Insight into the Types of Alkanolamines on the Properties of Copper(II) Formate-Based Conductive Ink.

Conductive inks are one of the most important functional materials for printed flexible electronic devices, and their properties determine the methods of subsequent patterning and metallization. In comparison with copper nanoparticle or nanowire inks, copper particle-free inks employing copper(II) formate (Cuf) as a precursor have attracted the interest of researchers due to their flexibility in preparation, excellent stability, and lower conversion temperature. Alkanolamines can provide Cuf with excellent solubility in alcohols while being less toxic and having a certain reducibility, making them preferable ligands in comparison with aliphatic amines and pyridine. However, there have been few studies on the effects of the alkanolamine types on the performance of Cuf inks. Also, the decomposition mechanism of copper-alkanolamine complex inks is not clear. In this work, different kinds of alkanolamines were chosen as ligands to formulate Cuf inks to address the mentioned issues. The influences of amine types on the stability, wettability, thermal decomposition behavior, and electrical performance of the formulated Cuf particle-free inks were investigated in detail. The results show that the utilization of alkanolamines could provide Cuf with excellent solubility in alcohols, resulting in an ink with good stability and favorable wetting properties. The thermal decomposition temperature and electrical performance of the formulated copper ink are largely dependent on the amine used. When amines with a longer carbon chain and more branches were utilized to prepare the ink, a decreased decomposition temperature was observed on the derived inks because of the steric hindrance effect. Copper films with good morphology and conductivity could be obtained at low temperatures by selecting the appropriate alkanolamine. Copper particle-free conductive ink from 2-amino-2-methyl-1-propanol demonstrated better morphology and electrical performance (16.09 µΩ·cm) and was successfully used for conductive circuits by direct-writing.

[Effect of Neodymium-Doped Yttrium Aluminum Garnet Laser Combined With Desensitizing Toothpaste on Dentinal Tubule Occlusion Against Acid Challenge].

Objective To assess the effects of different application sequences of neodymium-doped yttrium aluminum garnet(Nd∶YAG)laser and the desensitizing toothpaste containing stannous fluoride on dentinal tubule occlusion.Methods Twelve intact third molars freshly extracted from human were selected and prepared into dentin slices with a thickness of 0.8 mm.Each dentin slice was subdivided into four small slices,three of which were etched with 6% citric acid and randomly assigned to the following three groups(n=12):(1)control group:no treatment;(2)Nd∶YAG+toothbrushing(TB)group:first irradiated with Nd∶YAG laser and then brushed with desensitizing toothpaste;(3)TB+Nd∶YAG group:first brushed with desensitizing toothpaste and then irradiated with Nd∶YAG laser.The Nd∶YAG laser irradiation were carried out at 1 W,15 pulses/s,and the pulse width of 150 µs for 10 s(for a total of 6 cycles).After the above treatment,the 12 dentin slices from the Nd∶YAG+TB and TB+Nd∶YAG groups were randomly assigned to four subgroups(n=3)and subjected to acid etching in the Coca-Cola solution for 0,5,10,and 15 min.A scanning electron microscope was used to observe and photograph the dentin slices in each group,and eight single-blinded examiners scored the slices according to uniform criteria.The analysis of variance was carried out to compared the scores between groups.Results Before acid etching,the dentin tubule occlusion scores of the Nd∶YAG+TB and TB+Nd∶YAG groups were(4.83±0.09) scores and(3.85±0.66) scores,respectively,which had no significant difference between each other(P=0.0590)and were higher than that[(0.10±0.07)scores]of the control group(both P<0.0001).The dentin tubule occlusion scores of the Nd∶YAG+TB group after acid etching for 5,10,and 15 min were(4.33±0.60)scores,(4.27±0.24)scores,and(3.63±0.07)scores,respectively,which were not significantly different from those[(4.04±0.10)scores,(3.76±0.59)scores,and(3.17±0.29)scores,respectively]of the TB+Nd∶YAG group(all P>0.05).In the Nd∶YAG+TB subgroup,the dentin tubule occlusion score after acid etching for 15 min was significantly lower than that before acid etching(P=0.0011).In the TB+Nd∶YAG group,there was no statistically significant difference in the score between before and after acid etching(P>0.05).Conclusions Nd∶YAG laser irradiation with appropriate parameters combined with the use of desensitizing toothpaste could produce an excellent occluding effect on dentinal tubules regardless of the sequence.However,brushing with desensitizing toothpaste followed by Nd∶YAG laser irradiation produced more consistent dentin sealing after acid etching.

