In this study, in order to explore potential depressive biomarkers and potential regulatory targets of KXS on depression, we assessed the effects of Kai-Xin-San (KXS) on lipid metabolism in depressed ...patients (DPs) and rats exposed to chronic and unpredictable mild stress (CUMS).
Serum samples were collected from DPs, DPs with 8 weeks of KXS treatment (KXS) and healthy controls (HCs), and non-targeted lipidomics was used to analyze the effect of KXS on serum lipid metabolites in DPs. Based on UPLC-Q-TOF/MS technology, differential metabolites were validated in a large sample size. The potential regulatory network of KXS was analyzed by bioinformatic analysis, and the expressions of proteins in serum were verified using western boltting analysis. Moreover, effects of KXS on serum lipid and lipid metabolism-related hormone levels in CUMS rats were detected by enzyme-linked immunosorbent assay and enzymatic method.
We validated that the levels of six serum lipid metabolites (N-Desmethylcitalopram (HMDB14021), PC(14:1(9Z)/24:0) (HMDB07926), PC(P-18:1(11Z)/20:0) (HMDB11281), PC(O-18:0/20:4(8Z,11Z,14Z,17Z)) (HMDB13420), PC(16:0/P-18:0) (HMDB07995) and PC(16:0/P-18:1(11Z)) (HMDB07996)) between HC/DP groups and between DP/KXS groups were significantly different. Among these six metabolites, HMDB07995, HMDB07996, HMDB13420 and HMDB11281 were highly sensitive and specific for depression and KXS treatment by receiver operating characteristic (ROC) curve analysis. matrix metalloproteinases (MMPs) including MMP2 and MMP9, apolipoproteins (Apo) including APOA1 and APOC1 were up-regulated and apolipoproteins (Apo) including APOB, APOD and APOE, phospholipid transfer protein (PLTP), Paraoxonase 1 (PON1) were down-regulated in DPs, and KXS treatment could reverse these changes. In CUMS rats, KXS could increase the open-field score, sucrose preference and body weight, and reduce immobility time. Furthermore, KXS increased the serum levels of the above-mentioned six metabolites, reduced serum total cholesterol (TCH), triglyceride (TG) and free fatty acid (FFA) levels and increased the serum high-density lipoprotein cholesterol (HDL-C) level in CUMS rats. In addition, leptin and ghrelin were down-regulated by KXS.
The results suggested that KXS exerted antidepressant effects by regulating the signaling pathways involved in lipid metabolism disorders. The lipid metabolites might be potential biomarkers of depression and possible targets for KXS-based treatment of depression.
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Cadmium (Cd), a toxic element, often makes a serious threat to plant growth and development. Previous studies found that melatonin (Mel) reduced Cd accumulation and reestablished the redox balance to ...alleviate Cd stress in Medicago sativa L., however, the complex molecular mechanisms are still elusive. Here, comparative transcriptome analysis and biochemical experiments were conducted to explore the molecular mechanisms of Mel in enhancing Cd tolerance. Results showed that 7237 differentially expressed genes (DEGs) were regulated by Mel pretreatment to Cd stress compared to the control condition in roots of Medicago sativa L. Besides, in comparison with Cd stress alone, Mel upregulated 1081 DEGs, and downregulated 1085 DEGs. These DEGs were mainly involved in the transcription and translation of genes and folding, sorting and degradation of proteins, carbohydrate metabolism, and hormone signal network. Application of Mel regulated the expression of several genes encoding ribosomal protein and E3 ubiquitin-protein ligase involved in folding, sorting and degradation of proteins. Moreover, transcriptomic analyse suggested that Mel might regulate the expression of genes encoding pectin lyase, UDP-glucose dehydrogenase, sucrose-phosphate synthase, hexokinase-1, and protein phosphorylation in the sugar metabolism. Therefore, these could promote sucrose accumulation and subsequently alleviate the Cd damage. In conclusion, above findings provided the mining of important genes and molecular basis of Mel in mitigating Cd tolerance and genetic cultivation of Medicago sativa L.
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•A total of 2166 different expressed genes were simultaneously up- or down-regulated.•Melatonin regulated the expression of genes encoding E3 ubiquitin-protein ligase.•Sucrose mechanism was involved in melatonin-mediated Cd tolerance.•Hormone signalings were regulated by melatonin under Cd stress.
