Cytoskeletal proteins are involved in neuronal survival.Brain-derived neurotrophic factor can increase expression of cytoskeletal proteins during regeneration after axonal injury.However,the effect ...of neural stem cells genetically modified by brain-derived neurotrophic factor transplantation on neuronal survival in the injury site still remains unclear.To examine this,we established a rat model of traumatic brain injury by controlled cortical impact.At 72 hours after injury,2 × 10~7 cells/m L neural stem cells overexpressing brain-derived neurotrophic factor or naive neural stem cells（3 m L） were injected into the injured cortex.At 1–3 weeks after transplantation,expression of neurofilament 200,microtubule-associated protein 2,actin,calmodulin,and beta-catenin were remarkably increased in the injury sites.These findings confirm that brain-derived neurotrophic factor-transfected neural stem cells contribute to neuronal survival,growth,and differentiation in the injury sites.The underlying mechanisms may be associated with increased expression of cytoskeletal proteins and the Wnt/β-catenin signaling pathway.
The mitogen-activated protein kinases (MAPKs), as a part of the MAPKKK-MAPKK-MAPK cascade, play crucial roles in plant development as an intracellular signal transduction pathway to respond various ...environmental signals. However, few MAPKK have been functionally characterized in grapevine.
In the study, five MAPKK (MKK) members were identified in grapevine (cultivar 'Pinot Noir'), cloned and designated as VvMKK1-VvMKK5. A phylogenetic analysis grouped them into four sub-families based on the similarity of their conserved motifs and gene structure to Arabidopsis MAPKK members. qRT-PCR results indicated that the expression of VvMKK1, VvMKK2, VvMKK4, and VvMKK5 were up-regulated in mature leaf and young blades, and roots, but exhibited low expression in leaf petioles. VvMKK2, VvMKK3, and VvMKK5 genes were differentially up-regulated when grapevine leaves were inoculated with spores of Erisyphe necator, or treated with salicylic acid (SA), ethylene (ETH), H
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or exposed to drought, indicating that these genes may be involved in a variety of signaling pathways. Over expression of VvMKK2 and VvMKK4 genes in transgenic Arabidopsis plants resulted in the production of seeds with a significantly higher germination and survival rate, and better seedling growth under stress conditions than wild-type plants. Overexpression of VvMKK2 in Arabidopsis improved salt and drought stress tolerance while overexpression of VvMKK4 only improved salt stress tolerance.
Results of the present investigation provide a better understanding of the interaction and function of MAPKKK-MAPKK-MAPK genes at the transcriptional level in grapevine and led to the identification of candidate genes for drought and salt stress in grapes.
Inflammation is a self-defense response to protect individuals from infection and tissue damage, but excessive or persistent inflammation can have adverse effects on cell survival. Many individuals ...become especially susceptible to chronic-inflammation-induced sensorineural hearing loss as they age, but the intrinsic molecular mechanism behind aging individuals' increased risk of hearing loss remains unclear. FoxG1 (forkhead box transcription factor G1) is a key transcription factor that plays important roles in hair cell survival through the regulation of mitochondrial function, but how the function of FoxG1 changes during aging and under inflammatory conditions is unknown. In this study, we first found that FoxG1 expression and autophagy both increased gradually in the low concentration lipopolysaccharide (LPS)-induced inflammation model, while after high concentration of LPS treatment both FoxG1 expression and autophagy levels decreased as the concentration of LPS increased. We then used siRNA to downregulate Foxg1 expression in hair cell-like OC-1 cells and found that cell death and apoptosis were significantly increased after LPS injury. Furthermore, we used d-galactose (D-gal) to create an aging model with hair cell-like OC-1 cells and cochlear explant cultures in vitro and found that the expression of Foxg1 and the level of autophagy were both decreased after D-gal and LPS co-treatment. Lastly, we knocked down the expression of Foxg1 under aged inflammation conditions and found increased numbers of dead and apoptotic cells. Together these results suggest that FoxG1 affects the sensitivity of mimetic aging hair cells to inflammation by regulating autophagy pathways.