Robust Trajectory and Resource Optimization in UAV-Enabled IoT Networks under Probabilistic LoS Channel in Presence of Jammers.

This paper studies the anti-jamming problem of unmanned aerial vehicle (UAV)-enabled Internet of Things (IoT) communication networks in the presence of a jammer under the accurate probabilistic line-of-sight (LoS) model. Our goal is to maximize the information collection throughput of the system under the assumption that only the jammer's approximate location is known. To this end, we formulate a throughput maximization problem by optimizing the UAV trajectory, the IoT devices' transmit power, and communication scheduling under the accurate real-time probabilistic LoS channel. However, the proposed optimization problem is non-convex and coupled, and hence intractable to be solved. In order to tackle the problem, a robust iterative algorithm is proposed by leveraging the block coordinate descent (BCD) method, the successive convex approximation (SCA) technology, the difference of convex (D.C) programming approach, and the S-procedure. Extensive simulation results show that our proposed algorithm significantly improves the system throughput while achieving a practical anti-jamming effect compared with the benchmark algorithms.

[A Sampling Survey of the Oral Health Status and Awareness among Primary School Students in Lhasa].

Objective To investigate the oral health status and awareness of urban children in Lhasa,aiming to provide a data basis for the prevention and treatment of children's caries and the promotion of oral health education. Methods A total of 504 Tibetan students were selected by cluster sampling from 2 primary schools in Chengguan District of Lhasa.All the participants were required to take oral health examination and complete a questionnaire about oral health awareness and behavior. Results The caries prevalence rate and mean decayed-missing-filled tooth(DMFT)of permanent teeth were 75.00% and 2.18±1.91,respectively.The rates of pit and fissure sealant and filling of permanent teeth were 3.77% and 6.81%,respectively.The caries prevalence rate of first permanent molars was 47.62%.The mean DMFT of permanent teeth and caries prevalence rate of first permanent molar were significantly higher in female group(P=0.001 and P=0.007,respectively).The prevalence rate of dental fluorosis was 61.51%,and the detection rate of dental calculus was 71.83%.Multivariate logistic regression analysis showed that prevalence of caries was influenced by many independent factors including gender,oral health awareness,intention of dental intervention,and dental experience. Conclusion High caries prevalence rate,low filling rate,and poor oral hygiene and health awareness were found among the primary school students in Lhasa,which require continuous dentistry investment and oral health education for the local students and their parents.

An innovative hybrid model based on outlier detection and correction algorithm and heuristic intelligent optimization algorithm for daily air quality index forecasting.

Air pollution forecasting plays an important role in helping reduce air pollutant emission and guiding people's daily activities and warning the public in advance. Nevertheless, previous articles still have many shortcomings, such as ignoring the importance of outlier point detection and correction of original time series, and random initial parameters of models, and so on. A new hybrid model using outlier detection and correction algorithm and heuristic intelligent optimization algorithm is proposed in this study to address the above mentioned problems. First, data preprocessing algorithms are conducted to detect and correct outliers, excavate the main characteristics of the original time series; second, a widely used heuristic intelligent optimization algorithm is adopted to optimize the parameters of extreme learning machine to obtain the forecasting results of each subseries with improvement in accuracy; finally, experimental results and analysis show that the presented hybrid model provides accurate prediction, outperforming other comparison models, which emphasize the importance of outlier point detection and correction and optimization parameters of models, it also give a new feasible method for air pollution prediction, and contribute to make effective plans for air pollutant emissions.