Female germline stem cells (FGSCs) are rare population residing in cortex of ovary, with the potential to rescue female infertility caused by ovary failure. Recently, we reported that cadherin‐22 ...(CDH22), a member of cadherin family, regulates self‐renewal of mouse FGSCs via interaction with JAK‐STAT signal pathway and β‐catenin. In this study, the expression profiles of FGSCs and spermatogonial stem cells (SSCs) were analyzed to further reveal their similarity and difference, and AKT3 was predicted as a pivotal molecule for FGSCs self‐renewal. Then, we demonstrated that CDH22 interacted with PI3K to phosphorylate AKT3 and subsequently enhanced the expression levels of N‐myc and cyclin family in FGSCs to promote self‐renewal. Moreover, glial cell line‐derived neurotrophic factor (GDNF) was identified as an essential factor for FGSCs self‐renewal with a more complicated mechanism: GDNF‐GFRA1 activates AKT3 via PI3K or Src family kinase (SFK), and SFK upregulates its target genes, Bcl6b, Etv5, and Lhx1, to promote self‐renewal of FGSCs. However, Src, the key intermediate factor for SSCs, was not the functional molecule of SFK family in the GDNF signal network of FGSCs. Based on the observations of bioinformatics analysis and molecular evidence, we demonstrate the underlying links of potential factors which are critical to the self‐renewal in FGSC and imply the therapeutic potentials of FGSCs in cure of female infertility. Stem Cells 2019;37:1095–1107
The schematic illustration of cadherin‐22 and GDNF signal network in female germline stem cells.
Chronic kidney disease (CKD) is characterized by an irreversible decrease in kidney function and induction of various metabolic dysfunctions. Accumulated findings reveal that chronic hypoxic stress ...and endoplasmic reticulum (ER) stress are involved in a range of pathogenic conditions, including the progression of CKD. Because of the presence of an arteriovenous oxygen shunt, the kidney is thought to be susceptible to hypoxia. Chronic kidney hypoxia is induced by a number of pathogenic conditions, including renal ischemia, reduced peritubular capillary, and tubulointerstitial fibrosis. The ER is an organelle which helps maintain the quality of proteins through the unfolded protein response (UPR) pathway, and ER dysfunction associated with maladaptive UPR activation is named ER stress. ER stress is reported to be related to some of the effects of pathogenesis in kidney, particularly in the podocyte slit diaphragm and tubulointerstitium. Furthermore, chronic hypoxia mediates ER stress in blood vessel endothelial cells and tubulointerstitium via several mechanisms, including oxidative stress, epigenetic alteration, lipid metabolism, and the AKT pathway. In summary, a growing consensus considers that these stresses interact via complicated stress signal networks, which leads to the exacerbation of CKD (Figure 1). This stress signal network might be a target for interventions aimed at ameliorating CKD.
A large-signal electrothermal model for AlGaN/GaN HEMTs including gate and drain related trapping effects is proposed here. This nonlinear model is well formulated to preserve convergence ...capabilities and simulation times. Extensive measurements have demonstrated the impact of trapping effects on the shapes of I(V) characteristics, as well as load cycles. It is shown that accurate modeling of gate-and drain-lag effects dramatically improves the large-signal simulation results. This is particularly true when the output loads deviate from the optimum matching conditions corresponding to real-world simulations. This new model and its modeling approach are presented here. Large-signal simulation results are then reported and compared to load-pull and large-signal network analyzer measurements for several load impedances at high voltage standing wave ratio and at two frequencies.
We present the first application of the recently introduced dynamic-bias measurement to the acquisition of the scattering (S-) parameters of microwave transistors under large signal operating ...conditions. We demonstrate that by properly acquiring and processing dynamic-bias measurements, one can derive the S-parameters of a nonlinear device-under test across a time-varying large-signal operating point (LSOP). Interestingly, these time-varying S-parameters can be used similar to the conventional S-parameters for characterization and modeling purposes. As compared with similar existing approaches, like those based on the pulsed S-parameter measurements, with the proposed technique, one can obtain, as a result of one measurement, the frequency-dependent S-parameters at each instantaneous point touched by the LSOP. We report experimental dynamic-bias S-parameters of a 0.15-μm GaAs pHEMT and a 0.25-μm GaN HEMT.
This paper presents a new systematic and efficient method for the design of high-power varactor-based impedance tuners. By incorporating the varactor losses and voltage handling capabilities, the ...method allows the impedance tuning range to be maximized and losses to be minimized under high-power operating conditions. A 2.2-GHz large-signal double-stub tuner has been designed using the proposed methodology and SiC varactor diodes. Using comprehensive large-signal measurements, a 25-W input power handling is demonstrated up to <inline-formula> <tex-math notation="LaTeX">\Gamma _{\max } \approx ~0.8 </tex-math></inline-formula>. Two-tone linearity measurements show an input third-order intercept point exceeding 50 dBm for most impedances. These results clearly demonstrate the feasibility of the proposed technique for the design of high-performance large-signal tuners.
