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Objective: To investigate the inhibitory effect of Celastrus orbiculatus extracts (COE) on the proliferation of lymphoma cells and the immune regulation ability on inflammation and thrombophilia in vivo. Methods: The 38B9 lymphoma cells were treated with COE (160 µ g/mL) and CTX (25 µ mol/L). The apoptosis rate and cell cycle of each group were detected by flow cytometry. The secretion of inflammatory factors, including interleukin (IL)-6, IL-10, and tumor necrosis factor α (TNF-α), in cell supernatant was detected by enzyme-linked immunosorbent assay (ELISA). In vivo, BALB/c mice were subcutaneously injected with 38B9 lymphoma cells to establish lymphoma model. COE (3 mg·kg−1·d−1) and CTX (40 mg·kg−1·d−1) were administered to the model mice, respectively. The expression of plasma inflammatory factors (IL-6, IL-10 and TNF-α) and thrombus indexes, including D-dimer (D-D), von Willebrand factor (vWF) and tissue factor (TF), were detected by ELISA before tumor bearing (1 d), after tumor formation (14 d) and after intervention (21 d). PicoGreen dsDNA was used to detect the level of serum neutrophil extracellular traps (NETs). Flow cytometry was used to detect the expression of platelet activation marker calcium-dependent lectin-like receptor 2 (CLEC-2). The tumor growth and survival of mice were recorded. Results: The 38B9 lymphoma cells were apoptotic after the intervention of COE and CTX. The ratio of G2-M phase cells decreased in COE intervented cells compared with the control cells (P<0.05), and S phase cells decreased in CTX intervented cells (P<0.05). Also, the secretion level of IL-6 was significantly reduced after COE or CTX intervention (P<0.05), and IL-10 was significantly increased (P<0.05). Furthermore, the tumor mass was reduced, and the median survival time was longer in COE and CTX intervented tumor-bearing mice than in non-intervented mice. The significantly lower levels of TNF-α, IL-6, NETs, TF, DD and CLEC-2, as well as higher IL-10 were observed in COE and CTX treatment mice in comparision with the control mice (P<0.05). Conclusion: COE has a mild and stable anti-tumor effect, which can reduce the secretion of inflammatory factors by lymphoma cells and regulate thrombophilic state caused by tumor inflammatory microenvironment. [ABSTRACT FROM AUTHOR]

Drug repositioning is gaining attention as a method for developing new drugs due to its low cost, short cycle time, and high success rate. One important approach is to explore new uses for already marketed drugs. In this study, we utilized the strategy of drug repositioning, focusing on the Dan-Lou tablet. We predicted the efficacy of Dan-Lou tablet against non-small cell lung cancer based on gene expression similarity and verified it by in vitro experiments. Next, we performed further analysis and validation using network pharmacology, molecular docking and molecular dynamics. Based on the results, it was concluded that Dan-Lou tablet mainly acted through nine compounds, Quercetin, Luteolin, Scoparone, Isorhamnetin, Eugenol, Genistein, Coumestrol, Hederagenin, Succinic Acid, and mainly targeted CCL2, FEN1, TPI1, RMI2 by six pathways. This discovery not only provides a new idea for the development of Dan-Lou tablet but also provides useful predictive information for clinical treatment. The method we adopted has great development prospects as a way to predict the efficacy of new drugs and their main mechanisms of action, and it has a positive impact on the research and development of new drugs using drug repositioning and the modernization of traditional Chinese medicine. [ABSTRACT FROM AUTHOR]

Preimplantation embryonic arrest is an important pathogenesis of female infertility, but little is known about the genetic factors behind this phenotype. MEI4 is an essential protein for DNA double-strand break formation during meiosis, and Mei4 knock-out female mice are viable but sterile, indicating that MEI4 plays a crucial role in reproduction. To date, MEI4 has not been found to be associated with any human reproductive diseases. Here, we identified six compound heterozygous and homozygous MEI4 variants—namely, c.293C > T, p.(Ser98Leu), c.401C > G, p.(Pro134Arg), c.391C > G, p.(Pro131Ala), c.914A > T, p.(Tyr305Phe), c.908C > G, p.(Ala303Gly), and c.899A > T, p.(Gln300Leu)—in four independent families that were responsible for female infertility mainly characterized by preimplantation embryonic arrest. In vitro, we found that these variants reduced the interaction between MEI4 and DNA. In vivo, we generated a knock-in mouse model and demonstrated that female mice were infertile and were characterized by developmental defects during oogenesis. Our findings reveal the important roles of MEI4 in human reproduction and provide a new diagnostic marker for genetic counseling of clinical infertility patients. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BRCA) is one of the most common malignant tumors. The structural maintenance of chromosome (SMC) gene family has been shown to play an important role in human cancers. However, the role of SMC families in BRCA is unclear. This study aimed to explore the role and potential clinical value of whole SMCs in BRCA. Methods: TIMER and UALCAN database were used to analysis the expression level. Genetic variations were analyzed by cBioPortal. Promoter methylation and protein level were analyzed by UCLCAN. GO and KEGG were analyzed by Metascape database. Prognostic value of SMCs was analyzed by Kaplan–Meier and multivariate cox regression analyses. Immune infiltration analysis was conducted by CIBERSORT. Immunotherapy outcome prediction was conducted by Cancer Immunome Atlas. Targeted drug therapy outcome prediction was taken by GDSC and R language. The cell viability was tested by CCK8 and migration was tested by wound healing assay. Xenograft model was used to investigate the in vivo role of SMC2. Results: Expression levels of SMC1A, SMC2, SMC4, SMC5 and SMC6 mRNA were increased in BRCA tissues, and negatively correlated with promoter methylation. Overexpression of SMC2 and SMC4 was negatively correlated with survival. Function of SMCs family regulatory genes was mainly related to ATPase activity. Expression of most SMCs was negatively correlated with immunotherapy and drug therapy outcomes. Interfere SMC2 and SMC4 decreased IC50 values of 5-fluorouracil and oxaliplatin and inhibited the migration of MCF7 cells. Tumor growth and weights were significantly decreased in si-SMC2 groups. Conclusions: Combined bioinformatics and clinical specimen analysis verified SMC2 and SMC4 as independent prognostic factors in BRCA, suggesting their significance for the diagnosis and treatment of BRCA. [ABSTRACT FROM AUTHOR]

