Structure-Based Optimization and Biological Evaluation of Pancreatic Lipase Inhibitors as Novel Potential Antiobesity Agents

The unusual fused b-lactone vibralactone was isolated from cultures of the basidiomycete Boreostereum vibrans and has been shown to significantly inhibit pancreatic lipase.In this study,a structure-based lead optimization of vibralactone resulted in three series of 104 analogs,among which compound C1 exhibited the most potent inhibition of pancreatic lipase,with an IC50 value of 14 nM.This activity is more than 3000-fold higher than that of vibralactone.The effect of compound C1 on obesity was investigated using high-fat diet(HFD)-induced C57BL/6 J obese mice.Treatment with compound C1 at a dose of 100 mg/kg significantly decreased HFD-induced obesity,primarily through the improvement of metabolic parameters,such as triglyceride levels.

Nine New Farnesylphenols from the Basidiomycete Albatrellus Caeruleoporus

Nine previously-unreported farnesylphenols,involving eight neogrifolin derivatives(1–8)and one grifolin analogue(9),together with three known compounds,were isolated from the fruiting bodies of the mushroom Albatrellus caeruleoporus.Their structures were elucidated as(S)-17-hydroxy-18,20-ene-neogrifolin(1),(S)-18,19-dihydroxyneogrifolin(2),(S)-9-hydroxy-10,22-ene-neogrifolin(3),(9S,10R)-6,10-epoxy-9-hydroxyneo grifolin(4),(9S,10R)-6,9-epoxy-10-hydroxyneogrifolin(5),(-)-13,14-dihydroxyneogrifolin(6),albatrelin G(7),albatrelin H(8),and one grifolin analogue,(S)-10-hydroxygrifolin(9),grifolin(10),neogrifolin(11),and albatrellin(12)by extensive spectroscopic analyses and chemical methods.Compounds 7 and 8 showed weak cytotoxic activity to cell lines HL-60,SMMC-7721,A-549,and MCF-7,in vitro.

Six New Vibralactone Derivatives from Cultures of the Fungus Boreostereum vibrans

Phytochemical reinvestigation on the cultural broth of Boreostereum vibrans led to the isolation of six new vibralactone derivatives,vibralactone N(1),vibralactone O(2),vibralactone P(3),10-lactyl vibralactone G(4),(3S*,4R*)-6-acetoxymethyl-2,2-dimethyl-3,4-dihydro-2H-chromene-3,4-diol(5),vibralactone Q(6).Their structures were elucidated by extensive spectroscopic methods.

Synergy in magnetic Ni_(x)Co_(1)O_(y) oxides enables base-free selective oxidation of 5-hydroxymethylfurfural on loaded Au nanoparticles

The base-free aerobic oxidation of 5-hydroxymethylfurfural(HMF) to 2,5-furandicarboxylic acid(FDCA)in water is recognized as an important and sustainable upgrading process for cellulosic carbohydrates.However,selectivity control still remains a challenge.Here,we disclose that the unique synergy in magnetic Ni_(x)Co_(1)O_(y)(x=1,3 and 5) bimetallic oxides can induce reactive oxygen defects and simultaneously stabilize small-sized metallic Au nanoparticles in the Au/Ni_(x)Co_(1)O_(y)catalysts.Such catalytic features render effective adsorption and activation of O_(2),OH and C=O groups,realizing selective oxidation of HMF to FDCA.On a series of magnetic Au/Ni_(x)Co_(1)O_(y)catalysts with almost identical Au loadings(ca.0.5 wt%) and particle sizes(ca.2.7 nm),the variable Ni/Co molar ratios give rise to the tunable electron density of Au sites and synergistic effect between NiO and CoO_(y).The initial conversion rates of HMF and its derived intermediates(i.e., DFF,HMFCA and FFCA) show a volcano-like dependence on the number of oxygen defects(i.e.,O_(2)^(-)and O^(-)) and electron-rich Au0sites.The optimum Au/Ni3Co1Oycatalyst exhibits a highest productivity of FDCA(12.5 mmol_(FDCA)mol_(Au)^(-1)h^(-1)) among all the Au catalysts in the literature and achieves> 99% yield of FDCA at 120℃ and 10 bar of O_(2).In addition,this catalyst can be easily recovered by a magnet and show superior stability and reusability during six consecutive cycling tests.This work may shed a light on Au catalysis for the base-free oxidation of biomass compounds by smartly using the synergy in bimetallic oxide carriers.

Observation and mitigation of image distortion in high-energy electron radiography

Image distortion caused by the angular misalignment of quadrupole magnets in high-energy electron radiography has been studied systematically.We propose that the distortion originates from the coupling of the electron motions in the transverse directions,based on a theoretical analysis and the transfer-matrix method.The relative angular rotation between the second and third magnetic quadrupoles was identified as the main contributor to image distortion.This was verified by both a beam-dynamics simulation and experiments.Different strategies to mitigate this image distortion are also explored,including magnets online tuning,higher beam energy and larger magnification factor.This study provides criteria for designing experiments and paves the way for achieving higher image precision.

