Mechanism of Stochastic Resonance in a Quorum Sensing Network Regulated by Small RNAs

Bacterial quorum sensing (QS) is an important process of cell communication and more and more attention is paid to it. Moreover, the noises are ubiquitous in nature and often play positive role. In this paper, we investigate how the noise enhances the QS though the stochastic resonance (SR) and explain the mechanism of SR in this quorum sensing network. In addition, we also discuss the interaction between the small RNA and the other genes in this network and discover the biological importance

Studies on the inhibitory effect of isavuconazole on flumatinib metabolism in vitro and in vivo

As the validated agent for the treatment of chronic myelogenous leukemia (CML), flumatinib is a novel oral tyrosine kinase inhibitor (TKI) with higher potency and selectivity for BCR-ABL1 kinase compared to imatinib. Many patients experience aspergillosis infection and they may start using isavuconazole, which is an inhibitor of CYP3A4. However, there is no study on their interaction in vitro and in vivo. In the present study, the concentrations of flumatinib and its major metabolite M1 were rapidly determined using an stable ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method. The half-maximal inhibitory concentration (IC50) was 6.66 μM in human liver microsomes (HLM), while 0.62 μM in rat liver microsomes (RLM) and 2.90 μM in recombinant human CYP3A4 (rCYP3A4). Furthermore, the mechanisms of inhibition of flumatinib in human liver microsomes, rat liver microsomes and rCYP3A4 by isavuconazole were mixed. Moreover, ketoconazole, posaconazole, and isavuconazole showed more potent inhibitory effects than itraconazole, fluconazole, and voriconazole on HLM-mediated flumatinib metabolism. In pharmacokinetic experiments of rats, it was observed that isavuconazole could greatly change the pharmacokinetic parameters of flumatinib, including AUC(0−t), AUC(0−∞), Cmax and CLz/F, but had no effect on the metabolism of M1. According to the results of in vitro and in vivo studies, the metabolism of flumatinib was inhibited by isavuconazole, suggesting that isavuconazole may raise the plasma concentration of flumatinib. Thus, it is important to take special care of the interactions between flumatinib and isavuconazole in clinical applications

Enabling Flexibility through Forming and Evolving Systems of Systems

Flexibility is a highly desired attribute of many systems operating in changing or uncertain conditions. This paper presents a study of enabling flexibility through designing and operating systems of systems (SoSs). The paper analyzes flexibility mechanisms of SoSs and, accordingly, identifies needs for flexibility that SoSs can meet. Following that, it proposes a hierarchical network as a more flexible SoS architecture for complex or distributed large-scale systems. Then, decision problems for forming and evolving a SoS network are defined. A case that involves integrating distributed renewable energy sources with the main grid is presented to illustrate the implementation of the proposed methodology. Results from this study support the idea of acquiring and maintaining flexibility with SoSs. The paper also identifies research needs for advancing this particular use of SoSs

Serum 25-hydroxyvitamin D levels and the risk of idiopathic central precocious puberty in girls

Introduction: Prior studies have found inconsistent results regarding the relationship between vitamin D status and Idiopathic Central Precocious Puberty (ICPP). Objective: To assess the role of serum 25-hydroxyvitamin D (25 [OH]D) levels in ICPP development. Method: The authors retrospectively collected data from 221 girls with ICPP and 144 healthy girls between January 2017 and December 2019. The participants’ serum 25(OH)D levels were measured using an automatic chemiluminescence method, and the association between serum 25(OH)D levels and the risk of ICPP was assessed using multivariate logistic regression analysis. Odds Ratios (OR) with 95% Confidence Intervals (95% CI) were calculated as effect estimates. Results: Serum 25(OH)D levels in the ICPP group were significantly lower than those in healthy controls (p < 0.001). Multivariate analysis indicated that girls with insufficient vitamin D levels (OR = 0.201; 95% CI 0.094–0.428; p < 0.001) and sufficient vitamin D levels (OR = 0.141; 95% CI 0.053–0.375; p < 0.001) both had a lower risk of ICPP than girls with vitamin D deficiency. Moreover, the authors found that the height (p = 0.014), weight (p = 0.014), breast stage (p = 0.010), mother's height (p < 0.001), and luteinizing hormone/follicle-stimulating hormone ratio (p = 0.010) in girls with ICPP could be associated with levels of vitamin D. Conclusion: This study found that a low serum 25(OH)D level is an independent risk factor for ICPP, and several characteristics of girls with ICPP could be affected by their vitamin D status.

