Structural characterization and immunostimulant activities of polysaccharides fractionated by gradient ethanol precipitation method from Panax ginseng C. A. Meyer.

Panax ginseng C. A. Meyer is a dual-purpose plant for medicine and food, its polysaccharide is considered as an immune enhancer. Four polysaccharides, WGP-20-F, WGP-40-F, WGP-60-F and WGP-80-F were obtained from ginseng via water extraction and gradient ethanol precipitation with different molecular weights (Mw) of 1.720 × 106, 1.434 × 106, 4.225 × 104 and 1.520 × 104 Da, respectively. WGP-20-F and WGP-40-F which with higher Mw and a triple-helix structure are glucans composed of 4-ɑ-Glcp, do not show remarkable immunoregulatory effects. WGP-60-F and WGP-80-F are heteropolysaccharides mainly composed of 4-ɑ-Glcp and also contain t-ɑ-Araf, 5-ɑ-Araf and 3,5-ɑ-Araf. They are spherical branched conformations without a triple-helix structure and can effectively increase the index of immune organs, lymphocyte proliferation, activate macrophages to regulate the immune system in mice and further enhance immune functions by improving delayed-type hypersensitivity reaction and antibody response. These results indicated that WGP-60-F and WGP-80-F could be used as potential immune enhancers, and gradient ethanol precipitation can be applied for the preparation of ginseng bioactive polysaccharide.

Non-rigid scene reconstruction of deformable soft tissue with monocular endoscopy in minimally invasive surgery.

PURPOSE: The utilization of image-guided surgery has demonstrated its ability to improve the precision and safety of minimally invasive surgery (MIS). Non-rigid scene reconstruction is a challenge in image-guided system duo to uniform texture, smoke, and instrument occlusion, etc. METHODS: In this paper, we introduced an algorithm for 3D reconstruction aimed at non-rigid surgery scenes. The proposed method comprises two main components: firstly, the front-end process involves the initial reconstruction of 3D information for deformable soft tissues using embedded deformation graph (EDG) on the basis of dual quaternions, enabling the reconstruction without the need for prior knowledge of the target. Secondly, the EDG is integrated with isometric nonrigid structure from motion (Iso-NRSFM) to facilitate centralized optimization of the observed map points and camera motion across different time instances in deformable scenes. RESULTS: For the quantitative evaluation of the proposed method, we conducted comparative experiments with both synthetic datasets and publicly available datasets against the state-of-the-art 3D reconstruction method, DefSLAM. The test results show that our proposed method achieved a maximum reduction of 1.6 mm in average reconstruction error compared to method DefSLAM across all datasets. Additionally, qualitative experiments were performed on video scene datasets involving surgical instrument occlusions. CONCLUSION: Our method proved to outperform DefSLAM on both synthetic datasets and public datasets through experiments, demonstrating its robustness and accuracy in the reconstruction of soft tissues in dynamic surgical scenes. This success highlights the potential clinical application of our method in delivering surgeons with critical shape and depth information for MIS.

Design, synthesis, and biological evaluation of a series of indolone derivatives as novel FLT3 inhibitors for the treatment of acute myeloid leukemia.

FLT3-ITD mutant has been extensively studied as a drug discovery target for acute myeloid leukemia. Based on our previous discovered FLT3 inhibitor (2), a series of urea group based indolone derivatives were designed, synthesized, and biological evaluated as novel FLT3 inhibitors for the treatment of FLT3-ITD positive AML. Among them, compound LC-3 exhibited potent inhibitory effects against FLT3 (IC50 = 8.4 nM) and significantly inhibited the proliferation of FLT3-ITD positive AML cells MV-4-11 (IC50 = 5.3 nM). In the cellular context, LC-3 strongly inhibited FLT3-mediated signaling pathways and induced cellular apoptosis by arresting cell cycle in G1 phase. In the in vivo studies, LC-3 significantly suppressed the tumor growth on MV-4-11 xenograft models (10 mg/kg/day, TGI = 92.16%) without exhibiting obvious toxicity. These results suggested that compound LC-3 might be a potential drug candidate for FLT3-ITD positive AML.

