Search

Abstract Activating transcription factor 2 (ATF2), a member of the alkaline-leucine zipper family, is widely expressed in various tissues, and reportedly involved in inflammatory responses to various irritates, but its role in the central nervous system (CNS) remains unclear. This study aimed to investigate the expression and biological function of ATF2 in CNS inflammation. Utilizing the LPS-induced neuroinflammation model on mice, we first found ATF2 up-regulation and its co-localization with microglia in inflamed mice brain. In vitro, we revealed an increased expression, phosphorylation, and nuclear accumulation of ATF2 in LPS-treated BV2 microglia cells. Inhibiting ATF2 significantly decreased the expression of pro-inflammatory factors in LPS-treated microglia, and alleviated neuronal apoptosis induced by the conditioned medium of activated microglia. Knocking down TRAF6, an important adaptor of the TLR4/MAPK/NF-κB signaling pathway, suppressed the LPS-induced ATF2 expression and phosphorylation, accompanied by the decreased p38/JNK phosphorylation, in microglia. Blocking p38 or JNK signaling pathway by the specific inhibitors reversed the TRAF6-overexpression mediated ATF2 activation. Taken together, our data first proved the pro-inflammatory function of ATF2 in microglia, and suggested that the TRAF6-JNK/p38-ATF2 axis might promote microglial inflammatory activation and thus aggravate neuronal injury in brain, which might become a potential therapeutic target for CNS diseases. Highlights • LPS induces ATF2 expression and activation in microglia both in vivo and in vitro. • ATF2 promotes microglia activation and the subsequent neuronal apoptosis in vitro. • TRAF6 positively regulates ATF2 activation in LPS-treated microglia. • The TRAF6-p38/JNK-ATF2 axis contributes to microglia-mediated neuroinflammation. [ABSTRACT FROM AUTHOR]

Glial scar formation derived from astrocyte proliferation and migration influences the functional recovery after spinal cord injury. Cyclin-dependent kinase inhibitor p27 kip1 , whose activity is closely related to its phosphorylation state, reportedly regulates astrocyte proliferation and migration. In this study, we reported that p27 Kip1 undergoes O-GlcNAc modification at Ser 2, Ser 110 and Thr 197. Inhibiting O-GlcNAcylation on Ser 2 by gene mutation (S2A) attenuated the phosphorylation of Ser 10, and vice versa. Interestingly, compared with wild type p27 Kip1 , S2A p27 Kip1 displayed a decreased interaction with CRM1 and reduced nuclear export following serum starvation and release. In addition, the interaction between stathmin and S2A p27 Kip1 was also decreased. Cytoskeletal proteins microtubules appeared high density in astrocytes transfected with S2A p27 Kip1 especially at the leading edge of the scratch wound. Accordingly, scratch-wound assay revealed that the motility of astrocytes transfected with S2A p27 Kip1 was faster than that of control. Finally, we injected lentiviral vectors immediately after spinal cord contusion, and found the lesion volume of the rat injected with S2A p27 Kip1 was smaller than that of rat injected with wild type p27 Kip1 . Besides, the BBB and CBS behavioral tests showed greater functional recovery in S2A p27 Kip1 treated rats. Taken together, our findings revealed a novel function of O-GlcNAc modification of p27 Kip1 in mediating astrocytes migration and functional recovery after spinal cord contusion. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common neurodegenerative disorder in the world. The aggregation of both amyloid beta (Aβ) peptides extracellularly and Tau proteins intracellularly plays key roles in the pathological consequences of AD, which lead to cholinergic neurodegeneration and eventually death. Currently, there are no effective methods to stop the progression of AD. Using ex vivo , in vivo and clinical approaches, we investigated the functional effects of plasminogen on the widely used FAD, Aβ42 oligomer or Tau intracranial injection-induced AD mouse model and explored its therapeutic effects on patients with AD. The results show that intravenously injected plasminogen rapidly crosses the blood‒brain barrier (BBB); increases plasmin activity in the brain; colocalizes with and effectively promotes the clearance of Aβ42 peptide and Tau protein deposits ex vivo and in vivo ; increases the choline acetyltransferase (ChAT) level and decreases the acetylcholinesterase (AChE) activity; and improves the memory functions. Clinically, when GMP-level plasminogen was administered to 6 AD patients for 1–2 weeks, their average scores on the Minimum Mental State Examination (MMSE), which is a standard scoring system used to measure the memory loss and cognitive deficits, were extremely significantly improved by 4.2 ± 2.23 points, e.g., an average increase from 15.5 ± 8.22 before treatment to 19.7 ± 7.09 after treatment. The preclinical study and pilot clinical study suggest that plasminogen is effective in treating AD and may be a promising drug candidate. • Plasminogen crosses the blood‒brain barrier (BBB) and increases plasmin activity in the brain. • Plasminogen promotes the clearance of Aβ42 peptide and Tau protein. • Plasminogen improves the memory functions in AD mouse model. • Plasminogen increases the Minimum Mental State Examination (MMSE) score in AD patients. [ABSTRACT FROM AUTHOR]

