[SGK1 as a therapeutic target for central nervous system diseases].

Serum and glucocorticoid-regulated kinase 1 (SGK1) plays an important role in the physiological processes of hormone release, neuronal excitation and cell proliferation. SGK1 also participates in the pathophysiological processes of inflammation and apoptosis in the central nervous system (CNS). Increasing evidence demonstrates that SGK1 may serve as a target of the intervention of neurodegenerative diseases. In this article, we summarize the recent progress on the role and molecular mechanisms of SGK1 in the regulation of the function of the CNS. We also discuss the potential of newly discovered SGK1 inhibitors in the treatment of CNS diseases.

Identification of a novel SPT inhibitor WXP-003 by docking-based virtual screening and investigation of its anti-fungi effect.

Serine palmitoyltransferase (SPT) plays the key role on catalysing the formation of 3-ketodihydrosphingosine, which is the first step of the de novo biosynthesis of sphingolipids. SPT is linked to many diseases including fungal infection, making it a potential therapeutic target. Thus, a logical docking-based virtual screening method was used to screen selective SPT inhibitor against fungi, not human. We used myriocin-similarity database to identify compounds with good binding with fungal SPT and poor binding with homology human SPT model. Preliminary bio-assay led to the discovery of a promising inhibitor WXP-003, which displayed good inhibitory activity against diversity fungi strains with MIC ranging from 0.78 to 12.5 µg/mL. WXP-003 could significantly reduce sphingolipids content in fungi and no effect on mouse fibroblast cell line L929. Molecular dynamics simulation depicted that SPT/WXP-003 complex formed the favoured interactions. Taken together, discovery of WXP-003 provided valuable guide for the development of novel anti-fungal agents.

The investigation on sialic acid-modified pectin nanoparticles loaded with oxymatrine for orally targeting and inhibiting the of ulcerative colitis.

The aim of the study was to develop an oral targeting drug delivery system (OTDDS) of oxymatrine (OMT) to effectively treat ulcerative colitis (UC). The OTDDS of OMT (OMT/SA-NPs) was constructed with OMT, pectin, Ca2+, chitosan (CS) and sialic acid (SA). The obtained particles were characterized in terms of particle size, zeta potential, morphology, drug loading, encapsulation efficiency, drug release and stability. The average size of OMT/SA-NPs was 255.0 nm with a zeta potential of -12.4 mV. The loading content and encapsulation efficiency of OMT/SA-NPs were 14.65% and 84.83%, respectively. The particle size of OMT/SA-NPs changed slightly in the gastrointestinal tract. The nanoparticles can delivery most of the drug to the colon region. In vitro cell experiments showed that the SA-NPs had excellent biocompatibility and anti-inflammation, and the uptake of SA-NPs by RAW 264.7 cells was time and concentration-dependent. The conjugated SA can help the internalization of NPs into target cells. In vivo experiments showed that OMT/SA-NPs had a superior anti-inflammation effect and the effect of reducing UC, which was attributed to the delivery most of OMT to the colonic lumen, the specific targeting and retention in colitis site and the combined anti-inflammation of OMT and NPs.

2D absolute position measurement based on the hybrid encoding method.

This paper introduces a new method of absolute position measurement based on the hybrid encoding principle that can precisely measure the absolute position of a two-dimensional (2D) micro displacement table. The method uses pseudo-random sequences and binary codes to generate the long-distance position encoding sequences. It combines the encoding sequences with checkerboards to form a hybrid encoding to complete the design of the 2D encoding of plane positions. Then a 2D encoding disk is designed as a tool to measure 2D absolute position. Among them, the X and Y positions are designed by the modular approach, respectively, to efficiently detect the accuracy of 2D position values during the measurement. Moreover, the designed 2D encoding disk can quickly realize image correction. In order to verify the feasibility of the designed 2D encoding disk for measuring the 2D absolute position, the corresponding measurement system is built using a 2D encoding disk, a CCD camera, and a telecentric lens. The experimental results demonstrate that the average position deviation of the 2D absolute position measurement system is less than ±1 µm.

