Abstract:Relapse behavior after long-term abstinence is the key problem of addiction treatment. A major factor to induce relapse is the persistence of maladaptive drug-associated memories. Persistent changes in structure and function of prefrontal cortex-mesolimbic dopamine system caused by chronic drug abusing, lead to the formation of pathological drug-associated memories. This article reviews addiction with a focus on how it can be conceptualised as a disorder of maladaptive memory, considering the neural basis of drug-associated memories during the initial phase, the habituation phase and the maintenance phase of addictive behavior. The present review summarizes the clinical intervention methods of drug-associated memories in recent years including extinction training, extinction in multiple contexts to facilitate extinction and reconsolidation intervention to disrupt drug-associated memories directly, and the application of virtual reality technology and neuromodulation methods in addiction intervention. The intervention methods combined memory reconsolidation with virtual reality technology or neuromodulation methods are prospected to target drug-associated memories, providing new methods and new ideas to treat addiction in future clinical researches.

Abstract:Multiphoton microscopy is an important biomedical imaging modality with great potential in the diagnosis of various diseases, due to high resolution, low damage, and long-term imaging of living organisms. Especially for the research on brain diseases, multiphoton microscopy can be used to observe neuron,blood vessels,tumors, and their interactions,which can further reveal the pathogenesis of brain diseases and direct the developement of diagnosis and treatment methods. This review introduces the basic principles and characteristics of multiphoton microscopy, and its applications in the study of various brain diseases, such as Alzheimer"s disease,stroke and tumor. We highlight recent achievements in brain diseases using multiphoton microscopy and give an outlook on the development of multiphoton microscopy that isexpected to play a greater role in the study of brain diseases.

Abstract:The special structural unit on the brain"s capillaries supplies oxygen and nutrients to the brain, while at the same time forming a restrictive barrier called blood-brain barrier (BBB). The structural unit is mainly composed of a single layer of brain microvascular endothelial cells, surrounding by endothelial cells, as well as the neurons, microglia, and astrocytes, are involved in the formation of the blood-brain barrier. The blood-brain barrier is a selective permeation barrier，most of the central nervous system drug candidates have poor permeability in the blood-brain barrier. The disadvantages of drug screening experiments in laboratory animals are high cost, long cycle, and low accuracy. Besides, directly test in the human body is unethical. But establishing a reliable model of extracorporeal blood-brain barrier can simplify the experimental process, shorten the test period, and make the experimental results easier to determine. Therefore, the establishment of an in vitro BBB model can greatly accelerate the development of central nervous system drugs. The models that have been studied can be divided into three categories: single culture, co-culture, and triple culture. These models range from simple to complex, and more similar to blood-brain barrier in vivo. This article reviews the current blood-brain barrier model, and we expect it can provide new ideas for the design of in vitro BBB models in the future.

Abstract:Atrial fibrillation (AF) is a typical persistent arrhythmia, and revealing its pathogenesis and pathophysiological process is the key to AF diagnosis, prevention, and treatment. It also assists AF drug development and clinical equipment design. Experimental and clinical results can only show the local characteristics of cells or sub-cells and the macroscopic results of atrial fibrillation. However, with the development of bioinformatics acquisition technology and statistical analysis technology, using multi-scale virtual heart model to achieve the unity of macro-and micro-mechanism has attracted the attention of the research community. In this paper, we systematically reviewed the advances in virtual heart modeling at various levels, such as ion channels, cardiac cells, heart tissues and organs, and discussed the mechanisms of atrial fibrillation based on virtual heart models and the treatment of atrial fibrillation. This paper also presents the challenges and future development of atrial fibrillation.

Abstract:Understanding and explaining how proteins fold have been the ultimate challenges in molecular and structure biology. Protein folding should initiate from a thermodynamic metastable state of unfolded proteins, otherwise, it is difficult to explain how an unfolded protein chain folds exactly into its native 3D structure in an expeditious and reproducible manner under severe thermal disturbance from temperature. Considering dependency of protein folding on aqueous environments and unique physical properties of water molecules, this study uncovers an initial thermodynamic metastable state of unfolded proteins in aqueous environment that enables them to that resists thermal-motion and avoids misfolding. The existence of the thermodynamic metastable state of unfolded proteins are verified by analyzing the results available from experiments in the literature. The principles of physics are applied to estimate the breakage of the thermodynamic metastable state of specific amino acids, that enable the leading to the inferred as physical folding mechanisms and codes for proteins.