Abstract: Although effects of nickel(II) on the immune system have long been recognized, little is known about the effects of nickel(II) on the induction of apoptosis and related signaling events in T cells. In the present study, we investigated the roles and signaling pathways of nickel(II) in the induction of apoptosis in a human T cell line jurkat. The results showed that the cytotoxic effects of Ni involved significant morphological changes and chromosomal condensation (Hoechst 33258 staining). Analyses of hypodiploid cells and FITC–Annexin V and PI double staining showed significant increase of apoptosis in jurkat cells 6, 12 and 24 h after nickel(II) treatment. Flow cytometry analysis also revealed that the loss of mitochondrial membrane potential (MMP) occurred concomitantly with the onset of NiCl2-induced apoptosis. Induction of apoptotic cell death by nickel was mediated by reduction of bcl-2 expression. Furthermore, nickel stimulated the generation of nitric oxide (NO). These results suggest that nickel(II) chloride induces jurkat cells apoptosis via nitric oxide generation, mitochondrial depolarization and bcl-2 suppression. [Copyright &y& Elsevier]

Fiber quality is a major breeding goal in cotton, but phenotypically direct selection is often hindered. In this study, we identified fiber quality and yield related loci using GWAS based on 2.97 million SNPs obtained from 10.65× resequencing data of 1081 accessions. The results showed that 585 novel fiber loci, including two novel stable SNP peaks associated with fiber length on chromosomes At12 and Dt05 and one novel genome regions linked with fiber strength on chromosome Dt12 were identified. Furthermore, by means of gene expression analysis, GhM_A12G0090 , GhM_D05G1692 , GhM_D12G3135 were identified and GhM_D11G2208 function was identified in Arabidopsis. Additionally, 14 consistent and stable superior haplotypes were identified, and 25 accessions were detected as possessing these 14 superior haplotype in breeding. This study providing fundamental insight relevant to identification of genes associated with fiber quality and yield will enhance future efforts toward improvement of upland cotton. • A total of 909 novel fiber and yield loci were detected via WGRS with 10.65× coverage depth in 1,081 cotton accessions. • Three novel stable SNP peaks associated with FL and FS were found. • GhM_D11G2208 can promote cell elongation based up leaf trichome and dark-grown hypocotyls in Arabidopsis. • 14 consistent and stable superior haplotypes were detected based on 915 SNPs in Dt11 region. [ABSTRACT FROM AUTHOR]

Abstract: In this study, an electrochemical method to assay calcineurin activity is proposed. Although the enzyme could not exhibit electron transfer reactivity and the catalytic reaction of the substrate could not give any electrochemical wave, p-nitrophenol as the catalytic reaction production could be oxidized at the calcineurin/Triton X-100 film modified electrode to exhibit useful wave that might be employed to assay the enzyme activity. The effect of Ni2+ and Zn2+ on calcineurin was also investigated. Whereas Ni2+ was confirmed to be able to enhance the enzymatic activity, Zn2+ was found to be an inhibitor to calcineurin. [Copyright &y& Elsevier]

The evidence of interactive effect of the toxic metal (TM) mixture and apolipoprotein E (APOE) ε4 gene on cognitive impairment in older adults is scarce. We aimed to explore whether the associations of single TMs and their mixture with cognitive impairment depend on APOE ε4 in Chinese community-dwelling older people. A total of 1148 older adults from a subset of the baseline survey of a cohort study were included. Blood arsenic (As), cadmium (Cd), lead (Pb), strontium (Sr), and vanadium (V) were detected by inductively coupled plasma mass spectrometry. APOE gene (rs429358, rs7412) polymorphisms were analyzed by the Polymerase Chain Reaction instrument. Mixed effects logistic regression was applied to estimate the relationships of single TMs and APOE genotype with cognitive impairment. Weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models were performed to examine joint impacts of the TM mixture, as well as the interaction of the TM mixture with APOE ε4 genotype on cognitive impairment. Pb displayed a significant linear association with an increased odds of cognitive impairment after adjustment for covariates (P trend = 0.045). While APOE genotype did not show a significant correlation with cognitive impairment. WQS showed that the TM mixture was associated with an increased risk of cognitive impairment by 31.0% (OR= 1.31, 95% CI: 0.92, 1.87) while no significance was found. BKMR exhibited a significant linear association between the TM mixture and cognitive impairment. Moreover, both WQS and BKMR indicated that Pb contributed the most to cognitive impairment within the mixture. Significant interactions of Pb or the TM mixture and APOE genotype on cognitive impairment were observed, contributing to 38.1% and 38.2% of total effects, respectively. APOE ε4 allele amplifies the associations of single Pb or the TM mixture with cognitive impairment. These findings may help to develop precision prevention. [Display omitted] • The TM mixture showed a positive association with cognitive impairment, in which Pb was the most contributor in the mixture. • APOE ε4 genotype amplified the associations of Pb and the TM mixture with cognitive impairment in older adults. • Attributable proportions due to interaction effects of Pb and the mixture with APOE ε4 were 38.1% and 38.2%, respectively. [ABSTRACT FROM AUTHOR]