Novel silk protein/hyaluronic acid hydrogel loaded with azithromycin as an immunomodulatory barrier to prevent postoperative adhesions.

Peritoneal adhesions, a common postoperative complication of laparotomy, are still treated with physical barriers, but their efficacy and ease of use are controversial. In this paper, we developed a wound microenvironment-responsive hydrogel composed of Antheraea pernyi silk protein (ASF) from wild cocoons and tyramine-modified hyaluronic acid (HA-Ph) loaded with azithromycin (AZI), glucose oxidase (GOX), and horseradish peroxidase (HRP). In addition, GOX-catalyzed oxygen production enhanced the antibacterial ability of the hydrogel. Moreover, the drug-loaded hydrogel increased macrophage CD206 expression while decreasing IL-6 and TNF-α expression. More importantly, the retarding effect of this novel hydrogel system on AZI almost eliminated the appearance of postoperative adhesions in rats. It was also found that the novel hydrogel enhanced the modulation of the TLR-4/Myd88/NF-κB pathway and TGF-ß/Smad2/3 pathway by azithromycin in the locally damaged peritoneum of rats, which accelerated the remodeling of damaged tissues and dramatically reduced the deposition of collagen. Therefore, spraying the novel drug-loaded hydrogel on postoperative abdominal wounds can effectively inhibit the formation of postoperative adhesions.

Differential effects of climatic and non-climatic factors on the distribution of vegetation phenology trends on the Tibetan plateau.

The study of vegetation phenology changes is important because it is a sensitive indicator of climate change, affecting the exchange of carbon, energy and water fluxes between the land and the atmosphere. Previous studies have focused on the effects of climatic factors among environmental factors on vegetation phenology, thus the effects of non-climatic factors among environmental factors have not been well quantified. This study endeavors to scrutinize the spatiotemporal inconsistency in the start-of-season (SOS) and the end-of-season (EOS) on the Tibetan Plateau (TP) and to quantify the effects of environmental factors on phenology. To this end, the Moderate-resolution Imaging Spectroradiomater (MODIS) Normalized Difference Vegetation Index (NDVI) data from 2001 to 2018 and four common used methods were employed to extract SOS and EOS, and the site data was used to select the most appropriate phenology results. The Geodetector model was used to assess and measure the explanatory power of different environmental factors. The research results indicate that temperature exerts a more substantial impact on phenology than precipitation on TP. non-climatic factors such as longitude, latitude, and elevation are more influential in determining the distribution of phenological trends than climatic factors. Among these non-climatic factors, latitude has the most prominent effect on the trends of SOS. Furthermore, non-climatic factors exhibit a stronger effect on SOS, whereas EOS is more susceptible to climatic factors and less influenced by non-climatic factors. These discoveries bear great significance in comprehending the intricate outcomes of regional changes on vegetation phenology and enhancing phenology models.

An optical method based auto-collimation for measuring five degrees of freedom error motions of rotary axis.

The paper presents an optical method based on auto-collimation to simultaneously measure five degrees of freedom error motions of the rotary axis. The proposed method consists of the collimated lasers, beam splitters, focusing lens, quadrant photodiode detectors, a high-precision steel ball, and a special mirror fixed to the rotary axis. The mathematical model is established byoptical ray tracing, and the corresponding optical path is also simulated by OpticStudio. Meanwhile, an adjusting mechanism for X-Y micro-displacement, based on the elastic deformation of the material, is designed to adjust the installation eccentricity error of the high-precision steel ball. The calibration results of the proposed system demonstrate that the displacement errors are ±0.25 µm within the measuring range of ±10 µm, and the tilt angle errors are ±0.6 arcsec within the measuring range of ±25 arcsec. Taking a direct drive (DD) motor as the test object, the radial error motions of the rotary axis range from -3.2 to 4.1 µm, the axial error motions range from -4.9 to 4.7 µm, and the tilt error motions around the X and Y axes range from -2.8 to 1.8 arcsec and -2.6 to 2.0 arcsec, respectively.

Analysis of matched primary and recurrent BRCA1/2 mutation-associated tumors identifies recurrence-specific drivers.

