Passivity Analysis of Complex Delayed Dynamical Networks with Output Coupling

A new complex dynamical network model with output coupling is proposed. This paper is concerned with input passivity and output passivity of the proposed network model. By constructing new Lyapunov functionals, some sufficient conditions ensuring the input passivity and output passivity are obtained. Finally, two numerical examples are provided to demonstrate the effectiveness of the proposed results

Mdivi-1, a mitochondrial fission inhibitor, modulates T helper cells and suppresses the development of experimental autoimmune encephalomyelitis.

BACKGROUND: Unrestrained activation of Th1 and Th17 cells is associated with the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). While inactivation of dynamin-related protein 1 (Drp1), a GTPase that regulates mitochondrial fission, can reduce EAE severity by protecting myelin from demyelination, its effect on immune responses in EAE has not yet been studied. METHODS: We investigated the effect of Mdivi-1, a small molecule inhibitor of Drp1, on EAE. Clinical scores, inflammation, demyelination and Drp1 activation in the central nervous system (CNS), and T cell responses in both CNS and periphery were determined. RESULTS: Mdivi-1 effectively suppressed EAE severity by reducing demyelination and cellular infiltration in the CNS. Mdivi-1 treatment decreased the phosphorylation of Drp1 (ser616) on CD4+ T cells, reduced the numbers of Th1 and Th17 cells, and increased Foxp3+ regulatory T cells in the CNS. Moreover, Mdivi-1 treatment effectively inhibited IFN-γ+, IL-17+, and GM-CSF+ CD4+ T cells, while it induced CD4+ Foxp3+ regulatory T cells in splenocytes by flow cytometry. CONCLUSIONS: Together, our results demonstrate that Mdivi-1 has therapeutic potential in EAE by modulating the balance between Th1/Th17 and regulatory T cells

Selection and evaluation of phosphate-solubilizing bacteria from grapevine rhizospheres for use as biofertilizers

Phosphate-solubilizing bacteria (PSB) have the ability to solubilize insoluble phosphorus (P) and release soluble P. Extensive research has been performed with respect to PSB isolation from the rhizospheres of various plants, but little is known about the prevalence of PSB in the grapevine rhizosphere. In this study, we aimed to isolate and identify PSB from the grapevine rhizosphere in five vineyards of Northwest China, to characterize their plant-growth-promoting (PGP) traits, evaluate the effect of stress on their phosphate-solubilizing activity (PSA), and test their ability to stimulate the growth of Vitis vinifera L. cv. Cabernet Sauvignon. From the vineyard soils, 66 PSB isolates were screened, and 10 strains with high PSA were identified by 16S rRNA sequencing. Sequence analysis revealed that these 10 strains belonged to 4 genera and 5 species: Bacillus aryabhattai, B. megaterium, Klebsiella variicola, Stenotrophomonas rhizophila, and Enterobacter aerogenes. The selected PSB strains JY17 (B. aryabhattai) and JY22 (B. aryabhattai) were positive for multiple PGP traits, including nitrogen fixation and production of indole acetic acid (IAA), siderophores, 1-aminocyclopropane-1-carboxylate (ACC) deaminase, chitinase, and protease. JY17 and JY22 showed strong PSA under stress conditions of high pH, high salt, and high temperature. Therefore, these two isolates can be used as biofertilizers in saline-alkaline soils. The inoculation with PSB significantly facilitated the growth of V. vinifera cv. Cabernet Sauvignon under greenhouse conditions. Use of these PSB as biofertilizers will increase the available P content in soils, minimize P-fertilizer application, reduce environmental pollution, and promote sustainable agriculture

Effect of Prunella vulgaris L extract on hyperprolactinemia in vitro and in vivo

Purpose: To investigate the anti-hyperprolactinemic activity of Prunella vulgaris L. extract (PVE) in vivo and in vitro.Methods: Rats were given intraperitoneal (i. p.) metoclopramide (MCP, 150 mg/kg daily) for 10 days to prepare hyperprolactinemia (hyperPRL) model. Bromocriptine was used as positive control drug. High (5.6 g/kg), medium (2.8 g/kg) and low (1.4 g/kg) doses of PVE were administered to hyperPRL rats. The effect of PVE on serum prolactin (PRL), estradiol (E2), progesterone (PGN), follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels were investigated in the rats. MMQ cells derived from rat pituitary adenoma cells and GH3 cells from rat pituitary lactotropictumoral cells were used for in vitro experiments. The effect of PVE on PRL secretion were studied in MMQ cells and GH3 cells respectively.Results: Compared with the control group (446.21 ± 32.43 pg/mL), high (219.23 ± 10.62 pg/mL) and medium (245.47 ± 13.52 pg/mL) reduced PRL level of hyperPRL rats significantly (p 0.05). In MMQ cells, treatment with 5 mg/mL PVE or 10 mg/mL PVE) significantly suppressed PRL secretion and synthesis at 24h compared with controls (p < 0.01). Consistent with D2- action, PVE did not affect PRL in rat pituitary lactotropic tumor-derived GH3 cells that lack the D2 receptor expression, compared with controls.Conclusion: PVE showed anti-hyperPRL activity and can potentially be used for the treatment of hyperprolactinemi, but further studies are required to ascertain this.Keywords: Prunella vulgaris, Hyperprolactinemia, Prolactin, Bromocriptin

Changes in risk factors for food sensitization in early life: Analysis over a period of 10 years

