Abstract
Little is known about the transcriptomic plasticity and adaptive mechanisms of circulating tumor cells (CTCs) during hematogeneous dissemination. Here we interrogate the transcriptome of 113 ...single CTCs from 4 different vascular sites, including hepatic vein (HV), peripheral artery (PA), peripheral vein (PV) and portal vein (PoV) using single-cell full-length RNA sequencing in hepatocellular carcinoma (HCC) patients. We reveal that the transcriptional dynamics of CTCs were associated with stress response, cell cycle and immune-evasion signaling during hematogeneous transportation. Besides, we identify chemokine CCL5 as an important mediator for CTC immune evasion. Mechanistically, overexpression of CCL5 in CTCs is transcriptionally regulated by p38-MAX signaling, which recruites regulatory T cells (Tregs) to facilitate immune escape and metastatic seeding of CTCs. Collectively, our results reveal a previously unappreciated spatial heterogeneity and an immune-escape mechanism of CTC, which may aid in designing new anti-metastasis therapeutic strategies in HCC.
Carbon coated Si core–shell structures have been proposed to solve the adverse effects of Si-based anode. However, designing ideal core–shell architecture with excellent surface and interface ...properties is still a significant challenge. Herein, a novel peanut-like structure of B-doped silicon/carbon nanoparticle (Si@B-C) synthesized by sol–gel process and subsequent thermal reduction is reported. The peanut-like Si@B-C electrode demonstrates a superior cyclability of 534 mAh·g
−1
after 1000 cycles at high current density of 1000 mA·g
−1
. The exceptional electrochemical performance is attributed to the boric acid-induced highly interconnected peanut-like structure and boron heteroatom framework could provide a continuous electron pathway to reduce the irreversible lithium ion loss during rapid cycling. This work provides insight into the development of the heteroatom-doped Si-based anodes with stable cycling performance for LIBs.
Introduction
With the wide application of Scutellaria barbata D. Don for hepatitis and mastitis, its quality control issues have also received increasing attention. Based on the multi‐component and ...multi‐target characteristics of traditional Chinese medicine, there is an urgent need to establish a quality evaluation system.
Objectives
This study intends to integrate the “quality–activity–quantification” strategy and establish an activity‐related quality control method to ensure the safety and effectiveness of S. barbata.
Material and methods
Ultra‐high performance liquid chromatography/ion mobility–quadrupole time‐of‐flight mass spectrometry (UPLC/IM‐QTOF‐MS) was used to characterize the chemical components of S. barbata, and network pharmacological analysis was carried out on the identified components. The index components were determined on the basis of comprehensive activity prediction results and content information. At the same time, the contents of 16 batches of S. barbata from different origins were determined.
Results
A total of 94 compounds were identified according to mass spectrometric data, 12 of which were isolated and structure‐confirmed by nuclear magnetic resonance technology. Network pharmacological analysis was applied to predict their key targets and the major pathways mediating their anti‐inflammatory effects. On the basis of comprehensive activity prediction and content information, five components were chosen as crucial quality indicators of S. barbata, including scutellarin, scutellarein, luteolin, apigenin, and hispidulin.
Conclusion
In this study, 16 different S. barbata batches were compared, and five quality indicators were determined on the basis of qualitative and activity results. The present study provides useful information for evaluating the quality of S. barbata in different areas, and also provides a new basis for the development of quality evaluation methods.
A strategy combined chemical profiling and network pharmacology analysis for quality control of S. barbata. A total of 93 compounds were speculated by UPLC/IM‐QTOF‐MS. Five components were determined as quality indicators of S. barbata anti‐inflammation activities.
Odoroside A (OA) is an active ingredient extracted from the leaves of Nerium oleander Linn. (Apocynaceae). This study aims to examine the anticancer bioactivity of OA against CRC cells and to ...investigate the action mechanisms involved. As a result, OA can significantly inhibit cellular ability and induce apoptosis of CRC cells in a concentration‐dependent manner without any obvious cytotoxicity in normal colorectal epithelial cells. Then, quantitative proteomics combined with bioinformatics is adopted to investigate the alterations of proteins and signaling pathways in response to OA treatment. As suggested by the proteomic analysis, flow cytometry and Western blotting analyses validate that exposure of CRC cells to OA causes cell cycle arrest and apoptosis, accompanied with the activation of the ROS/p53 signaling pathway. This observation demonstrates that OA, as a natural product, can induce oxidative stress to suppress tumor cell growth, implicating a novel therapeutic agent against CRC without obvious side effects.