Recurrence is a major cause of death among BRCA1/2 mutation carriers with breast (BrCa) and ovarian cancers (OvCa). Herein we perform multi-omic sequencing on 67 paired primary and recurrent BrCa and OvCa from 27 BRCA1/2 mutation carriers to identify potential recurrence-specific drivers. PARP1 amplifications are identified in recurrences (False Discovery Rate q = 0.05), and PARP1 is significantly overexpressed across primary BrCa and recurrent BrCa and OvCa, independent of amplification status. RNA sequencing analysis finds two BRCA2 isoforms, BRCA2-201/Long and BRCA2-001/Short, respectively predicted to be sensitive and insensitive to nonsense-mediated decay. BRCA2-001/Short is expressed more frequently in recurrences and associated with reduced overall survival in breast cancer (87 vs. 121 months; Hazard Ratio = 2.5 [1.18-5.5]). Loss of heterozygosity (LOH) status is discordant in 25% of patient's primary and recurrent tumors, with switching between both LOH and lack of LOH found. Our study reveals multiple potential drivers of recurrent disease in BRCA1/2 mutation-associated cancer, improving our understanding of tumor evolution and suggesting potential biomarkers.

Electrophysiological characterization of NSCs after differentiation induced by OEC conditioned medium.

PURPOSE: We induced neural stem cells (NSCs) to neurons by olfactory ensheathing cell (OEC) conditioned medium and characterized their electrophysiological properties after neuronal differentiation. METHODS: Fetal NSCs and OECs were cultured from embryonic day 14 SD rats and the conditioned medium was collected and stored at -20°C when the cell number was up to 80% of the culture flasks. The experiment groups were divided into a control group (cultured with DMEM/F12 without FBS) and an OECs induction group (cultured with OEC conditioned medium and DMEM/F12 without FBS). Immunocytochemistry staining was carried out to identify the neurons derived from NSCs and their electrophysiological properties were characterized after neuronal differentiation using a patch-clamp technique. RESULTS: The NSCs divided rapidly in the expansion medium, forming small proliferating spheres after 7 days. The OECs induction group presented an evident neuron-like type 7 days after adding OEC conditioned medium, and the nestin immunochemistry staining was positive. The electrophysiological characterization showed that the derived neurons presented a transient inward sodium current and slow outward potassium current under proper electric stimulus, which were blocked by tetrodotoxin (TTX) and tetraethylammonium (TEA). CONCLUSION: OEC conditioned medium can induce NSCs to form neurons, and electrophysiological characterization demonstrated that the derived neurons presented active electrophysiological properties which are essential for nervous excitation.

Mechanism of Cordyceps Cicadae in Treating Diabetic Nephropathy Based on Network Pharmacology and Molecular Docking Analysis.

OBJECTIVE: To systematically study the mechanism of cordyceps cicadae in the treatment of diabetic nephropathy (DN) with the method of network pharmacology and molecular docking analysis, so as to provide theoretical basis for the development of new drugs for the treatment of DN. METHODS: TCMSP, Symmap, PubChem, PubMed, and CTD database were used to predict and screen the active components and therapeutic targets for DN. The network of active components and targets was drawn by Cytoscape 3.6.0, the protein-protein interaction (PPI) was analyzed by the STRING database, and the DAVID database was used for the enrichment analysis of intersection targets. Molecular docking studies were finished by Discovery Studio 3.5. RESULTS: A total of 36 active compounds, including myriocin, guanosine, and inosine, and 378 potential targets of cordyceps cicadae were obtained. PPI network analysis showed that AKT1, MAPK8, and TP53 and other targets were related to both cordyceps cicadae and DN. GO and KEGG pathway analysis showed that these targets were mostly involved in R-HSA-450341, 157.14-3-3 cell cycle, and PDGF pathways. Docking studies suggested that myriocin can fit in the binding pocket of two target proteins (AKT1 and MAPK8). CONCLUSION: Active ingredients of cordyceps cicadae such as myriocin may act on DN through different targets such as AKT1, MAPK8, and TP53 and other targets, which can help to develop innovative drugs for effective treatment of DN.