Analysis and Design of Adaptive Synchronization of a Complex Dynamical Network with Time-Delayed Nodes and Coupling Delays

This paper is devoted to the study of synchronization problems in uncertain dynamical networks with time-delayed nodes and coupling delays. First, a complex dynamical network model with time-delayed nodes and coupling delays is given. Second, for a complex dynamical network with known or unknown but bounded nonlinear couplings, an adaptive controller is designed, which can ensure that the state of a dynamical network asymptotically synchronizes at the individual node state locally or globally in an arbitrary specified network. Then, the Lyapunov-Krasovskii stability theory is employed to estimate the network coupling parameters. The main results provide sufficient conditions for synchronization under local or global circumstances, respectively. Finally, two typical examples are given, using the M-G system as the nodes of the ring dynamical network and second-order nodes in the dynamical network with time-varying communication delays and switching communication topologies, which illustrate the effectiveness of the proposed controller design methods

Bis[2-(2-pyridylmethyl­eneamino)benzene­sulfonato-κ3 N,N′,O]cadmium(II) dihydrate

The title complex, [Cd(Paba)2]·2H2O or [Cd(C12H9N2O3S)2]·2H2O, was synthesized by the reaction of the potassium salt of 2-(2-pyridylmethyl­eneamino)benzene­sulfonic acid (PabaK) with CdCl2·2.5H2O in methanol. The CdII atom lies on a crystallographic twofold axis and is coordinated by four N atoms and two O atoms from two deprotonated tridentate 2-(2-pyridylmethyl­eneamino)benzene­sulfonate ligands in a slightly distorted octa­hedral environment. There are extensive hydrogen bonds of the type O—H⋯O between the uncoordinated water molecules and the sulfonate O atoms, through which the complex forms a layered structure parallel to (001)

Activation of AMP-Activated Protein Kinase Is Required for Berberine-Induced Reduction of Atherosclerosis in Mice: The Role of Uncoupling Protein 2

Berberine, a botanical alkaloid purified from Coptidis rhizoma, is reported to activate the AMP-activated protein kinase (AMPK). Whether AMPK is required for the protective effects of berberine in cardiovascular diseases remains unknown. This study was designed to determine whether AMPK is required for berberine-induced reduction of oxidative stress and atherosclerosis in vivo.ApoE (ApoE⁻/⁻) mice and ApoE⁻/⁻/AMPK alpha 2⁻/⁻ mice that were fed Western diets were treated with berberine for 8 weeks. Atherosclerotic aortic lesions, expression of uncoupling protein 2 (UCP2), and markers of oxidative stress were evaluated in isolated aortas.In ApoE⁻/⁻ mice, chronic administration of berberine significantly reduced aortic lesions, markedly reduced oxidative stress and expression of adhesion molecules in aorta, and significantly increased UCP2 levels. In contrast, in ApoE⁻/⁻/AMPK alpha 2⁻/⁻ mice, berberine had little effect on those endpoints. In cultured human umbilical vein endothelial cells (HUVECs), berberine significantly increased UCP2 mRNA and protein expression in an AMPK-dependent manner. Transfection of HUVECs with nuclear respiratory factor 1 (NRF1)-specific siRNA attenuated berberine-induced expression of UCP2, whereas transfection with control siRNA did not. Finally, berberine promoted mitochondrial biogenesis that contributed to up-regulation of UCP2 expression.We conclude that berberine reduces oxidative stress and vascular inflammation, and suppresses atherogenesis via a mechanism that includes stimulation of AMPK-dependent UCP2 expression

Inhibition of cyclin-dependent kinase 7 down-regulates yes-associated protein expression in mesothelioma cells.

Cyclin-dependent kinase 7 (CDK7) is a protein kinase that plays a major role in transcription initiation. Yes-associated protein (YAP) is a main effector of the Hippo/YAP signalling pathway. Here, we investigated the role of CDK7 on YAP regulation in human malignant pleural mesothelioma (MPM). We found that in microarray samples of human MPM tissue, immunohistochemistry staining showed correlation between the expression level of CDK7 and YAP (n = 70, r = .513). In MPM cells, CDK7 expression level was significantly correlated with GTIIC reporter activity (r = .886, P = .019). Inhibition of CDK7 by siRNA decreased the YAP protein level and the GTIIC reporter activity in the MPM cell lines 211H, H290 and H2052. Degradation of the YAP protein was accelerated after CDK7 knockdown in 211H, H290 and H2052 cells. Inhibition of CDK7 reduced tumour cell migration and invasion, as well as tumorsphere formation ability. Restoration of the CDK7 gene rescued the YAP protein level and GTIIC reporter activity after siRNA knockdown in 211H and H2052 cells. Finally, we performed a co-immunoprecipitation analysis using an anti-YAP antibody and captured the CDK7 protein in 211H cells. Our results suggest that CDK7 inhibition reduces the YAP protein level by promoting its degradation and suppresses the migration and invasion of MPM cells. Cyclin-dependent kinase 7 may be a promising therapeutic target for MPM

Kinetics and specificity of paternal mitochondrial elimination in Caenorhabditis elegans

In most eukaryotes, mitochondria are inherited maternally. The autophagy process is critical for paternal mitochondrial elimination (PME) in Caenorhabditis elegans, but how paternal mitochondria, but not maternal mitochondria, are selectively targeted for degradation is poorly understood. Here we report that mitochondrial dynamics have a profound effect on PME. A defect in fission of paternal mitochondria delays PME, whereas a defect in fusion of paternal mitochondria accelerates PME. Surprisingly, a defect in maternal mitochondrial fusion delays PME, which is reversed by a fission defect in maternal mitochondria or by increasing maternal mitochondrial membrane potential using oligomycin. Electron microscopy and tomography analyses reveal that a proportion of maternal mitochondria are compromised when they fail to fuse normally, leading to their competition for the autophagy machinery with damaged paternal mitochondria and delayed PME. Our study indicates that mitochondrial dynamics play a critical role in regulating both the kinetics and the specificity of PME

Inhibition of yes-associated protein suppresses brain metastasis of human lung adenocarcinoma in a murine model.

