Search

Objective: To conduct a bibliometric analysis of the literature in the field of amino acid radiation protection over the past decade using CiteSpace software, exploring the formation, development, hotspots, and trends in this domain. Methods: The data source is the core collection of the Web of Science database, which include 413 papers on radiation damage of amino acids after deduplication and screening. CiteSpace software is used to visualize these papers, and the keywords and their clusters in this field are summarized from multiple dimensions and perspectives. Results: According to these papers, this field is dynamic and continuously growing, attracting interest from many scholars. Regarding country/institution distribution, China, the United States, and India have higher publication volumes, while the UK and India have more vital centrality in their publications. Keyword analysis reveals that the research hotspots in this field include ultraviolet radiation, oxidative stress, mycotoxin amino acids, and antioxidant activity. In contrast, emerging keywords such as DNA damage, photoprotection, and porphyrin-334 show research potential. Cluster analysis find that ultraviolet radiation protection, mycotoxin amino acids, glutamate, and adjuvant radiotherapy are the main research directions in this field. According to ionizing and non-ionizing radiation classification, the representative papers of the past decade sorted out the amino acids and their derivatives related to radiation protection. Conclusion: The visualization of the current situation, hotspots, and trends in the field of amino acid radiation protection provides valuable guidance and prospects for the development of amino acid food and the research of radiation protection in the future. Since the nuclear leakage accidents caused widespread concern, the demand for natural and harmless radiation protection products has surged, especially the development potential of amino acid radiation protection food. However, the current research on the structure-activity or mechanism of amino acid radiation protection needs to be more in-depth. It is still necessary to strengthen multi-agency cooperation and multi-center communication and focus on research hotspot keywords to help the development of amino acid radiation protection foods. In the context of the continuous spread of nuclear sewage, food technology is used as a shield to safeguard people's health.

Specifically inducing the degradation of acidic nucleoplasmic DNA-binding protein 1 (And1) is a promising antitumor strategy. Our previous study identified Bazedoxifene (BZA) and CH3 as specific And1 degraders and validated their activity in reversing radiotherapy resistance in vitro and in vivo. However, unelucidated structure-activity relationships and moderate activity have limited their application. In this study, 27 novel CH3 derivatives were designed and synthesised based on the cavity topology of the WD40 domain of And1. Among them, A15 with a “V” conformation significantly induced And1 degradation in NSCLC cells. In addition, this study demonstrated a potential synthetic lethal effect of And1 degraders and PARP1 inhibitors. 1 µM of Olaparib in combination with 5 µM of A15 significantly inhibited the proliferation of A549 and H460 cells. Overall, these compounds are valuable tools for elucidating And1 biology, and their special spatial conformation make them promising candidates for future optimisation studies.

Abstract Clear cell renal cell carcinoma (ccRCC) demonstrates enhanced glycolysis, critically contributing to tumor development. Programmed death-ligand 1 (PD-L1) aids tumor cells in evading T-cell-mediated immune surveillance. Yet, the specific mechanism by which glycolysis influences PD-L1 expression in ccRCC is not fully understood. Our research identified that the glycolysis-related gene (GRG) HK3 has a unique correlation with PD-L1 expression. HK3 has been identified as a key regulator of O-GlcNAcylation in ccRCC. O-GlcNAcylation exists on the serine 900 (Ser900) site of EP300 and can enhance its stability and oncogenic activity by preventing ubiquitination. Stably expressed EP300 works together with TFAP2A as a co-transcription factor to promote PD-L1 transcription and as an acetyltransferase to stabilize PD-L1 protein. Furthermore, ccRCC exhibits interactive dynamics with tumor-associated macrophages (TAMs). The uridine 5′-diphospho-N-acetylglucosamine (UDP-GlcNAc), which serves as a critical substrate for the O-GlcNAcylation process, facilitates TAMs polarization. In ccRCC cells, HK3 expression is influenced by IL-10 secreted by M2 TAMs. Our study elucidates that HK3-mediated O-GlcNAcylation of EP300 is involved in tumor immune evasion. This finding suggests potential strategies to enhance the efficacy of immune checkpoint blockade therapy.