Abstract:3-Ketoacy ACP reducatase (FabG), the key enzyme for bacteria growth, catalyzes the first reduction step in fatty acid synthesis. Pseudomonas putida has important application values in environmental pollution bioremediation and industrial polyhydroxy fatty acid (PHA) production. Bioinformatics analysis showed Pseudomonas putida genome encodes six FabG homologues with E. coli FabG, of which PpFabG5 shows the highest sequence similarity (76.5%) and other five PpFabGs also have high similarity (about 50%). Except PpFabG4, the other homologs have the conserved catalytic activity sites and N-terminal cofactor binding sites. So the paper used different methods, including the genetic complementary, catalytic activity analysis in vitro, gene deletion in vivo, and mutant characteristic analysis, to study the biological functions of the six homologs. The results showed that only PpfabG1, PpfabG3 and PpfabG5 could restore the growth of E.coli fabG temperature-sensitive mutant CL104 at 42℃, and the complementary strain of PpfabG1 grew weakly. While in vitro analysis, PpFabG1, PpFabG3 and PpFabG5 also showed the catalytic activities in the initial and extension reactions of fatty acid synthesis, although the activity of PpFabG1 was really weak. PpFabG6 only had catalytic activity in the initial reaction. PpfabG5 is an essential gene for growth, which can’t be deleted in the genome. While the deletion of the other PpfabG individually does not affect bacteria growth or the compositions of fatty acids comparing with wild type strain. However, the motility of PpfabG1 or PpfabG3 deletion mutant decreased, PpfabG3 or PpfabG6 deletion affected the biofilm formation, and PpfabG3 or PpfabG6 deletion mutant showed higher tolerance to H₂O₂. These results proved different FabG homologs contained different biological functions, especially when countered with stressful conditions.

Abstract:Chinese yam is a traditional Chinese medicine. It has many benefits for people, such as antidiarrhea, anti-inflammation, antidiabetic, hypocholesterolemia, antioxidation, antitumor, and immunomodulation. However, in the process of contacting yam, it often causes itching. However, the pruritus compound in yam is very unclear. We extract allantoin crystal from fresh Chinese yam using ethanol extraction, membrane filtration, ion exchange chromatography, suspension drop method. The content of allantoin extracted from yam (origin from Jiaozuo, Henan) is about 3.567 mg/g. Allantoin is an important compound in plants and animals. Our results show that allantoin could induce more scratch numbers in mice than control group. Allantoin also directly actives dorsal root ganglia neurons, induces calcium influx and inward current in neurons.

Abstract:CryoEM single particle reconstruction technique is a widely used method for solving macromolecular structures in structural biology. However, there are still some shortcomings in the current processes of single particle three-dimensional reconstruction. None of the current single particle reconstruction software has implemented the function of automatically finding soft mask for binary mapping out the reconstructed map, which can import bias in the computation of statistical model of noise, influencing effectiveness of three-dimensional reconstruction. To solve this problem and to improve the solvent flattening operation in single particle reconstruction, here, we report a new method for automatically finding soft mask for mapping out the reconstructed map in single particle reconstruction, by using Gaussian filtering, Canny edge detection, minimum error thresholding etc., for processing reconstructed map. This new method is derived from the solvent flattening method, which is widely used in X-ray crystallography for solving and improving macromolecular phases. In the experiment, we implemented FSC between reconstructed maps, Euler angular error scatter plot etc. methods to assess effect of auto-mask method. It was shown that mask map generated by auto-mask method can soundly cover molecular signal region of reconstructed map, and our new auto-mask method in three-dimensional reconstruction can help to improve resolution of three-dimensional reconstruction.