1α,25-dihydroxyvitamin D3 promotes osseointegration of titanium implant via downregulating AGEs/RAGE pathway in T2DM

Diabetes-induced advanced glycation end products (AGEs) overproduction would result in compromised osseointegration of titanium implant and high rate of implantation failure. 1α,25-dihydroxyvitamin D3 (1,25VD3) plays a vital role in osteogenesis, whereas its effects on the osseointegration and the underlying mechanism are unclear. The purpose of this study was to investigate that 1,25VD3 might promote the defensive ability of osseointegration through suppressing AGEs/RAGE in type 2 diabetes mellitus. In animal study, streptozotocin-induced diabetic rats accepted implant surgery, with or without 1,25VD3 intervention for 12 weeks. After killing, the serum AGEs level, bone microarchitecture and biomechanical index of rats were measured systematically. In vitro study, osteoblasts differentiation capacity was analyzed by alizarin red staining, alkaline phosphatase assay and Western blotting, after treatment with BSA, AGEs, AGEs with RAGE inhibitor and AGEs with 1,25VD3. And the expression of RAGE protein was detected to explore the mechanism. Results showed that 1,25VD3 could reverse the impaired osseointegration and mechanical strength, which possibly resulted from the increased AGEs. Moreover, 1,25VD3 could ameliorate AGEs-induced damage of cell osteogenic differentiation, as well as downregulating the RAGE expression. These data may provide a theoretical basis that 1,25VD3 could work as an adjuvant treatment against poor osseointegration in patients with type 2 diabetes mellitus

Catalyst size dependent growth of Pd-catalyzed one-dimensional InAs nanostructures

In this study, Pd was used as catalyst to grow one-dimensional InAs nanostructures on GaAs (111)(B) substrates in order to explore the growth mechanism and the effect of non-gold catalysts in growing epitaxial III-V nanostructures. With detailed morphological, structural, and chemical characterizations using electron microscopy, coupled with analysis of the Pd-In binary phase diagram, it was found that size of Pd nanoparticles plays a key role in determining the growth mechanism of one-dimensional InAs nanostructures. (C) 2013 AIP Publishing LLC

(Arg) 9 -SH2 superbinder: A novel promising anticancer therapy to melanoma by blocking phosphotyrosine signaling

Background: Melanoma is a malignant tumor with high misdiagnosis rate and poor prognosis. The bio-targeted therapy is a prevailing method in the treatment of melanoma; however, the accompanying drug resistance is inevitable. SH2 superbinder, a triple-mutant of the Src Homology 2 (SH2) domain, shows potent antitumor ability by replacing natural SH2-containing proteins and blocking multiple pY-based signaling pathways. Polyarginine (Arg) 9 , a powerful vector for intracellular delivery of large molecules, could transport therapeutic agents across cell membrane. The purpose of this study is to construct (Arg) 9 -SH2 superbinder and investigate its effects on melanoma cells, expecting to provide potential new approaches for anti-cancer therapy and overcoming the unavoidable drug resistance of single-targeted antitumor agents. Methods: (Arg) 9 and SH2 superbinder were fused to form (Arg) 9 -SH2 superbinder via genetic engineering. Pull down assay was performed to identify that (Arg) 9 -SH2 superbinder could capture a wide variety of pY proteins. Immunofluorescence was used to detect the efficiency of (Arg) 9 -SH2 superbinder entering cells. The proliferation ability was assessed by MTT and colony formation assay. In addition, wound healing and transwell assay were performed to evaluate migration of B16F10, A375 and A375/DDP cells. Moreover, apoptosis caused by (Arg) 9 -SH2 superbinder was analyzed by flow cytometry-based Annexin V/PI. Furthermore, western blot revealed that (Arg) 9 -SH2 superbinder influenced some pY-related signaling pathways. Finally, B16F10 xenograft model was established to confirm whether (Arg) 9 -SH2 superbinder could restrain the growth of tumor. Results: Our data showed that (Arg) 9 -SH2 superbinder had the ability to enter melanoma cells effectively and displayed strong affinities for various pY proteins. Furthermore, (Arg) 9 -SH2 superbinder could repress proliferation, migration and induce apoptosis of melanoma cells by regulating PI3K/AKT, MAPK/ERK and JAK/STAT signaling pathways. Importantly, (Arg) 9 -SH2 superbinder could significantly inhibit the growth of tumor in mice. Conclusions: (Arg) 9 -SH2 superbinder exhibited high affinities for pY proteins, which showed effective anticancer ability by replacing SH2-containing proteins and blocking diverse pY-based pathways. The remarkable ability of (Arg) 9 -SH2 superbinder to inhibit cancer cell proliferation and tumor growth might open the door to explore the SH2 superbinder as a therapeutic agent for cancer treatment

