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The clinical application of 5-fluorouracil (5-Fu), a potent chemotherapeutic agent, is often hindered by its well-documented cardiotoxic effects. Nevertheless, natural polyphenolic compounds like resveratrol (RES), known for their dual anti-tumor and cardioprotective properties, are potential adjunct therapeutic agents. In this investigation, we examined the combined utilization of RES and 5-Fu for the inhibition of gastric cancer using both in vitro and in vivo models, as well as their combined impact on cardiac cytotoxicity. Our study revealed that the co-administration of RES and 5-Fu effectively suppressed MFC cell viability, migration, and invasion, while also reducing tumor weight and volume. Mechanistically, the combined treatment prompted p53-mediated apoptosis and autophagy, leading to a considerable anti-tumor effect. Notably, RES mitigated the heightened oxidative stress induced by 5-Fu in cardiomyocytes, suppressed p53 and Bax expression, and elevated Bcl-2 levels. This favorable influence enhanced primary cardiomyocyte viability, decreased apoptosis and autophagy, and mitigated 5-Fu-induced cardiotoxicity. In summary, our findings suggested that RES holds promise as an adjunct therapy to enhance the efficacy of gastric cancer treatment in combination with 5-Fu, while simultaneously mitigating cardiotoxicity.

The development of tissue engineering and regeneration research has created new platforms for bone transplantation. However, the preparation of scaffolds with good fiber integrity is challenging, because scaffolds prepared by traditional printing methods are prone to fiber cracking during solvent evaporation. Human skin has an excellent natural heat-management system, which helps to maintain a constant body temperature through perspiration or blood-vessel constriction. In this work, an electrohydrodynamic-jet 3D-printing method inspired by the thermal-management system of skin was developed. In this system, the evaporation of solvent in the printed fibers can be adjusted using the temperature-change rate of the substrate to prepare 3D structures with good structural integrity. To investigate the solvent evaporation and the interlayer bonding of the fibers, finite-element analysis simulations of a three-layer microscale structure were carried out. The results show that the solvent-evaporation path is from bottom to top, and the strain in the printed structure becomes smaller with a smaller temperature-change rate. Experimental results verified the accuracy of these simulation results, and a variety of complex 3D structures with high aspect ratios were printed. Microscale cracks were reduced to the nanoscale by adjusting the temperature-change rate from 2.5 to 0.5 °C s−1. Optimized process parameters were selected to prepare a tissue engineering scaffold with high integrity. It was confirmed that this printed scaffold had good biocompatibility and could be used for bone-tissue regeneration. This simple and flexible 3D-printing method can also help with the preparation of a wide range of micro- and nanostructured sensors and actuators.

Summary: Research on returned samples can provide ground truth for the study of the geological evolution history of the Moon. However, previous missions all collected samples from the near side of the Moon, which is significantly different from the far side of the Moon in terms of the thickness of the lunar crust, magma activity, and composition. Therefore, the samples from the far side of the Moon are of great significance for a comprehensive understanding of the history of the Moon. China’s Chang’e-6 (CE-6) probe has successfully landed on the lunar far side and will return samples in the coming days. With the precise location of the CE-6 landing site, a detailed analysis of the geological background is conducted in this research. The landing site of CE-6 is within the Apollo crater, which is inside the largest impact basin on the Moon, i.e., the South Pole-Aitken (SPA) basin. According to the numerical simulation of the formation process of the SPA basin, CE-6 landed at the edge of the SPA impact melting zone, which is presumably composed of impact melt of the lunar mantle. The Apollo crater subsequently excavated deep material again, which constitutes the basement of the CE-6 landing area. Later, erupted basalt covered these basement rocks, and they also constitute the main source of the CE-6 samples. Based on the dating method of crater size-frequency distribution, we find that the basalt is ∼2.50 Ga. The CE-6 samples also possibly contain basement rocks as excavated and ejected by craters, and they can provide crucial information for our understanding of lunar geological history along with the basalt samples.

