Evaluation of Disk carbapenemase test using improved disks for rapid detection and differentiation of clinical isolates of carbapenemase-producing Enterobacterales.

OBJECTIVES: Rapid detection of carbapenemase-producing Enterobacterales (CPE) is important to control spread of the resistance. We previously reported that imipenem disks prepared from injectable imipenem-cilastatin could rapidly detect KPC- and NDM-type carbapenemases. In the present study, we evaluated performance of disks of IPM and combined disks of imipenem-tazobactam and imipenem-EDTA, which were prepared from powders of imipenem and inhibitors. METHODS: Isolates of Enterobacterales were recovered from specimens of patients at a tertiary care hospital in Korea during January 2017 and March 2018. Routine CPE detection was performed by the CPE surveillance personnel whereas evaluation of the Disk carbapenemase test (DCT) was performed by the other personnel without knowing the results of surveillance. The DCT was carried out by pressing disks on to colonies and rehydrating in Petri plates and observing color change. RESULTS: The DCT differentiated 688 of 694 (sensitivity 99.1%) carbapenemase-producing isolates in 2.5-20 min: 630 with KPC, 51 with NDM, three with IMP, one with VIM, two with KPC and IMP, and one with NDM and OXA-181. The DCT failed to detect six OXA- 48-like enzyme-producing isolates, but the modified method using 96-well flat-bottom microplates with mineral oil cover detected all 29 OXA-48-like enzyme-producing isolates in 20-120 min. The DCT was negative for all 440 ertapenem-nonsusceptible, carbapenemase gene-negative isolates (specificity 100%). CONCLUSION: The procedure of DCT is simple and can differentiate isolates of Enterobacterales with KPC-, NDM-, IMP- and VIM-type carbapenemases rapidly, and the modified DCT can detect isolates with OXA-48-like enzymes rapidly.

Contralesional Application of Transcranial Direct Current Stimulation on Functional Improvement in Ischemic Stroke Mice.

BACKGROUND AND PURPOSE: The therapeutic use of transcranial direct current stimulation (tDCS), an adjuvant tool for stroke, induces long-term changes in cortical excitability, for example, the secretion of activity-dependent growth factors. We assessed the proper therapeutic configuration of high-definition tDCS (HD-tDCS) in the subacute stage of ischemic stroke and its underlying expression profiling of growth factors to propose a new method for ensuring better therapeutic effects. METHODS: Male C57BL/6J mice were subjected to middle cerebral artery occlusion, after which repetitive HD-tDCS (20 minutes, 55 µA/mm2, charge density 66 000 C/m2) was applied from subacute phases of their ischemic insult. Behavioral tests assessing motor and cognitive functions were used to determine suitable conditions and HD-tDCS stimulation sites. Gene expression profiling of growth factors and their secretion and activation were analyzed to shed light on the underlying mechanisms. RESULTS: Anodal HD-tDCS application over the contralesional cortex, especially the motor cortex, was more effective than ipsilesional stimulation in attenuating motor and cognitive deficits. In the HD-tDCS application over the contralesional motor cortex, positive changes in Bmp8b, Gdf5, Il4, Pdgfa, Pgf, and Vegfb were observed in the ipsilesional site. The expression of GDF5 (growth/differentiation factor 5) and PDGFA (platelet-derived growth factor subunit A) tended to similarly increase in both ipsi- and contralesional striata. However, higher expression levels of GDF5 and PDGFA and their receptors were observed in the peri-infarct regions of the striatum after HD-tDCS, especially in PDGFA expression. A higher number of proliferating or newly formed neuronal cells was detected in ipsilesional sites such as the subventricular zone. CONCLUSIONS: Application of anodal HD-tDCS over the contralesional cortex may enhance beneficial recovery through the expression of growth factors, such as GDF5 and PDGFA, in the ipsilesional site. Therefore, this therapeutic configuration may be applied in the subacute stage of ischemic stroke to ameliorate neurological impairments.