Simulation research on collisions between highway corrugated beam guardrails and vehicles based on LS-DYNA

To explore the safety of highway traffic operations,the vehicle state and guardrail deformation during highway guardrail collisions are simulated and analyzed.The vehicle-guardrail collision is simulated by finite element software such as LS-DYNA and HyperMesh.The vehicle speed settings are 60,80,100 and 120 km/h,and the collision angles are 5°,10°,15°and 20°.The guardrail deformation,vehicle acceleration and energy changes under different collision speeds and angles are studied.The research results show that at the same collision speed,an increase in the collision angle causes more serious damage to the vehicle,a greater transverse displacement of the guardrail,and a greater range of car acceleration fluctuations.When the collision angle is the same,an increase in the collision speed causes greater lateral displacement of the guardrail,a greater vehicle acceleration fluctuation range,and more serious vehicle damage.The results of the study can provide a reference for demonstrating highway guardrail safety.

Review on application of phase change materials in asphalt pavement

Phase change materials(PCMs)can regulate the temperature in asphalt pavement and minimize temperature-related problems,such as rutting and thermal cracking,because of their ability to store and release latent heat.Suitable PCMs can also enable additional road surface functions,such as snow melting ability,freeze-thaw cycle resistance,and heat island reduction.These functions are helpful in achieving intelligent,green,and sustainable transportation systems.Although the research on PCMs for asphalt pavement has been carried out for more than 10 years,a systematic material system and mature application technology have not yet been formed.The main reasons for restricting the development of this technology include the lack of suitability between the PCMs and asphalt pavement,the quantitative characterization of phase change temperature regulation property,and the evaluation of the effect of phase change energy storage on improving pavement performance.Although the published review has made a comprehensive summary of the existing research,it has yet to identify the key restricting the development of this technology and carry out a review and discussion based on it.To grasp the development status of the application of PCMs in asphalt pavement,sort out the development needs and break through the technical barriers,this study systematically summarizes the preparation and performance of PCMs for asphalt pavement,compares the performance and evaluation methods of asphalt mixtures with different PCMs,and summarizes the numerical simulation methods of phase change asphalt mixtures.Finally,this study presents potential approaches to address critical technical issues and discusses possible future research.

Cell Cycle Arrest, Apoptosis, and Autophagy Induced by chabamide in Human Leukemia Cells

Objective To investigate the antitumor effect of chabamide in K562 （human leukemia cell line） cells. Methods The cytotoxicity was assessed by a standard colorimetric assay using 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT）. The morphological changes were observed by Hoechst 33258 staining. Induction of apoptosis, loss of the mitochondrial membrane potential （A ~＇m）, and cell cycle analysis were evaluated by flow cytometry （FCM） analysis. Levels of apoptosis-related proteins, ceil cycle-related proteins, and LC3 protein were detected by Western blotting. Moreover, the autophagy induced by chabamide was also detected by MDC fluorescent staining. Results Chabamide significantly inhibited cell proliferation by cell cycle arrest in the Go/G1 phase. This phenomenon was associated with an obvious increase in p21 expression and decrease in cyclin D1 and cyclin-dependent kinase 2/4/6 protein expression. Moreover, chabamide could regulate the changes in mitochondrial membrane potential, increase the expression of apoptosis-related proteins, such as Bax and cytochrome C, and decrease the protein expression of Bcl-2, caspase-9, caspase-3, and PARP-1. JNK, ERK1/2, and p38 were also regulated by chabamide in K562 cells. Furthermore, induction of autophagy, marked by autophagic vacuole formation, was detected. Conversion of LC3-1 to LC3-11, a marker of active autophagosome formation, was also detected following chabamide treatment. Conclusion The antitumor activity of chabamide with the results of apoptosis and autophagy induction was confirmed in K562 cells.

CSC-GCN:Contrastive semantic calibration for graph convolution network

Graph convolutional networks(GCNs)have been successfully applied to node representation learning in various real-world applications.However,the performance of GCNs drops rapidly when the labeled data are severely scarce,and the node features are prone to being indistinguishable with stacking more layers,causing over-fitting and over-smoothing problems.In this paper,we propose a simple yet effective contrastive semantic calibration for graph convolution network(CSC-GCN),which integrates stochastic identity aggregation and semantic calibration to overcome these weaknesses.The basic idea is the node features obtained from different aggregation operations should be similar.Toward that end,identity aggregation is utilized to extract semantic features from labeled nodes,while stochastic label noise is adopted to alleviate the over-fitting problem.Then,contrastive learning is employed to improve the discriminative ability of the node features,and the features from different aggregation operations are calibrated according to the class center similarity.In this way,the similarity between unlabeled features and labeled ones from the same class is enhanced while effectively reducing the over-smoothing problem.Experimental results on eight popular datasets show that the proposed CSC-GCN outperforms state-ofthe-art methods on various classification tasks.