Analyzing Power Beacon Assisted Transmission with Imperfect CSI in Wireless Powered Sensor Networks.

This paper proposes the maximal ratio transmission (MRT) and maximal ratio combining (MRC) protocols for the power beacon (PB) assisted wireless powered sensor networks and analyzes the impact of the imperfect channel state information (CSI) on the performance using the Markov chain theory. The wireless powered sensor chooses to transmit information to the destination or harvest energy from the PB when its energy can or cannot supply a transmission, respectively. The energy arrival and departure of the sensor is characterized, and the analytical expressions of the network transmit probability, and effective and overall ergodic capacities are formulated and derived. We also optimize the sensor transmit power to maximize the overall ergodic capacity. Our results reveal that the transmit probability and the effective ergodic capacity can be greatly improved with increasing the number of antennas at the PB and the destination, and can also be significantly degraded by decreasing the channel correlation factors. We also demonstrate the effectiveness of the sensor transmit power optimization in improving the overall ergodic capacity.

Phosphorylation of Tudor-SN, a novel substrate of JNK, is involved in the efficient recruitment of Tudor-SN into stress granules.

Posttranslational modifications of certain stress granule (SG) proteins are closely related to the assembly of SGs, a type of cytoplasmic foci structure. Our previous studies revealed that the Tudor staphylococcal nuclease (Tudor-SN) protein participates in the formation of SGs. However, the functional significance of potential Tudor-SN modifications during stress has not been reported. In this study, we demonstrated that the Tudor-SN protein was phosphorylated at threonine 103 (T103) upon stimulation with arsenite. In addition, c-Jun N-terminal kinase (JNK) was found to be responsible for Tudor-SN phosphorylation at the T103 site. We further illustrated that either a T103A mutation or the suppression of phosphorylation of T103 by the JNK inhibitor SP600125 inhibited the efficient recruitment of Tudor-SN into SGs. In addition, the T103A mutation could affect the physical binding of Tudor-SN with the G3BP (Ras-GAP SH3 domain-binding protein) protein but not with the HuR (Hu antigen R) protein and AGTR1-3'UTR (3'-untranslated region of angiotensin II receptor, type 1) mRNA cargo. These data suggested that JNK-enhanced Tudor-SN phosphorylation promotes the interaction between Tudor-SN and G3BP and facilitates the efficient recruitment of Tudor-SN into SGs under conditions of sodium arsenite-induced oxidative stress. This finding provides novel insights into the physiological function of Tudor-SN modification.

Secure Transmission of Cooperative Zero-Forcing Jamming for Two-User SWIPT Sensor Networks.

In this paper, the secrecy performance of the two-user simultaneous wireless information and power transfer (SWIPT) sensor networks is studied and a novel secure transmission scheme of cooperative zero-forcing (ZF) jamming is proposed. The two sensors opportunistically conduct the SWIPT and cooperative ZF jamming, respectively, where the energy required for jamming the eavesdropper is provided by the SWIPT operation so as to keep the energy balance at the sensors in the long run. By deriving the exact closed-form expressions of the secrecy outage probability and the secrecy throughout, we provide an effective approach to precisely assess the impacts of key parameters on the secrecy performance of the system. It has been shown that the secrecy outage probability is a monotonically increasing function of the growth of secrecy rate ( R s ), and a monotonically decreasing function of the increase of the transmit signal-to-noise ratio ( γ S ), and energy conversion efficiency ( η ). Furthermore, the secrecy throughput could be enhanced when η increases, which becomes especially obvious when a large γ S is provided. Moreover, the existence of an optimum R s maximizing the secrecy throughput is depicted, which also grows with the increase of γ S . Simulations are provided for the validation of the analysis.

Integration of spectral computed tomography in arterial imaging.