Axon-First Neuritogenesis on Vertical Nanowires.

In this work, we report that high-density, vertically grown silicon nanowires (vg-SiNWs) direct a new in vitro developmental pathway of primary hippocampal neurons. Neurons on vg-SiNWs formed a single, extremely elongated major neurite earlier than minor neurites, which led to accelerated polarization. Additionally, the development of lamellipodia, which generally occurs on 2D culture coverslips, was absent on vg-SiNWs. The results indicate that surface topography is an important factor that influences neuronal development and also provide implications for the role of topography in neuronal development in vivo.

Annealed Au-assisted epitaxial growth of si nanowires: control of alignment and density.

The epitaxial growth of 1D nanostructures is of particular interest for future nanoelectronic devices such as vertical field-effect transistors because it directly influences transistor densities and 3D logic or memory architectures. Silicon nanowires (SiNWs) are a particularly important 1D nanomaterial because they possess excellent electronic and optical properties. What is more, the scalable fabrication of vertically aligned SiNW arrays presents an opportunity for improved device applications if suitable properties can be achieved through controlling the alignment and density of SiNWs, yet this is something that has not been reported in the case of SiNWs synthesized from Au films. This work therefore explores the controllable synthesis of vertically aligned SiNWs through the introduction of an annealing process prior to growth via a Au-catalyzed vapor-liquid-solid mechanism. The epitaxial growth of SiNWs was demonstrated to be achievable using SiCl4 as the Si precursor in chemical vapor deposition, whereas the alignment and density of the SiNWs could be controlled by manipulating the annealing time during the formation of Au nanoparticles (AuNPs) from Au films. During the annealing process, gold silicide was observed to form on the interface of the liquid-phase AuNPs, depending on the size of the AuNPs and the annealing time. This work therefore makes a valuable contribution to improving nanowire-based engineering by controlling its alignment and density as well as providing greater insight into the epitaxial growth of 1D nanostructures.

Therapeutic effects of a novel electrode for transcranial direct current stimulation in ischemic stroke mice.

Rationale: Non-invasive transcranial direct current stimulation (tDCS), a promising stimulation tool to modulate a wide range of brain disorders, has major limitations, such as poor cortical stimulation intensity and focality. We designed a novel electrode for tDCS by conjugating a needle to a conventional ring-based high-definition (HD) electrode to enhance cortical stimulation efficacy. Method: HD-tDCS (43 µA/mm2, charge density 51.6 kC/m2, 20 min) was administered to male C57BL/6J mice subjected to early-stage ischemic stroke. Behavioral tests were employed to determine the therapeutic effects, and the underlying mechanisms of HD-tDCS were determined by performing RNA sequencing and other biomedical analyses. Results: The new HD-tDCS application, showing a higher electric potential and spatial focality based on computational modeling, demonstrated better therapeutic effects than conventional HD-tDCS in alleviating motor and cognitive deficits, with a decrease in infarct volume and inflammatory response. We assessed different electrode configurations in the new HD electrode; the configurations variously showed potent therapeutic effects, ameliorating neuronal death in the peri-infarct region via N-methyl-D-aspartate-dependent sterol regulatory element-binding protein 1 signaling and related inflammatory factors, further alleviating motor and cognitive deficits in stroke. Conclusion: This new HD-tDCS application showed better therapeutic effects than those with conventional HD-tDCS in early-stage stroke via the amelioration of neuronal death in the penumbra. It may be applied in the early stages of stroke to alleviate neurological impairment.

Sex-specific responses to juvenile stress on the dopaminergic system in an animal model of attention-deficit hyperactivity disorder.