Flexible silicone materials have excellent elastic properties and can maintain excellent structural stability under high-intensity repeated deformation. They are ideal materials for preparing piezoresistive flexible sensors. However, traditional silicone materials exhibit strong insulation properties. The solid block structure is also not conducive to improving sensitivity. Inspired by the irregular hole structure of Taihu Lake stone, this paper prepared a porous silica gel skeleton (rGO/CTAB/SG) based on reduced graphene oxide film coating, which was equipped with flexible interdigital electrodes to achieve electrical signal derivation. The "honeycomb" shaped sensing module prepared in this way achieves an extremely wide elastic deformation range (20-200%). In the pressure feedback layer, the rGO film is evenly coated on the SG surface, which greatly improves the device conductivity and sensing performance (high sensitivities of 89.4 kPa− 1 and 25.4 kPa− 1 are achieved within 0-30.2 kPa and 30.2–42 kPa, ultra-high durability under more than 22,000 load-unload cycles.) Numerical simulation analysis results confirmed that the structure of the flexible substrate SG prepared by this method maintained well when extreme deformation occurred, and no fracture or stress concentration occurred. As an elastic sensor, after being integrated with a microprocessor, it can easily monitor and analyze human body movement in real time. It has huge potential in areas such as daily training and health monitoring of athletes. [ABSTRACT FROM AUTHOR]

Cloud products from geostationary satellites are the main alternative to surface synoptic cloud observations (SYNOP), and have become the baseline products for the development and construction of the Quality Management System (QMS) of integrated meteorological observation in China. This study addresses the needs of the China Meteorological Administration (CMA) for such an operational reform, and it is carried out using real-time observations obtained from the Fengyun-2E (FY-2E) geostationary satellite in 2012 to derive cloud total amount and classification using two different methods. Compared to surface SYNOP observations, the cloud total amount estimated by FY-2E is generally significantly lower (about 30% lower on average). The cloud classification resulting from the two methods used in this study is also significantly different from the classification obtained from surface observations (difference between 22 and 32%). The difference is smaller for the classification method, which uses additional auxiliary temperature profiles. [ABSTRACT FROM AUTHOR]

Pathologic α-synuclein (α-syn) spreads from cell-to-cell, in part, through binding to the lymphocyte-activation gene 3 (Lag3). Here we report that amyloid β precursor-like protein 1 (Aplp1) interacts with Lag3 that facilitates the binding, internalization, transmission, and toxicity of pathologic α-syn. Deletion of both Aplp1 and Lag3 eliminates the loss of dopaminergic neurons and the accompanying behavioral deficits induced by α-syn preformed fibrils (PFF). Anti-Lag3 prevents the internalization of α-syn PFF by disrupting the interaction of Aplp1 and Lag3, and blocks the neurodegeneration induced by α-syn PFF in vivo. The identification of Aplp1 and the interplay with Lag3 for α-syn PFF induced pathology deepens our insight about molecular mechanisms of cell-to-cell transmission of pathologic α-syn and provides additional targets for therapeutic strategies aimed at preventing neurodegeneration in Parkinson's disease and related α-synucleinopathies. Pathologic α-synuclein spreads from cell-to-cell through binding to the lymphocyteactivation gene 3 (Lag3). Here, the authors demonstrate that the amyloid β precursor-like protein 1 (Aplp1) interacts with Lag3 and facilitates the binding, internalization, transmission, and toxicity of pathologic α-synuclein. [ABSTRACT FROM AUTHOR]

Currently, in vitro cultured corneal epithelial transplantation is effective in treating limbal stem cell dysfunction (LSCD). Selecting carriers is crucial for constructing the corneal epithelium through tissue engineering. In this study, the traditional amniotic membrane (AM) was modified, and mesenchymal stem cells (MSCs) were inoculated into the ultra-thin amniotic membrane (UAM) stroma to construct a novel UAM-MSC tissue-engineered corneal epithelial carrier, that could effectively simulate the limbal stem cells (LSCs) microenvironment. The structure of different carriers cultured tissue-engineered corneal epithelium and the managed rabbit LSCD model corneas were observed through hematoxylin–eosin staining. Cell phenotypes were evaluated through fluorescence staining, Western blotting, and RT-qPCR. Additionally, cell junction genes and expression markers related to anti-neovascularization were evaluated using RT-qPCR. Corneal epithelium cell junctions were observed via an electron microscope. The tissue-engineered corneal epithelium culture medium was analyzed through mass spectrometry. Tissue-engineered corneal epithelial cells expanded by LSCs on UAM-MSCs had good transparency. Simultaneously, progenitor cell (K14, PNCA, p63) and corneal epithelial (PAX6) gene expression in tissue-engineered corneal epithelium constructed using UAM-MSCs was higher than that in corneal epithelial cells amplified by UAM and de-epithelialized amniotic membrane. Electron microscopy revealed that corneal epithelial cells grafted with UAM-MSCs were closely connected. In conclusion, the UAM-MSCs vector we constructed could better simulate the limbal microenvironment; the cultured tissue-engineered corneal epithelium had better transparency, anti-neovascularization properties, closer intercellular connections, and closer resemblance to the natural corneal epithelial tissue phenotype. [ABSTRACT FROM AUTHOR]

This work explores the manipulation method for controlling the dynamic behavior of impacting droplets using surface patterns. By designing and implementing four radially patterned surfaces with strategically positioned obstacles, the study reveals the direct correlation between surface patterns and droplet behavior upon impact. The experimental results demonstrate that, the maximum stretching length of the droplet after impact is significantly inhibited due to the enhanced viscous dissipation of the droplet on these patterned surfaces. Furthermore, the formation of satellite droplets delays and the number of satellite droplets also significantly decreases. Through an analysis of energy distribution during the impact process, we concluded that the surface energy and kinetic energy of the droplets exhibit a linear growth relationship with We0.25, whereas the dissipated energy We0.5. As the number of obstacles increases, the viscosity dissipation of the droplet enhances during the impact, resulting in a decrease in the kinetic energy and surface energy. Consequently, the droplets become more resistant to breaking, resulting in a reduced formation of satellite droplets. Therefore, the special designed surface patterns can be expected to manipulate the stretching shape, stretching length of the droplet, and formation of satellite droplets after impacting. The findings provide valuable insights into the manipulation and control of droplet dynamics, offering potential applications in various fields such as surface engineering, anti-icing and liquid-based technologies. [ABSTRACT FROM AUTHOR]