Artery imaging, a crucial component in the diagnosis and management of vascular disease, assumes a significant role in the field of medical research. Utilizing advanced imaging modalities such as computed tomography (CT) and magnetic resonance angiography (MRA), artery imaging provides detailed insights into blood flow, detecting conditions such as atherosclerosis, aneurysms, and other vascular abnormalities with high precision. Spectral CT is an innovative imaging technique that goes beyond traditional CT scans, capturing data at multiple energy levels to provide detailed insights into the composition of tissues and materials within the scanned region. Notably, recent studies and clinical applications have underscored the diagnostic advantages offered by spectral CT in the detection and characterization of various arterial diseases. The integration of spectral CT into the realm of arterial imaging presents a promising avenue for improving the diagnosis and management of vascular disease. This comprehensive review aims to provide an extensive overview, delving into the potential benefits, optimization, challenges, and future of spectral CT in arterial imaging.

Flexible Wearable Tri-notched UWB Antenna Printed with Silver Conductive Materials.

The advancement of Internet of Things and associated technologies has led to the widespread usage of smart wearable devices, greatly boosting the demand for flexible antennas, which are critical electromagnetic components in such devices. Additive manufacturing technologies provide a feasible solution for the creation of wearable and flexible antennas. However, performance reliability under deformation and radiation safety near the human body are two issues that need to be solved for such antennas. Currently, there are few reports on compact, flexible ultrawideband (UWB) antennas with more notch numbers, reliable bendability, and radiation safety. In this paper, a UWB antenna with trinotched characteristics for wearable applications was proposed and developed using printable conductive silver materials consisting of silver microflakes or silver nanoparticles. The antenna has a compact size of 18 × 20 × 0.12 mm3 and adopts a gradient feeder and a radiation patch with three folding slots. It was fabricated on transparent and flexible poly(ethylene terephthalate) film substrates, using screen printing and inkjet printing. The measurement results demonstrated that the fabricated antennas could cover the UWB band (2.35-10.93 GHz) while efficiently filtering out interferences from the C-band downlink satellite system (3.43-4.21 GHz), wireless local area networks (4.66-5.29 GHz), and X-band uplink satellite system (6.73-8.02 GHz), which was consistent with the simulation results. The bendability and radiation safety of the antennas were evaluated, proving their feasibility for usage under bending conditions and near the human body. Additionally, it was found that the screen-printed antenna performed better after bending. The research is expected to provide guidance on designing flexible antennas that are both safe to wear and easily conformable.

Layout analysis of the RCEP international airline network based on hub identification using improved contribution matrix.

The signing of the Regional Comprehensive Economic Partnership agreement brings new opportunities for the development of international air transportation. Faced with fierce competition, it is worth studying how hub airports should enhance competitiveness, and how low-cost carriers and full-service carriers should optimize the RCEP international airline network layout for better development. Aiming at providing suggestions for the development of hub airports, low-cost and full-service carriers in the RCEP international airline network, this paper identifies the hub airports, analyzes the layout of the RCEP international airline network, and the multi-layered characteristics based on an improved contribution matrix using data from 2010 to 2019 collected from the Official Airline Guide (OAG). This method comprehensively considers attributes of hub airports and the multi-layered characteristics of the airports and routes. The layout analysis indicates that the RCEP international transportation market presents a more open environment for competition and cooperation where base carriers are often the biggest supporters of hub construction. The multi-layered characteristics analysis reveals that low-cost carriers contribute more towards opening up new RCEP routes than full-service carriers. It is advised that carriers newly entering the RCEP international aviation transportation market and low-cost carriers dedicate to establishing new routes around their hub airports to monopolize this market and enhance their market share, whilst full-service carriers consolidate existing routes and increase route density to achieve economic benefits.

A compact tri-notched flexible UWB antenna based on an inkjet-printable and plasma-activated silver nano ink.