The etiology of attention-deficit hyperactivity disorder (ADHD) strongly suggests a genetic component as the main cause; however, environmental factors such as early adverse experiences in childhood may play an interactive role with the genetic susceptibility. Spontaneously hypertensive rats (SHRs), a genetic ADHD model, and control Wistar Kyoto rats (WKYs) were subjected to chronic unpredictable mild stress during the juvenile period. The behavioral characteristics were monitored, and dopamine-related factors in the core regions of dopaminergic pathways were measured. Higher ADHD symptom-related behaviors were observed in response to juvenile stress in male SHRs than control WKYs. For the SHRs subjected to juvenile stress, hyperactivity in males, recognition in females, and depressant potential in both sexes were markedly observed. In the expression of 17 dopamine-related genes and proteins, greater changes were detected in male SHRs subjected to juvenile stress, especially in dopamine metabolic factors. Dopamine clearance factors involved in dopamine degradation and transport, especially catechol-O-methyltransferase (COMT) and dopamine transporter (DAT), showed sex-specific differences induced by juvenile stress in dopamine metabolite assays. Moreover, stressed male SHRs treated with methylphenidate showed better improvement in behavior than the females, resulting in different levels of COMT and DAT amelioration. These results suggest that juvenile stress potentially increased the incidence of ADHD in a genetic rat model, which showed sex-specific differences based on the expression of COMT and DAT. Therefore, our results could help develop gender-specific diagnostics and healthcare options for juvenile stress in patients with ADHD.

Feasibility study of storing CO2 in the ocean by marine environmental impact assessment.

Since the industrial revolution, which was accompanied with the use of fossil fuels as an energy source, the content of carbon dioxide (CO2) in the atmosphere has increased. To mitigate global warming, industries that utilize fossil fuels have continuously explored new approaches to reduce CO2 emissions and convert it to alternative fuels. The ocean is a vast source of absorbed CO2 on Earth, and various studies have been conducted on the use of the ocean to reduce global CO2. This study focused on reducing CO2 in the atmosphere by storing it as bicarbonate, a form of CO2 that exists in the ocean. The optimum condition for the conversion of CO2 into bicarbonate was investigated by considering the dissolved inorganic carbon (DIC; HCO3-, CO32-, H2CO3) concentration and pH. To confirm the biological impact of this conversion, biological impact experiments were conducted under various DIC concentrations using Skeletonema japonicum, a phytoplankton present in most areas of the sea. Based on the DIC concentration (2.09 mM) of the seawater, the DIC concentrations used in the Lab-scale experiment ranged from 2.5 mM to 18.75 mM, and the concentration with the highest conversion rate (< 6.38 mM) was applied in the pilot plant. Marine environmental impact modeling was performed to observe the effect of discharge to the ocean and its movement. The results revealed a slight growth inhibition of phytoplankton at DIC concentrations higher than the base concentration. Nevertheless, the change in the DIC concentration exerted no effect on the phytoplankton growth except at extremely high concentrations. Moreover, the high DIC concentration can be diluted by the ocean current flow rate, thus counterbalancing the growth inhibition effect. The results obtained in this study demonstrate the feasibility of CO2 storage in the form of DIC, and will be helpful for further development of CO2 mitigation.

Effects of electroacupuncture on the functionality of NG2-expressing cells in perilesional brain tissue of mice following ischemic stroke.