Copyright of Rare Metals is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Electrochemical hydrogen peroxide (H2O2) production (EHPP) via a two-electron oxygen reduction reaction (2e- ORR) provides a promising alternative to replace the energy-intensive anthraquinone process. M-N-C electrocatalysts, which consist of atomically dispersed transition metals and nitrogen-doped carbon, have demonstrated considerable EHPP efficiency. However, their full potential, particularly regarding the correlation between structural configurations and performances in neutral media, remains underexplored. Herein, a series of ultralow metal-loading M-N-C electrocatalysts are synthesized and investigated for the EHPP process in the neutral electrolyte. CoNCB material with the asymmetric Co-C/N/O configuration exhibits the highest EHPP activity and selectivity among various as-prepared M-N-C electrocatalyst, with an outstanding mass activity (6.1 × 105 A gCo−1 at 0.5 V vs. RHE), and a high practical H2O2 production rate (4.72 mol gcatalyst−1 h−1 cm−2). Compared with the popularly recognized square-planar symmetric Co-N4 configuration, the superiority of asymmetric Co-C/N/O configurations is elucidated by X-ray absorption fine structure spectroscopy analysis and computational studies. The relationship between the structural configurations of M-N-C electrocatalysts and their performances in neutral environments has been insufficiently investigated. Here the authors demonstrate that an ultralow metal-loaded Co-N-C electrocatalyst, featuring the asymmetric Co-C/N/O configuration, exhibit exceptional efficiency in electrochemically producing hydrogen peroxide under neutral conditions. [ABSTRACT FROM AUTHOR]

Aim: Abnormalities in oocyte maturation, fertilization, and early embryonic development are major causes of primary infertility in women who are undergoing IVF/ICSI attempts. Although many genetic factors responsible for these abnormal phenotypes have been identified, there are more additional pathogenic genes and variants yet to be discovered. Previous studies confirmed that bi-allelic PATL2 deficiency is an important factor for female infertility. In this study, 935 infertile patients with IVF/ICSI failure were selected for whole-exome sequencing, and 18 probands carrying PATL2 variants with a recessive inheritance pattern were identified. Methods: We estimated that the prevalence contributed by PATL2 was 1.93% (18/935) in our study cohort. Results: 15 novel variants were found in those families, including c.1093C > T, c.1609dupA, c.1204C > T, c.643dupG, c.877-2A > G, c.1228C > G, c.925G > A, c.958G > A, c.4A > G, c.1258T > C, c.1337G > A, c.1264dupA, c.88G > T, c.1065-2A > G, and c.1271T > C. The amino acids altered by the corresponding variants were highly conserved in mammals, and in silico analysis and 3D molecular modeling suggested that the PATL2 mutants impaired the physiologic function of the resulting proteins. Diverse clinical phenotypes, including oocyte maturation defect, fertilization failure, and early embryonic arrest might result from different variants of PATL2. Conclusions: These results expand the spectrum of PATL2 variants and provide an important reference for genetic counseling for female infertility, and they increase our understanding of the mechanisms of oocyte maturation arrest caused by PATL2 deficiency. [ABSTRACT FROM AUTHOR]

This study aims to measure anatomical data of the capitate bone, develop an external fixator for treating late-stage osteonecrosis of lunate through Ilizarov technique, and evaluate its biomechanical performance. We selected eight wrist joint specimens to measure various parameters of the capitate bone, including its length, the distance from the junction of capitate head and body to the proximal end, as well as the width of its proximal head and distal body. Additionally, we measured these same indicators in 107 patients who had undergone wrist X-ray examination. Based on our measurements, we categorized the capitate bone into two groups and designed two types of capitate bone Ilizarov external fixator (CIEF) for it. Then, we compared it with the orthofix external fixator (OEF) through dynamic fatigue biomechanical experiments and pull-out resistance experiments. The results of the measurement revealed two categories of general patterns in the capitate bone. The first type maintains a consistent longitudinal axis between the proximal and distal ends. The second type is characterized by its proximal end being close to the radial side and its distal end being close to the ulnar side. In the dynamic tensile fatigue test, CIEF-A and CIEF-B had smaller maximum displacement values compared to the OEF (P < 0.05). In the anti-pull-out experiment, both CIEF-A and CIEF-B exhibited higher maximum pull-out force than the OEF (P < 0.05). CIFE is a treatment for advanced osteonecrosis of the lunate bone. It is specifically designed to align with the anatomical characteristics of the capitate bone, providing excellent biomechanical properties and a simple clinical procedure. However, additional clinical experiments are needed to confirm its effectiveness in the future. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Aplp1 interacts with Lag3 to facilitate transmission of pathologic α-synuclein" published in Nature Communications. The correction addresses errors in Figure 4 of the original article. The statistical significance for conditions 410C9 versus Lag3−/− in panel 4i was reported incorrectly as not significant when it is actually significant. The correct version of Figure 4 has been provided in the correction notice. The correction also includes an update to the figure legend of Figure 4, providing the correct p-values for the comparisons made. [Extracted from the article]

Oocyte maturation defects are major phenotypes resulting in female infertility. Although many genetic factors have been found to be responsible for these phenotypes, the underlying pathogenic genes and variants remain to be identified. The anaphase promoting complex or cyclosome (APC/C) is known to be essential in the metaphase-to-anaphase transition. In this study, we identified two homozygous missense variants (c.986A > G, p.Y329C and c.988C > T, p.R330C) in CDC23 that are responsible for female infertility characterized by oocyte maturation defects in three infertile individuals. CDC23 (cell division cycle 23) is one of the core subunits of the APC/C. In vitro experiments showed that the variant c.986A > G (p.Y329C) led to a decrease in CDC23 protein level and the variant c.988C > T (p.R330C) changed the localization of CDC23 in HeLa cells and mouse oocytes. In vivo studies showed that Cdc23Y329C/Y329C mice successfully mimicked the patients' phenotype by causing low expression of CDC23 and APC4 and the accumulation of securin and cyclin B1 in oocytes. AZ3146 treatment was able to rescue the phenotype. Taken together, our findings reveal the important roles of CDC23 in human oocyte maturation and provide a new genetic marker for female infertility. [ABSTRACT FROM AUTHOR]

