Activity

Here we introduce SBMOpenMM, a Python library to build force fields for SBMs, that uses the OpenMM framework to create and run SBM simulations. The code is flexible and user-friendly and profits from the high customizability and performance provided by the OpenMM platform.With the increase of food allergy events related to not properly cooked kidney beans (Phaseolus vulgaris L.), more and more researchers are paying attention to the sensitization potential of lectin, one of the major storage and defensive proteins with the specific carbohydrate-binding activity. The immunoglobulin E (IgE), non-IgE, and mixed allergic reactions induced by the lectins were inducted in the current paper, and the detection methods of kidney bean lectin, including the purification strategies, hemagglutination activity, specific polysaccharide or glycoprotein interactions, antibody combinations, mass spectrometry methods, and allergomics strategies, were summarized, while various food processing aspects, such as the physical thermal processing, physical non-thermal processing, chemical modifications, and biological treatments, were reviewed in the potential of sensitization reduction. It might be the first comprehensive review on lectin allergen detection from kidney bean and the desensitization strategy in food processing and will provide a basis for food safety control.A series of oxadiazole derivatives were synthesized and evaluated as 5-hydroxytryptamine-4 receptor (5-HT4R) partial agonists for the treatment of cognitive deficits associated with Alzheimer’s disease. Starting from a reported 5-HT4R antagonist, a systematic structure-activity relationship was conducted, which led to the discovery of potent and selective 5-HT4R partial agonist 1-isopropyl-3-5-[1-(3-methoxypropyl) piperidin-4-yl]-[1,3,4]oxadiazol-2-yl-1H-indazole oxalate (Usmarapride, 12l). ML385 It showed balanced physicochemical-pharmacokinetic properties with robust nonclinical efficacy in cognition models. It also showed disease-modifying potential, as it increased neuroprotective soluble amyloid precursor protein alpha levels, and dose-dependent target engagement and correlation of efficacy with oral exposures. Phase 1 clinical studies have been completed and projected efficacious concentration was achieved without any major safety concerns. Phase 2 enabling long-term safety studies have been completed with no concerns for further development.Conventional kinesin, a motor protein that transports cargo within cells, walks by taking multiple steps toward the plus end of the microtubule (MT). While significant progress has been made in understanding the details of the walking mechanism of kinesin, there are many unresolved issues. From a computational perspective, a central challenge is the large size of the system, which limits the scope of time scales accessible in standard computer simulations. Here, we create a general multiscale coarse-grained model for motors that enables us to simulate the stepping process of motors on polar tracks (actin and MT) with a focus on kinesin. Our approach greatly shortens the computation times without a significant loss in detail, thus allowing us to better describe the molecular basis of the stepping kinetics. The small number of parameters, which are determined by fitting to experimental data, allows us to develop an accurate method that may be adopted to simulate stepping in other molecular motors. The model enables us to simulate a large number of steps, which was not possible previously. We show in agreement with experiments that due to the docking of the neck linker (NL) of kinesin, sometimes deemed as the power stroke, the space explored diffusively by the tethered head is severely restricted, allowing the step to be completed in tens of microseconds. We predict that increasing the interaction strength between the NL and the motor head, achievable by mutations in the NL, decreases the stepping time but reaches a saturation value. Furthermore, the full three-dimensional dynamics of the cargo are fully resolved in our model, contributing to the predictive power and allowing us to study the important aspects of cargo-motor interactions.Type 1 diabetes mellitus (T1DM), as an autoimmune deficiency disease, is associated with an absolute deficiency of insulin subject to islet β-cell destruction. Insulin-producing cells (IPCs) differentiated from induced pluripotent stem cells are an ideal replacement origin of β-cells, which can be applied for cell transplantation therapies in T1DM. At present, more strategies focus on inducing and differentiating to obtain IPCs; however, the unsatisfactory differentiation efficiency and the lack of ideal carriers for in vivo transplantation limited their application. It is necessary to consider the cell microenvironment by constructing a biomimetic niche to improve the differentiation and transplantation efficiency. The main components of the extracellular matrix derived from pancreatic (the niche of β-cells) decellularization were retained, which could provide the ideal extracellular microenvironment for IPCs. In this research, a hydrogel prepared with alginate (Alg) and the pancreatic extracellular matrix (pECM) was assessed for the beneficial outcomes on encapsulated IPCs. The results showed that pECM/Alg improved the differentiation efficiency and promoted insulin secretion and the expression of insulin-related genes as well. Besides, pECM/Alg-encapsulated IPCs exhibited obvious biocompatibility in vivo, which can prolong the transplantation effect and hypoglycemic function by reducing the inflammatory reaction. RNA-seq indicated that the PI3K/Akt pathway may be related to the improvement of the differentiation efficiency and function of IPCs. In general, the pECM/Alg hydrogel provides an ideal biomimetic microenvironment for IPCs and is suitable for in vivo transplantation.In this study, we fabricate and characterize a Ti/TiO2/Si device with different dopant concentrations on a silicon surface for neuromorphic systems. We verify the device stack using transmission electron microscopy (TEM). The Ti/TiO2/p++Si device exhibits interface-type bipolar resistive switching with long-term memory. The potentiation and depression by the pulses of various amplitudes are demonstrated using gradual resistive switching. Moreover, pattern-recognition accuracy (>85%) is obtained in the neuromorphic system simulation when conductance is used as the weight in the network. Next, we investigate the short-term memory characteristics of the Ti/TiO2/p+Si device. The dynamic range is well-controlled by the pulse amplitude, and the conductance decay depends on the interval between the pulses. Finally, we build a reservoir computing system using the short-term effect of the Ti/TiO2/p+Si device, in which 4 bits (16 states) are differentiated by various pulse streams through the device that can be used for pattern recognition.