BackgroundAlthough epidemiological trends of childhood food sensitization (FS) in IgE-mediated food allergy were reported in China, few studies have examined at changes in its risk factors.ObjectiveTo investigate the change in early-life risk factors associated with childhood food sensitization during 2009–2019 in China.MethodsData from two cross-sectional surveys conducted in 2009 and 2019 (401 and 513 children, respectively) were analyzed. The results of skin prick tests and information on food sensitization-related risk factors in children were summarized, including family history of atopic disease (FHA), demographic characteristics, method of delivery, feeding patterns, sibship size, pet ownership, and vitamin D supplementation. Binary logistic regression was used to calculate the odds ratio and the regression coefficient β-value of risk factors in the 2009 and 2019 surveys separately. Then, coefficient β-value differences between the two surveys were analyzed by the bdiff command in STATA to describe the change in risk factors over 10 years.ResultsThe 2009 survey revealed that FHA, age, only child, and feeding patterns were associated with food sensitization. The 2019 survey showed that food sensitization was affected by age, sex, and feeding patterns. However, from 2009 to 2019, the probability of food sensitization in the only-child group significantly increased by 226.0% (β-value difference = 0.81, P = 0.024) and decreased by 65.0% in female children (β-value difference = −1.06, P = 0.008). The effect of age on food sensitization decreased by 50.0% (β-value difference = −0.69, P < 0.001) over 10 years.ConclusionThe effect of FHA and common lifestyle factors on food sensitization did not significantly change during 2009−2019. However, the influence of demographic characteristics on food sensitization has changed since 2009; that is, older age, male gender, and only child are more likely to develop food sensitization, which needs to be considered in future epidemiological surveys.Clinical Trial Registrationhttp://www.chictr.org.cn/, identifier ChiCTR1900024338

Unidirectional Cross-Activation of GRPR by MOR1D Uncouples Itch and Analgesia Induced by Opioids

SummarySpinal opioid-induced itch, a prevalent side effect of pain management, has been proposed to result from pain inhibition. We now report that the μ-opioid receptor (MOR) isoform MOR1D is essential for morphine-induced scratching (MIS), whereas the isoform MOR1 is required only for morphine-induced analgesia (MIA). MOR1D heterodimerizes with gastrin-releasing peptide receptor (GRPR) in the spinal cord, relaying itch information. We show that morphine triggers internalization of both GRPR and MOR1D, whereas GRP specifically triggers GRPR internalization and morphine-independent scratching. Providing potential insight into opioid-induced itch prevention, we demonstrate that molecular and pharmacologic inhibition of PLCβ3 and IP3R3, downstream effectors of GRPR, specifically block MIS but not MIA. In addition, blocking MOR1D-GRPR association attenuates MIS but not MIA. Together, these data suggest that opioid-induced itch is an active process concomitant with but independent of opioid analgesia, occurring via the unidirectional cross-activation of GRPR signaling by MOR1D heterodimerization

VASP Activation via the Gα13/RhoA/PKA Pathway Mediates Cucurbitacin-B-Induced Actin Aggregation and Cofilin-Actin Rod Formation

Cucurbitacin B (CuB), a potent antineoplastic agent of cucurbitacin triterpenoids, induces rapid disruption of actin cytoskeleton and aberrant cell cycle inhibiting carcinogenesis. However, the underlying molecular mechanism of such anticancer effects remains incompletely understood. In this study, we showed that CuB treatment rapidly induced vasodilator-stimulated phosphoprotein (VASP) phosphorylation (i.e. activation) at the Ser157 residue and generated VASP clumps which were co-localized with amorphous actin aggregates prior to the formation of highly-ordered cofilin-actin rods in melanoma cells. Knockdown of VASP or inhibition of VASP activation using PKA-specific inhibitor H89 suppressed CuB-induced VASP activation, actin aggregation and cofilin-actin rod formation. The VASP activation was mediated by cAMP-independent PKA activation as CuB decreased the levels of cAMP while MDL12330A, an inhibitor of adenylyl cyclase, had weak effect on VASP activation. Knockdown of either Gα13 or RhoA not only suppressed VASP activation, but also ameliorated CuB-induced actin aggregation and abrogated cofilin-actin rod formation. Collectively, our studies highlighted that the CuB-induced actin aggregation and cofilin-actin rod formation was mediated via the Gα13/RhoA/PKA/VASP pathway

Therapeutic effect of Rho kinase inhibitor FSD-C10 in a mouse model of Alzheimer\u27s disease.

Fasudil, a Rho kinase (ROCK) inhibitor, effectively inhibits disease severity in a mouse model of Alzheimer\u27s disease (AD). However, given its significant limitations, including a relatively narrow safety window and poor oral bioavailability, Fasudil is not suitable for long-term use. Thus, screening for ROCK inhibitor(s) that are more efficient, safer, can be used orally and suitable for long-term use in the treatment of neurodegenerative disorders is required. The main purpose of the present study is to explore whether FSD-C10, a novel ROCK inhibitor, has therapeutic potential in amyloid precursor protein/presenilin-1 transgenic (APP/PS1 Tg) mice, and to determine possible mechanisms of its action. The results showed that FSD-C10 effectively improved learning and memory impairment, accompanied by reduced expression of amyloid-β1-42 (Aβ 1-42 ), Tau protein phosphorylation (P-tau) and β-site APP-cleaving enzyme in the hippocampus and cortex area of brain. In addition, FSD-C10 administration boosted the expression of synapse-associated proteins, such as postynaptic density protein 95, synaptophsin, α-amino 3-hydroxy-5-methyl-4-isoxa-zolep-propionate receptor and neurotrophic factors, e,g., brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. Taken together, our results demonstrate that FSD-C10 has therapeutic potential in the AD mouse model, possibly through inhibiting the formation of Aβ 1-42 and P-tau, and promoting the generation of synapse-associated proteins and neurotrophic factors