Caudal autotomy is a phenomenon observed in many reptile taxa, and tail loss is a pivotal functional trait for reptiles, with potentially negative implications for organism fitness due to its ...influence on locomotion. Some lizard species can regenerate a lost tail, which sometimes can lead to the development of more than one tail (i.e., abnormal tail regeneration) in the process. However, little is currently known about the impact of abnormal tail regeneration on locomotor performance. In this study, we document abnormal tail regeneration in Eremias yarkandensis, a reptile species native to northwestern China. Additionally, we investigated the sprint speed and endurance performance of these lizards. This study provides the first report on abnormal tail regeneration and its locomotor performance on a Chinese reptile. We suggest that the abnormal regeneration of tails may contribute to the accumulation of food reserves in the species. In light of our findings, we propose that herpetologists continue to share their sporadic observations and assess the locomotor performance of species experiencing abnormal tail regeneration, further expanding our understanding of this intriguing phenomenon.
Little is currently known about the impact of abnormal tail regeneration on locomotor performance. In this study, we document abnormal tail regeneration in Eremias yarkandensis, a reptile species native to northwestern China.
Introduction
Alkaloids exist in various herbal medicine widely and exhibit diverse biological and pharmacological activities. p‐Sulphonatocalix6arenes (SC6A) and p‐sulphonatocalix8arenes (SC8A) are ...water‐soluble supramolecular macrocycles and are applied to the extraction of alkaloids from herbal products.
Objective
In this study, an innovative method of SC6A/SC8A assisted extraction of the alkaloids from herbs was established.
Methods
SC6A and SC8A were designed to extract 27 alkaloids from seven herbal medicines. Based on the significant solubilisation and extraction effect, Stephaniae Tetrandrae Radix (Fangji, FJ) was selected to obtain the optimal extraction process by adopting single factor test and orthogonal experiment. Then, the alkaloids and SC6A/SC8A were separated by one‐step alkalisation and SCnA were reused. The host–guest complexes between alkaloids and SCnA were determined by competitive fluorescence titration, differential scanning calorimetry (DSC), Fourier‐transform infrared (FTIR) and proton nuclear magnetic resonance (1H‐NMR) analysis.
Results
The optimum condition for SC6A assisted extraction was 5:1:80 (g/g/mL) for herbs/SC6A/solution ratio, 355–250 μm particle size and ultrasonicate 0.5 h, whilst 10:1:40 (g/g/mL) for herbs/SC8A/solution ratio, 355–250 μm particle size and ultrasonicate 0.5 h for SC8A assisted extraction. The total yield of alkaloids (fangchinoline and tetrandrine) from FJ was increased by 4.87 times and 5.97 times with SC6A and SC8A. Moreover, a good reusability of SC6A/SC8A was achieved by alkalisation dissociation. Host–guest complexes were determined by competitive fluorescence titration at a molar ratio of 1:1 between most alkaloids (25/27, except evodiamine and rutaecarpine) and SC6A/SC8A. The complex structure was proved by DSC, FTIR and 1H‐NMR analysis.
Conclusion
The study provided an effective eco‐friendly and energy‐saving extraction method of alkaloids from herbal medicine.
In this study, an innovative method of p‐sulphonatocalix6arenes (SC6A) and p‐sulphonatocalix8arenes (SC8A) assisted extraction alkaloids from herbs was established. Stephaniae Tetrandrae Radix was selected to obtain the optimal extraction processing by adopting single factor test and orthogonal experiment. Alkaloids and SC6A/SC8A were separated by one‐step alkalization and SCnA were reused. Host–guest complexes were determined by competitive fluorescence titration at a molar ratio of 1:1 between most alkaloids and SC6A/SC8A. The complex structure was proved by DSC, FT‐IR, and 1H‐NMR analysis.
In this paper, we consider a cellular downlink multiple-input-single-output (MISO) nonorthogonal multiple access (NOMA) secure transmission system, where users are grouped as multiple clusters. Each ...cluster consists of a central user and a cell-edge user. The central user is an entrusted user, and the cell-edge user is a potential eavesdropper. We focus on the secure beamforming and power allocation design optimization problem which maximizes the sum achievable secrecy rate of central users subject to the transmit power constraint at the base station and transmission rate requirements at cell-edge users. The problem is nonconvex because of coupling optimization variables in the considered fractional quadratically constrained quadratic programming. We propose an alternating optimization-based solution and a constrained concave-convex procedure-based solution to the considered problem. Simulation results demonstrate that our proposed NOMA schemes outperform the conventional orthogonal multiple access scheme.
•Structural characterization of two polysaccharides from Dendrobium officinale were described.•DOP performed the hypoglycemic activity via stimulating GLP-1 secretion in STZ-induced diabetic rats and ...STC-1 cells.•Ca2+/CaM/CaMKII and MAPK pathways might involve in the intracellular DOP-induced GLP-1 secretion.•The repeated unit of backbone of DOP-1 and DOP-2 might be the effective unit of DOP-induced GLP-1 secretion.