Neural/glial antigen 2 (NG2)-expressing cells has multipotent stem cell activity under cerebral ischemia. Our study examined the effects of electroacupuncture (EA) therapy (2 Hz, 1 or 3 mA, 20 minutes) at the Sishencong acupoint on motor function after ischemic insult in the brain by investigating the rehabilitative potential of NG2-derived cells in a mouse model of ischemic stroke. EA stimulation alleviated motor deficits caused by ischemic stroke, and 1 mA EA stimulation was more efficacious than 3 mA EA stimulation or positive control treatment with edaravone, a free radical scavenger. The properties of NG2-expressing cells were altered with 1 mA EA stimulation, enhancing their survival in perilesional brain tissue via reduction of tumor necrosis factor alpha expression. EA stimulation robustly activated signaling pathways related to proliferation and survival of NG2-expressing cells and increased the expression of neurotrophic factors such as brain-derived neurotrophic factor, tumor growth factor beta, and neurotrophin 3. In the perilesional striatum, EA stimulation greatly increased the number of NG2-expressing cells double-positive for oligodendrocyte, endothelial cell, and microglia/macrophage markers (CC1, CD31, and CD68). EA therapy also greatly activated brain-derived neurotrophic factor/tropomyosin receptor kinase B and glycogen synthase kinase 3 beta signaling. Our results indicate that EA therapy may prevent functional loss at the perilesional site by enhancing survival and differentiation of NG2-expressing cells via the activation of brain-derived neurotrophic factor -induced signaling, subsequently ameliorating motor dysfunction. The animal experiments were approved by the Animal Ethics Committee of Pusan National University (approval Nos. PNU2019-2199 and PNU2019-2884) on April 8, 2019 and June 19, 2019.

Transcranial alternating current stimulation rescues motor deficits in a mouse model of Parkinson's disease via the production of glial cell line-derived neurotrophic factor.

BACKGROUND: Therapeutic effects of transcranial alternating current stimulation (tACS) for treating Parkinson's disease (PD) are limited to modulating abnormally synchronized oscillations; however, long-lasting tACS effects may involve non-neuronal mechanisms like the regulation of neurotrophic factors. OBJECTIVES/HYPOTHESIS: We investigated whether tACS exerts neuroprotective effects on dopaminergic neurons in a mouse model of PD by regulating endogenous glial cell line-derived neurotrophic factor (GDNF). METHODS: Repeated high-definition tACS (HD-tACS, 20 min, 89.1 µA/mm2) was administered over the primary motor cortex of C57BL/6J 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice. Behavioral tests assessing motor function, immunohistochemistry, western blots, enzyme-linked immunosorbent assays, and flow cytometric analyses were performed to examine suitable tACS conditions and its underlying mechanisms. RESULTS: Stimulation at representative frequencies (theta to gamma; 20-Hz beta frequency, in particular) attenuated motor dysfunction and protected the dopaminergic neurons with increased GDNF production. Beta-frequency (20 Hz) tACS application significantly attenuated motor deficits to levels comparable with those of levodopa treatment. Moreover, beta-frequency tACS induced the survival of dopaminergic neurons in the substantia nigra with upregulated production of endogenous GDNF in striatal parvalbumin-positive interneurons. An inhibitor of the GDNF receptor-associated rearranged during transfection (RET) kinase suppressed most aspects of the tACS-induced behavioral recovery, dopaminergic cell survival, and GDNF production. Beta-frequency tACS activated RET-related survival signaling for dopaminergic neurons in the substantia nigra. CONCLUSIONS: Application of tACS over the primary motor cortex may exert protective effects on dopaminergic neurons in the substantia nigra via activation of endogenous GDNF production by striatal parvalbumin-positive interneurons and its survival signaling.

Design of a Novel Theranostic Nanomedicine (III): Synthesis and Physicochemical Properties of Tumor-Targeting Cisplatin Conjugated to a Hydrophilic Polyphosphazene.