Adhesive bonding is widely used in structural connection of composite components due to its capacity to effectively avoid inducing stress concentration and damage in composite components. This work applies a design optimization methodology on the geometry of cross section and ply thickness in adhesively bonded CFRP (carbon fiber-reinforced plastic), hat-shaped, thin-walled beam in automobiles to achieve car body lightweight design. A multi-objective and multi-constraint design optimization problem was formulated to find the optimum key cross-section size and ply thickness of the hat thin-walled beam. The minimum total material cost and maximum energy absorption (EA) during the axial crushing test of the CFRP beam were selected as the optimization objectives. The non-dominated sorting genetic algorithm II (NSGA-II) was introduced to search for global optimum solution, and radial basis function (RBF) approximations for the objective functions were applied to reduce the computational cost. It was revealed that EA increased by 8.28%, while the total weight and cost decreased by 3.14% and 3.23%, respectively, and can thus provide a guidance in vehicle composite component design.

Background: Clear cell renal cell carcinoma (ccRCC) stands as the prevailing variant kidney cancer in humans. Unfortunately, patients with disseminated RCC at diagnosis often have a diminished prognosis. Rapid tumor growth necessitates efficient blood supply for oxygen and nutrients, involving the circulation of blood from vessels to tumor tissues, facilitating tumor cell entry into the extracellular matrix. Vasculogenic mimicry (VM) significantly contributes to tumor growth and metastasis. Within this investigation, we identified vasculogenic mimicry-related genes (VMRGs) by analyzing data from 607 cases of kidney renal clear cell carcinoma (KIRC) in The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/). These findings offer insights into ccRCC progression and metastasis.Method: We identified VMRGs-related subtypes using consistent clustering methods. The signature of the VMRGs was created using univariate Cox regression and LASSO Cox regression analyses. To evaluate differences in immune cell infiltration, we employed ssGSEA. Afterwards, we created an innovative risk assessment model, known as the VM index, along with a nomogram to forecast the prognosis of ccRCC. Additionally, we verified the expression of an important gene related to VM, peroxiredoxin 2 (PRDX2), in tissue samples. Furthermore, we assessed the sensitivity to drugs in various groups by utilizing the pRRophetic R package.Results: Significant predictors of survival rates in both high- and low-risk groups of KIRC patients were identified as VMRGs. The independent prognostic factors for RCC were confirmed by both univariate and multivariate Cox regression analyses, validating VMRG risk signatures. Differences were observed in drug sensitivity, immune checkpoint expression, and responses to immune therapy between patients classified into high- and low-VMRG-risk groups. Our nomograms consistently demonstrated precise predictive capabilities. Finally, we experimentally verified PRDX2 expression levels and their impact on prognosis.Conclusion: The signature predicts patient prognosis and therapy response, laying the groundwork for future clinical strategies in treating ccRCC patients.

Abstract The lack of efficacious treatments for clear cell renal cell carcinoma (ccRCC) has led to a poor 5-year survival rate. Here, we found that the expression of ADAM metallopeptidase with thrombospondin type 1 motif 9 (ADAMTS9) antisense RNA 1 (ADAMTS9-AS1) is commonly decreased in ccRCC tissues. Decreased ADAMTS9-AS1 is associated with advanced stages and poor prognosis in ccRCC patients. Additionally, we found that promoter hypermethylation contributes to the suppression of ADAMTS9-AS1 expression in ccRCC that contained relatively low levels of ADAMTS9-AS1. Further functional studies demonstrated that ADAMTS9-AS1 inhibits cell growth and drug resistance through enhancing mRNA stability of ADAMTS9 in ccRCC. Mechanistically, ADAMTS9-AS1 directly bound to Human Antigen R (HuR). Then, the ADAMTS9-AS1-HuR complex was guided to the ADAMTS9 3’UTR through specific RNA–RNA interaction. Moreover, ADAMTS9-AS1 expression is positively correlated with ADAMTS9 expression in ccRCC tissues. In summary, our data not only highlight the important role of ADAMTS9-AS1 in ccRCC progression, but also reveal new regulatory mechanisms of ADAMTS9, which provides important insights into novel treatment strategies targeting ADAMTS9-AS1-HuR- ADAMTS9 axis in ccRCC.