Three novel Mn(II)/Co(II)-based 3D metal-organic frameworks (MOFs), namely {[Mn 2 (L)(tib)(H 2 O)]·3DMA·4H 2 O} n (1), {[Co 2 (L)(bipd) 2 ]·3H 2 O} n (2) and {[Co(L) 0.5 (bimb)]·3H 2 O·0.5O 2 } n (3) (H 4 L ​= ​5,5'-(1,4-xylylenediamino) diisophthalic acid, tib ​= ​1,3,5-tris(1-imidazolyl)benzene, bipd ​= ​3,5-bis(1-imidazoly)pyridine, and bimb ​= ​1,4-bis(lmidazol)-butane), have been successfully synthesized using the mixed-ligand as functionalized organic linker. The structural characterization revealed that both MOFs 1 and 2 exhibited an unprecedented 4-nodal 3D framework that enriching crystal engineering, while MOF 3 featured a 2-nodal three-interpenetrating bbf topology framework with a Schläfli symbol of (64·82)(66) 2. The title MOFs have been exploited as photocatalysts for degradation of methylene blue (MB), methyl violet (MV) and malachite green (MG). The photocatalytic results demonstrated that MOFs 2 and 3 exhibited efficient photocatalytic abilities to degrade the three aromatic dyes under UV irradiation. The possible catalytic mechanism was also explored and discussed in detail. Moreover, the variable-temperature magnetic analyses indicated that MOFs 1 – 3 exhibited weak antiferromagnetic behavior between Mn(II)/Co(II) ions. [Display omitted] • Three novel Mn(II)/Co(II)-based 3D MOFs under solvothermal or hydrothermal condition in one-step, for the first time, were synthesized. • The MOFs 2 and 3 act as efficient heterogeneous photocatalyst for degradation of three aromatic dyes. • The possible catalytic mechanism was explored and discussed in detail. • MOFs 1 – 3 exhibit antiferromagnetic coupling between neighboring central ions. [ABSTRACT FROM AUTHOR]

Neuroinflammation is critically involved in nerve injury-induced neuropathic pain, characterized by local and systemic increased levels of proinflammatory cytokines. Interleukin-24 (IL-24), a key member of the IL-10 family, has been extensively studied for its therapeutic potential in various diseases, including cancer, autoimmune disorders, and bacterial infections, but whether it is involved in the regulation of neuropathic pain caused by peripheral nerve injury (PNI) has not been well established. In this study, we reported that spared nerve injury (SNI) induced a significant upregulation of IL-24 in fibroblasts, neurons, and oligodendrocyte precursor cells (OPCs, also called NG2-glia) in the affected spinal dorsal horns (SDHs), as well as dorsal root ganglions (DRGs). We also found that tumor necrosis factor α (TNF-α) induced the transcriptional expression of IL-24 in cultured fibroblasts, neurons, and NG2-glia; in addition, astrocytes, microglia, and NG2-glia treated with TNF-α exhibited a prominent increase in interleukin-20 receptor 2 (IL-20R2) expression. Furthermore, we evaluated the ability of IL-24 and IL-20R2 to attenuate pain in preclinical models of neuropathic pain. Intrathecal (i.t.) injection of IL-24 neutralizing antibody or IL-20R2 neutralizing antibody could effectively alleviate mechanical allodynia and thermal hyperalgesia after PNI. Similarly, intrathecal injection of IL-24 siRNA or IL-20R2 siRNA also alleviated mechanical allodynia after SNI. The inhibition of IL-24 reduced SNI-induced proinflammatory cytokine (IL-1β and TNF-α) production and increased anti-inflammatory cytokine (IL-10) production. Meanwhile, the inhibition of IL-20R2 also decreased IL-1β mRNA expression after SNI. Collectively, our findings revealed that IL-24/IL-20R might contribute to neuropathic pain through inflammatory response. Therefore, targeting IL-24 could be a promising strategy for treating neuropathic pain induced by PNI. [Display omitted] • IL-24 was secreted by activated fibroblasts, neurons and NG2-glia after SNI. • TNF-α induced IL-20R2 expression in cultured astrocytes, microglia and NG2-glia. • Inhibiting IL-24 or IL-20R2 significantly ameliorated PNI-induced neuropathic pain. [ABSTRACT FROM AUTHOR]