Commercially pure titanium sheets with high strength and elongation were produced via asymmetric cryorolling and subsequent low-temperature short-time annealing. Results show that the yield strength of the asymmetric cryorolled TA2 Ti sheets with an average grain size of 460 nm reached 892 ± 13 MPa, 170 MPa higher than that of the room-temperature rolled specimens, and their elongation to failure was 6.0 ± 0.9%. After vacuum annealing at 573 K for 30 min, the elongation of the TA2 Ti sheets increased to 13.2 ± 2.0%, and their yield strength was 741 ± 7 MPa. Under the action of additional shear stress at cryogenic temperature, the grain refinement and dislocation accumulation were more significant in the samples subjected to asymmetric cryorolling plus annealing process than those subjected to room-temperature rolling and annealing. Besides, uniform distribution of dislocations and texture, finer grain sizes, and a higher proportion of high angle grain boundaries in samples via asymmetric cryorolling plus annealing provide favorable conditions for uniform plastic deformation and delay the stress concentration during tensile testing. Therefore, the elongations to failure of those samples are similar to the samples subjected to room-temperature rolling plus annealing. [ABSTRACT FROM AUTHOR]

Loss of the PTEN tumour suppressor is one of the most common oncogenic drivers across all cancer types1. PTEN is the major negative regulator of PI3K signalling. The PI3Kβ isoform has been shown to play an important role in PTEN-deficient tumours, but the mechanisms underlying the importance of PI3Kβ activity remain elusive. Here, using a syngeneic genetically engineered mouse model of invasive breast cancer driven by ablation of both Pten and Trp53 (which encodes p53), we show that genetic inactivation of PI3Kβ led to a robust anti-tumour immune response that abrogated tumour growth in syngeneic immunocompetent mice, but not in immunodeficient mice. Mechanistically, PI3Kβ inactivation in the PTEN-null setting led to reduced STAT3 signalling and increased the expression of immune stimulatory molecules, thereby promoting anti-tumour immune responses. Pharmacological PI3Kβ inhibition also elicited anti-tumour immunity and synergized with immunotherapy to inhibit tumour growth. Mice with complete responses to the combined treatment displayed immune memory and rejected tumours upon re-challenge. Our findings demonstrate a molecular mechanism linking PTEN loss and STAT3 activation in cancer and suggest that PI3Kβ controls immune escape in PTEN-null tumours, providing a rationale for combining PI3Kβ inhibitors with immunotherapy for the treatment of PTEN-deficient breast cancer.A mouse model of invasive breast cancer in which Pten and Trp53 are simultaneously inactivated links PTEN loss with STAT3 activation and indicates that immune escape in PTEN-null tumours is mediated by PI3Kβ. [ABSTRACT FROM AUTHOR]

The refractory organic matters in the reverse osmosis concentrate of coal gasification wastewater were reduced via catalytic ozonation. Activated carbon-supported Cu–Co–Mn catalysts were prepared and the removal efficiency improved 9.6% than Cu–Mn catalysts with the second catalytic activity. The parameters of catalyst preparation were optimized by univariate analysis and response surface methodology. At the loading rate of 6.46%, calcination temperature of 625 °C, and calcination time of 5.0 h, the removal efficiency of chemical oxygen demand (COD) was highest at 80.67% under the pH of 9, ozone concentration of 1 g/L, and catalyst dosing rate of 1.10 g/L. It is confirmed that metal oxides were homogeneously distributed in the form of CuO, Co3O4, MnO2, and Mn2O3. Enhancement of specific surface area increased the number of activity sites and oxygen vacancies accelerated the formation of ·OH. Hence, the activity of ozonation for refractory organic matters was improved. [ABSTRACT FROM AUTHOR]

The diffusion of odour caused by excavation disturbance during the restoration of pesticide sites adversely affects the surrounding environment. Therefore, it is essential to develop a new type of odour inhibitor that has both adsorption and oxidation functions and can effectively block odour. In this study, bentonite-modified cetyltrimethyl ammonium bromide (CTAB) was synthesised, and the structural changes of bentonite before and after modification were analysed by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and other characterisation methods. Urea peroxide was loaded on modified bentonite (150C-Bent) by in situ synthesis method, and the preparation conditions were optimised. The effects of temperature, humidity and species on the adsorption behaviour and adsorption kinetics were studied by adsorption experiments. It is demonstrated that CTAB is embedded in bentonite through ion exchange, and the interlayer spacing expands from 1.42 to 3.11 nm. The optimal loading mass ratio of modified bentonite to urea peroxide was 1:1.5 and pH was 3. When the relative humidity is 54.3% and the temperature is 55 °C, the removal effect of paraxylene is the best; the optimal removal reached 82.4%. The adsorption behaviour of 1.5UHP-Bent conforms to the pseudo-second-order kinetic adsorption model. The adsorption pathway of paraxylene on UHP-Bent mainly includes partition effect and hydroxyl radical capture. [ABSTRACT FROM AUTHOR]

The variation in niche breadth can affect how species respond to environmental and resource changes. However, there is still no clear understanding of how seasonal variability in food resources impacts the variation of individual dietary diversity, thereby affecting the dynamics of a population's dietary niche breadth. Optimal foraging theory (OFT) and the niche variation hypothesis (NVH) predict that when food resources are limited, the population niche breadth will widen or narrow due to increased within-individual dietary diversity and individual specialization or reduced within-individual dietary diversity, respectively. Here, we used DNA metabarcoding to examine the composition and seasonality of diets of the avivorous bat Ia io. Furthermore, we investigated how the dietary niches changed among seasons and how the population niche breadth changed when the availability of insect resources was reduced in autumn. We found that there was differentiation in dietary niches among seasons and a low degree of overlap, and the decrease of insect resource availability and the emergence of ecological opportunities of nocturnal migratory birds might drive dietary niche shifts toward birds in I. io. However, the population's dietary niche breadth did not broaden by increasing the within-individual dietary diversity or individual specialization, but rather became narrower by reducing dietary diversity via predation on bird resources that served as an ecological opportunity when insect resources were scarce in autumn. Our findings were consistent with the predictions of OFT, because birds as prey for bats provided extremely different resources from those of insects in size and nutritional value. Our work highlights the importance of size and quality of prey resources along with other factors (i.e., physiological, behavioral, and life-history traits) in dietary niche variation. [ABSTRACT FROM AUTHOR]