Two polysaccharides, named DOP-1 and DOP-2, with molecular weights of 6.8 kDa and 14.3 kDa, respectively, were isolated and purified from the stems of Dendrobium officinale. Monosaccharide composition, Fourier-transform infrared spectroscopy, methylation, and nuclear magnetic resonance analyses indicated that DOP-1 and DOP-2 may have a backbone consisted of →4)-β-d-Glcp-(1→, →4)-β-d-Manp-(1→, →4)-2-O-acetyl-β-d-Manp-(1→ and →4)-3-O-acetyl-β-d-Manp-(1→. In vivo assays showed that D. officinale polysaccharides (DOPs) exerted significant hypoglycemic effects accompanying increased serum insulin and glucagon-like peptide-1 (GLP-1) levels in streptozotocin-induced diabetic rats. Further in vitro experiments showed that DOP-induced GLP-1 secretion was inhibited by an intracellular calcium chelator, a Ca2+/calmodulin-dependent protein kinase (CaMK) II inhibitor, a specific calcium-sensing receptor antagonist, and a p38-mitogen-activated protein kinases (MAPK) inhibitor. These results indicated that DOPs may decrease fasting blood sugar levels by stimulating GLP-1 secretion and that intracellular DOP-induced GLP-1 secretion involved the Ca2+/calmodulin/CaMKII and MAPK pathways.
A novel polysaccharide (MSP-1) was isolated from the fruiting body of Morchella sextelata and purified using DEAE-52 and Sephadex G-75. The molecular weight of MSP-1 was 1.17 × 104 Da, as detected by ...HPLC analysis. The monosaccharide composition of MSP-1 was mannose and glucose at a ratio of 1.00: 1.25. Methylation and NMR results revealed that the backbone of MSP-1 was composed of →4)-β-D-Manp-(1→, →4)-β-D-Glcp-(1→, →4)-α-D-Glcp-(1→, and →4, 6)-α-D-Glcp-(1→. SEM images of MSP-1 presented a dense network structure with porous characterizations. The immunomodulatory activities of MSP-1 were evaluated using RAW264.7 cells, and the results showed that MSP-1 promoted proliferative and phagocytic activity and increased the production of NO, TNF-α and IL-6. These results indicated that MSP-1 exhibited significant immunomodulatory activities.
•A novel heteropolysaccharide (MSP-1) was purified from the fruiting body of Morchella sextelata.•The complete structure of M. sextelata polysaccharide was exhibited for the first time in the present study.•The 3D structure of MSP-1 presented a dense network structure with porous characterizations.•MSP-1 exhibited strong immunomodulatory activities by promoting proliferative and phagocytic activity and obviously increasing the production of NO, TNF-α and IL-6 on RAW264.7 cells.
Nerigoside (NG), a cardenolide isolated from a commonfolk medicine, Nerium oleander Linn. (Apocynaceae), has not been explored for its biological effects. To date, cardenolides have received ...considerable attention in pharmacology studies due to their direct effects of apoptosis-induction or growth-inhibitory against tumor in vitro and in vivo. Whether and how NG exerts anticancer effects against colorectal cancer remains to be elucidated.
The aim of this study was to investigate the anticancer effect of NG in human colorectal cancer cells.
To test anticancer effect, we compared potency of NG in two colorectal cancer cell lines, HT29 and SW620 by WST-1 and colony proliferation assays. And we investigated mechanism of anticancer activities by analyzing players in apoptotic and ERK/GSK3β/β-catenin signaling pathways in HT29 and SW620 cells treated with NG.
In this study, we showed that NG markedly suppressed the cell viability and colony formation of colorectal cancer cells HT29 and SW620, with no significant toxic effect on non-cancer cells NCM460. Annexin V-FITC/PI and CFSE labeling results revealed that NG suppressed cell proliferation in low concentration, along with reducing expression of PCNA, while NG induced apoptosis in high concentration,. Meanwhile, NG significantly arrested cell migration by reversal of EMT and cell cycle on G2/M. Then, we found that the ERK and GSK3β/β-catenin signaling pathway were noticeably blocked in CRC cells after treatment with NG. According to western blot, NG upregulated the expression of p-GSK3β/GSK3β and decreased especially the expression of β-catenin in nuclear. In addition, Wnt signaling and its target genes were suppressed in response to NG. Then, the Ser9 phosphorylation of GSK3β can be reduced / raised by GÖ 6983 / LiCl, respectively. Thus, we further confirmed that the GSK3β/β-catenin axis is involved in NG-prevented cell proliferation.
NG inhibited the growth of colorectal cancer cells by suppressing ERK/GSK3β/β-catenin signaling pathway. And the GSK3β/β-catenin axis is involved in preventing cell proliferation and migration by NG-treatment. These results suggest that NG may be used to treat colorectal cancer, with better outcome by combining with GSK3β inhibitor to block Wnt pathway.
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