The functions of exosomes targeting astrocytes and astrocyte-derived exosomes targeting other cell types

Astrocytes are the most abundant glial cells in the central nervous system;they participate in crucial biological processes,maintain brain structure,and regulate nervous system function.Exosomes are cell-derived extracellular vesicles containing various bioactive molecules including proteins,peptides,nucleotides,and lipids secreted from their cellular sources.Increasing evidence shows that exosomes participate in a communication network in the nervous system,in which astrocyte-derived exosomes play important roles.In this review,we have summarized the effects of exosomes targeting astrocytes and the astrocyte-derived exosomes targeting other cell types in the central nervous system.We also discuss the potential research directions of the exosome-based communication network in the nervous system.The exosome-based intercellular communication focused on astrocytes is of great significance to the biological and/or pathological processes in different conditions in the brain.New strategies may be developed for the diagnosis and treatment of neurological disorders by focusing on astrocytes as the central cells and utilizing exosomes as communication mediators.

Allosteric Mechanism of Calmodulin Revealed by Targeted Molecular Dynamics Simulation

Calmodulin （CAM） is involved in the regulation of a variety of cellular signaling pathways. To accomplish its physiological functions, CaM binds with Ca2＋ at its EF-hand Ca2＋ binding sites which induce the conformational switching of CaM. However, the molecular mechanism by which Ca2＋ binds with CaM and induces conformational switching is still obscure. Here we combine molecular dynamics with targeted molecular dynamics simulation and achieve the state-transition pathway of CaM. Our data show that Ca2＋ binding speeds up the conformational transition of CaM by weakening the interactions which stabilize the closed state. It spends about 6.5 ns and 5.25 ns for transition from closed state to open state for apo and holo CaM, respectively. Regarding the contribution of two EF-hands, our data indicate that the first EF-hand triggers the conformational transition and is followed by the second one. We determine that there are two interaction networks which contribute to stabilize the closed and open states, respectively.

Fusion network for small target detection based on YOLO and attention mechanism

Target detection is an important task in computer vision research, and such an anomaly detection and the topic of small target detection task is more concerned. However, there are still some problems in this kind of researches, such as small target detection in complex environments is susceptible to background interference and poor detection results. To solve these issues, this study proposes a method which introduces the attention mechanism into the you only look once(YOLO) network. In addition, the amateur-produced mask dataset was created and experiments were conducted. The results showed that the detection effect of the proposed mothed is much better.

Perspectives on bone-targeted nano-drug carriers for bone tumor treatment

Bone tumour is one of most common primary cancer which exhibits cancerous osteoblastic differentiation and malignant osteoid in patients.At present,chemotherapy(pre-and post-operative)is used as a standard treatment protocol for bone tumour.However,drugs used in the treatment of bone tumour induce high toxicity to normal tissues including anaemia,neutropenia,thrombocytopenia,and heart damage which further reduce the survival rate of patients.Therefore,there is an urgent need to develop a new therapeutic approach for the treatment such that it induce maximum cell killing effect in tumor cells while sparing the healthy bone cells.In this article,some new perspectives were provided on the development of bone-targeted nano-drug carriers for bone cancer treatment.We hope such discussions wouldencourage more detailed and careful studies to support product development of bone-targeted drug carriers for bone cancer treatment.

Advances in understanding the molecular mechanism of pancreatic cancer metastasis

BACKGROUND： Pancreatic cancer（PC） is usually diagnosed at the late-stage and therefore, has widespread metastasis and a very high mortality rate. The mechanisms underlying PC metastasis are not well understood. Recent advances in genomic sequencing have identified groups of gene mutations that affect PC metastasis, but studies elucidating their roles are lacking. The present review was to investigate the molecular mechanisms of PC metastasis.DATA SOURCES： Relevant articles on PC metastasis were searched in MEDLINE via Pub Med prior to April 2015. The search was limited in English publications.RESULTS： PC metastatic cascades are multi-factorial events including both intrinsic and extrinsic elements. This review highlights the most important genetic alterations and other mechanisms that account for PC invasion and metastasis, with particular regard to epithelial-mesenchymal transition, inflammation, stress response, and circulating tumor cells.CONCLUSIONS： Analyses of relevant gene functions and signaling pathways are needed to establish the gene regulatory network and to define the pivotal modulators. Another promising area of study is the genotyping and phenotyping of circulating tumor cells, which could lead to a new era of personalized therapy by identifying specific markers and targets.

A natural nano-platform:Advances in drug delivery system with recombinant high-density lipoprotein

Developing natural nano-platforms with high biocompatibility and natural targeting ability represents great significance for drug delivery.High-density lipoprotein(HDL),a natural lipid-protein complex,plays important roles in physiological activities,particularly in reverse cholesterol transport(RCT)and be closely associated with atherosclerotic cardiovascular diseases.Recent studies have demonstrated that HDLs have the potential to serve as ideal drug carriers.Recombinant HDLs(r HDLs)have been used to encapsulate substances such as small interfering RNA(siRNA),drugs,and contrast agents,fully utilizing the biocompatibility and targeting ability of r HDL in the body and providing new strategies for drug delivery and disease treatment.In this review,we discussed in detail the basic principles of HDL as a drug delivery system,the mechanisms of targeted drug delivery,and several methods for preparing HDL nanoparticles.Afterward,we comprehensively reviewed the applications of HDL as a drug carrier in cardiovascular diseases,cancer treatment(such as glioblastoma,breast cancer,hepatocellular carcinoma and urologic cancers)and some other fields.Finally,we reviewed the therapeutic effects and safety of HDL nanoparticles in clinical studies.Through a review and summary of these research advances,we aim to fully understand the potential of HDL as a drug carrier in clinical applications,providing valuable references and guidance for future research and expedites the translational application of HDL as drug carriers.