Background: Reactive oxygen species (ROS), predominantly generated by mitochondria, play a crucial role in the pathogenesis of intervertebral disc degeneration (IVDD). Reduction of ROS levels may be an effective strategy to delay IVDD. In this study, we assessed whether umbilical cord mesenchymal stem cell-exosomes (UCMSC-exos) can be used to treat IVDD by suppressing ROS production caused by mitochondrial dysfunction. Materials and methods: Human UCMSC-exos were isolated and identified. Nucleus pulposus cells (NPCs) were stimulated with H2O2 in the presence or absence of exosomes. Then, 4D label free quantitative (4D-LFQ) proteomics were used to analyze the differentially expressed (DE) proteins. Mitochondrial membrane potential (MMP), mitochondrial ROS and protein levels were determined via immunofluorescence staining, flow cytometry and western blotting respectively. Additionally, high-throughput sequencing was performed to identify the DE miRNAs in NPCs. Finally, therapeutic effects of UCMSC-exos were investigated in a puncture-induced IVDD rat model. Degenerative grades of rat IVDs were assessed using magnetic resonance imaging and histochemical staining. Results: UCMSC-exos effectively improved the viability of NPCs and restored the expression of the extracellular matrix (ECM) proteins, collagen type II alpha-1 (COL2A1) and matrix metalloproteinase-13 induced by H2O2. Additionally, UCMSC-exos not only reduced the total intracellular ROS and mitochondrial superoxide levels, but also increased MMP in pathological NPCs. 4D-LFQ proteomics and western blotting further revealed that UCMSC-exos up-regulated the levels of the mitochondrial protein, mitochondrial transcription factor A (TFAM), in H2O2-induced NPCs. High-throughput sequencing and qRT-PCR uncovered that UCMSC-exos down-regulated the levels of miR-194-5p, a potential negative regulator of TFAM, induced by H2O2. Finally, in vivo results showed that UCMSC-exos injection improved the histopathological structure and enhanced the expression levels of COL2A1 and TFAM in the rat IVDD model. Conclusions: Our findings suggest that UCMSC-exos promote ECM synthesis, relieve mitochondrial oxidative stress, and attenuate mitochondrial dysfunction in vitro and in vivo, thereby effectively treating IVDD. The translational potential of this article: This study provides solid experimental data support for the therapeutic effects of UCMSC-exos on IVDD, suggesting that UCMSC-exos will be a promising nanotherapy for IVDD.

Background: Ketamine, as a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, was originally used in general anesthesia. Epidemiological data show that ketamine has become one of the most commonly abused drugs in China. Ketamine administration might cause cognitive impairment; however, its molecular mechanism remains unclear. The glymphatic system is a lymphoid system that plays a key role in metabolic waste removal and cognitive regulation in the central nervous system. Methods: Focusing on the glymphatic system, this study evaluated the behavioral performance and circulatory function of the glymphatic system by building a short-term ketamine administration model in mice, and detected the expression levels of the 5-HT2c receptor, ΔFosb, Pten, Akt, and Aqp4 in the hippocampus. Primary astrocytes were cultured to verify the regulatory relationships among related indexes using a 5-HT2c receptor antagonist, a 5-HT2c receptor short interfering RNA (siRNA), and a ΔFosb siRNA. Results: Ketamine administration induced ΔFosb accumulation by increasing 5-HT2c receptor expression in mouse hippocampal astrocytes and primary astrocytes. ΔFosb acted as a transcription factor to recognize the AATGATTAAT bases in the 5′ regulatory region of the Aqp4 gene (−1096 bp to −1087 bp), which inhibited Aqp4 expression, thus causing the circulatory dysfunction of the glymphatic system, leading to cognitive impairment. Conclusions: Although this regulatory mechanism does not involve the Pten/Akt pathway, this study revealed a new mechanism of ketamine-induced cognitive impairment in non-neuronal systems, and provided a theoretical basis for the safety of clinical treatment and the effectiveness of withdrawal.

Abstract Excessive osteoclast formation and bone resorption are related to osteolytic diseases. Delta drosophila homolog-like 2 (Dlk2), a member of the epidermal growth factor (EGF)-like superfamily, reportedly regulates adipocyte differentiation, but its roles in bone homeostasis are unclear. In this study, we demonstrated that Dlk2 deletion in osteoclasts significantly inhibited osteoclast formation in vitro and contributed to a high-bone-mass phenotype in vivo. Importantly, Dlk2 was shown to interact with synapse-associated protein 1 (Syap1), which regulates Akt phosphorylation at Ser473. Dlk2 deletion inhibited Syap1-mediated activation of the AktSer473, ERK1/2 and p38 signaling cascades. Additionally, Dlk2 deficiency exhibits increased bone mass in ovariectomized mice. Our results reveal the important roles of the Dlk2-Syap1 signaling pathway in osteoclast differentiation and osteoclast-related bone disorders.