For understanding the structural characteristics and the proteome of Perna shell, the microstructure, polymorph, and protein composition of the adult Perna viridis shell were investigated. The P. ...viridis shell have two distinct mineral layers, myostracum and nacre, with the same calcium carbonate polymorph of aragonite, determined by scanning electron microscope, Fourier transform infrared spectroscopy, and x-ray crystalline diffraction. Using Illumina sequencing, the mantle transcriptome of P. viridis was investigated and a total of 69,859 unigenes was generated. Using a combined proteomic/transcriptomic approach, a total of 378 shell proteins from P. viridis shell were identified, in which, 132 shell proteins identified with more than two matched unique peptides. Of the 132 shell proteins, 69 are exclusive to the nacre, 12 to the myostracum, and 51 are shared by both. The Myosin-tail domain containing proteins, Filament-like proteins, and Chitin-binding domain containing proteins represent the most abundant molecules. In addition, the shell matrix proteins (SMPs) containing biomineralization-related domains, such as Kunitz, A2M, WAP, EF-hand, PDZ, VWA, Collagen domain, and low complexity regions with abundant certain amino acids, were also identified from P. viridis shell. Collagenase and chitinase degradation can significantly change the morphology of the shell, indicating the important roles of collagen and chitin in the shell formation and the muscle-shell attachment. Our results present for the first time the proteome of P. viridis shell and increase the knowledge of SMPs in this genus.
A series of novel disulfides containing 1,3,4-thiadiazole moiety were designed, synthesized, and the structures of all products were identified by spectral data (IR, NMR, and high resolution ...(HR)-MS). Their in vitro antiproliferative activities were evaluated using 2-(2-methoxy-4-nitro-phenyl)-3-(4-nitro-phenyl)-5-(2,4-disulfopheyl)-2H-tetrazolium monosodium salt (CCK-8) assay against human cancer cell lines, A549 (human lung cancer cell), HeLa (human cervical cancer cell), SMMC-7721 (human liver cancer cell) and normal cell lines L929. The bioassay results indicated that most of the tested compounds 6a–k, 7a–k and 8a–k exhibited antiproliferation with different degrees, and some compounds showed better effects than positive control 5-fluorouracil (5-FU) against various cancer cell lines. Among these compounds, compound 6e exhibited the most potent inhibitory activity against A549 cells with IC50 value of 3.62 µM. Compounds 6i, 7a, 7g, 8a and 8b showed significantly antiproliferative activities against HeLa cells with IC50 values of 3.88, 3.76, 3.59, 3.38 and 3.12 µM, respectively. Compounds 6a, 7a and 8a owned high antiproliferative activities against SMMC-7721 cells with IC50 values of 2.54, 2.69 and 2.31 µM, respectively. Furthermore, all of the tested compounds showed weak cytotoxic effect against the normal cell lines L929. Based on the preliminary results, the substituent groups are vital for improving the potency and selectivity of this class of compounds.
This study was conducted to assess this association between early life antibiotic exposure and the risk of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) in later ...life. The results showed that early life antibiotic exposure was associated with an increased risk of ASD (OR = 1.13, 95% confidence interval (CI): 1.07–1.21) or ADHD (OR = 1.18, 95% CI: 1.1–1.27). However, this association for ASD (OR = 1.04, 95% CI: 0.97–1.11) or ADHD (OR = 0.98, 95% CI: 0.94–1.02) disappeared when data from sibling-matched studies were pooled. The statistically significant association between early life antibiotic exposure and ASD or ADHD in later life can be partially explained by unmeasured genetic and familial confounding factors.
•The anatase TiO2 has better antibacterial effect than rutile.•Ag3PO4/TiO2 heterojunctions could completely collapse the high concentration bacterial cells.•The Ag3PO4/TiO2 heterojunctions show more ...pronounced antibacterial performance in Gram-negative than Gram-positive bacteria.•The Ag3PO4/TiO2 heterojunctions could partially prevent the photo corrosion of Ag3PO4.