The rapid development of ultrawideband (UWB) communication systems has resulted in increasing performance requirements for the antenna system. In addition to a wide bandwidth, fast propagation rates and compact dimensions, flexibility, wearability or portability are also desirable for UWB antennas, as are excellent notch characteristics. Although progress has been made in the development of flexible/wearable antennas desired notch properties are still rather limited. Moreover, most presently available flexible UWB antennas are fabricated using environmentally not attractive subtractive etching-based processes. The usage of facile additive sustainably inkjet printing processes also utilizing low temperature plasma-activated conductive inks is rarely reported. In addition, the currently used tri-notched flexible UWB antenna designs have a relatively large footprint, which poses difficulties when integrated into miniaturized and compact communication devices. In this work, a silver nano ink is used to fabricate the antenna via inkjet printing and an efficient plasma sintering procedure. For the targeted UWB applications miniaturized tri-notched flexible antenna is realized on a flexible polyethylene terephthalate (PET) substrate with a compact size of 17.6 mm × 16 mm × 0.12 mm. The antenna operates in the UWB frequency band (2.9-10.61 GHz), and can shield interferences from WiMAX (3.3-3.6 GHz), WLAN (5.150-5.825 GHz) and X-uplink (7.9-8.4 GHz) bands, as well as exhibits a certain of bendability. Three nested "C" slots of different sizes were adopted to achieve notch features. The simulation and test results demonstrate that the proposed antenna can generate signal radiation in the desired UWB frequency band while retaining the desired notch properties and having acceptable SAR values on-body, making it a viable candidate for usage in flexible or wearable communication transmission devices. The research provides a facile and highly efficient method for fabricating flexible/wearable UWB antennas, that is, the effective combination of inkjet printing processing, flexible substrates, low temperature-activated conductive ink and antenna structure design.

The role of USP7-YY1 interaction in promoting colorectal cancer growth and metastasis.

Colorectal cancer (CRC) remains a significant global health issue with high incidence and mortality. Yin Yang 1 (YY1) is a powerful transcription factor that acts dual roles in gene activation and repression. High expression level of YY1 has been reported in CRC, indicating the existence of stable factors of YY1 in CRC cells. We aimed to identify the key molecules and underlying mechanisms responsible for stabilizing YY1 expression in CRC. Mass spectrometry analysis was utilized to identify USP7 as a potential molecule that interacted with YY1. Mechanically, USP7 stabilizes YY1 expression at the protein level by interfering its K63 linkage ubiquitination. YY1 exerts its oncogenic function through transcriptionally activating TRIAP1 but suppressing LC3B. In addition, at the pathological level, there is a positive correlation between the expression of YY1 and the budding of CRC. This study has revealed the intricate interplay between YY1 and USP7 in CRC, suggesting that they could serve as novel therapeutic targets or predictive biomarkers for CRC patients.

Phosphorylated FOXQ1, a novel substrate of JNK1, inhibits sorafenib-induced ferroptosis by activating ETHE1 in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly heterogeneous and malignant cancer with poor overall survival. The application of sorafenib is a major breakthrough in the treatment of HCC. In our study, FOXQ1 was significantly overexpressed in sorafenib-resistant HCC cells and suppressed sorafenib-induced ferroptosis. We found that phosphorylation of FOXQ1 at serine 248 is critical for the suppression of sorafenib-induced ferroptosis. Furthermore, as the upstream phosphorylation kinase of FOXQ1, JNK1, which is activated by sorafenib, can directly phosphorylate the serine 248 site of FOXQ1. Then, the phosphorylated FOXQ1 got a high affinity for the promoter of ETHE1 and activates its transcription. Further flow cytometry results showed that ETHE1 reduced intracellular lipid peroxidation and iron levels. Collectively, our study implicated the JNK1-FOXQ1-ETHE1 axis in HCC ferroptosis induced by sorafenib, providing mechanistic insight into sensitivity to sorafenib therapy of HCC.

The role of transcription factor Yin Yang-1 in colorectal cancer.