PURPOSE: A new theranostic nanomedicine involving anticancer-active cisplatin moiety was designed to study its tumor-targeting properties as well as its drug efficacy and toxicity. METHODS: A cisplatin carrier polymer was prepared by grafting equimolar polyethylene glycol of a molecular weight of 550 (PEG550) and aminoethanol to the poly(dichlorophosphazene) backbone. Cisplatin was conjugated to the carrier polymer using cis-aconitic acid as a linker. RESULTS: The cisplatin-loaded polyphosphazene, named "Polycisplatin" was found to be amphiphilic in aqueous solution and self-assembled into nanoparticles with an average particle size of 18.6 nm in diameter. The time-dependent organ distribution study of Cy5.5-labeled Polycisplatin in the A549-tumor-bearing mice exhibited a high tumor selectivity of Polycisplatin by EPR effect despite the relatively small particle size. In order to compare the in vivo efficacy of Polycisplatin and cisplatin, their xenograft trials were performed using nude mice against the human gastric cell line MKN-28. Polycisplatin exhibited slightly less tumor suppression effect compared with cisplatin at the same dose of 1.95 mg Pt/kg, which is the maximum tolerate dose of cisplatin, but at the higher double dose of 3.9 mg Pt/kg, Polycisplatin exhibited a little better efficacy than cisplatin. Furthermore, mice treated with cisplatin at the dose of 1.95 mg Pt/kg exhibited severe body weight decrease by about 25%, while mice treated with Polycisplatin did not show serious body weight decrease even at its double dose of 3.9 mg Pt/kg. Furthermore, kidney indicators including kidney index, BUN, and creatinine values measured displayed that Polycisplatin is much less nephrotoxic than cisplatin. CONCLUSION: Nanoparticular Polycisplatin was successfully prepared by conjugating cisplatin to a hydrophilic polyphosphazene carrier polymer using the acid-cleavable cis-aconitic acid. Polycisplatin nanoparticles exhibit excellent tumor-targeting properties by EPR effect. The xenograft trials exhibited excellent antitumor efficacy and reduced systemic toxicity of Polycisplatin.

Electroacupuncture Therapy Ameliorates Motor Dysfunction via Brain-Derived Neurotrophic Factor and Glial Cell Line-Derived Neurotrophic Factor in a Mouse Model of Parkinson's Disease.

Parkinson's disease (PD) is characterized by dopaminergic neuron loss in the substantia nigra. However, specific sensory stimulation via electroacupuncture (EA) therapy may attenuate this loss by promoting the expression of endogenous neurotrophic factors in a manner similar to physical therapy. We investigated the potential protective effects of EA on dopaminergic neurons in a mouse model of PD and whether these effects are associated with the promotion of endogenous brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF). Mouse models of PD were generated using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine. Motor performance was assessed using behavioral tests, and Western blot experiments, enzyme-linked immunosorbent assays (ELISAs), and immunohistochemical assays were performed. In both mouse models, EA treatment ameliorated motor impairments and dopaminergic neuron loss; these changes were accompanied by increases in BDNF and GDNF. In the MPTP group, EA treatment improved motor dysfunction by attenuating dopaminergic neuron loss in the substantia nigra, similar to the effects of levodopa. EA treatment significantly upregulated BDNF and GDNF expression in both the substantia nigra and striatum. Moreover, EA treatment induced the expression of cAMP response element binding protein (CREB) as well as Akt and Pitx3 in dopaminergic neurons in the substantia nigra. However, levodopa treatment did not induce BDNF/GDNF activation or related signaling factors. Thus, EA therapy may exert protective effects on dopaminergic neurons by upregulating the expression of BDNF, GDNF, and related signaling factors, thereby improving motor function. Hence, EA may represent an effective adjuvant therapy for motor deficits in patients with PD.

Electroacupuncture on the Scalp over the Motor Cortex Ameliorates Behavioral Deficits Following Neonatal Hypoxia-Ischemia in Rats via the Activation of Neural Stem Cells.

Electroacupuncture (EA) therapy via alternating current stimulation on the scalp over the motor cortex is used for the treatment of brain disorders. Perinatal hypoxia-ischemia (HI), a brain injury in newborns, leads to long-term neurologic complications. Here, we investigated whether EA could promote functional improvements and neurogenesis in a neonatal HI rat model. A neonatal HI rat model was induced by permanent ligation of the left carotid artery in postnatal day 7 pups. EA for neonatal HI rats was performed at 2 Hz (1, 3, or 5 mA; 20 min) from 4-6 weeks after birth. HI rats undergoing EA had improved motor and memory function, with the greatest improvement after 3 mA EA. The corpus callosum was significantly thicker and showed a significant increase in proliferating astrocytes in the 3 mA EA group. We observed proliferating cells and a greater number of newly developed neurons and astrocytes in the subventricular zone and dentate gyrus of the 3 mA EA group than in those of the HI group. These results suggest that EA promotes functional improvements following neonatal HI assault via the proliferation and differentiation of neural stem cells. This effect was the strongest after 3 mA EA, suggesting that this is the optimal treatment dose.