Radiation protection drugs are often accompanied by toxicity, even amifostine, which has been the dominant radio-protecting drug for nearly 30 years. Furthermore, there is no therapeutic drug for radiation-induced intestinal injury (RIII). This paper intends to find a safe and effective radio-protecting ingredient from natural sources. The radio-protecting effect of Ecliptae Herba (EHE) was discovered preliminarily by antioxidant experiments and the mouse survival rate after 137Cs irradiation. EHE components and blood substances in vivo were identified through UPLC‒Q-TOF. The correlation network of “natural components in EHE-constituents migrating to blood–targets-pathways” was established to predict the active components and pathways. The binding force between potential active components and targets was studied by molecular docking, and the mechanism was further analyzed by Western blotting, cellular thermal shift assay (CETSA), and ChIP. Additionally, the expression levels of Lgr5, Axin2, Ki67, lysozyme, caspase-3, caspase-8,8-OHdG, and p53 in the small intestine of mice were detected. It was found for the first time that EHE is active in radiation protection and that luteolin is the material basis of this protection. Luteolin is a promising candidate for RⅢ. Luteolin can inhibit the p53 signaling pathway and regulate the BAX/BCL2 ratio in the process of apoptosis. Luteolin could also regulate the expression of multitarget proteins related to the same cell cycle.

The poly (ADP-ribose) polymerase (PARP) inhibitors play a crucial role in cancer therapy. However, most approved PARP inhibitors cannot cross the blood-brain barrier, thus limiting their application in the central nervous system. Here, 55 benzodiazepines were designed and synthesised to screen brain penetrating PARP-1 inhibitors. All target compounds were evaluated for their PARP-1 inhibition activity, and compounds with better activity were selected for further assays in vitro. Among them, compounds H34, H42, H48, and H52 displayed acceptable inhibition effects on breast cancer cells. Also, computational prediction together with the permeability assays in vitro and in vivo proved that the benzodiazepine PARP-1 inhibitors we synthesised were brain permeable. Compound H52 exhibited a B/P ratio of 40 times higher than that of Rucaparib and would be selected to develop its potential use in neurodegenerative diseases. Our study provided potential lead compounds and design strategies for the development of brain penetrating PARP-1 inhibitors.HIGHLIGHTSStructural fusion was used to screen brain penetrating PARP-1 inhibitors.55 benzodiazepines were evaluated for their PARP-1 inhibition activity.Four compounds displayed acceptable inhibition effects on breast cancer cells.The benzodiazepine PARP-1 inhibitors were proved to be brain permeable.

In view of the high computational complexity in spatial pulse position modulation systems when using maximum likelihood detection algorithm, a step-by-step classification detection algorithm based on K-means clustering was proposed according to the characteristics of signal matrix with spatial pulse position modulation.The signal vector detection algorithm was utilized to detect the index of light source in the training samples.The on K-means clustering algorithm was utilized to acquire the mapping rule between centroid of samples and modulated symbol by offline training.Subsequently, online detection of modulated symbols was achieved based on the mapping rule, and then the index of light sources was detected by exhaustive search.In addition, Monte Carlo method was used to investigate the effects of key parameters such as the number of clusters and initialization times on the system bit error rate (BER) performance.Simulation results demonstrate that the proposed algorithm can achieve an approximate BER performance as the maximum likelihood algorithm on the basis of greatly reducing the computational complexity.Compared with the linear decoding algorithms, the proposed algorithm is also applicable to scenarios where the number of detectors is less than the number of light sources.