To conduct structural health monitoring, it is important to establish mathematical monitoring models with good prediction and interpretation performance. Generally, the thermal deformation effect interpreted in a displacement monitoring model of concrete dams is represented by the seasonal harmonic factor. The main purpose of this paper is to replace this factor with directly measured dam body temperatures. This approach is conducted by optimally selecting a very small number of the most representative members from hundreds of temperature monitoring points on the dam body, during which the importance of modelling factors is evaluated by a support vector machine (SVM), and automatic and manual criteria are formulated to eliminate the large number of unimportant or similar temperature monitoring points. Then, a hysteretic effect-considered hydraulic, exponential, thermal and time (HETT) model is established, and a causal interpretation of dam deformation behaviour is carried out using a partial dependence diagram to separate displacement components from the SVM model. The world's highest concrete dam, the Jinping I arch dam, is assessed in a case study. Research results demonstrate the efficiency and rationality of the proposed approach. On average, among the 140 total temperature monitoring points in the central cantilever dam section, only 6.3% of them are selected as temperature deformation factors, and these factors can fully characterise the temporal and spatial evolution characteristics of the measured dam temperature field. The prediction accuracy of the HETT model is significantly improved, in which the mean square error, maximum error and correlation coefficient of multiple displacement monitoring points are 60.1%, 86.5% and 101.5% of those of the hydraulic, exponential, seasonal and time (HEST) model, respectively. The thermal deformation effect interpreted by the HETT model is more in accordance with the actual operation condition of the Jinping I arch dam. [ABSTRACT FROM AUTHOR]

This study simulated catechol concentration of coal chemical wastewater to acclimate activated sludge. The degradation performance of catechol, the variation of organic toxicity and bacterial community structure in sludge during acclimation were investigated. The results showed that the ability of sludge to degrade COD and catechol was increased through the acclimation process. With the deepening of acclimation, the sludge organic toxicity was 54.3 ± 2.0%, 82.4 ± 3.0% and 91.6 ± 3.3% in blank group, mid-acclimation stage (catechol concentration was 50 mg/L) and end-acclimation stage (catechol concentration was 100 mg/L), respectively, and the organic matter with molecular weight of 5 K to 10 kDa was the main contributor to sludge toxicity. Moreover, metagenomic analysis revealed that the original bacterial expressed stress responses under the catechol toxicity inhibition at mid-acclimation stage. As the adjustment of enzyme system caused by the stress responses, the functional degradation enzymes gradually formed and the functional genes were enriched at end-acclimation stage, which were shown to be the emergence of dominant bacterial groups (Azoarcus, Thauera, Dechloromonas). The enzyme content and the abundance of dominant bacterial groups at end-acclimation stage increased by 20.6% and 45.0%, respectively, which enhanced the degradation performance of high concentration catechol and secondary metabolites of sludge. [ABSTRACT FROM AUTHOR]

Copyright of Rare Metals is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The restoration of bone defects caused by osteoporosis remains a challenge for surgeons. Strontium ranelate has been applied in preventative treatment approaches due to the biological functions of the trace element strontium (Sr). In this study, we aimed to fabricate bioactive scaffolds through Sr incorporation based on our previously developed modified amino-functional mesoporous bioactive glass (MBG) and to systematically investigate the bioactivity of the resulting scaffold in vitro and in vivo in an osteoporotic rat model. The results suggested that Sr-incorporated amino-functional MBG scaffolds possessed favorable biocompatibility. Moreover, with the incorporation of Sr, osteogenic and angiogenic capacities were upregulated in vitro. The in vivo results showed that the Sr-incorporated amino-functional MBG scaffolds achieved better bone regeneration and vessel formation. Furthermore, bioinformatics analysis indicated that the Sr-incorporated amino-functional MBG scaffolds could reduce reactive oxygen species levels in bone marrow mesenchymal stem cells in the osteoporotic model by activating the cAMP/PKA signaling pathway, thus playing an anti-osteoporosis role while promoting osteogenesis. This study demonstrated the feasibility of incorporating trace elements into scaffolds and provided new insights into biomaterial design for facilitating bone regeneration in the treatment of osteoporosis. [ABSTRACT FROM AUTHOR]

Considering both the grinding parameters and dynamic mechanical properties of the silicon nitride ceramics, the dynamic critical grinding depth model of the ductile regime grinding was established. The grinding experiment of the silicon nitride ceramics was carried out on a surface grinder MGK7120 × 6/F. The grinding force was compared with the critical load for the cracking, then the material removal mode was analyzed. The pixel mesh method was used to calculate the proportion of the brittle regime, and the material removal mode was further validated. The material removal mode of the silicon nitride ceramic grinding was predicted using the maximum undeformed grinding thickness model and dynamic critical grinding depth model. The predicted results were consistent with the results of the experimental analysis, and the correctness of the dynamic critical grinding depth model of the ductile regime grinding was verified. The mechanism of the grinding strain rate on the material removal mode was analyzed, and it was found that increasing the strain rate was conducive to achieving the ductile material removal, then improving the grinding quality. The research is useful to optimize the grinding parameters to reduce the damage in the ceramic grinding. [ABSTRACT FROM AUTHOR]

Both the yield strength and ductility of cryorolled nickel were improved after short-time annealing at low temperatures. The yield strength, tensile strength, uniform elongation, and elongation to failure of annealed pure nickel reached 990 MPa, 1041 MPa, 6.4, and 8.7 pct, an increase of 18, 12, 700, and 521 pct, respectively, compared to unannealed state. The improvement in mechanical properties was attributed to the heterostructure formed by annealing, formation of stacking faults, and nano-twins. [ABSTRACT FROM AUTHOR]