Chang’e-6 (CE-6) is the first sample-return mission from the lunar farside and will be launched in May of 2024. The landing area is in the south of the Apollo basin inside the South Pole Aitken basin. Statistics and analyses of impact craters in the landing area are essential to support safe landing and geologic studies. In particular, the crater size–frequency distribution information of the landing area is critical to understanding the provenance of the CE-6 lunar samples to be returned and can be used to verify and refine the lunar chronology model by combining with the radioisotope ages of the relevant samples. In this research, a digital orthophoto map (DOM) mosaic with resolution of 3 m/pixel of the CE-6 landing area was generated from the 743 Narrow Angle Camera of the Lunar Reconnaissance Orbiter Camera. Based on the DOM, craters were extracted by an automated method and checked manually. A total of 770,731 craters were extracted in the whole area of 246 km × 135 km, 511,484 craters of which were within the mare area. Systematic analyses of the crater distribution, completeness, spatial density, and depth-to-diameter ratio were conducted. Geologic model age estimation was carried out in the mare area that was divided into three geologic units according to the TiO2 abundance. The result showed that the east part of the mare had the oldest model age of μ3.27−0.045+0.036 Ga, and the middle part of the mare had the youngest model age of μ2.49−0.073+0.072 Ga. The crater catalogue and the surface model age analysis results were used to support topographic and geologic analyses of the pre-selected landing area of the CE-6 mission before the launch and will contribute to further scientific researches after the lunar samples are returned to Earth.

Abstract At present, no study has established a survival prediction model for non-metastatic primary malignant bone tumors of the spine (PMBS) patients. The clinical features and prognostic limitations of PMBS patients still require further exploration. Data on patients with non-metastatic PBMS from 2004 to 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate regression analysis using Cox, Best-subset and Lasso regression methods was performed to identify the best combination of independent predictors. Then two nomograms were structured based on these factors for overall survival (OS) and cancer-specific survival (CSS). The accuracy and applicability of the nomograms were assessed by area under the curve (AUC) values, calibration curves and decision curve analysis (DCA). Results: The C-index indicated that the nomograms of OS (C‐index 0.753) and CSS (C‐index 0.812) had good discriminative power. The calibration curve displays a great match between the model’s predictions and actual observations. DCA curves show our models for OS (range: 0.09–0.741) and CSS (range: 0.075–0.580) have clinical value within a specific threshold probability range compared with the two extreme cases. Two nomograms and web-based survival calculators based on established clinical characteristics was developed for OS and CSS. These can provide a reference for clinicians to formulate treatment plans for patients.

Abstract Backgrounds MIR31 host gene (MIR31HG) polymorphisms play important roles in the occurrence of osteonecrosis. However, the association of MIR31HG polymorphisms with the risk of steroid-induced osteonecrosis of the femoral head (SONFH) remains unclear. In this study, we aimed to investigate the correlation between MIR31HG polymorphisms and SONFH susceptibility in the Chinese Han population. Methods A total of 708 volunteers were recruited to detect the effect of seven single nucleotide polymorphisms (SNPs) in the MIR31HG gene on SONFH risk in the Chinese Han population. Genotyping of MIR31HG polymorphisms was performed using the Agena MassARRAY platform. The odds ratio (OR) and 95% confidence interval (95% CI) were used to evaluate the correlation between MIR31HG polymorphisms and SONFH risk using logistic regression model. Results According to the results of genetic model, rs10965059 in MIR31HG was significantly correlated with the susceptibility to SONFH (OR = 0.56, p = 0.002). Interestingly, the stratified analysis showed that rs10965059 was associated with the reduced risk of SONFH in subjects aged > 40 years (OR = 0.30, p

The Moderate Resolution Imaging Camera (MoRIC) onboard the orbiter of China’s Tianwen-1 Mars mission aims to map the surface of Mars globally and to explore its topography and geomorphology. This camera’s wide field of view can be used to overlap adjacent images sufficiently for topographic reconstruction. This study aimed to assess the topographic mapping potential of MoRIC images via a systematic accuracy analysis of MoRIC stereo mapping based on theoretical calculation and experimental validation. Experimental analyses were conducted using digital elevation models (DEMs) based on MoRIC images covering the Zhurong rover landing area and Mars Chart 11 region. Comparisons between these DEMs and reference DEMs revealed that the elevation accuracy of the former was approximately one ground sampling distance of the MoRIC image, which is consistent with the theoretical accuracy. Based on these results, MoRIC can be used to effectively map the Martian surface via stereo photogrammetry. These results serve as a useful guideline for topographic mapping based on MoRIC images and their application in various streams of research.