Abstract The phosphate group functionalized metal-organic frameworks (MOFs) as the adsorbent for removal of U(VI) from aqueous solution still suffer from low adsorption efficiency, due to the low grafting rate of groups into the skeleton structure. Herein, a novel phosphate group functionalized metal–organic framework nanoparticles (denoted as Fe3O4@SiO2@UiO-66-TPP NPs) designed and prepared by the chelation between Zr and phytic acid, showing fast adsorption rate and outstanding selectivity in aqueous media including 10 coexisting ions. The Fe3O4@SiO2@UiO-66-TPP was properly characterized by TEM, FT-IR, BET, VSM and Zeta potential measurement. The removal performance of Fe3O4@SiO2@UiO-66-TPP for U(VI) was investigated systematically using batch experiments under different conditions, including solution pH, incubation time, temperature and initial U(VI) concentration. The adsorption kinetics, isotherm, selectivity studies revealed that Fe3O4@SiO2@UiO-66-TPP NPs possess fast adsorption rates (approximately 15 min to reach equilibrium), high adsorption capacities (307.8 mg/g) and outstanding selectivity (S u = 94.4%) towards U(VI), which in terms of performance are much better than most of the other magnetic adsorbents. Furthermore, the adsorbent could be reused for U(VI) removal without obvious loss of adsorption capacity after five consecutive cycles. The research work provides a novel strategy to assemble phosphate group-functionalized MOFs.

Background: Icaritin is a natural product with a wide range of anti-tumor effects. However, its anti-tumor mechanism has not been thoroughly studied. This study examined the inhibitory effect of icaritin on nasopharyngeal cancer and its underlying mechanism using network pharmacology along with in vivo and in vitro experiments.Methods: MTT and clone formation assays were used to detect the effects of icaritin on the viability and proliferation of nasopharyngeal carcinoma cells, followed by the construction of a HONE1 xenograft tumor model to evaluate the anti-tumor efficacy of icaritin in vivo. A public database was used to predict prospective targets, built a protein-protein interaction (PPI) network, and analyze gene enrichment and biological processes. Based on network pharmacological data, cell cycle-related proteins were identified using western blotting. Besides, cell cycle distribution, apoptosis, and intracellular reactive oxygen species (ROS) generation were identified using flow cytometry. In addition, SA-β-Gal staining was performed to detect cellular senescence, and western blotting was performed to detect the expression of P53, P21, and other proteins to verify key signaling pathways.Results: Icaritin effectively inhibited the viability and proliferation of nasopharyngeal carcinoma cell lines and showed good anti-tumor activity against HONE1 nasopharyngeal carcinoma cells in vivo. Key protein targets, including AKT1, HSP90AA1, CDK4, CCND1, and EGFR, were screened using PPI network topology analysis. GO and KEGG analysis revealed that the cell cycle, p53 signaling, and cell senescence pathways may be the main regulatory pathways. Flow cytometry and western blot experiments showed that icaritin caused S-phase arrest and promoted an increase in ROS. SA-β-Gal staining showed that icaritin significantly induced cellular senescence, and western blotting showed that the expression of senescence-related proteins p53 and P21 increased significantly. Moreover, inhibition of ROS levels by N-Acetylcysteine (NAC) enhanced cell viability, reversed cellular senescence and reduced cellular senescence-associated protein expression.Conclusion: The results of network pharmacological analysis and in vivo and in vitro experiments showed that icaritin effectively inhibited the growth of nasopharyngeal carcinoma cells, promoted ROS production, induced cellular senescence, and inhibited tumor cells, which are related to the regulation of P53/P21 signal pathway.

BackgroundPoor prognosis of kidney renal clear cell carcinoma (KIRC) is often related to angiogenesis. The lncRNAs that regulate angiogenesis could also affect the prognosis of KIRC. It is meaningful for us to use lncRNAs related to angiogenesis to construct a generic, individualized prognostic signature for patients with KIRC.MethodsWe identified eight angiogenesis-associated genes (AAGs) by differential expression analysis and univariate Cox regression from The Cancer Genome Atlas dataset, including 537 KIRC samples and 72 normal samples. In total, 23 prognostic lncRNAs were screened out after Pearson correlation analysis and univariate Cox regression analysis. Then, we performed least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression to establish a four-AAG-related lncRNA prognostic signature.ResultsThe risk score was calculated for each KIRC patients by using a four-AAG-related lncRNA prognostic signature. We divided the KIRC patients into high- and low-risk groups by the median of the risk score. It was confirmed that the AAG-related lncRNA prognostic signature has good prognostic value for KIRC patients by time-dependent receiver operating characteristic and Kaplan–Meier survival analysis. We identified 3,399 differentially expressed genes between the high- and low-risk groups and performed their functional enrichment analyses. The AAG-related lncRNA prognostic signature was an independent prognostic predictor for KIRC patients and was used to perform a combined nomogram. We reevaluated them in terms of survival, clinic characteristics, tumor-infiltrating immune cells and tumor mutation burden.ConclusionOur research indicates that the AAG-related lncRNA prognostic signature is a promising and potential independent prognostic indicator for KIRC patients. Then, it could offer new insights into the prognosis assessment and potential treatment strategies of KIRC patients.