Herein, we analyzed the antibacterial effect of the TiO2 polymorphs and Ag3PO4/TiO2 heterojunctions. The sol-gel-derived TiO2 was calcined at 400 °C, 550 °C and 700 °C to get different polymorphs. Subsequently, Ag3PO4/TiO2 composites were synthesized by the in-situ precipitation method. These photocatalysts were characterized by XRD, TEM, UV–VIS–NIR, XPS, FP, AAS, and SEM. Photocatalytic sterilization was employed by the transferring and spreading tests with Gram-positive S. aureus (ATCC 25933) and Gram-negative E. coli (ATCC 25922) bacteria. It was noted that the anatase TiO2 has better antibacterial effect than rutile. And there was an existing synergetic effect between these two polymorphs. Besides partially preventing the photo corrosion, the Ag3PO4/TiO2 heterojunctions exhibit a remarkable bactericidal activity and almost completely collapse the high concentration bacterial cells. Moreover, The Ag3PO4/TiO2 heterojunctions show more pronounced in E. coli than S. aureus for their different cellular structure. The sterilization of the tolerant Gram-positive bacteria often needs the assistance of Ag-ion, while Gram-negative E. coli is more sensitive to •O2− radicals, and h+ during the photocatalytic sterilization.
Abstract Background Adenosine A2A receptors (A2A R) modulate dopamine and glutamate signaling and thereby may influence some of the psychomotor and cognitive processes associated with schizophrenia. ...Because astroglial A2A R regulate the availability of glutamate, we hypothesized that they might play an unprecedented role in some of the processes leading to the development of schizophrenia, which we investigated using a mouse line with a selective deletion of A2A R in astrocytes (Gfa2-A2A R knockout KO mice. Methods We examined Gfa2-A2A R KO mice for behaviors thought to recapitulate some features of schizophrenia, namely enhanced MK-801 psychomotor response (positive symptoms) and decreased working memory (cognitive symptoms). In addition, we probed for neurochemical alterations in the glutamatergic circuitry, evaluating glutamate uptake and release and the levels of key proteins defining glutamatergic signaling (glutamate transporter-I GLT-I, N -methyl-D-aspartate receptors NMDA-R and α-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors AMPA-R) to provide a mechanistic understanding of the phenotype encountered. Results We show that Gfa2-A2A R KO mice exhibited enhanced MK-801 psychomotor response and decreased working memory; this was accompanied by a disruption of glutamate homeostasis characterized by aberrant GLT-I activity, increased presynaptic glutamate release, NMDA-R 2B subunit upregulation, and increased internalization of AMPA-R. Accordingly, selective GLT-I inhibition or blockade of GluR1/2 endocytosis prevented the psychomotor and cognitive phenotypes in Gfa2-A2A R KO mice, namely in the nucleus accumbens. Conclusions These results show that the dysfunction of astrocytic A2A R, by controlling GLT-I activity, triggers an astrocyte-to-neuron wave of communication resulting in disrupted glutamate homeostasis, thought to underlie several endophenotypes relevant to schizophrenia.
•Both the tensile strength and plasticity of the CrMnFeCoNi high-entropy alloy were enhanced significantly at high strain rates.•High strain rate embrittlement effect of CrMnFeCoNi high-entropy alloy ...is suppressed.•Cooperation of twins and dislocations is the crucial mechanism for the synchronous enhancement of strength and plasticity in this alloy under dynamic tension.•A thermo-viscoplastic dynamic constitutive model based on dislocation and twin evolution was developed.
High-entropy alloys (HEAs), recently emerging alloy materials with numerous excellent performances, may have a wide application prospect in impact engineering. However, previous research regarding the mechanical behavior of HEAs has primarily focused on quasi-static testing, whereas the dynamic mechanical behavior of HEAs at high strain rates remains elusive. In this paper, the unusual simultaneous strength-plasticity enhancement and the inhibition of the high strain rate embrittlement of CrMnFeCoNi HEA in impact tension were revealed via split Hopkinson tensile bar (SHTB) with high-speed photography. Quantitative microstructural analysis indicates that the cooperation of twins and dislocations is the crucial mechanism for the synchronous enhancement of strength-plasticity in this alloy under impact tension. A thermo-viscoplastic constitutive model based on dislocations and twins evolution was developed to describe dynamic mechanical behavior. The high plastic hardening under dynamic tension was revealed to be induced by high dislocation forest hardening and strong resistance of twins to dislocation motion. The excellent combination of dynamic strength-plasticity of CrMnFeCoNi HEA makes it becoming a promising candidate for impact engineering applications.
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