Application of UPLC-Orbitrap-HRMS targeted metabolomics in screening of allelochemicals and model plants of ginseng.

Continuous cropping of ginseng leads to serious declines in yield and quality because of self-toxicity of allelochemicals and other factors in soil. However, because of the long growth cycle and low survival rate of ginseng, rapid screening of autotoxic activity is difficult. Therefore, it is important to analyze the allelochemicals and identify a model plant with autotoxic responses similar to those of ginseng. In this study, UPLC-Orbitrap-HRMS targeted metabolomics and verification of autotoxic activity were used to analyze a problem soil from continuously cropped ginseng. Allelochemical markers were screened by OPLS-DA. Seeds and seedlings of maize, Chinese cabbage, cucumber, green beans, wheat, sunflower, and oats were selected to identify potential model plants. Model plants with autotoxic responses similar to those of ginseng were evaluated by comparing morphological, physiological, and biochemical characteristics. The n-butanol extract of the continuously cropped problem soil had the most significant autotoxic activity. Twenty-three ginsenosides and the contributions to autotoxic effects were screened and evaluated. Of potential model plants, seeds and seedlings of cucumber showed similar growth inhibition to that of ginseng under the action of allelochemicals. Thus, metabolomics can be used to screen allelochemicals in soil and predict the autotoxic effects, and the cucumber plant model can be used to rapidly screen allelopathic activity of ginseng. The study will provide reference for methodology in allelopathy research on ginseng.

Comparative Study on Chemical Constituents of Ginseng Flowers with Four Consecutive Cultivation Age.

The harvest period of cultivated ginseng is generally 4-6 years. Ginseng flowers (GFs), the nonmedicinal parts, are usually removed every autumn, in which components are generally believed to stay unchanged with the increasing cultivation age. Recently, few documents were reported on the variation of volatile organic compounds (VOCs) and other components about ginseng flowers. This study had an insight into the variation of the chemical constituents with the cultivation ages through the comparison of the volatile organic compounds, gross ginsenosides, crude polysaccharide, and gross proteins of ginseng flowers from 3-, 4-, 5-, and 6-yr-old (GF3, GF4, GF5, and GF6) which were conducted by headspace solid-phase microextraction-gas chromatography-triple quadrupole mass spectrometry (HS-SPME-GC-QQQ/MS) and spectroscopic analysis combined with multivariate statistical analysis, including one-way ANOVA analysis and T test. The results indicated that the crude polysaccharide contents raised significantly depending on cultivation age except 6-yr-old, whereas the gross ginsenosides and the gross protein content were indistinctive. According to the peak intensity of determined VOCs, the contents of most differential compounds arranged in an order from high to low are GF3, GF4, GF5, and GF6, such as the compounds 2-15, 17-19, 22, and 25-26, therefore, they can be inferred that they are important markers to identify the age of GFs. 461 common differential compounds were gained and 26 common volatile organic compounds were identified with RSI >800 and RI and RIx no more than 30, including alcohols (such as 11, 12, and 15), sesquiterpenes (such as 2, 3, and 4), esters (such as 1 and 26), naphthalene and naphthol (such as 7 and 20), which had potential effects on curing Alzheimer's disease, inflammatory diseases, and prostate cancer based on network pharmacology analysis. This paper firstly revealed the variation rules of constitutions of GFs, which may provide a reference for the harvest and making rational application.

Single-cell transcriptome reveals core cell populations and androgen-RXFP2 axis involved in deer antler full regeneration.