Motivation: Kidney renal clear cell carcinoma, which is a common type and accounts for 70–80% of renal cell carcinoma, can easily lead to metastasis and even death. A reliable signature for diagnosis of this cancer is in need. Hence, we seek to select miRNAs for identifying kidney renal clear cell carcinoma.Method: A feature selection strategy is used and improved to identify microRNAs for diagnosis of kidney renal clear cell carcinoma. Samples representing kidney renal clear cell carcinoma and normal tissues are split into training and testing groups. Accumulated scores representing the variable importance of each miRNA are derived from an iteration of resampling, training, and scoring. Those miRNAs with higher scores are selected based on the Gaussian mixture model. The sample split is repeated ten times to get more central miRNAs.Results: A total of 611 samples are downloaded from TCGA, each of which contains 1,343 miRNAs. The improved feature selection method is implemented, and five miRNAs are identified as a biomarker for diagnosis of kidney renal clear cell carcinoma. GSE151419 and GSE151423 are selected as the independent testing sets. Experimental results indicate the effectiveness of the selected signature. Both data-driven measurements and knowledge-driven evidence are given to show the effectiveness of our selection results.

Accumulating evidence suggests that DNA methylation has essential roles in the development of renal cell carcinoma (RCC). Aberrant DNA methylation acts as a vital role in RCC progression through regulating the gene expression, yet little is known about the role of methylation and its association with prognosis in RCC. The purpose of this study is to explore the DNA methylation-driven genes for establishing prognostic-related molecular clusters and providing a basis for survival prediction. In this study, 5,198 differentially expressed genes (DEGs) and 270 DNA methylation-driven genes were selected to obtain 146 differentially expressed DNA methylation-driven genes (DEMDGs). Two clusters were distinguished by consensus clustering using 146 DEMDGs. We further evaluated the immune status of two clusters and selected 106 DEGs in cluster 1. Cluster-based immune status analysis and functional enrichment analysis of 106 DEGs provide new insights for the development of RCC. To predict the prognosis of patients with RCC, a prognostic model based on eight DEMDGs was constructed. The patients were divided into high-risk groups and low-risk groups based on their risk scores. The predictive nomogram and the web-based survival rate calculator (http://127.0.0.1:3496) were built to validate the predictive accuracy of the prognostic model. Gene set enrichment analysis was performed to annotate the signaling pathways in which the genes are enriched. The correlation of the risk score with clinical features, immune status, and drug susceptibility was also evaluated. These results suggested that the prognostic model might be a promising prognostic tool for RCC and might facilitate the management of patients with RCC.

Laser shock processing (LSP) is an innovative approach, which effectively improves the mechanical behavior of metallic structures by introducing compressive residual stress. To evaluate the residual stress evolution in low-carbon 13Cr4Ni martensitic stainless steel multi-pass butt-welded joints induced by LSP, a two-step numerical simulation including welding analysis, at first, followed by LSP calculation with the simulated welding stress results being taken into account, was performed based on ABAQUS software. Effects of LSP parameters such as power density, spot size, overlapping rate and numbers of laser shock on the residual stress variations, were systematically investigated. To validate the reliability and accuracy of the numerical simulation, experiments of welding and LSP were conducted in sequence. The residual stress after welding and LSP were investigated by x-ray diffraction method. Results demonstrate that the simulated results show a good agreement with the experimental datas. The welding residual stress distribution is uneven. Larger tensile stresses appear on the weld surface and its adjacent heat-affected zone, which could be converted into high-level compressive stress after LSP. Furthermore, an ideal residual stress field can be obtained after two successive laser shocks with an overlap rate of 75% when the power density, spot diameter, and pulse width are 7.6 GW cm ^−2 , 4 mm, and 25 ns, respectively.