Yes-associated protein (YAP) is a main mediator of the Hippo pathway and promotes cancer development and progression in human lung cancer. We sought to determine whether inhibition of YAP suppresses metastasis of human lung adenocarcinoma in a murine model. We found that metastatic NSCLC cell lines H2030-BrM3(K-rasG12C mutation) and PC9-BrM3 (EGFRΔexon19 mutation) had a significantly decreased p-YAP(S127)/YAP ratio compared to parental H2030 (K-rasG12C mutation) and PC9 (EGFRΔexon19 mutation) cells (P < .05). H2030-BrM3 cells had significantly increased YAP mRNA and expression of Hippo downstream genes CTGF and CYR61 compared to parental H2030 cells (P < .05). Inhibition of YAP by short hairpin RNA (shRNA) and small interfering RNA (siRNA) significantly decreased mRNA expression in downstream genes CTGF and CYR61 in H2030-BrM3 cells (P < .05). In addition, inhibiting YAP by YAP shRNA significantly decreased migration and invasion abilities of H2030-BrM3 cells (P < .05). We are first to show that mice inoculated with YAP shRNA-transfected H2030-BrM3 cells had significantly decreased metastatic tumour burden and survived longer than control mice (P < .05). Collectively, our results suggest that YAP plays an important role in promoting lung adenocarcinoma brain metastasis and that direct inhibition of YAP by shRNA suppresses H2030-BrM3 cell brain metastasis in a murine model

Opioid-free anesthesia reduces the severity of acute postoperative motion-induced pain and patient-controlled epidural analgesia-related adverse events in lung surgery: randomized clinical trial

BackgroundOpioids have been used as pain relievers for thousands of years. However, they may also cause undesirable side effects. We therefore performed this study to compare the effect of opioid-free anesthesia (OFA) versus opioid-sparing anesthesia (OSA) on postoperative pain and patient-controlled epidural analgesia (PCEA)-related events.MethodsThis is a single center randomized clinical trial that was recruited patients aged from 18 to 70 years who received video-assisted lung surgery between October 2021 and February 2022. Participants were 1:1 randomly assigned to OFA or OSA. Patients in the OFA group received propofol, rocuronium, esmolol, lidocaine, and magnesium sulfate intravenously with epidural ropivacaine. Patients in the OSA group received propofol, rocuronium, remifentanil, and sufentanil intravenously with epidural hydromorphone and ropivacaine.ResultsA total number of 124 patients were randomly allocated to the OFA or OSA group. In the OFA group, the severity of pain during coughs on the first postoperative days (PODs; VAS score 1.88 ± 0.88 vs. 2.16 ± 1.1, p = 0.044) was significantly lower than that in the OSA group. The total ratio of PCEA-related adverse events in the OFA group [11 (19.6%) vs. 26 (47.3%), p = 0.003] was significantly lower than in the OSA group.ConclusionOFA in patients who received video-assisted lung surgery led to lower severity of acute postoperative motion-induced pain and fewer PCEA-related adverse events on the first POD than in the patients in the OSA group.Clinical trial registrationclinicaltrials.gov, identifier (NCT05063396)

Linking Incomplete Reprogramming to the Improved Pluripotency of Murine Embryonal Carcinoma Cell-Derived Pluripotent Stem Cells

Somatic cell nuclear transfer (SCNT) has been proved capable of reprogramming various differentiated somatic cells into pluripotent stem cells. Recently, induced pluripotent stem cells (iPS) have been successfully derived from mouse and human somatic cells by the over-expression of a combination of transcription factors. However, the molecular mechanisms underlying the reprogramming mediated by either the SCNT or iPS approach are poorly understood. Increasing evidence indicates that many tumor pathways play roles in the derivation of iPS cells. Embryonal carcinoma (EC) cells have the characteristics of both stem cells and cancer cells and thus they might be the better candidates for elucidating the details of the reprogramming process. Although previous studies indicate that EC cells cannot be reprogrammed into real pluripotent stem cells, the reasons for this remain unclear. Here, nuclei from mouse EC cells (P19) were transplanted into enucleated oocytes and pluripotent stem cells (P19 NTES cells) were subsequently established. Interestingly, P19 NTES cells prolonged the development of tetraploid aggregated embryos compared to EC cells alone. More importantly, we found that the expression recovery of the imprinted H19 gene was dependent on the methylation state in the differential methylation region (DMR). The induction of Nanog expression, however, was independent of the promoter region DNA methylation state in P19 NTES cells. A whole-genome transcriptome analysis further demonstrated that P19 NTES cells were indeed the intermediates between P19 cells and ES cells and many interesting genes were uncovered that may be responsible for the failed reprogramming of P19 cells. To our knowledge, for the first time, we linked incomplete reprogramming to the improved pluripotency of EC cell-derived pluripotent stem cells. The candidate genes we discovered may be useful not only for understanding the mechanisms of reprogramming, but also for deciphering the transition between tumorigenesis and pluripotency