Deer antlers constitute a unique mammalian model for the study of both organ formation in postnatal life and annual full regeneration. Previous studies revealed that these events are achieved through the proliferation and differentiation of antlerogenic periosteum (AP) cells and pedicle periosteum (PP) cells, respectively. As the cells resident in the AP and the PP possess stem cell attributes, both antler generation and regeneration are stem cell-based processes. However, the cell composition of each tissue type and molecular events underlying antler development remain poorly characterized. Here, we took the approach of single-cell RNA sequencing (scRNA-Seq) and identified eight cell types (mainly THY1+ cells, progenitor cells, and osteochondroblasts) and three core subclusters of the THY1+ cells (SC2, SC3, and SC4). Endothelial and mural cells each are heterogeneous at transcriptional level. It was the proliferation of progenitor, mural, and endothelial cells in the activated antler-lineage-specific tissues that drove the rapid formation of the antler. We detected the differences in the initial differentiation process between antler generation and regeneration using pseudotime trajectory analysis. These may be due to the difference in the degree of stemness of the AP-THY1+ and PP-THY1+ cells. We further found that androgen-RXFP2 axis may be involved in triggering initial antler full regeneration. Fully deciphering the cell composition for these antler tissue types will open up new avenues for elucidating the mechanism underlying antler full renewal in specific and regenerative medicine in general.

By-Product of the Red Ginseng Manufacturing Process as Potential Material for Use as Cosmetics: Chemical Profiling and In Vitro Antioxidant and Whitening Activities.

Red ginseng (RG), which is obtained from heated Panax ginseng and is produced by steaming followed by drying, is a valuable herb in Asian countries. Steamed ginseng dew (SGD) is a by-product produced in processing red ginseng. In the present study, phytochemical profiling of extracts of red ginseng and steamed ginseng dew was carried out using gas chromatography-mass spectrometry (GC-MS) and rapid resolution liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (RRLC-Q-TOF-MS) analysis. Additionally, antioxidant activities (DPPH, ·OH, and ABTS scavenging ability) and whitening activities (tyrosinase and elastase inhibitory activity) were analyzed. Phytochemical profiling revealed the presence of 66 and 28 compounds that were non-saponin components in chloroform extracts of red ginseng and steamed ginseng dew (RG-CE and SGD-CE), respectively. Meanwhile, there were 20 ginsenosides identified in n-butanol extracts of red ginseng and steamed ginseng dew (RG-NBE and SGD-NBE). By comparing the different polar extracts of red ginseng and steamed ginseng dew, it was found that the ethyl acetate extract of red ginseng (RG-EAE) had the best antioxidant capacity and whitening effect, the water extract of steamed ginseng dew (SGD-WE) had stronger antioxidant capacity, and the SGD-NBE and SGD-CE had a better whitening effect. This study shows that RG and SGD have tremendous potential to be used in the cosmetic industries.

96-well plate format in conjunction with ultra-high-performance liquid chromatography coupled to orbitrap mass spectrometry for high-throughput screening protein binders from ginseng.

Conventional strategies for screening of protein binders cannot be used for complicated samples such as ligand libraries created by combinatorial chemistry or from natural product extracts. In the current study, we developed a novel method in a competitive binding configuration for screening protein binders from complicated samples by a combination of streptavidin-coated 96-well plate format in conjunction with ultra-high-performance liquid chromatography coupled with Orbitrap mass spectrometry (UHPLC-Orbitrap-MS). The concanavalin A (Con A) modified 96-well plate and lysozyme modified 96-well plate (as control) were incubated with oligosaccharide standards respectively, and the compounds with the decreased peak areas in experimental group compared to those in the control group were detected as binders by UHPLC-ESI-MS. The factors such as incubation time, incubation temperature, and buffer, which might affect the binding affinity and reproducibility were optimized. The potential of the approach is examined using the extracts of Radix ginseng cruda and American ginseng. The relative binding degrees (RBDs) of the detected disaccharides were relatively high in the extracts of Radix ginseng cruda, and those of the trisaccharides were similar in the extracts of the two kinds of ginseng. To our knowledge, it's the first time to reveal the differences and analogies in lectin peanut agglutinin (PNA)-binding capabilities of oligosaccharides between the extracts of radix ginseng cruda and American ginseng, indicating the efficiency of the method for analysis of complicated samples.

Simultaneous Quantification of Four Ginsenosides in Rat Plasma and Its Application to a Comparative Pharmacokinetic Study in Normal and Depression Rats Using UHPLC-MS/MS.