Four novel Co(II)-MOFs based on the 3,3′-azodibenzoic acid (H 2 L), namely [CoL (bimb) 0.5 ] n (1), {[CoL (bimmb)]·DMF} n (2), [CoL (bimmb) 0.5 ] n (3), and [CoL (bbibp)] n (4) (bimb = 1,4-bisimidazole, bimmb = 4-bis(imidazole-1-ylmethyl)benzene, bbibp = 4,4′-bis(benzoimidazo-1-yl)biphenyl and DMF = N, N′-dimethylformamide) have been synthesized under solvothermal conditions and characterized by elemental analysis, IR spectra, powder X-ray diffraction (PXRD), thermogravimetric (TG) analysis and single crystal X-ray diffraction. Single crystal X-ray diffraction analysis shows that complex 1 and complex 3 possesses the same structure as uninodal 6-connected 3D (three-dimensional) pcu topology framework with the point symbol (412.63), whereas complex 2 possesses an uninodal 3-connected hcb topology framework with the point symbol (63) and complex 4 displays a 4-connected sql topology framework with the point symbol of (44.62). In addition, the photocatalytic degradation properties of the four complexes have been investigated. Significantly, complex 4 is the best photocatalyst for the degradation of three organic dyes (MV/MB/RhB). Complex 2 is the good photocatalyst for the degradation of two organic dyes (RhB/MB). Complex 3 is the good photocatalyst for the degradation of two organic dyes (MV/MB) and complex 1 is the good photocatalyst for the degradation of only one organic dyes (MV). Image 1 [ABSTRACT FROM AUTHOR]

Ischemic stroke is one of the most lethal and highly disabling diseases that seriously affects the human health and quality of life. A therapeutic angiogenic strategy has been proposed to alleviate ischemia-induced injury by promoting angiogenesis and improving cerebrovascular function in the ischemic regions. The insulin-like growth factor 1 (IGF-1)/insulin-like growth factor 1 receptor (IGF1R) axis is crucial for cerebral angiogenesis and neurogenesis. However, effective drugs that prevent cerebral ischemic injury by inducing cerebral angiogenesis via activation of the IGF1R pathway are lacking. Here, we screened a pro-angiogenic agent ginsenoside F1 (GF1), a ginseng saponin isolated from a traditional Chinese medicine that was widely used in ischemic stroke treatment. It promoted the proliferation, mobility and tube formation of human umbilical vein endothelial cells and human brain microvascular endothelial cells, as well as pericytes recruitment to the endothelial tubes. GF1 stimulated vessel sprouting in the rat arterial ring and facilitated neovascularization in chicken embryo chorioallantoic membrane (CAM). In the in vivo experiments, GF1 rescued the axitinib-induced vascular defect in zebrafish. It also increased the microvessel density (MVD) and improved focal cerebral blood perfusion in the rat middle cerebral artery occlusion (MCAO) model. Mechanism studies revealed that GF1-induced angiogenesis depended on IGF1R activation mediated by the autocrine IGF-1 loop in endothelial cells. Based on our findings, GF1-induced activation of the IGF-1/IGF1R pathway to promote angiogenesis is an effective approach to alleviate cerebral ischemia, and GF1 is a potential agent that improves cerebrovascular function and promotes recovery from ischemic stroke. [ABSTRACT FROM AUTHOR]

Epithelial-mesenchymal transition (EMT) plays an important role in prostate cancer (PCa) metastasis; thus, developing EMT inhibitors may be a feasible treatment for metastatic PCa. Here, we discovered that arenobufagin and four other bufadienolides suppressed PC3 cell EMT. These compounds modulated EMT marker expression with elevating E-cadherin and reducing ZEB1, vimentin and slug expression, and attenuated the migration and invasion of PC3 cells. Among these five compounds, arenobufagin exhibited the most potent activity. We found that the mRNA and protein expression of β-catenin and β-catenin/TCF4 target genes, which are related to tumor invasion and metastasis, were down-regulated after arenobufagin treatment. Overexpression of β-catenin in PC3 cells antagonized the EMT inhibition effect of arenobufagin, while silencing β-catenin with siRNA enhanced the inhibitory effect of arenobufagin on EMT. In addition, arenobufagin restrained xenograft tumor EMT, as demonstrated by decreased mesenchymal marker expression and increased epithelial marker expression, and reduced the tumor metastatic foci in lung. This study demonstrates a novel anticancer activity of arenobufagin, which inhibits PC3 cell EMT by down-regulating β-catenin, thereby reducing PCa metastasis. In addition, it also provides new evidence for the development of arenobufagin as a treatment for metastatic prostate cancer. [ABSTRACT FROM AUTHOR]