BACKGROUND: Yin Yang-1 (YY1) is identified as a transcription factor with multiple functions. However, the role of YY1 in tumorigenesis remains controversial and its regulatory effects may depend upon not only cancer types, but also its interacting partners, chromatin structure, and the context in which it acts. It has been detected that YY1 was highly expressed in colorectal cancer (CRC). Intriguingly, many YY1-repressed genes exhibit tumor suppressive potential while YY1 silencing is related to chemotherapy resistance. Therefore, it is crucial to meticulously explore YY1 protein structure and the dynamic alteration of its interactome in each cancer type. This review attempts to describe the structure of YY1, summarize the mechanism that influence the expression level of YY1 and also highlight the recent advances in our understanding of regulatory insights of YY1 functions in CRC. METHODS: Related studies were identified through scoping search of PubMed, Web of science, Scopus and Emhase concerning the terms of "colorectal cancer", colorectal carcinoma" or CRC with "YY1". The retrieval strategy included title, abstract, and keywords with no language limitations. All the included articles were categorized depending on the mechanisms they explored. RESULTS: In total, 170 articles were identified for further screening. After removing the duplication, not relevant outcomes and review articles, 34 were finally included in the review. Among them, 10 articles revealed the reasons of YY1 high expression in CRC, 13 articles explored YY1 function in CRC, and 11 articles fell into both aspects. In addition, we also summarized 10 clinical trials concerning the expression and activity of YY1 in various diseases, which offers a hint for future application. CONCLUSIONS: YY1 is highly expressed in CRC and broadly recognized as an oncogenic factor during the whole course of CRC. Sporadic controversial views are raised in term of CRC treatment, reminding us that future studies should take the influence of therapeutic regimens into concern.

Corrigendum: YY1 Promotes Endothelial Cell-Dependent Tumor Angiogenesis in Hepatocellular Carcinoma by Transcriptionally Activating VEGFA.

[This corrects the article DOI: 10.3389/fonc.2019.01187.].

Efficacy of Er:YAG laser-assisted direct pulp capping in permanent teeth with cariously exposed pulp: A pilot study.

Direct pulp capping is a minimally invasive method to preserve pulp integrity. We evaluated the treatment efficacy of Er:YAG laser irradiation combined with direct pulp capping for pulp exposure due to caries. A total of 21 patients with 22 teeth were enrolled in the conventional group (calcium hydroxide), and 24 patients with 25 teeth were enrolled in the laser-assisted group (Er:YAG laser irradiation at settings of 10 Hz, 50 mJ; combined with calcium hydroxide). The cumulative success rate of the conventional group and the laser-assisted group was 68.2% and 91.7% at 12 months, respectively. Results showed that the laser-assisted procedure increased the survival time (ß = 0.04, OR = 0.07), while proximal-occlusal cavities in molars decreased the survival time (ß = 0.03, OR = 12.5). Er:YAG lasers improve the effectiveness of conventional direct pulp capping (using Dycal) with limited side-effects and can be applied clinically.

YY1 Promotes Endothelial Cell-Dependent Tumor Angiogenesis in Hepatocellular Carcinoma by Transcriptionally Activating VEGFA.

Hepatocellular carcinoma (HCC) is a typical hypervascular solid tumor that requires neoangiogenesis for growth. The vascular endothelial growth factor (VEGF) is the most potent proangiogenic factor in neovascularization. The multifunctional Yin-Yang 1 (YY1) is involved in the regulation of tumor malignancy of HCC. However, the relationship between YY1 and endothelial cell-dependent tumor angiogenesis in HCC remains unclear. In this study, we observed that YY1 is positively correlated with microvessel density (MVD) and poor prognosis in HCC tissues. We further found that YY1 promotes the transcriptional activity of VEGFA by binding its promoter in HCC. The secreted VEGFA from HCC cells activates phosphorylation of VEGFR2 to promotes tube formation, cell migration, and invasion of vascular endothelial cells in vitro, and promotes tumor growth and angiogenesis in vivo. In addition, upregulation of YY1 enhanced resistance of bevacizumab in HCC cells. These results indicate that YY1 plays essential roles in HCC angiogenesis and resistance of bevacizumab by inducing VEGFA transcription and that YY1 may represent a potential molecular target for antiangiogenic therapy during HCC progression.