A sensitive method has been developed for simultaneous determination of ginsenoside Rh1 (G-Rh1), ginsenoside Rb1 (G-Rb1), ginsenoside Rc (G-Rc), and ginsenoside Rd (G-Rd) in rat plasma of normal and depression model group after oral administration of their solutions by using Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-QQQ-MS). The biological samples were prepared by protein precipitation. Ginsenoside Rg3 (G-Rg3) was used as an internal standard (IS). MS analysis was performed under the multiple reaction monitoring (MRM) with electron spray ionization (ESI) operated in the negative mode. The method showed good linearity over a wide concentration range (R 2 > 0.999) and obtained lower limits of quantification (LLOQ) of 5 ng/mL. The whole analysis procedure could be completed in as short as 16.5 min. The intraday precisions, interday precisions, and stabilities were less than 10%. The extraction recoveries from rat plasma were exceeded 86.0%. The results indicated that there were significant differences between the two groups on pharmacokinetics parameters; the absorptions of four analytes in the depression group were higher than those in the normal group because the liver metabolism and internal environment of the model rats had been affected.

Automatic skull defect restoration and cranial implant generation for cranioplasty.

A fast and fully automatic design of 3D printed patient-specific cranial implants is highly desired in cranioplasty - the process to restore a defect on the skull. We formulate skull defect restoration as a 3D volumetric shape completion task, where a partial skull volume is completed automatically. The difference between the completed skull and the partial skull is the restored defect; in other words, the implant that can be used in cranioplasty. To fulfill the task of volumetric shape completion, a fully data-driven approach is proposed. Supervised skull shape learning is performed on a database containing 167 high-resolution healthy skulls. In these skulls, synthetic defects are injected to create training and evaluation data pairs. We propose a patch-based training scheme tailored for dealing with high-resolution and spatially sparse data, which overcomes the disadvantages of conventional patch-based training methods in high-resolution volumetric shape completion tasks. In particular, the conventional patch-based training is applied to images of high resolution and proves to be effective in tasks such as segmentation. However, we demonstrate the limitations of conventional patch-based training for shape completion tasks, where the overall shape distribution of the target has to be learnt, since it cannot be captured efficiently by a sub-volume cropped from the target. Additionally, the standard dense implementation of a convolutional neural network tends to perform poorly on sparse data, such as the skull, which has a low voxel occupancy rate. Our proposed training scheme encourages a convolutional neural network to learn from the high-resolution and spatially sparse data. In our study, we show that our deep learning models, trained on healthy skulls with synthetic defects, can be transferred directly to craniotomy skulls with real defects of greater irregularity, and the results show promise for clinical use. Project page: https://github.com/Jianningli/MIA.

Low Molecular Weight Oligosaccharide from Panax ginseng C.A. Meyer against UV-Mediated Apoptosis and Inhibits Tyrosinase Activity In Vitro and In Vivo.

To find new anti-UV and whitening agents, 21 fractions isolated from three preparations of ginseng (white, red, and black ginseng) were screened, and their antioxidant effects on AAPH- or H2O2-induced damage were investigated. Furthermore, the protective effect against UV-mediated apoptosis and the tyrosinase inhibitory activity of the targeted fractions were evaluated in vitro and in a zebrafish model. Among all fractions, F10 from white ginseng was selected as having the strongest anti-UV and antimelanogenesis activities. This fraction exhibited excellent inhibitory effects on the pigmentation of zebrafish, which may be due to its potential tyrosinase inhibitory activity. Additionally, the chemical composition of F10 was evaluated by UPLC-MS and NMR instruments. The results indicated that F10 had a carbohydrate content of more than 76%, and the weight-average molecular weight was approximately 239 Da. Disaccharide sucrose was the main active compound in F10. These results suggest that F10 could be used as an ingredient for whitening cosmetics and regarded as an anti-UV filter in the future.

The development of computer-aided patient-specific template design software for 3D printing in cranio-maxillofacial surgery.