Introduction: A large number of studies have explored the potential biomarkers for detecting liver cirrhosis in an early stage, yet consistent conclusions are still warranted. Objectives: To conduct a review and a meta-analysis of the existing studies that test the serum level of bile acids in cirrhosis as the potential biomarkers to predict cirrhosis. Methods: Six databases had been searched from inception date to April 12, 2021. Screening and selection of the records were based on the inclusion criteria. The risk of bias was assessed with the Newcastle–Ottawa quality assessment scale (NOS). Mean difference (MD) and confidence intervals 95% (95% CI) were calculated by using the random effect model for the concentrations of bile acids in the meta-analysis, and I2 statistic was used to measure studies heterogeneity. This study was registered on PROSPERO. Results: A total of 1583 records were identified and 31 studies with 2679 participants (1263 in the cirrhosis group, 1416 in the healthy control group) were included. The quality of included studies was generally high, with 25 studies (80.6%) rated over 7 stars. A total of 45 bile acids or their ratios in included studies were extracted. 36 increased in the cirrhosis group compared with those of the healthy controls by a qualitative summary, 5 decreased and 4 presented with mixing results. The result of meta-analysis among 12 studies showed that 13 bile acids increased, among which four primary conjugated bile acids showed the most significant elevation in the cirrhosis group: GCDCA (MD = 11.38 μmol/L, 95% CI 8.21–14.55, P < 0.0001), GCA (MD = 5.72 μmol/L, 95% CI 3.47–7.97, P < 0.0001), TCDCA (MD = 3.57 μmol/L, 95% CI 2.64–4.49, P < 0.0001) and TCA (MD = 2.14 μmol/L, 95% CI 1.56–2.72, P < 0.0001). No significant differences were found between the two groups in terms of DCA (MD = − 0.1 μmol/L, 95% CI − 0.18 to − 0.01, P < 0.0001) and LCA (MD = − 0.01 μmol/L, 95% CI − 0.01 to − 0.02, P < 0.0001), UDCA (MD = − 0.14 μmol/L, 95% CI − 0.04 to − 0.32, P < 0.0001), and TLCA (MD = 0 μmol/L, 95% CI 0–0.01, P < 0.0001). Subgroup analysis in patients with hepatitis B cirrhosis showed similar results. Conclusion: Altered serum bile acids profile seems to be associated with cirrhosis. Some specific bile acids (GCA, GCDCA, TCA, and TCDCA) may increase with the development of cirrhosis, which possibly underlay their potential role as predictive biomarkers for cirrhosis. Yet this predictive value still needs further investigation and validation in larger prospective cohort studies. [ABSTRACT FROM AUTHOR]

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A novel ternary heterojunction composite photocatalyst g-C3N4/TiO2/NiWO4 was fabricated using a simple hydrothermal method. The synthesized samples were characterized using X-ray diffraction (XRD), scanning electronic microscopy (SEM), energy-dispersive spectrum (EDS), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), ultraviolet–visible (UV–Vis) absorption spectra, photoluminescence (PL) spectra, transient photocurrent responses, and electrochemical impedance spectroscopies (EIS). The results indicated that the composite of g-C3N4/TiO2/NiWO4 had been successfully synthesized. By constructing a ternary heterojunction, the electron migration rate and light absorption of the material are further improved; the photogenerated electron–hole recombination is inhibited. The ternary composite photocatalyst shows the highest photocatalytic activity for the degradation of rhodamine B (RhB) than that of g-C3N4, TiO2, NiWO4, and g-C3N4/TiO2 photocatalyst. The degradation efficiency of RhB using g-C3N4/TiO2/NiWO4 can reach 99% after visible-light irradiation for 40 min. Finally, the migration mechanism of charge carriers in the ternary system has been schematically illustrated by the active species capture experiment. Our research can pave the way for the fabrication of ternary heterojunction composite photocatalyst with high photocatalytic activity for the environmental contaminants treatment. [ABSTRACT FROM AUTHOR]

Purpose: Pancreatic surgery is a complex operation that has been associated with severe intraoperative and postoperative complications, especially in patients with previous abdominal surgery (PAS). Our study aimed to assess the impact of PAS on pancreatic surgery. Methods: A total of 1430 patients who underwent pancreatic surgery were included in this retrospective study and classified into the following 3 groups: previous upper abdominal surgery (PUAS) (n = 135); previous lower abdominal surgery (PLAS) (n = 161), and no history of abdominal surgery (non-PAS) (n = 1134). Using propensity score matching (PSM), patients were matched to one another at a 1:1:1 ratio with balanced baseline characteristics. Intraoperative factors, surgical complications, hospital costs, and postoperative hospitalization were collected and compared. Results: A longer operative duration was observed in the PUAS group compared to the non-PAS group (187.54 vs. 150.50 min, p = 0.016). The intraoperative blood loss in the PUAS group was significantly higher (193.68 vs. 150.51 and 156.81 mL, p < 0.05), while the intraoperative plasma transfusion volume was higher in PLAS patients than in non-PAS patients (183.8 vs. 102.7 mL, p = 0.008). Intra-abdominal adhesions in PUAS patients were most severe, and non-PAS patients exhibited significantly lower intra-abdominal adhesion grading (p < 0.001). No significant differences were observed in postoperative complications, postoperative histopathology, postoperative hospitalization, or hospital cost. Conclusion: PAS has no significant influences on surgical outcomes, and pancreatic surgery is relatively safe in this patient population. A patient history of PAS may prolong operation duration and increase intraoperative blood loss but has no impact on postoperative complications and does not increase the economic burden. [ABSTRACT FROM AUTHOR]

The metal-support interfaces between metals and oxide supports have long been studied in catalytic applications, thanks to their significance in structural stability and efficient catalytic activity. The metal-rare earth oxide interface is particularly interesting because these early transition cations have high electrophilicity, and therefore good binding strength with Lewis basic molecules, such as H2O. Based on this feature, here we design a highly efficient composite Ni-Y2O3 catalyst, which forms abundant active Ni-NiOx-Y2O3 interfaces under the water-gas shift (WGS) reaction condition, achieving 140.6 μmolCO gcat−1 s−1 rate at 300 °C, which is the highest activity for Ni-based catalysts. A combination of theory and ex/in situ experimental study suggests that Y2O3 helps H2O dissociation at the Ni-NiOx-Y2O3 interfaces, promoting this rate limiting step in the WGS reaction. Construction of such new interfacial structure for molecules activation holds great promise in many catalytic systems. Developing effective and stable catalytic interfaces in the medium temperature region is a practical route to replace the existing water gas shift (WGS) process. Here the authors designed a composite Ni-Y2O3 catalyst achieving the highest WGS activity for Ni based catalysts. [ABSTRACT FROM AUTHOR]