Fiber Metal Laminates (FMLs) are hybrid materials that combine metal components with fiber-reinforced composites. The properties and failure modes of CArbon fiber Reinforced composites/Aluminum Laminates (CARALLs) composed of T700/PA6 unidirectional prepreg and 6061 aluminum alloy were studied using experimental and numerical simulation analysis. Through three-point bending experiments, the bending behavior of CARALLs with different composite/metal layer methods was examined. It was found that FMLs in the 2/1 patch form (one layer of aluminum and two layers of T700/PA6 unidirectional prepreg) show the highest bending modulus and strength compared with other stacking sequences. With the metal volume fraction increased, the bending properties of CARALLs decreased, suggesting the important role of the carbon fiber composite layer in the load-bearing capacity. Lastly, the Linde and Hashin failure criteria were employed to analyze the bending behavior and damage mechanism of CARALLs with different stacking sequences. The simulation results were in good agreement with the experimental results, which provides more insight into the prediction of the bending behavior of CARALLs hybrids.

BackgroundGlioblastoma multiforme (GBM) is extensively genetically and transcriptionally heterogeneous, which poses challenges for classification and management. Long noncoding RNAs (lncRNAs) play a critical role in the development and progression of GBM, especially in tumor-associated immune processes. Therefore, it is necessary to develop an immune-related lncRNAs (irlncRNAs) signature.MethodsUnivariate and multivariate Cox regression analyses were utilized to construct a prognostic model. GBM-specific CeRNA and PPI network was constructed to predict lncRNAs targets and evaluate the interactions of immune mRNAs translated proteins. GO and KEGG pathway analyses were used to show the biological functions and pathways of CeRNA network-related immunity genes. Consensus Cluster Plus analysis was used for GBM gene clustering. Then, we evaluated GBM subtype-specific prognostic values, clinical characteristics, genes and pathways, immune infiltration access single cell RNA-seq data, and chemotherapeutics efficacy. The hub genes were finally validated.ResultsA total of 17 prognostically related irlncRNAs were screened to build a prognostic model signature based on six key irlncRNAs. Based on GBM-specific CeRNAs and enrichment analysis, PLAU was predicted as a target of lncRNA-H19 and mainly enriched in the malignant related pathways. GBM subtype-A displayed the most favorable prognosis, high proportion of genes (IDH1, ATRX, and EGFR) mutation, chemoradiotherapy, and low risk and was characterized by low expression of four high-risk lncRNAs (H19, HOTAIRM1, AGAP2-AS1, and AC002456.1) and one mRNA KRT8. GSs with poor survival were mainly infiltrated by mesenchymal stem cells (MSCs) and astrocyte, and were more sensitive to gefitinib and roscovitine. Among GSs, three hub genes KRT8, NGFR, and TCEA3, were screened and validated to potentially play feasible oncogenic roles in GBM.ConclusionConstruction of lncRNAs risk model and identification of GBM subtypes based on 17 irlncRNAs, which suggesting that irlncRNAs had the promising potential for clinical immunotherapy of GBM.

Context Ursolic acid (UA), a natural product, shows a broad spectrum of anticancer effects. However, the poor bioavailability and efficacy of UA limit its clinical application. Objective We developed novel analogues of UA with enhanced antitumor activities by the extensive chemical modification of UA. Materials and methods We developed multiple compounds by structural modification of UA, and found that UA232 had stronger activity than UA. The effects of UA232 (0–50 μM) on inhibiting the proliferation of A549 and H460 cells were determined by CCK-8 for 24, 48, or 72 h. The proapoptotic effect of UA232 was analyzed by microscopy and flow cytometry, and the potential signal pathway affected by UA232 was further validated by Western blotting and flow cytometry. Results Compared with UA, UA232 showed a stronger ability to inhibit the proliferation of lung cancer cells (IC50 = 5.4–6.1 μM for A549 and 3.9–5.7 μM for H460 cells). UA232 could induce not only cell cycle arrest in the G0/G1 phase but also apoptosis in both A549 and H460 cells. The treatment of UA232 could lead to an increase of CHOP expression rather than an increase in Bax or caspase-8, indicating that the apoptosis induced by UA232 was correlated with the endoplasmic reticulum stress (ER stress) pathway. Treatment with the ER stress-specific inhibitor, 4-PBA, decreased the ability of UA232 to induce apoptosis in A549 and H460 cells. Conclusion UA232 induced apoptosis through the ER stress pathway, and showed stronger growth-inhibitory effects in A549 and H460 cells compared to UA, which may be a potential anticancer drug to suppress the proliferation of lung cancer.