As VLSI technology advances towards nanoscale devices, interconnect delay is becoming increasingly important, and could be effectively reduced using buffer insertion. The widely-used buffer insertion technique in industry is to insert a set of buffers on the chip, which may overlap some gates, and then greedily move the buffers to the nearest available buffer holes. The moving distance of inserted buffers largely affects the wirelength which may result in the increase of the interconnect delay. This necessitates efficient algorithms to minimize the moving distance of buffers for effective buffer insertion to obtain high-performance VLSI designs. This paper proposes an efficient, perturbation constrained buffer planning algorithm to maximize the candidate buffer holes with regarding to the feature of CPS based buffering design framework. Instead of directly moving buffers to the existing available buffer holes, the proposed algorithm changes the original placement by moving some gates tinily to provide more flexibility for buffer insertion. The integer linear programming based technique is designed for the physical design flow which allows small moving range of gates. Parallel technique is utilized to solve the ILP problems efficiently when the scale of chip is increasing. Experimental results have shown that the proposed algorithm achieves at most 41.49 % increase in the available buffer holes when compared to the algorithm with no gate movement. [ABSTRACT FROM AUTHOR]

Septins are GTP-binding proteins that regulate cell polarity, cytokinesis and cell morphogenesis. Fusarium head blight (FHB), caused by Fusarium graminearum , is one of the most devastating diseases worldwide. In this study, we have functionally characterized the core septins, Cdc3, Cdc10, Cdc11 and Cdc12 in F. graminearum. The loss of FgCdc3, FgCdc11, FgCdc12, but not FgCdc10, mutants showed significant reduction in growth, conidiation and virulence. Microscopic analyses revealed that all of them were involved in septum formation and nuclear division. Moreover, disruption of septin genes resulted in morphological defects in ascospores and conidia. Interestingly, conidia produced by ΔFgcdc3 , ΔFgcdc11 and ΔFgcdc12 mutants exhibited deformation with interconnecting conidia in contrast to their parent wild-type strain PH-1 and the ΔFgcdc10 mutant that produced normal conidia. Using yeast two-hybrid assays, we determined the interactions among FgCdc3, FgCdc10, FgCdc11 and FgCdc12. Taken together, our results indicate that septins play important roles in the nuclear division, morphogenesis and pathogenicity in F. graminearum . [ABSTRACT FROM AUTHOR]

The suppressor of cytokine signaling SOCS1 is a member of the cytokine signaling pathway inhibitor family, which is induced by the IFN-γ induced JAK signaling pathway. The expression of SOCS1 has been found to increase in Crohn's disease (CD) patients, but the role of SOCS1 in intestinal epithelium is unclear. This study was designed to investigate whether SOCS1 has a role in the death of intestinal epithelial cells and intestinal injury. The results showed that the expression of SOCS1 increased in CD patients, and the expression of SOCS1, p-p53 and PUMA increased in the mouse TNBS induced colitis model. Using IFN-γ treated HT-29 cells as an apoptotic model of intestinal epithelial cells in vitro, we confirmed that SOCS1 promoted apoptosis of intestinal epithelial cells by activating p53. In HT-29 cells which were treated with IFN-γ, the interaction between p53 and SOCS1 and phosphorylation of p53 were significantly higher than untreated cells. When knocking SOCS1 down by using SOCS1 siRNA, phosphorylation of p53 and apoptosis of intestinal epithelial cells which was induced by IFN-γ were significantly inhibited. In summary, our findings suggest that SOCS1 may promote apoptosis of intestinal epithelial cells at least partly through mediating p53 signaling. [ABSTRACT FROM AUTHOR]

Objective Karyopherin alpha 2 (KPNA2) is a member of the importin α family, which acts as an adaptor to deliver P65 to the nucleus by recognizing the classic nuclear localization signal (NLS) of the cargo protein, and which has been reported as being involved in the pathogenesis of many diseases. This study was undertaken to determine the expression and possible functions of KPNA2 in osteoarthritis (OA). Methods KPNA2 expression in cartilage tissues of OA patients and normal controls was detected by RT-PCR and immunohistochemistry. SW1353 cells were stimulated with IL-1β to establish the chondrocyte injury model in vitro. The expression of KPNA2 and catabolic genes in IL-1β-treated SW1353 cells were determined by Western blot. The interaction between KPNA2 and P65 was analyzed by co-immunoprecipitation, the subcellular distribution and transportation of P65 were detected by the subcellular fractionation followed by immunoblot analysis and immunofluorescence. Furthermore, we used RNA interference to analyze the role of KPNA2 in IL-1β-induced P65 nuclear importation and MMP13, ADAMTS-5 expression in SW1353 cells. Results Cartilage expression of KPNA2 was higher in patients with OA compared with normal controls and mainly locating in chondrocytes. In IL-1β-treated SW1353 cells, up-regulation of KPNA2 was accompanied by the elevated expression of the catabolic marker protein levels, including MMP13 and ADAMTS-5, and increased NF-κB P65 nuclear importation. Knock-down of KPNA2 resulted in decreased catabolic marker protein levels in IL-1β-treated SW1353 cells. KPNA2 interacted with p65, and loss of KPNA2 caused decreased nuclear translocation of the active p50/p65 NF-κB complex. Conclusions These findings suggested that KPNA2 may promote NF-κB activation via facilitating P65 nuclear transportation, and thus subsequently accelerate the catabolic events of osteoarthritis. [ABSTRACT FROM AUTHOR]