Stabilizing the purchase cost of metal raw materials is of great significance to the metal manufacturing industry. Most enterprises use futures hedging strategies to cope with the risks arising from fluctuations in the prices of metal raw materials. However, the difference between spot and futures prices of metals makes it impossible to fully control the risk. In order to further improve the efficiency of hedging and controlling corporate risks, it is necessary to accurately predict futures prices. However, the decomposition algorithms in traditional mixed models are prone to modal aliasing and have limited ability to extract nonlinear features from futures prices. Therefore, this paper proposes a variational modal decomposition-sample entropy-Cascaded Long Short-Term Memory Neural Network Model (VMD-SE-CLSTM). This paper proposes SE combined with VMD algorithm to determine the decomposition number to suppress the aliasing phenomenon of subsequence patterns, and introduces CLSTM network to improve the extraction ability of nonlinear features in futures data. The experiments are compared with 10 mainstream model methods and the method proposed in this paper. The experimental results show that the model reduces the prediction error and improves the prediction accuracy of the model, which is of great significance for enterprises to improve hedging efficiency, reduce operating risks and control production costs.

ObjectiveTo detect the influences of postoperative out-of-bed activity restriction on recurrence rate, low back and leg pain, functional rehabilitation after percutaneous endoscopic lumbar discectomy (PELD).MethodsIn this research, 213 patients with lumbar intervertebral disc herniation (LDH) who underwent PELD were divided into the out-of-bed activity restriction group and out-of-bed activity non-restriction group. The visual analog scale (VAS) and Oswestry disability index (ODI) scores were used to evaluate postoperative clinical efficacy at 1 and 3 months after the operation, and to count the recurrence rates. All of these operations were performed between August 2017 and July 2020, and they were followed in the outpatient department for 12 months at least.ResultsBoth of the groups showed significantly lower VAS and higher ODI scores at 1 month and 3 months post-operation, respectively, when compared with pre-operation. At 1 month after the operation, the restriction group performed lower VAS scores of low back pain compared with the non-restriction group, but this advantage disappeared at 3months post-operation. However, there was no statistical difference in the VAS scores of leg pain and ODI scores between the two groups, neither at 1 nor 3 months after the surgery. The recurrence rate is significantly lower in the restriction group than in the non-restriction group at a 12-month follow-up after the surgery.ConclusionOut-of-bed activity restriction in the early postoperative period of PELD could reduce LDH recurrence effectively, and it may relieve the low back pain to some extent. It has no benefit in the recovery of leg pain and functional rehabilitation.

This paper presents a brief overview of the geospatial technologies developed and applied in Chang’e-3 and Chang’e-4 lunar rover missions. Photogrammetric mapping techniques were used to produce topographic products of the landing site with meter level resolution using orbital images before landing, and to produce centimeter-resolution topographic products in near real-time after landing. Visual positioning techniques were used to determine the locations of the two landers using descent images and orbital basemaps immediately after landing. During surface operations, visual-positioning-based rover localization was performed routinely at each waypoint using Navcam images. The topographic analysis and rover localization results directly supported waypoint-to-waypoint path planning, science target selection and scientific investigations. A GIS-based digital cartography system was also developed to support rover teleoperation.

Digital elevation models (DEMs) provide fundamental data for scientific and engineering applications in lunar exploration missions. Lunar DEMs have been mainly generated by laser altimetry and stereophotogrammetry. Complementarity to stereo photogrammetry, reflection-based surface reconstruction methods, such as shape from shading (SFS), have been studied and applied in lunar DEM reconstruction from a single image. However, this method often suffers from solution ambiguity and instability. In this paper, we propose a generative adversarial network (GAN)-based method that is able to generate high-resolution pixel-scale DEMs from a single image aided by a low-resolution DEM. We have evaluated the accuracy of the reconstructed high-resolution DEMs from 25 LROC NAC images of four regions using LROC NAC DEMs (2 m/pixel) as ground truth. The experimental results demonstrate good accuracy and adaptability to changes in illumination conditions. The root mean square error (RMSE) can reach about 2 m in areas where the degree of elevation variation is less than 100 m, and the RMSE value ranges from around 3 m to 10 m without considering the degree of the elevation variation in large-area reconstruction. As high-resolution monocular images and low-resolution DEMs are available for the entire lunar surface, the proposed GAN-based method has great potential in high-resolution lunar DEM reconstruction for lunar mapping applications.

Tianwen-1, China’s first Mars exploration mission, was successfully landed in the southern part of Utopia Planitia on 15 May 2021 (UTC+8). Timely and accurately determining the landing location is critical for the subsequent mission operations. For timely localization, the remote landmarks, selected from the panorama generated by the earliest received Navigation and Terrain Cameras (NaTeCam) images, were matched with the Digital Orthophoto Map (DOM) generated by high resolution imaging camera (HiRIC) images to obtain the initial result based on the triangulation method. Then, the initial localization result was refined by the descent images received later and the NaTeCam DOM. Finally, the lander location was determined to be (25.066°N, 109.925°E). Verified by the new orbital image with the lander and Zhurong rover visible, the localization accuracy was within a pixel of the HiRIC DOM.

