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Glucagon receptor (GCGR) is a class B1 G-protein-coupled receptor that plays a crucial role in maintaining human blood glucose homeostasis and is a significant target for the treatment of type 2 diabetes mellitus (T2DM). Currently, six small molecules (Bay 27-9955, MK-0893, MK-3577, LY2409021, PF-06291874, and LGD-6972) have been tested or are undergoing clinical trials, but only the binding site of MK-0893 has been resolved. To predict binding sites for other small molecules, we utilized both the crystal structure of the GCGR and MK-0893 complex and dynamic conformations. We docked five small molecules and selected the best conformation based on binding mode, docking score, and binding free energy. We performed MD simulations to verify the binding mode of the selected small molecules. Moreover, when selecting conformations, results of competitive binding were referred to. MD simulation indicated that Bay 27-9955 exhibits moderate binding stability in Pocket 3. MK-3577, LY2409021, and PF-06291874 exhibited highly stable binding to Pocket 2, consistent with experimental results. However, LY2409021 may also bind to Pocket 5. Additionally, LGD-6972 exhibited relatively stable binding in Pocket 5. We also conducted structural modifications of LGD-6972 based on the results of MD simulations and predicted its analogues' bioavailability, providing a reference for the study of GCGR small molecules. [ABSTRACT FROM AUTHOR]

Deep learning techniques have gradually attracted considerable research interest in numerous application scenarios because of their capacity to simplify and accelerate calculations. Several researchers have adopted deep learning models, primarily end-to-end long short-term memory networks, to predict structural seismic responses in a data-driven manner and have achieved remarkable improvements. However, further research is required to reduce the training cost and complexity while maintaining the prediction accuracy of end-to-end models. In this study, a pre-training strategy was developed to meet these requirements. In brief, a generic base model was pre-trained by embedding the knowledge of calculating the response of single-degree-of-freedom systems, which was used as the basis for building tailored top models for the online prediction of seismic responses of different structures. This strategy modularized and simplified deep-learning-based seismic response prediction for training while maintaining the advantages of the end-to-end method. Proposed method was verified by using both simulation and actual datasets. The results demonstrated that a significantly lower training cost and complexity were required to achieve a prediction accuracy similar to that of the classic end-to-end method. Specifically, there was a reduction in FLOPs ranging from 20% to 80%, and a decrease in training time ranging from 44% to 82%. Moreover, the performance of deep learning with limited actual data was discussed. [ABSTRACT FROM AUTHOR]

Taking into account the issues faced by self-driving vehicles in multilane expressway scenarios, a lane-change decision planning framework that considers two adjacent lanes is proposed. Based on this framework, the lateral stability of an autonomous vehicle under near-limit conditions during lane change is studied by the phase-plane method. Firstly, a state-machine-based driving logic is designed and a decision method is proposed to design the lane-change intention based on the surrounding traffic information and to consider the influence of the motion state of other vehicles in the adjacent lanes on the self-driving vehicle. In order to realize adaptive cruising under the full working conditions of the vehicle, a safety distance model is established for different driving speeds and switching strategies for fixed-speed cruising, following driving, and emergency braking are developed. Secondly, for the trajectory planning problem, a lane-change trajectory based on a quintuple polynomial optimization method is proposed. Then, the vehicle lateral stability boundary is investigated; the stability boundary and rollover boundary are incorporated into the designed path-tracking controller to improve the tracking accuracy while enhancing the rollover prevention capability. Finally, a simulation analysis is carried out through a joint simulation platform; the simulation results show that the proposed method can ensure the driving safety of autonomous vehicles in a multilane scenario.

Abstract Aim To assess the effectiveness of decision aids in the treatment, prevention and screening of breast cancer patients. Design A systematic review and meta‐analysis. Methods The review protocol was registered in the CRD Prospero database(CRD42020173028). A literature search was carried out in five databases: PubMed, Cochrane, EMBASE, Scopus and Web of science data in January 2020. We used The Cochrane risk bias assessment tool to evaluate the literature quality of included trials and the Review Manager 5.2 software to analyse data. Results We included 22 studies. Compared with the conventional methods, decision aids reduced treatment decision conflicts and had no significant effect on screening decision conflicts (WMD=−2.25, 95% CI = ‐ 2.64,‐1.87, p

To evaluate the effects of calcium supplementation on bone mineral density in children.

Abstract Background The stem cells of the stem cell banks have prominent problems for insufficient sources, easy contamination, unstable biological characteristics after serial subcultivations, and high cost. Methods After collecting the construction processes of the existing stem cell banks and suggestions from authoritative experts in the past 10 years, 230 reference principles were obtained, and finally, the principles of “5C” for the establishment of modern standardized stem cell banks were summarized, and their related applications on the management of sports injuries were reviewed as well. Results The basic principles of “5C” for the establishment of modern standardized stem cell banks include (1) principle of informed consent, (2) confidentiality principle, (3) conformity principle, (4) contamination-free principle, and (5) commonweal principle. The applications of stem cells on repairs, reconstructions, and regenerations of sports injuries were also reviewed, especially in tissue-engineered cartilage, tissue-engineered meniscus, and tissue-engineered ligament. Conclusions The proposal of the basic principles of “5C” is conducive to relevant stem cell researchers and clinical medical experts to build modern stem cell banks in a more standardized and efficient manner while avoiding some major mistakes or problems that may occur in the future. On this basis, stem cells from stem cell banks would be increasingly used in the management of sports injuries. More importantly, these days, getting stem cell samples are difficult in a short time, and such banks with proper legal consent may help the scientific community.

In recent years, surface tilt deformation of soil landslides has become an important indicator of landslide monitoring and early warning, but few studies have been done on the relationship between the slope surface tilt deformation and development characteristics of landslides. In this paper, a series of rainfall model tests combined with field tests was carried out to explore the relationship between the displacement and tilt deformation of slope surface in the process of landslide disaster evolution. A landslide warning method based on the curve of slope surface tilt deformation with time was established. The test results showed that the surface tilt deformation of soil landslides accelerates in the failure stage. There is a linear relationship between the reciprocal of tilt rate and the residual time of landslide before the failure, which can be used to predict the final failure time of landslides. In addition, in the process of landslide sliding, the surface tilt deformation and displacement of the landslide also show a linear correlation, and the corresponding slope is consistent with the sliding radius. The findings reveal, for the first time, the relationship between the slope surface tilt deformation and the geometric characteristics of the sliding zone, also provide the experimental basis for the prediction method of landslide sliding zone based on slope tilt surface deformation.