The mevalonate pathway is an efficient biosynthesis pathway that yields isoprenoids for promoting different crucial cellular functions, including ergosterol synthesis and growth regulation. Acetoacetyl-CoA acetyltransferase (EC2.3.1.9) is the first major catalytic enzyme constituting the mevalonate pathway and catalyzes the transformation of Acetoacetyl-CoA from two molecules of acetyl-CoA enroute ergosterol production in fungi. We identified two homologous genes encoding Acetoacetyl-CoA acetyltransferase (MoAcat1 and MoAcat2) in Magnaporthe oryzae , the rice blast fungus. Phylogenetic analysis indicates these two genes have different evolutionary history. We subsequently, conducted targeted gene deletion using homologous recombination technology to ascertain the unique roles of the two MoAcat homologues during the fungal morphogenesis and pathogenesis. The findings from our investigations showed that the activity of MoAcat1 promoted virulence in the rice blast fungus as such, the ΔMoacat1 mutants generated exhibited defect in virulence, whilst ΔMoacat1 mutants did not portray growth defects. ΔMoacat2 mutants on the other hand were characterized by reduction in growth and virulence. Furthermore, MoAcat1 and MoAcat2 showed different expression patterns and subcellular localizations in M. oryzae . From our investigations we came to the conclusion that, different subcellular localization contributes to the diverse functions of MoAcat1 and MoAcat2, which helps the successful establishment of blast disease by promoting efficient development of cell morphology and effective colonization of host tissue. [ABSTRACT FROM AUTHOR]

In this paper, we study the parkinson oscillation mechanism in a computational model by bifurcation analysis and numerical simulation. Oscillatory activities can be induced by abnormal coupling weights and delays. The bidirectional Hopf bifurcation phenomena are found in simulations, which can uniformly explain the oscillation mechanism in this model. The Hopf1 represents the transition between the low firing rate stable state (SS) and oscillation state (OS), the Hopf2 represents the transition between the high firing rate stable state (HSS) and the OS, the mechanisms of them are different. The Hopf1 and Hopf2 bifurcations both show that when the state transfers from the stable region to the oscillation region, oscillatory activities originate from the beta frequency band or the gamma frequency band. We find that the changing trends of the frequency (DF) and oscillation amplitude (OSAM) are contrary in many cases. The effect of the delay in inhibitory pathways is greater than that of in excitatory pathways, and appropriate delays improve the discharge activation level (DAL) of the system. In all, we infer that oscillations can be induced by the follow factors: 1. Improvement of the DAL of the globus pallidus externa (GPe); 2. Reduce the DAL of the GPe from the HSS or the discharge saturation state; 3. The GPe can also resonate with the subthalamic nucleus (STN). [ABSTRACT FROM AUTHOR]

Highlights: [•] Magnaporthe oryzae encodes eight putative RhoGAP proteins. [•] MoRga1 regulates conidial morphology and appressorial formation. [•] MoLrg1 is required for conidiogenesis, vegetative growth and pathogenicity. [•] Both MoRga1 and MoLrg1 interact with MoRac1 and MoCdc42. [•] LIM domain, RhoGAP domain and Arginine 1032 are all essential for MoRga1 function. [ABSTRACT FROM AUTHOR]

Two novel Co (II) MOFs based on 5-(4-(imidazolyl-1-yl)phenyl) isophthalic acid (H 2 L), namely [Co(L)(tib)(H 2 O) 2 ] n (CP 1) and [Co(L)(bip) 0.5 ] n (CP 2) (tib ​= ​1,3,5-tirs (1-imidazolyl) benzene, bip ​= ​3,5-bis(1-imidazolyl) pyridine ether) have been synthesized under solvothermal conditions and characterized by powder X-ray diffraction, single crystal X-ray diffraction. The photodegradation studies demonstrate that CPs 1 – 2 show high-efficiency degradation of MV (Methyl violet), and the mechanism studies demonstrate that the main active species are ⋅OH radicals. Meanwhile, electrochemistry studies demonstrate that CPs 1 – 2 can catalyze water oxidation under alkaline conditions, and CPs 1 – 2 only need the overpotential of 348 ​mV–760 mV to deliver the current density of 1 ​mA ​cm−2. Two novel Co (II) MOFs (CP 1 and CP 2) have been synthesized by H 2 L, tib, and bip. The photodegradation studies demonstrate that CPs 1-2 show high-efficiency degradation of MV. Simultaneously, electrochemistry studies show that CPs 1-2 could catalyze water oxidation with relatively low overpotential. [Display omitted] • Two novel Co-based MOFs were synthesized by solvothermal method. • Exhibit efficient photocatalytic degradation abilities towards MV/MB in aqueous solution. • Only need the overpotential of 348 ​mV–760 mV to deliver the current density of 1 ​mA ​cm−2. [ABSTRACT FROM AUTHOR]