Therapeutic effects of anodal transcranial direct current stimulation in a rat model of ADHD.

Most therapeutic candidates for treating attention-deficit hyperactivity disorder (ADHD) have focused on modulating the dopaminergic neurotransmission system with neurotrophic factors. Regulation of this system by transcranial direct current stimulation (tDCS) could contribute to the recovery of cognitive symptoms observed in patients with ADHD. Here, male spontaneously hypertensive rats (SHR) were subjected to consecutive high-definition tDCS (HD-tDCS) (20 min, 50 µA, current density 63.7 A/m2, charge density 76.4 kC/m2) over the prefrontal cortex. This treatment alleviated cognitive deficits, with an increase in tyrosine hydroxylase and vesicular monoamine transporter two and significantly decreased plasma membrane reuptake transporter (DAT). HD-tDCS application increased the expression of several neurotrophic factors, particularly brain-derived neurotrophic factor (BDNF), and activated hippocampal neurogenesis. Our results suggest that anodal HD-tDCS over the prefrontal cortex may ameliorate cognitive dysfunction via regulation of DAT and BDNF in the mesocorticolimbic dopaminergic pathways, and therefore represents a potential adjuvant therapy for ADHD.

Combined therapy involving electroacupuncture and treadmill exercise attenuates demyelination in the corpus callosum by stimulating oligodendrogenesis in a rat model of neonatal hypoxia-ischemia.

We investigated whether electroacupuncture (EA) and treadmill (TM) exercise improve behaviors related to motor and memory dysfunction in a cerebral palsy-like rat model via activation of oligodendrogenesis. A neonatal hypoxia-ischemia model was created using Sprague-Dawley rats (P7), and these underwent EA stimulation and treadmill training from 3 to 5weeks after hypoxia-ischemia induction. EA treatment was delivered via electrical stimulation (2Hz, 1mA) at two acupoints, Baihui (GV20) and Zusanli (ST36). Behavioral tests showed that EA alleviated motor dysfunction caused by hypoxia-ischemia on a rotarod test, and TM exercise alleviated motor and memory dysfunction seen on cylinder and passive avoidance tests. Combined therapy with EA and TM exercise showed synergistic effects on the cylinder, rotarod, and catwalk tests. TM exercise significantly restored corpus callosum thickness, and combined therapy with EA and TM restored myelin basic protein (MBP) levels in this region. While EA stimulation only increased activation of cAMP-response element binging protein (CREB) in oligodendrocytes of the corpus callosum, TM exercise increased newly generated oligodendrocyte progenitor cells or oligodendrocytes via activation of CREB. Synergistic effects on oligodendrogenesis were also observed by the combined therapy. Furthermore, the combined therapy induced mature brain-derived neurotrophic factor (BDNF) expression in the cerebral cortex. These results demonstrate that combined therapy with EA and TM exercise may restore myelin components following neonatal hypoxia-ischemia via upregulation of oligodendrogenesis involving CREB/BDNF signaling, which subsequently improves motor and memory function. Therefore, combined therapy with EA and TM exercise offers another treatment option for functional recovery from injuries caused by neonatal hypoxia-ischemia, such as cerebral palsy.

Positive effects of α-asarone on transplanted neural progenitor cells in a murine model of ischemic stroke.

