Abstract:Olfactory receptors (OR) are not only expressed in the olfactory sensory neurons, but also widely expressed in all other human tissues tested to date, and playing important physiological roles. In this review, the existing data concerning the expression of olfactory receptors, as well as the functions in non-olfactory tissues and cells. The functions of these ORs are primarily to maintain normal physiological functions by controlling the endogenous chemicals surrounding the cells, and to represent specific functions when stimulated by selected exogenous ligands. In the field of medicine, about 40% of listed drugs are targeted at the G protein coupled receptors (GPCRs) family, and ORs are the largest member of GPCR subfamily. We speculate that these olfactory receptors may become important drug targets in the future. This review of OR functions, on the one hand, is beneficial to use OR as a potential drug target to develop new drugs; on the other hand, it also provides a new research idea for the pharmacological action of volatile monomers in traditional Chinese medicine.

Abstract:Cancer is a serious threat to human health and life safety. The number of cancer patients has been increasing worldwide. Therefore, it is of great significance to develop efficient cancer treatment methods. Currently, the main clinical methods for cancer therapy include surgery, radiotherapy, chemotherapy, immunotherapy, and so on. In recent decades, nanomaterials-based cancer treatment methods have shown great potential and value in radiotherapy, chemotherapy and immunotherapy. Metal-organic framework (MOFs) is a kind of material composed of metal nodes and organic ligands. The metal-organic frameworks have many advantages, such as large porosity, adjustable aperture and size, good biocompatibility, adjustable composition and surface modification, which make it promising in the field of cancer therapy. In this review, the methods for constructing MOFs-based drug delivery system (DDS) were firstly introduced. In particular, small molecule drugs can be efficiently loaded into metal-organic frameworks using non-covalent penetration, covalent cross-linking, and so on. At the same time, biomacromolecules-MOF system could be constructed based on the methods such as pore-penetrating and de novo approach. MOF-enzyme complex is more resistant to hush circumstances or protein inactivating agents than naked enzyme. Moreover, the metal-organic framework itself can be designed to be highly efficient nano-drug by using pharmaceutically active organic molecules or metal ions as ligands or metal ions. General surface modification methods were also reviewed due to their important roles for improving the solubility and stability of MOF-based DDS. In this review, recent numerous researches on the cancer therapy of MOF-based DDS have been summarized. According to the type of treatment methods, the applications of MOF-based DDS in chemotherapy, photodynamic therapy, biomacromolecules-MOF based therapy, and other combined therapies (such as radiotherapy, and immunotherapy) for cancer were introduced, respectively. Finally, we summarized the advantages and challenges of MOFs in cancer therapy, and prospected the opportunities and development of this research field.

Abstract:Hyperosmolality-induced [Ca²⁺]_i increase (OSCA)/Transmembrane protein 63 (TMEM63) family proteins are multi-pass membrane proteins. They are broadly presented in eukaryotic cells. Previous study showed that OSCA1.1 from Arabidopsis mediated the hyperosmolality induced calcium increase in plants. Additional studies showed OSCA1.1 and its homologues were mechanosensitive ion channels. High resolution cryo-EM structures revealed that OSCA proteins were symmetric dimers and each subunit harbored an ion permeation pathway. The review will focus on recent progress on the studies of the function, structure and structural-functional relationship of OSCA channels.

Abstract:Ubiquitination is a prevalent posttranslational modification in eukaryotic cells. Ubiquitination almost regulates all eukaryotic signaling pathways, thereby playing essential roles in eukaryotic cellular processes including immune responses. Bacterial pathogens inject a series of virulence proteins, named effectors, via special protein secretion systems, such as typeⅢ and typeⅣ secretion systems, into the host cells to modulate host signaling pathways. Many effectors harbor unique enzymatic activities to modify ubiquitin or the ubiquitin-conjugating enzyme Ubc13, or have E3 ubiquitin ligase or deubiquitinase activities. This review summarizes the progresses and the newest discoveries on mechanisms of host ubiquitination modulation by bacterial effector proteins.

Abstract:The mechanism underlying the alteration of neural activity in the human brain and the vigilance level during sleep deprivation (SD) remains a subject of ongoing investigation, particularly with regard to the sensorimotor and visual systems. Resting-state functional magnetic resonance imaging (rfMRI), a noninvasive imaging technology reflecting spontaneous activity of the human brain, is widely used in SD research. In the present study, nine repeated rfMRI sessions followed by a psychomotor vigilance task (PVT) were used to explore the alteration of neural activity and vigilance level during 36 h of SD in 23 volunteers. Mean reaction time (MRT) and lapse ratio (LR) based on PVT were measured to assess variation in vigilance level. The sensorimotor network (SMN) and visual network (VN) are the most vulnerable areas after obtaining SD measures from ReHo (regional homogeneity) and ALFF (amplitude of low-frequency fluctuation) based on rfMRI. Group-ICA was used to parcellate the visual-related regions into visual area Ⅰ, visual area Ⅱ, and the visual association area. Sensorimotor-related regions, including the bilateral precentral/postcentral gyrus, the bilateral paracentral lobule, and the supplementary motor area (SMA), were extracted from the anatomical automatic labeling (AAL) templates. Brain neural activity and vigilance level were deteriorated at 16-30 h of SD. A 2 × 3 repeated-measures ANOVA was used to explore the effects of sleep pressure and circadian rhythm and their interaction on neural activities of sensorimotor-related and visual-related regions. Significant effects of sleep pressure and interaction on all sensorimotor-related and visual-related regions were observed. Pearson’s correlation coefficients were used to explore the relationships between variation in vigilance level and alteration in brain neural activities of sensorimotor-related and visual-related regions. Significant correlations were observed between the neural activities of all sensorimotor-related regions and variation in vigilance during SD. Our results confirmed that SD alters the vigilance level and neural activity of the SMN and the VN, beginning at 24:00 on the first day, and sleep pressure and circadian rhythm regulate the neural activity of the SMN and VN during SD. Furthermore, sleep pressure significantly regulates the effects of circadian rhythm. The enhancement of ReHo in the SMN and VN leads to a weakening of their remote connections, which may be the cause of the slowing of response time during SD.

Abstract:The major histocompatibility complex (MHC)Ⅰ binding affinity models have contributed to screen the candidate peptides, and have assisted the experiments in determining the peptides that can form complexes with MHCⅠmolecules to activate cytotoxic T cells. The transporter associated with antigen processing (TAP) binding models could also be used for screening the candidate peptides. How to make the best of the two types of binding affinity models for screening out the candidate peptides, the similarities and differences between the selectivity of TAP and MHCⅠmolecules in peptides and the biological mechanism of that similarities and differences, these three questions remains obscure. Herein, we rearranged the TAP binding test set, increasing its size to 699. The established TAP binding model based on Kernel-function stabilized matrix method (KSMM) had a higher prediction accuracy than that of the state of the art, achieving a relevant correlation coefficient of 0.89 on a 5-fold cross-validation. The integrative prediction of HLA-A3 affinity and TAP affinity models remarkedly improved the discrimination accuracy, with the AUC value increasing from ~0.82 to 0.87. This improvement is due to the different preferences of the two types of affinity models for the best defined amino acids on 2nd and 9th positions, as well as to the complementarity of such different preferences. The results of TAP-peptide docking also supported this conclusion. The TAP model is available online: http://www.bilologymaths.top/mbtwo/major.aspx.