As the most important complementary medication against a variety of diseases, traditional Chinese medicines (TCMs) have been extensively applied over thousands of years. Current quality control of herbal medicines, however, is in great dispute. Unlike chemical drugs, which have clear and validated quality standards, the content of only one (or a few) compounds of many herbs and preparations is currently assessed as an indicator of quality, even though the assessed compound(s) is neither closely associated with the efficacy nor representative of the medicine as a whole. Based on the clinical use, compatibility of multiple component prescriptions, and manufacturing process of TCM, the new concept of a TCM quality marker that was proposed in previous work is discussed further here. In addition, practical technological approaches are described for the qualitative analysis and quantification of TCMs including herbs, processed products, and preparations, which lead to the discovery and identification of specific chemicals as quality markers and new quality control patterns. The progress that has been made in TCM quality control is also addressed. This work provides useful information for the quality control of herbal medicines in the future. Keywords: Traditional Chinese medicine, Quality marker, Quality control

Abstract Gastric cancer peritoneal dissemination (GCPD) has been recognized as the most common form of metastasis in advanced gastric cancer (GC), and the survival is pessimistic. The injury of mesothelial cells plays an important role in GCPD. However, its molecular mechanism is not entirely clear. Here, we focused on the sphingosine kinase 1 (SPHK1) in human peritoneal mesothelial cells (HPMCs) which regulates HPMCs autophagy in GCPD progression. Initially, we analyzed SPHK1 expression immunohistochemically in 120 GC peritoneal tissues, and found high SPHK1 expression to be significantly associated with LC3B expression and peritoneal recurrence, leading to poor prognosis. Using a coculture system, we observed that GC cells promoted HPMCs autophagy and this process was inhibited by blocking TGF‐β1 secreted from GC cells. Autophagic HPMCs induced adhesion and invasion of GC cells. We also confirmed that knockdown of SPHK1 expression in HPMCs inhibited TGF‐β1‐induced autophagy. In addition, SPHK1‐driven autophagy of HPMCs accelerated GC cells occurrence of GCPD in vitro and in vivo. Moreover, we explored the relationship between autophagy and fibrosis in HPMCs, observing that overexpression of SPHK1 induced HPMCs fibrosis, while the inhibition of autophagy weakened HPMCs fibrosis. Taken together, our results provided new insights for understanding the mechanisms of GCPD and established SPHK1 as a novel target for GCPD.

With the improvement of people’s living standard, car has become an indispensable means of transportation, and the specialized car service industry is developing rapidly. Therefore, for the car repair stores, it is the core issue to choose suitable location according to the characteristics of car owners and existing competition. This study puts forward a model aiming at the maximum profit rate considering choice preference of car owners, competition, consumption capacity of owners, and capital limit. Then, a genetic algorithm improved in four aspects is proposed to solve the proposed model. Finally, an example and a case study of Dalian expound the application of the proposed models and algorithms in practice. It proved to be effective to China’s national conditions through the analysis of the results.