BACKGROUND: The patient-specific templates for osteotomy often have complex surface features. Using current commercial software to design such templates is quite complicated, tedious and unrepeatable. AIMS: In this study, a novel surgical planning system for oral and maxillofacial surgery named EasyTemplate is developed, aiming to help doctors shorten the modelling time and assure the reliability in template design. MATERIALS & METHODS: In the simplified design process of an osteotomy guide, the main template can be formed efficiently using a surface offsetting algorithm, which is based on isosurface extraction and oriented bounding box. Thereafter, the cutting grooves can be generated automatically. RESULTS: A complicated surgical guide could be built accurately in about 10 min. Clinical orthognathic cases were conducted successfully using osteotomy and repositioning templates designed by EasyTemplate. DISCUSSION: Compared with commercially available softwares, higher efficiency and simpler design process were achieved, moreover, the time cost is one-third or even less. CONCLUSION: EasyTemplate can be a useful alternative to traditional softwares. This software allows the auto-generation algorithm which helps avoid a tedious modeling process while providing basic shapes for designers.

Computer-aided porous implant design for cranio-maxillofacial defect restoration.

The porous structure of the implant contributes significantly to prosthetic osseointegration in cranio-maxillofacial defect repair surgeries. This study establishes a system called EasyImplant that can easily and efficiently design customized cranio-maxillofacial implant with porous structure. Healthy side of the skull model is used to obtain the initial implant model on defective side by mirroring method. According to the curvature of undamaged surface, the initial model can be adjusted and repaired. Based on the initial implant model, porous implant structure can be generated efficiently using create sample points, distance Field and marching Cube algorithms. Finally, the connection plate is obtained through surface extruding and model merging. With EasyImplant, a complete porous implant model can be designed in a short time. The proposed methods can contribute to shorten the period of facial implant designing and reduce the incidence of surgical infection.

A review on computer-aided design and manufacturing of patient-specific maxillofacial implants.

Introduction: Various prefabricated maxillofacial implants are used in the clinical routine for the surgical treatment of patients. In addition to these prefabricated implants, customized CAD/CAM implants become increasingly important for a more precise replacement of damaged anatomical structures. This paper reviews the design and manufacturing of patient-specific implants for the maxillofacial area.Areas covered: The contribution of this publication is to give a state-of-the-art overview in the usage of customized facial implants. Moreover, it provides future perspectives, including 3D printing technologies, for the manufacturing of patient-individual facial implants that are based on patient's data acquisitions, like Computed Tomography (CT) or Magnetic Resonance Imaging (MRI).Expert opinion: The main target of this review is to present various designing software and 3D manufacturing technologies that have been applied to fabricate facial implants. In doing so, different CAD designing software's are discussed, which are based on various methods and have been implemented and evaluated by researchers. Finally, recent 3D printing technologies that have been applied to manufacture patient-individual implants will be introduced and discussed.

miR-522 facilitates the prosperities of endometrial carcinoma cells by directly binding to monoamine oxidase B.

It is well known that microRNAs (miRNAs) are crucial regulatory factors in tumorigenesis, as tumor suppressors or cancer-promoting factors. However, the study of endometrial carcinoma relevance in miR-522 is rare, indicating an undefined molecular mechanism for its role. Therefore, we performed this study to examine the role of miR-522 on the biological behaviors of endometrial carcinoma. In this work, we found that miR-522 was highly expressed in endometrial carcinoma and negatively regulated monoamine oxidase B (MAOB) expression. They also have the opposite effect on prognosis of endometrial carcinoma patients. More importantly, miR-522 could decreased MAOB expression by binding to MAOB with a putative site, thereby promoting cell proliferation, migration, and invasion through in vitro functional analyses, including MTT assay, wound-healing and transwell invasion experiments. Upregulation of MAOB rescued the impacts of miR-522 mimic on cell behaviors. In conclusion, our observations demonstrated that miR-522 accelerated the progression of endometrial carcinoma by inhibiting MAOB, which might lead to a novel therapeutic therapy for endometrial carcinoma.