Prim-O-glucosylcimifugin enhances the antitumour effect of PD-1 inhibition by targeting myeloid-derived suppressor cells.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are immunosuppressive cells that play an important role in immune evasion, PD-1/PD-L1 inhibitor tolerance and tumour progression. Therefore, MDSCs are potential targets for cancer immunotherapy. In this study, we screened an effective polymorphonuclear MDSC (PMN-MDSC) inhibitor from the Traditional Chinese Medicine Library and evaluated its synergistic antitumour effects with PD-1 inhibitor. METHODS: In the present study, we found that PMN-MDSCs accumulate heavily in the spleen and bone marrow of melanoma (B16-F10) tumour-bearing mice. Then, we determined the top 10 key proteins in the upregulated KEGG pathways of PMN-MDSCs in tumour-bearing mice through proteomics and Cytoscape analysis. The key proteins were then used as targets for the screening of PMN-MDSC inhibitors from the traditional Chinese Medicine Library (20000 compounds) through molecular docking and weight calculation of the docking score. Finally, the inhibitory effect of the inhibitor was verified through proteomics and metabolomics analysis in vitro and melanoma (B16-F10) and triple-negative breast cancer (4 T1) mouse tumour models in vivo. RESULTS: Traditional Chinese medicine saposhnikovia root extract Prim-O-glucosylcimifugin (POG) could bind well to the target proteins and inhibit the proliferation, metabolism and immunosuppressive ability of PMN-MDSCs by inhibiting arginine metabolism and the tricarboxylic acid cycle (TCA cycle). POG could also increase CD8 T-lymphocyte infiltration in the tumours and enhance the antitumour effect of PD-1 inhibitor in B16-F10 and 4 T1 mouse tumour models. CONCLUSIONS: POG was successfully screened from the traditional Chinese Medicine library as a PMN-MDSC inhibitor. POG exhibited a good synergistic antitumour effect with PD-1 inhibitor. This study provided a potential option for enhancing the efficacy of PD-1 inhibitors in clinical applications.

6-Gingerol stabilized the p-VEGFR2/VE-cadherin/ß-catenin/actin complex promotes microvessel normalization and suppresses tumor progression.

BACKGROUND: Anti-angiogenic therapies demonstrate anti-tumor effects by decreasing blood supply to tumors and inhibiting tumor growth. However, anti-angiogenic therapy may leads to changes in tumor microenvironment and increased invasiveness of tumor cells, which in turn promotes distant metastasis and increased drug resistance. METHODS: The CO-IP assays, N-STORM and cytoskeleton analysis were used to confirm the mechanism that p-VEGFR2/VE-cadherin/ß-catenin/actin complex regulates vascular remodeling and improves the tumor microenvironment. 6-gingerol (6G), the major bioactive component in ginger, stabilized this complex by enhancing the binding of VEGFa to VEGFR2 with non-pathway dependent. Biacore, pull down and molecular docking were employed to confirm the interaction between 6G and VEGFR2 and enhancement of VEGFa binding to VEGFR2. RESULTS: Here, we report that microvascular structural entropy (MSE) may be a prognostic factor in several tumor types and have potential as a biomarker in the clinic. 6G regulates the structural organization of the microvascular bed to decrease MSE via the p-VEGFR2/VE-cadherin/ß-catenin/actin complex and inhibit tumor progression. 6G promotes the normalization of tumor vessels, improves the tumor microenvironment and decreases MSE, facilitating the delivery of chemotherapeutic agents into the tumor core and thereby reducing tumor growth and metastasis. CONCLUSIONS: This study demonstrated the importance of vascular normalization in tumor therapy and elucidated the mechanism of action of ginger, a medicinal compound that has been used in China since ancient times.