Angiogenesis is critical for many diseases. Previously, we reported that Down Syndrome Candidate Region 1 isoform 1L (DSCR1-1L) was one of the most up-regulated genes in endothelial cells induced by VEGF and histamine, and regulated endothelial cell proliferation and Matrigel angiogenesis in mice. However, it was not known whether DSCR1-1L regulated angiogenesis in vivo and what was the molecular mechanism underlying it. In this study, gene knockdown and overexpression models were established to study the role of DSCR1-1L in angiogenesis in vivo. Further, the downstream regulatory target of DSCR1-1L was explored with molecular biological methods in vascular endothelial cells. We found that DSCR1-1L shRNAs significantly inhibited angiogenesis induced by VEGF in mice (p < 0.0001). In the gain-of-function assay, overexpression of DSCR1-1L cDNA in mouse endothelium of EC-FH-DSCR1-1L transgenic mice was sufficient to induce angiogenesis significantly (p < 0.01). DSCR1-1L regulated angiogenesis in the early stage by down-regulation of the VE-cadherin expression through targeting its transcription, but not mRNA stability. Three DSCR1-1L-targeted DNA elements in the VE-cadherin promoter were identified by promoter reporter assays, among which, a novel specific transcriptional complex was found. The DNA sequence (CTTCTG) in the VE-cadherin promoter was identified to directly interact with proteins by Electrophoresis Mobility Shift Assays and DNase I footprint assay. Hence, DSCR1-1L is an excellent therapeutic target for angiogenic diseases through down-regulating the formation of a novel transcriptional complex on the VE-cadherin promoter. DSCR1-1L shRNAs and cDNA have the potential to be developed for clinical application. Our results also contribute significantly to the field of mechanistic studies. • Down Syndrome Candidate Region 1 Isoform 1L shRNAs inhibited angiogenesis in vivo. • overexpression of DSCR1-1L cDNA in mouse endothelium was induce angiogenesis. • DSCR1-1L down-regulated the VE-cadherin transcription, but not mRNA stability. • A novel specific transcriptional complex regulated by DSCR1-1L was found. • The DNA sequence was identified to directly interact with proteins. [ABSTRACT FROM AUTHOR]

Abstract: Damage-associated molecular patterns (DAMPs) are signals released from dying cells evoking the immune system response in several inflammatory disorders. In normal situations, many of DAMPs are nuclear or cytosolic proteins with defined intracellular function, but they could be found on the cell surface following tissue injury. The biological function of the translocated DAMPs is still not well known and an efficient delivery of these molecules on the cell surface is required to clarify their biological effects. In this study, we demonstrated that an unclassical secretory signal peptide, N-terminal 18 amino acids of HASPB (HASPB-N18), could efficiently deliver Hsp60, Hsp70, and HMGB1 on the cell surface. Furthermore, the delivery of these molecules on the cell surface by HASPB-N18 is not limited to a special cell line because several cell lines could use this delivery signal to deliver these molecules on the cell surface. Moreover, we demonstrated that Hsp60 on the cell surface delivered by HASPB-N18 could be recognized by a soluble form of LOX-1, which implies that DAMPs on the cell surface delivered by HASPB-N18 have a proper conformation during transport. Therefore, delivery of DAMPs by HASPB-N18 is a reliable model to further understand the biological significance of DAMPs on the cell surface. [ABSTRACT FROM AUTHOR]

Microplastics (MPs), a growing class of emerging pollutants in the environment, have attracted widespread attention due to their adsorption properties. Recent research on MPs has mainly concentrated on seawater, and little work has been conducted on freshwater. Investigating and predicting the adsorption behavior of organic pollutants by MPs are necessary in freshwater. In this study, the adsorption behavior of 13 organic chemicals by polyethylene (PE) and chlorinated polyethylene (CPE) MPs was determined under freshwater conditions. Results shows the majority of the organic chemicals exhibit no distinctive differences in their adsorption on two MPs. However, the adsorption of polycyclic aromatic hydrocarbons and chlorobenzene on CPE is obviously stronger than that on PE, and the result is a counter for two pesticides. Quantitative structure activity relationship (QSAR) analysis was performed for the prediction of adsorption capacity. A QSAR model with acceptable performance (R 2 = 0.8586) was built to predict the adsorptive affinity (expressed as log K d) of organic compounds on the PE MPs via multivariable linear regression (MLR) on forty-nine determined and collected data. The octanol/water partition coefficient (log K ow) and excess molar refractive index (E) play dominant roles in the model. A QSAR model with satisfactory performance (R 2 = 0.9302) was also established for log K d values from CPE MPs in freshwater by using 13 adsorption data determined. The log K ow and most negative charge on Cl atom (Q - max,cl) play decisive roles in the adsorption. The findings can provide a scientific basis for the risk assessment of waters contaminated by MPs and organic pollutants. • The adsorption of organics on microplastics was investigated in freshwater. • The adsorption affinity of 13 organic compounds on PE and CPE was compared. • QSAR models were established to predict the adsorption affinity. • The structural factors of compounds ascribing to adsorption were discussed. [ABSTRACT FROM AUTHOR]

