.1% though an Efficient Global Optimization (EGO) process. Keywords: Blended-wing-body underwater glider, Shape optimization, Gliding range, Energy consumption model, Lift to drag rati

The Influence of Climate Change on Three Dominant Alpine Species under Different Scenarios on the Qinghai–Tibetan Plateau

The Qinghai–Tibetan Plateau (QTP) with high altitude and low temperature is one of the most sensitive areas to climate change and has recently experienced continuous warming. The species distribution on the QTP has undergone significant changes especially an upward shift with global warming in the past decades. In this study, two dominant trees (Picea crassifolia Kom and Sabina przewalskii Kom) and one dominant shrub (Potentilla parvifolia Fisch) were selected and their potential distributions using the MaxEnt model during three periods (current, the 2050s and the 2070s) were predicted. The predictions were based on four shared socio-economic pathway (SSPs) scenarios, namely, SSP2.6, SSP4.5, SSP7.0, SSP8.5. The predicted current potential distribution of three species was basically located in the northeastern of QTP, and the distribution of three species was most impacted by aspect, elevation, temperature seasonality, annual precipitation, precipitation of driest month, Subsoil CEC (clay), Subsoil bulk density and Subsoil CEC (soil). There were significant differences in the potential distribution of three species under four climate scenarios in the 2050s and 2070s including expanding, shifting, and shrinking. The total suitable habitat for Picea crassifolia shrank under SSP2.6, SSP4.5, SSP7.0 and enlarged under SSP8.5 in the 2070s. On the contrary, the total suitable habitat for Sabina przewalskii enlarged under SSP2.6, SSP4.5, SSP7.0 and shrank under SSP8.5 in the 2070s. The total suitable habitat for Potentilla parvifolia continued to increase with SSP2.6 to SSP8.5 in the 2070s. The average elevation in potentially suitable habitat for Potentilla parvifolia all increased except under SSP8.5 in the 2050s. Our study provides an important reference for the conservation of Picea crassifolia, Sabina przewalskii, Potentilla parvifolia and other dominant plant species on the QTP under future climate change

A Two-Dimensional Deflection Sensor Based on Force Sensing Resistors

A flexible deflection sensor for elastic shaft with the capability of measuring the amplitude and direction of bending is introduced in this paper. A thin force sensing resistors (FSR) film is taken as its basic material, which is sandwiched by an elastomer layer and a printed circuit board (PCB) with detecting electrode grids. Two fix rings are used to fix the three thin components perpendicularly to the longitudinal direction of the flexible shaft. When the shaft bends under forces, the fix rings will generate a normal pressure on FSR, which will cause the change of the resistance. Therefore, the amplitude of bending can be got based on the value of resistance. The electrode grid on the PCB is divided into four detection areas used to estimate the distribution of normal pressure on the FSR; thus the bending direction of shaft can also be obtained. Test results of a prototype (140 mm in length) show that the amplitude of deflection can reach 30 mm and the sensitivities of sensor are 40.37, 32.8, 37.77, and 39.47 mV/mm in the four directions, respectively. The proposed flexible deflection sensor can be applied in continuum robots or other applications, which require rapid measurement of bending amplitude and direction

Electrochemical Sensing of α-Fetoprotein Based on Molecularly Imprinted Polymerized Ionic Liquid Film on a Gold Nanoparticle Modified Electrode Surface

A molecularly imprinted sensor was fabricated for alpha-fetoprotein (AFP) using an ionic liquid as a functional monomer. Ionic liquid possesses many excellent characteristics which can improve the sensing performances of the imprinted electrochemical sensor. To demonstrate this purpose, 1-[3-(N-cystamine)propyl]-3-vinylimidazolium tetrafluoroborate ionic liquid [(Cys)VIMBF4] was synthesized and used as a functional monomer to fabricate an AFP imprinted polymerized ionic liquid film on a gold nanoparticle modified glassy carbon electrode (GCE) surface at room temperature. After removing the AFP template, a molecularly imprinted electrochemical sensor was successfully prepared. The molecularly imprinted sensor exhibits excellent selectivity towards AFP, and can be used for sensitive determination of AFP. Under the optimized conditions, the imprinted sensor shows a good linear response to AFP in the concentration range of 0.03 ng mL−1~5 ng mL−1. The detection limit is estimated to be 2 pg mL−1

Hepatotoxicity evaluation of traditional Chinese medicines using a computational molecular model

<p><b>Background:</b> Liver injury caused by traditional Chinese medicines (TCMs) is reported from many countries around the world. TCM hepatotoxicity has attracted worldwide concerns.</p> <p><b>Objective:</b> This study aims to develop a more applicable and optimal tool to evaluate TCM hepatotoxicity.</p> <p><b>Methods:</b> A quantitative structure-activity relationship (QSAR) analysis was performed based on published data and U.S. Food and Drug Administration’s Liver Toxicity Knowledge Base (LTKB).</p> <p><b>Results:</b> Eleven herbal ingredients with proven liver toxicity in the literature were added into the dataset besides chemicals from LTKB. The finally generated QSAR model yielded a sensitivity of 83.8%, a specificity of 70.1%, and an accuracy of 80.2%. Among the externally tested 20 ingredients from TCMs, 14 hepatotoxic ingredients were all accurately identified by the QSAR model derived from the dataset containing natural hepatotoxins.</p> <p><b>Conclusions:</b> Adding natural hepatotoxins into the dataset makes the QSAR model more applicable for TCM hepatotoxicity assessment, which provides a right direction in the methodology study for TCM safety evaluation. The generated QSAR model has the practical value to prioritize the hepatotoxicity risk of TCM compounds. Furthermore, an open-access international specialized database on TCM hepatotoxicity should be quickly established.</p