Stem cell therapy is a promising treatment in regenerative medicine. Human adipose-derived stem/stromal cells (hASCs), a type of mesenchymal stem cell, are easy to harvest. In plastic and aesthetic ...surgery, hASC may be applied in the treatment of fat grafting, wound healing, and scar remodeling. Platelet-rich plasma (PRP) contains various growth factors, including platelet-derived growth factor (PDGF), which accelerates wound healing. We previously reported that PRP promotes the proliferation of hASC via multiple signaling pathways, and we evaluated the effect of PRP on the stimulation of hASC adhesion and migration, leading to the proliferation of these cells. When hASCs were treated with PRP, AKT, ERK1/2, paxillin and RhoA were rapidly activated. PRP treatment led to the formation of F-actin stress fibers. Strong signals for integrin β1, paxillin and RhoA at the cell periphery of RPR-treated cells indicated focal adhesion. PRP promoted cell adhesion and movement of hASC, compared with the control group. Imatinib, an inhibitor of the PDGF receptor tyrosine kinase, inhibited the promotion of PRP-dependent cell migration. PDGF treatment of hASCs also stimulated cell adhesion and migration but to a lesser extent than PRP treatment. PRP promoted the adhesion and the migration of hASC, mediated by the activation of AKT in the integrin signaling pathway. PRP treatment was more effective than PDGF treatment in enhancing cell migration. Thus, the ability of PRPs to promote migration of hASC to enhance cell growth is evident.
This work aims to analyze and construct a novel competing endogenous RNA (ceRNA) network in ankylosing spondylitis (AS) with bone bridge formation, lncRNA. Using RNA sequencing and bioinformatics, we ...analyzed expression profiles of long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in whole blood cells from 5 AS patients and 3 healthy individuals. Next, we verified the expression levels of candidate lncRNAs in 97 samples using the ΔΔCt value of real-time quantitative polymerase chain reaction (qRT-PCR). We used multivariate logistic regression analysis to screen lncRNAs and clinical indicators for use in the prediction model. Both SPSS 24.0 and R software were used for data analysis and prediction model construction. The results showed that compared with the normal controls, 205 long noncoding RNAs (lncRNAs), 961 microRNAs (miRNAs), and 200 mRNAs (DEmRNAs) were differentially expressed in the AS patients. We identified lncRNA 122K13.12 and lncRNA 326C3.7 among 205 lncRNAs differentially expressed between AS patients and healthy humans. Then, we noted that 30 miRNAs and five mRNAs formed a ceRNA network together with these two lncRNAs. These ceRNA networks might regulate the tumor necrosis factor (TNF) signaling pathway in AS development. In addition, the expression level of lncRNA 122K13.12 and lncRNA 326C3.7 correlated with various structural damage indicators in AS. Specifically, the lncRNA 326C3.7 expression level was an independent risk factor in bone bridge formation area under the ROC curve (AUC) = 0.739 (0.609–0.870) and
p
= 0.003, and the best Youden Index was 0.405 (sensitivity = 0.800 and specificity = 0.605). Moreover, we constructed a lncRNA-based nomogram that could effectively predict bone bridge formation AUC = 0.870 (0.780–0.959) and
p
< 0.001, and the best Youden Index was 0.637 (sensitivity = 0.900 and specificity = 0.737). In conclusion, we uncovered a unique ceRNA signaling network in AS with bone bridge formation and identified novel biomarkers and prediction models with the potential for clinical applications.
For more than a decade, the GNSS Service at the Geodetic Institute of Slovenia has been managing the national GNSS CORS network SIGNAL, and since 2016 also the GNSS part of the national Zero-Order ...Geodetic Network. During this period, different problems in the operation of CORS networks have been encountered, and much experience in the field of management and quality control of CORS networks has been gained. In cooperation with the Chair of Mathematical and Physical Geodesy and Navigation at the UL FGG and the Surveying and Mapping Authority of the Republic of Slovenia, a research project named The increase of reliability of public GNSS network SIGNAL and combined zero-order geodetic network was carried out in 2018 and 2019. Based on all the experience gained, a methodology for upgrading and improving the current procedures for management of both national CORS networks, with an emphasis on improving operational reliability and the quality control of both networks, was developed. In this article, the results of that project are presented.
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