Three novel Zn(II)-based coordination polymers (Zn-CPs), namely {[Zn(1,3,5-tib) 2 (H 2 O) 2 ·2(NO 3)} n (1), [Zn(1,3,5-tib)(4,4′-saba)] n (2), and {[Zn(1,3-bit)(4,4′-cpmb)]·0.5(1,3-bit)} n (3), have been hydrothermally synthesized and successfully characterized by single crystal X-ray diffraction (1,3,5-tib ​= ​1,3,5-tris(1-imidazolyl)benzene), 4,4′-Hsaba ​= ​4-(4-sulfoacid)-benzoic acid, 1,3-bit ​= ​1,3-bis(l-imidazoly)toluene, and 4,4′-H 2 cpmb ​= ​4-(4-carboxylphenylmethylthio)benzoic acid). Structural analysis reveals that complex 1 manifests a 2D planar structure with an unprecedented (2,4)-c topological network. Complex 2 and complex 3 display a 3-c fes and 6-fold classical Ia interpenetrated dia framework with 4-c (66) sqc6 topology framework, respectively. Among the three complexes, CPs 1 and 2 demonstrate excellent performance for Azo organic dyes' adsorption, for which the selectivity and kinetics have been comprehensively studied. CPs 3 shows great luminescent intensity in aqueous solution. It is further applied as a fluorescence sensor to detect Fe3+ cation, Cr 2 O 7 2− anion, and tetracycline antibiotic. Three Zn(II) coordination polymers (Zn-CPs), {[Zn(1,3,5-tib) 2 (H 2 O) 2 ·2(NO 3)} n (1), [Zn(1,3,5-tib)(4,4′-saba)] n (2), and {[Zn(1,3-bit)(4,4′-cpmb)]·0.5(1,3-bit)} n (3), have been hydrothermally prepared. While 1 – 2 could be applied as a CR dye adsorbent, and 3 could be as a potential sensing material for detection of Fe3+, Cr 2 O 7 2−, and TC. Image 1 • Three new Zn (II) coordination polymers (Zn-CPs) have been hydrothermally prepared and characterized. • Complexes 1 – 2 could selectively removal CR dye molecule from aqueous solution. • Complex 3 could be used to detect Fe3+, Cr 2 O 7 2−, and TC with high selectivity, anti-interference, and repeat-ability. [ABSTRACT FROM AUTHOR]

To investigate the effects of Bacillus methylotrophicus SY200 on Salmonella typhimurium (STM) infection in mice, a total of 36 three-week-old male mice were selected and randomly divided into 3 equal groups (N = 12). Group A and group B were fed with basal diet while group C was fed the basal diet supplemented with 0.1% (w/w) B. methylotrophicus SY200 during the 21 days experimental period. On the 14th day of the experiment, mice of group A were intragastrically administered with 0.5 ml of normal saline, group B and C were orally administered with 0.5 ml of STM suspension. On the first day and seventh day after STM challenge, the number of total white blood cells (WBCs) and neutrophils, relative weight of visceral organs, the number of Salmonella spp., Escherichia coli , Lactobacillus spp. and Bifidobacterium spp. in ileum and cecum, and diversity of cecal microflora were measured. The results showed that: on the first day and seventh day after STM challenge, the number of WBCs and neutrophils in the blood of the mice was the highest in group B, then followed by group C, and group A. On the first day after STM challenge, the relative weight of spleen in group C was significantly higher than that in group B (p < 0.05), moreover, compared with group B, B. methylotrophicus SY200 significantly reduced the number of Salmonella spp. and E. coli (p < 0.05), and increased the number of Lactobacillus spp. and Bifidobacterium spp. (p < 0.05) in the intestines of mice, and improved the Shannon-Wiener diversity (H), Simpson (E) and richness (S) indices of cecal flora of mice (p < 0.05). The results indicated that B. methylotrophicus SY200 could alleviate the inflammatory reaction after STM infection and resist the adverse effects of STM infection on mice intestinal flora. • Prevention of Bacillus methylotrophicus SY200 on Salmonella typhimurium (STM) infection in mice. • Bacillus methylotrophicus SY200 could alleviate the inflammatory reaction after STM infection. • Bacillus methylotrophicus SY200 could resist the adverse effects of STM infection on mice intestinal flora. [ABSTRACT FROM AUTHOR]