BACKGROUND: Some traditional Oriental herbal medicines, such as Acorus tatarinowii and Acorus gramineus, produce beneficial effects for cognition enhancement. An active compound in rhizomes and the bark of these plants is α-asarone. PURPOSE: This study investigated the effects of α-asarone on the proliferation and differentiation of neural progenitor cells (NPCs) in a primary culture and a murine model of ischemic stroke. METHODS: NPCs were isolated from mouse fetal cerebral cortices on embryonic day 15, and all experiments were performed using passage 3 NPCs. We utilized a cell counting kit-8 assay, flow cytometry, western blot, and immunohistochemical analysis to assess proliferation and differentiation of NPCs and employed α-asarone in NPC transplanted ischemic stroke mice to evaluate stroke-related functional recovery using behavioral and immunohistochemical analysis. RESULT: Treatment with 1 µM, 3 µM, or 10 µM α-asarone induced significant NPC proliferation compared to vehicle treatment. Induced NPCs expressed the neuronal marker neuronal nuclei (NeuN) or the astrocyte marker S100 calcium-binding protein B (S100ß). Both immunohistochemistry and flow cytometry revealed that treatment with α-asarone increased the number of NeuN-immunoreactive cells and decreased the number of S100ß-immunoreactive cells. Treatment with α-asarone also increased the expression of ß-catenin, cyclin D1, and phosphorylated extracellular signal-regulated kinase (ERK) compared to vehicle treatment. In a murine model of ischemic stroke, treatment with α-asarone and transplanted NPCs alleviated stroke-related functional impairments. The corner and rotarod test results revealed that treatment with α-asarone in the NPC transplanted group had greater-than-additive effects on sensorimotor function and motor balance. Moreover, α-asarone treatment promoted the differentiation of transplanted NPCs into NeuN-, glial fibrillary acidic protein (GFAP)-, platelet-derived growth factor-α (PDGFR-α)-, and 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase)-immunoreactive cells. CONCLUSION: α-asarone may promote NPC proliferation and differentiation into neuron-lineage cells by activating ß-catenin, cyclin D1, and ERK. Moreover, α-asarone treatment facilitated neurofunctional recovery after NPC transplantation in a murine model of ischemic stroke. Therefore, α-asarone is a potential adjunct treatment to NPC therapy for functional restoration after brain injuries such as ischemic stroke.

Potential benefits of mesenchymal stem cells and electroacupuncture on the trophic factors associated with neurogenesis in mice with ischemic stroke.

The beneficial effects of mesenchymal stem cells (MSCs) and electroacupuncture (EA) on neurogenesis and related trophic factors remain unclear. Bone marrow MSCs (mBMSC) were transplanted into the striatum of mice with middle cerebral artery occlusion (MCAO), and EA stimulation was applied at two acupoints, Baihui and Dazhui. EA treatment significantly improved motor function, and a synergistic effect of combined mBMSC and EA treatment was observed. Combined mBMSC and EA treatment reduced prominent atrophic changes in the striatum and led to proliferation of neural progenitor cells in the subventricular zone (SVZ) and the surrounding areas of the striatum (SVZ + striatum) of MCAO mice. The mBMSC and EA treatment markedly enhanced mature brain-derived neurotrophic factor (mBDNF) expression in the SVZ + striatum and hippocampus of mice with MCAO, and combined treatment enhanced neurotrophin-4 (NT4) expression. The number of mBDNF- and NT4-positive neurons in the SVZ + striatum and hippocampus increased following EA treatment. Combined treatment led to an increase in the expression levels of phosphorylated cAMP response element binding protein in the neuroblasts of the striatum. Our results indicate that combined MSC and EA treatment may lead to a better therapeutic effect via co-regulation of neurotrophic factors in the brain, by regulating neurogenesis more than single therapy.

Surface Diffusion Directed Growth of Anisotropic Graphene Domains on Different Copper Lattices.