Topographic products are important for mission operations and scientific research in lunar exploration. In a lunar rover mission, high-resolution digital elevation models are typically generated at waypoints by photogrammetry methods based on rover stereo images acquired by stereo cameras. In case stereo images are not available, the stereo-photogrammetric method will not be applicable. Alternatively, photometric stereo method can recover topographic information with pixel-level resolution from three or more images, which are acquired by one camera under the same viewing geometry with different illumination conditions. In this research, we extend the concept of photometric stereo to photogrammetric-photometric stereo by incorporating collinearity equations into imaging irradiance model. The proposed photogrammetric-photometric stereo algorithm for surface construction involves three steps. First, the terrain normal vector in object space is derived from collinearity equations, and image irradiance equation for close-range topographic mapping is determined. Second, based on image irradiance equations of multiple images, the height gradients in image space can be solved. Finally, the height map is reconstructed through global least-squares surface reconstruction with spectral regularization. Experiments were carried out using simulated lunar rover images and actual lunar rover images acquired by Yutu-2 rover of Chang’e-4 mission. The results indicate that the proposed method achieves high-resolution and high-precision surface reconstruction, and outperforms the traditional photometric stereo methods. The proposed method is valuable for ground-based lunar surface reconstruction and can be applicable to surface reconstruction of Earth and other planets.

Chang’e-5, China’s first unmanned lunar sample-return mission, was successfully landed in Northern Oceanus Procellarum on 1 December 2020. Determining the lander location precisely and timely is critical for both engineering operations and subsequent scientific research. Localization of the lander was performed using radio-tracking and image-based methods. The lander location was determined to be (51.92°W, 43.06°N) by both methods. Other localization results were compared for cross-validation. The localization results greatly contributed to the planning of the ascender lifting off from the lander and subsequent maneuvers, and they will contribute to scientific analysis of the returned samples and in situ acquired data.

In planetary rover missions, rover path planning is critical to ensure the safety and efficiency of the rover traverse and in situ explorations. In the Chang’e-4 (CE-4) mission, we have proposed and developed vision-based decision support methods comprising obstacle map generation and path evaluation for the rover. At each waypoint along the rover traverse, digital elevation model (DEM) is automatically generated, which is then used for obstacle map generation and path searching. For path evaluation, the searched path and the predicted wheel trajectories are projected onto the original images captured by different cameras to coincide with the real observation scenario. The proposed methods have been applied in the CE-4 mission to support teleoperation of the rover, and examples of multiple applications used in the mission are presented in this paper. Under the support of the proposed techniques, by the end of the 14th lunar day (3 February 2020), the rover has already travelled 367.25 meters on the far side of the Moon.

Structured-light three-dimensional (3D) vision measurement is currently one of the most common approaches to obtain 3D surface data. However, the existing structured-light scanning measurement systems are primarily constructed on the basis of single sensor, which inevitably generates three obvious problems: limited measurement range, blind measurement area, and low scanning efficiency. To solve these problems, we developed a novel 3D wide FOV scanning measurement system which adopted two multiline structured-light sensors. Each sensor is composed of a digital CCD camera and three line-structured-light projectors. During the measurement process, the measured object is scanned by the two sensors from two different angles at a certain speed. Consequently, the measurement range is expanded and the blind measurement area is reduced. More importantly, since six light stripes are simultaneously projected on the object surface, the scanning efficiency is greatly improved. The Multiline Structured-light Sensors Scanning Measurement System (MSSS) is calibrated on site by a 2D pattern. The experimental results show that the RMS errors of the system for calibration and measurement are less than 0.092 mm and 0.168 mm, respectively, which proves that the MSSS is applicable for obtaining 3D object surface with high efficiency and accuracy.

In the study of SLAM problem using an RGB-D camera, depth information and visual information as two types of primary measurement data are rarely tightly coupled during refinement of camera pose estimation. In this paper, a new method of RGB-D camera SLAM is proposed based on extended bundle adjustment with integrated 2D and 3D information on the basis of a new projection model. First, the geometric relationship between the image plane coordinates and the depth values is constructed through RGB-D camera calibration. Then, 2D and 3D feature points are automatically extracted and matched between consecutive frames to build a continuous image network. Finally, extended bundle adjustment based on the new projection model, which takes both image and depth measurements into consideration, is applied to the image network for high-precision pose estimation. Field experiments show that the proposed method has a notably better performance than the traditional method, and the experimental results demonstrate the effectiveness of the proposed method in improving localization accuracy.