Hydroquinone is one of the main pollutants in coal-gasification wastewater, which is biologically toxic and difficult to remove. The aerobic biodegradation rate, organic toxicity, and microbial community structure at different acclimation stages of degradation of hydroquinone by activated sludge were investigated. In each acclimation cycle, the removal of hydroquinone reached 100% after 5 days, indicating that high-concentration hydroquinone in the activated sludge could be completely biodegraded. When the microbial flora was inhibited by the influent hydroquinone, the enzyme system experienced stress conditions and led to the secretion of secondary metabolites, extracellular protein of 5–10 kDa mainly contributing to the sludge organic toxicity. Microbial diversity analysis showed that with the increase of the concentration of hydroquinone, β-Proteus bacteria such as Azoarcus and Dechloromonas gradually accumulated, which improved the removal of hydroquinone with aerobic activated sludge in the sequencing batch reactor (SBR) system. As the inhibition degree exceeded the appropriate tolerance range of microorganisms, bacteria would secrete much more secondary metabolites, and the organic toxicity of sludge would reach a relatively high level. [ABSTRACT FROM AUTHOR]

Chronic immune thrombocytopenia (CITP) is an autoimmune disease with many immune dysfunctions, including T helper type 17 cell (Th17)/regulatory T cells (Tregs) imbalance. Low quality of life and side effects of drugs are severe, especially in pediatrics. This study aimed to determine Th17/Treg polarization in pediatric CITP when first diagnosing ITP and evaluate its use as a predictive marker for pediatric CITP. This was a pilot study from a multi-center. Setting the effective data size to 100 patients, data entry ended in the 142nd patient who had completed a 1-year follow-up. The percentages of Treg cells and Th17 cells were quantified by flow cytometry when new diagnosed ITP patients first arrived. The association between the Th17/Treg ratio and CITP was analyzed statistically. The percentages of Treg cells and Th17 cells were lower (P = 0.0008) and higher (P = 0.0001), respectively, in the CITP-outcome group compared with the remission group. The receiver operating characteristic analysis showed that the area under the curve (AUC) of Treg and Th17 cells was 0.811 and 0.834, respectively. The ratio of Th17/Treg exhibited the largest AUC of 0.897 (cutoff value 0.076). Conclusions: Thus, the percentage of Th17 /Treg ratio of pediatric CITP is elevated at new diagnosed ITP stage. It is a promising predictive marker for the development of CITP to some extent. Trial registration: ChiCTR1900022419 (10th April 2019) What is Known: • The percentage of Th17 /Treg ratio of pediatric CITP is elevated. What is New: • This study shows that the percentage of Th17 /Treg ratio of pediatric CITP is elevated at new diagnosed ITP stage. This work may provide a new point for pediatric CITP's prediction. The imbalanced ratio of Th17/Treg was obvious when first diagnose ITP in pediatric CITP patients, rendering them as potential predictive tools for discriminating CITP to facilitate with the management of pediatric patient care. In addition, the combination of them may serve as a predictive marker in pediatric CITP. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cell (MSCs)-derived exosomes have been frequently used as useful tools in disease control. This research aimed to study the function of MSC-derived exosomes (Exo) in the stemness of cancer stem cells (CSCs) of hepatocellular carcinoma (HCC) and the molecular mechanism. Exo from the procured human bone marrow-MSCs were extracted and identified. CSCs from HCC cell lines were collected. The CSCs were treated with Exo, and then the proliferation, migration, invasion, angiogenesis-stimulating and self-renewal abilities of the Hep3B-CSCs and HuH7-CSCs were significantly reduced. C5orf66-AS1 was found as the most upregulated long noncoding RNAs (lncRNAs) in CSCs after Exo treatment. The integrated bioinformatic analyses and luciferase assays suggested that C5orf66-AS1 upregulated DUSP1 expression through sequestering microRNA-127-3p (miR-127-3p). Either artificial overexpression of miR-127-3p or silencing of DUSP1 blocked the inhibitory functions of Exo in the CSCs. DUSP1 inhibition increased the phosphorylation of ERK. Similar results were reproduced in vivo where Exo reduced the growth of xenograft formed by CSCs in nude mice, and this reduction was blocked upon miR-127-3p overexpression or DUSP1 silencing. To conclude, this research reported that MSC-derived Exo block malignant behaviors of HCC-sourced CSCs through a C5orf66-AS1/miR-127-3p/DUSP1/ERK axis. [ABSTRACT FROM AUTHOR]

Immune thrombocytopenia (ITP) is one of the most common acquired immune-mediated bleeding disorders found in children. Prednisone is usually considered a first-line therapeutic agent for ITP in children. Yet, prolonged exposure to prednisone has been associated with certain side effects. This prospective randomized study comparatively assessed the efficacy and safety of short-course high-dose dexamethasone (HDD) and standard prednisone (PDN) as a first-line treatment for children with previously untreated primary ITP. Two hundred eleven children were randomized into the HDD (n = 110) and PDN (n = 101) groups. There was no difference in baseline characteristics between the two groups (p > 0.05). Early response rates were 92.7% and 93% (p = 0.923); initial response rates were 93.6% and 95% (p = 0.658) and durable response rates were 90% and 91% (p = 0.787) in the HDD and PDN groups, respectively. More remission patients in the HDD group compared with the PDN group (86.3% vs. 80.1%) at 12th month after treatment, yet no statistical difference was observed (p = 0.703). Bleeding events were 10.9% and 14.8% (p = 0.105), and bleeding score improvement rates were 78.2% and 76.2% (p = 0.284) in the HDD and PDN groups, respectively. Cushing's disease, weight gain and infection rates were higher in the PDN group compared to the HDD group (80% vs. 10%, p = 0.001; 74.2% vs. 13.6%, p = 0.001; and 26% vs. 11.8%, p = 0.012) 1 month after treatment. HDD showed non-inferior efficacy and fewer glucocorticoid-related adverse effects compared with PDN. These findings indicated that HDD could be considered as a first-line treatment in children with previously untreated primary ITP, thus replacing standard PDN. [ABSTRACT FROM AUTHOR]