Anisotropic graphene domains are of significant interest since the electronic properties of pristine graphene strongly depend on its size, shape, and edge structures. In this work, considering that the growth of graphene domains is governable by the dynamics of the graphene-substrate interface during growth, we investigated the shape and defects of graphene domains grown on copper lattices with different indices by chemical vapor deposition of methane at either low pressure or atmospheric pressure. Computational modeling identified that the crystallographic orientation of copper strongly influences the shape of the graphene at low pressure, yet does not play a critical role at atmospheric pressure. Moreover, the defects that have been previously observed in the center of four-lobed graphene domains grown under low pressure conditions were demonstrated for the first time to be caused by a lattice mismatch between graphene and the copper substrate.

Identification of a resveratrol tetramer as a potent inhibitor of hepatitis C virus helicase.

BACKGROUND AND PURPOSE: Hepatitis C virus (HCV) infection is responsible for various chronic inflammatory liver diseases. Here, we have identified a naturally occurring compound with anti-HCV activity and have elucidated its mode of antiviral action. EXPERIMENTAL APPROACH: Luciferase reporter and real-time RT-PCR assays were used to measure HCV replication. Western blot, fluorescence-labelled HCV replicons and infectious clones were employed to quantitate expression levels of viral proteins. Resistant HCV mutant mapping, in vitro NS3 protease, helicase, NS5B polymerase and drug affinity responsive target stability assays were also used to study the antiviral mechanism. KEY RESULTS: A resveratrol tetramer, vitisin B from grapevine root extract showed high potency against HCV replication (EC50 = 6 nM) with relatively low cytotoxicity (EC50 >10 µM). Combined treatment of vitisin B with an NS5B polymerase inhibitor (sofosbuvir) exhibited a synergistic or at least additive antiviral activity. Analysis of a number of vitisin B-resistant HCV variants suggested an NS3 helicase as its potential target. We confirmed a direct binding between vitisin B and a purified NS3 helicase in vitro. Vitisin B was a potent inhibitor of a HCV NS3 helicase (IC50 = 3 nM). In vivo, Finally, we observed a preferred tissue distribution of vitisin B in the liver after i.p. injection in rats, at clinically attainable concentrations. Conclusion and Implications Vitisin B is one of the most potent HCV helicase inhibitors identified so far. Vitisin B is thus a prime candidate to be developed as the first HCV drug derived from natural products.

Growth mechanism of graphene on graphene films grown by chemical vapor deposition.

We report an approach for the synthesis of mono- or bilayer graphene films by atmospheric-pressure chemical vapor deposition that can achieve a low defect density through control over the growth time. Different heating ramp rates were found to lead to variation in the smoothness and grain size of the Cu foil substrate, which directly influenced the density of the graphene domains. The rough Cu surface induced by rapid heating creates a high density of graphene domains in the initial stage, ultimately resulting in a graphene film with a high defect density due to an increased overlap between domains. Conversely, a slow heating rate resulted in a smooth and flat Cu surface, thereby lowering the density of the initial graphene domains and ensuring a uniform monolayer film. From this, we demonstrate that the growth mechanism of graphene on existing graphene films is dependent on the density of the initial graphene domains, which is affected by the heating ramp rate.

Atmospheric Pressure Chemical Vapor Deposition of Graphene Using a Liquid Benzene Precursor.

Graphene has attracted great attention owing to its unique structural and electrical properties. Among various synthetic approaches of the graphene, metal assisted chemical vapor deposition (CVD) is the most reasonable and proper method to produce large-scale and low-defect graphene films. Until now, CVD from gaseous hydrocarbon sources has shown great promises for large-scale graphene growth, but high growth temperature is required for such growth. A recent work by using liquid benzene precursor has shown that monolayer graphene could be obtained at 300 degrees C by low pressure, required for high vacuum equipment. Here, we report the first successful attempt of atmospheric pressure CVD graphene growth on Cu foil using liquid benzene as a precursor. We investigated the effect of hydrogen partial pressure, growth time, and precursor temperature on the domain size of as-grown graphene. Also, micro-Raman analysis confirmed that these reaction parameters influenced the number of layer and uniformity of the graphene.