At the request of the Author, the following article Zhang, W, Hou, W, Hu, Ping and Ma, Z (2014) The Nonlinear Compressive Response and Deformation of an Auxetic Cellular Structure under In-Plane Loading Advances in Mechanical Engineering published 17 November 2014. doi: 10.1155/2014/214681 has been retracted due to errors discovered by the authors. On Page 3, the definition of component force in Equation 4 is incorrect. (2) On Page 4, the definition of component force in Equation 11 is incorrect. Moreover this equation should not have parameterM(length of cell wall), because a mistake was made in the process of calculation. Because of the above reasons, the conclusion obtained from the mechanical model is incorrect and should instead state that the Elastic Buckling and Plastic Collapse are both yield modes of this structure (3) On Page 5, the FEA model used in this article is not appropriate, because the deformation of single cell is not homogeneous, which means that the geometrical non-linear effect on single cell model is greater. So in the actual whole structure we may not obtain the results that were described in Page 6 Paragraph 2. (4) The data in figures 8 (page 6) and 9 (page 7) is incorrect and the values of effective Young’s modulus and plateau stress are much larger than reasonable values. The definition of effective stress is wrong in the FEA model, which means the effective stress should be calculated by the total width of cell instead of length of horizontal cell wall. For example, in Figure 8, the plateau stress can reach 140Mpa, this is not reasonable because there are many holes in this cellular structure, and its mechanical properties should be much lower than material properties of cell wall. The reasonable plateau stress should be around 2Mpa. The authors takes responsibility for these errors and regret the publication of invalid results. The nonlinear compressive response and deformation of an auxetic cellular structure that has periodic negative Poisson's ratio (NPR) cell were studied through theoretical and numerical method. The in-plane deformation and process of absorbing energy of this NPR cellular structure were discussed. The relative density of NPR cell was determined by geometric parameters and a theoretical approach to the strength of NPR cell was carried out to analyze the failure process under in-plane compression. Thus, to prove the effective of unit cell mechanical model, the size effect of this NPR cellular structure was discussed. The simulations of two different NPR cellular structures under in-plane compression were generated and their effective properties, strain-stress curves, and absorbed energy were analyzed. It can be concluded that the NPR cell that has lower relative density may have better capability of absorbing energy with enhanced Young's modulus. Finally the parametric analyses related to relative density were presented with NPR unit cell model and a set of quasistatic compressive experiments was carried out, which can be used to reveal the nonlinear properties of NPR cellular structure and to prove the effectiveness of theoretical method.

Classical Chinese pharmacopeias describe numerous excellent herbal formulations, and each prescription is an outstanding pool of effective compounds for drug discovery. Clarifying the bioactivity of the combined mechanisms of the ingredients in complex traditional Chinese medicine formulas is challenging. A classical formula known as Qingfei Xiaoyan Wan, used clinically as a treatment for prevalent chronic lung disease, was investigated in this work. A mutually enhanced bioactivity-guided ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) characterization system was proposed, coupled with a dual-luciferase reporter assay for β2AR-agonist cofactor screening. Arctiin, arctigenin, descurainoside and descurainolide B, four lignin compounds that showed synergistic bronchodilation effects with ephedrine, were revealed. The synergistic mechanism of arctigenin with the β2ARagonist involved with the reduction of free Ca2+ was clarified by a dual-luciferase reporter assay for intracellular calcium and the Ca2+ indicator fluo-4/AM to monitor changes in the fluorescence. The relaxant and contractile responses of airway smooth muscle are regulated by crosstalk between the intracellular cAMP and calcium signaling pathways. Our data indicated the non-selective βAR agonist ephedrine as the principal bronchodilator of the formula, whereas the lignin ingredients served as adjuvant ingredients. A greater understanding of the mechanisms governing the control of these pathways, based on conventional wisdom, could lead to the identification of novel therapeutic targets or new agents for the treatment of asthma and COPD.

Multilayer perceptron (MLP) and convolutional neural network (CNN) encounter a critical scalability issue when applied to the performance evaluation task for frame structure designs. Specifically, a model of MLP or CNN is limited to structures of a particular topology type and fails immediately when applied to other topology types. In order to tackle this challenge, we propose a scalable performance evaluation method (called FrameGraph) for frame structure designs using graph neural network (GNN), offering applicability to a wide range of topology types simultaneously. FrameGraph consists of two main parts: (1) Components and their connections in a frame structure are denoted as edges and vertices in a graph, respectively. Subsequently, a graph dataset for frame structure designs with different topologies is constructed. (2) A well-defined GNN design space is established with a general GNN layer, and a controlled random search approach is employed to derive the optimal GNN model for this performance evaluation task. In numerical experiments of car door frames and car body frames, FrameGraph achieved the highest prediction precisions (96.28% and 97.87%) across all structural topologies compared to a series of classical GNN algorithms. Furthermore, the comparison with MLP and FEM highlighted FrameGraph's significant efficiency advantage. This verifies the feasibility and optimality of FrameGraph for the performance evaluation task of frame structures with different topologies. [ABSTRACT FROM AUTHOR]