To demonstrate the identification of corneal diseases using a novel deep learning algorithm. A novel hierarchical deep learning network, which is composed of a family of multi-task multi-label learning classifiers representing different levels of eye diseases derived from a predefined hierarchical eye disease taxonomy was designed. Next, we proposed a multi-level eye disease-guided loss function to learn the fine-grained variability of eye diseases features. The proposed algorithm was trained end-to-end directly using 5,325 ocular surface images from a retrospective dataset. Finally, the algorithm's performance was tested against 10 ophthalmologists in a prospective clinic-based dataset with 510 outpatients newly enrolled with diseases of infectious keratitis, non-infectious keratitis, corneal dystrophy or degeneration, and corneal neoplasm. The area under the ROC curve of the algorithm for each corneal disease type was over 0.910 and in general it had sensitivity and specificity similar to or better than the average values of all ophthalmologists. Confusion matrices revealed similarities in misclassification between human experts and the algorithm. In addition, our algorithm outperformed over all four previous reported methods in identified corneal diseases. The proposed algorithm may be useful for computer-assisted corneal disease diagnosis. [ABSTRACT FROM AUTHOR]

Boric acid mixed with SiO2 nanospheres was used as a boron source in the spin-on method to improve p+ layer doping quality in the surface of p-type single crystal silicon (c-Si) wafers with pyramid structure texture. The effects of boric acid concentration, diffusion temperature and diffusion time on diffusion uniformity, surface hole concentration, junction depth and minority carrier lifetime were investigated. It was found that the addition of SiO2 nanospheres in boric acid could result in a high degree of diffusion uniformity more than 96%. When the boric acid concentration was 5 g/100 mL and diffusion was at 940 °C for 40 min, the obtained p+ layer in silicon wafer showed a best overall performance with a surface hole concentration of 8 × 1018 cm−3, a sheet resistance (RS) of 70.2 Ω/□, a junction depth of 0.28 μm and minority carrier lifetime of 3.39 μs. [ABSTRACT FROM AUTHOR]

In order to better understand the key regulatory mechanisms of PGC1α in muscle fiber type transition, the RNA-seq was used to compare the change of gene expression in gastrocnemius muscles between wild type pigs and transgenic pigs with overexpression of PGC1α gene in muscle. 371 differentially expressed genes (P ≤ 0.05 and Ratio ≥ 2), including 184 up-regulated genes and 187 down-regulated genes, were identified. Five main signaling pathways including metabolic pathways, ECM-receptor interaction, PPAR signaling pathway, adipocytokine signaling pathway and insulin signaling pathway, were authenticated using KEGG pathway analysis. Our results indicate that the fat metabolism pathway plays an important role in the transformation of muscle fiber types regulated by PGC1α. [ABSTRACT FROM AUTHOR]

N-trinitromethyl-4,5-dicyano-2H-1,2,3-triazole was readily synthesized from 4,5-dicyano-2H-1,2,3-triazole. Its crystal structure was obtained for the first time and its crystalline density in 296 K was 1.729 g cm−3. It shows high nitrogen and oxygen content up to 77.6%, high calculated solid heat of formation (564 kJ mol−1), and superior detonation pressure and detonation velocity (D = 8619 m s−1, P = 30.8 GPa). This new hydrogen-absent explosive shows high impact and friction sensitivities (IS: 1.25 J, FS: 32 N), which is lower than commercial primary explosive 2-diazonium-4,6-dinitrophenol (DDNP) (IS: 1 J, FS: 5 N). The relationship between intermolecular interaction and sensitivity as well as thermal stability of the title compound was investigated by Hirshfeld surface analysis and fingerprint plot. Its thermodynamic properties were studied by non-isothermal kinetic methods based on the results of differential scanning calorimeter. It is interesting that apparent activation energy (Ea) at Tp1 (210.89-214.17 kJ mol−1) is higher than those at Tp2 (133.90-134.87 kJ mol−1). In addition, gaseous product of this new energetic compound was analyzed by the rapid scanning Fourier transform infrared spectroscopy from 20 to 200 °C and its detonation products was theoretically predicted. Based on the decomposition products, its decomposition mechanism was discussed under inert atmosphere. It is undoubted that these significant physicochemical properties make N-trinitromethyl-4,5-dicyano-2H-1,2,3-triazole a potential hydrogen-absent primary explosive. [ABSTRACT FROM AUTHOR]

Abstract: Increasing evidence indicates that muscular dysfunction or alterations in skeletal muscle fiber-type composition not only are involved in muscle metabolism and function but also can limit functional capacity. Therefore, understanding the mechanisms regulating key events during skeletal myogenesis is necessary. Betaine is a naturally occurring component of commonly eaten foods. Here, we showed that 10 mM betaine supplementation in vitro significantly repressed myoblast proliferation and enhanced myoblast differentiation. This effect can be mediated by regulation of miR-29b-3p. Further analysis showed that betaine supplementation in vitro regulated skeletal muscle fiber-type composition through the induction of NFATc1 and the negative regulation of MyoD expression. Furthermore, mice fed with 10 mM betaine in water for 133 days showed no impairment in overall health. Consistently, betaine supplementation increased muscle mass, promoted muscle formation, and modulated the ratio of fiber types in skeletal muscle in vivo. These findings shed light on the diverse biological functions of betaine and indicate that betaine supplementation may lead to new therapies for diseases such as muscular dystrophy or other diseases related to muscle dysfunction.Key messages: Betaine supplementation inhibits proliferation and promotes differentiation of C2C12 myoblasts.Betaine supplementation regulates fast to slow muscle fiber-type conversion and is associated with NFATc1/MyoD.Betaine supplementation enhances skeletal myogenesis in vivo.Betaine supplementation does not impair health of mice. [ABSTRACT FROM AUTHOR]

A series of podophyllotoxin derivatives (M1–M16) that were selectively acylated by various phenoxy acids at the C-4 position of podophyllotoxin were synthesized, and their biological activities were also evaluated. Among them, compound M4 showed the most potent anti-cancer activity against HeLa cells with an IC50 value of 1.64 ± 0.41 μM. Additionally, flow cytometry analysis results indicated that it could cause a remarkable cell cycle arrest at G2/M phase, but the effect on apoptosis inducing was not significant. Moreover, the expression of cell cycle relative protein CDK1 was up regulated while cyclin B1 and Cdc25C, two proteins required for mitotic initiation were down regulated. Furthermore, the confocal assay and extracellular polymerized tubulin expression analysis also demonstrated that M4 was a potent tubulin polymerization inhibitor and the effect was comparable to that of colchicine. Finally, docking simulation results showed that M4 could nicely bind to the colchicine binding site of tubulin which further comfirmed the tubulin inhibiton activity of M4. [ABSTRACT FROM AUTHOR]