Serotonin-mediated modulation of Na+/K+ pump current in rat hippocampal CA1 pyramidal neurons

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to investigate whether serotonin (5-hydroxytryptamine, 5-HT) can modulate Na⁺/K⁺pump in rat hippocampal CA1 pyramidal neurons.</p> <p>Results</p> <p>5-HT (0.1, 1 mM) showed Na⁺/K⁺pump current (Ip) densities of 0.40 ± 0.04, 0.34 ± 0.03 pA/pF contrast to 0.63 ± 0.04 pA/pF of the control of 0.5 mM strophanthidin (Str), demonstrating 5-HT-induced inhibition of Ip in a dose-dependent manner in hippocampal CA1 pyramidal neurons. The effect was partly attenuated by ondasetron, a 5-HT₃receptor (5-HT₃R) antagonist, not by WAY100635, a 5-HT_1AR antagonist, while 1-(3-Chlorophenyl) biguanide hydrochloride (m-CPBG), a 5-HT₃R specific agonist, mimicked the effect of 5-HT on Ip.</p> <p>Conclusion</p> <p>5-HT inhibits neuronal Na⁺/K⁺pump activity via 5-HT₃R in rat hippocampal CA1 pyramidal neurons. This discloses novel mechanisms for the function of 5-HT in learning and memory, which may be a useful target to benefit these patients with cognitive disorder.</p

Overproduction of Mitochondrial Fission Proteins in Membranous Nephropathy in Children

Background/Aims: The molecules involved in nephrotic syndrome (NS) have not been fully clarified. Mitochondrial fission proteins are found to be involved in podocyte injury in vitro. Increased glomerular expression of mitochondrial fission proteins was found in adriamycin nephropathy in our previous study. Whether or not mitochondrial fission proteins are involved in podocyte injury in NS is not clear. This study explored the glomerular expression and possible pathological significance of mitochondrial fission-associated proteins, including dynamin-related protein 1 (Drp1) and mitochondrial fission protein 1 (Fis1), in children with NS. Methods: Eighteen children with primary NS, including 6 with minimal change disease, 6 with focal segmental glomerulosclerosis, 6 with membranous nephropathy, 6 children with isolated haematuria and 3 normal controls were included. The glomerular expression of Drp1, phospho-Drp1 (Ser616) and Fis1, urinary protein measurements, and podocyte mitochondrial density under electron microscopy were investigated and compared. Results: Glomerular expression of Drp1, phospho-Drp1 (Ser616) and Fis1 was mainly increased in children with NS with membranous nephropathy. No relationship was found between glomerular expression of Drp1, phospho-Drp1 (Ser616) and Fis1 and podocyte mitochondrial density or urinary protein measurements. Conclusion: Glomerular overproduction of Drp1, phospho-Drp1 (Ser 616) and Fis1 occurred mainly in children with membranous nephropathy. The pathological significance deserves further investigation

Improved electrochemical performance of 5 V spinel LiNi0.5Mn1.5O4 microspheres by F-doping and Li4SiO4 coating

AbstractPorous spinel LiNi0.5Mn1.5O4 microspheres were synthesized by a co-precipitation method. F-doping and Li4SiO4-coating were used as two effective ways to enhance the electrochemical performance of LiNi0.5Mn1.5O4 at both room temperature and elevated temperature. All the samples were characterized by thermogravimetric analysis/differential scanning calorimetry (TG/DSC), X-ray diffraction (XRD), inductive coupled plasma-atomic emission spectroscopy (ICP-AES), Raman spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and electrochemical tests, respectively. According to the SEM images, the LiNi0.5Mn1.5O4 microspheres are hollow with porous shell, and each microsphere is made up of nano-sized spinel grains. This hollow and porous structure favors the sufficient contact between electrolyte and the cathode material. It is indicated that 2 wt.% Li4SiO4-coated LiNi0.5Mn1.5O3.98F0.02 exhibits more superior performance than the pristine one. The doped fluorine ions that enhance the bonding can stabilize the structure of cathode material. The Li4SiO4 coating can suppress side reactions between electrolyte and cathode material as a protective material, and it is a superionic conductor with a three-dimensional lithium ion transfer network to decrease the charge-transfer resistance. The discharge capacity retention of 2 wt.% Li4SiO4-coated LiNi0.5Mn1.5O3.98F0.02 is 97.8% at 25 °C and 94.2% at 55 °C after 150 cycles, respectively