Utilization of Interaction with Dielectric Barrier Discharge Plasma and Impregnated Surface Nano-Particles for Plasma Applications.

This paper describes utilization of dielectric barrier discharge (DBD) plasma interaction with impregnated surface nano-particles for plasma applications. The plasma generation characteristics on DBD plasma actuator and packed-bed reactor are investigated with unexpected objects as impregnated catalysts. The streamer generation of DBD plasma is influenced by different surface nano-particles of the impregnated catalyst between the discharge gaps. The practical use of DBD plasma-catalyst interaction is discussed.

Study on Surface Damage and Performance Degradation of Impregnated Catalyst in Dielectric Barrier Discharge Plasma-Assisted Methane Conversion Processes.

This paper describes the performance degradation of impregnated catalyst in the dielectric barrier discharge (DBD) plasma-assisted methane conversion process. Mn and Ni mixed copper-zinc catalysts, and bare γ-Al2O3 support were exposed to the DBD plasma generated at 1 kHz and 9 kV under CH4 direct conversion for 4 hours. The performance degradation due to the surface damage of the catalyst by the plasma was investigated by SEM analysis.

Neogenin Promotes BMP2 Activation of YAP and Smad1 and Enhances Astrocytic Differentiation in Developing Mouse Neocortex.

UNLABELLED: Neogenin, a DCC (deleted in colorectal cancer) family receptor, is highly expressed in neural stem cells (NSCs). However, its function in NSCs remains to be explored. Here we provide in vitro and in vivo evidence for neogenin's function in NSCs to promote neocortical astrogliogenesis, but not self-renewal or neural differentiation. Mechanistically, neogenin in neocortical NSCs was required for BMP2 activation of YAP (yes associated protein). The active/nuclear YAP stabilized phospho-Smad1/5/8 and was necessary for BMP2 induction of astrocytic differentiation. Deletion of yap in mouse neocortical NSCs caused a similar deficit in neocortical astrogliogenesis as that in neogenin mutant mice. Expression of YAP in neogenin mutant NSCs diminished the astrocytic differentiation deficit in response to BMP2. Together, these results reveal an unrecognized function of neogenin in increasing neocortical astrogliogenesis, and identify a pathway of BMP2-neogenin-YAP-Smad1 for astrocytic differentiation in developing mouse neocortex. SIGNIFICANCE STATEMENT: Astrocytes, a major type of glial cells in the brain, play important roles in modulating synaptic transmission and information processing, and maintaining CNS homeostasis. The abnormal astrocytic differentiation during development contributes to dysfunctions of synaptic plasticity and neuropsychological disorders. Here we provide evidence for neogenin's function in regulation of the neocortical astrocyte differentiation during mouse brain development. We also provide evidence for the necessity of neogenin in BMP2/Smad1-induced astrocyte differentiation through YAP. Thus, our findings identify an unrecognized function of neogenin in mouse neocortical astrocyte differentiation, and suggest a signaling pathway, BMP2-neogenin-YAP-Smad1, underlying astrogliogenesis in developing mouse neocortex.

Low temperature plasma induces angiogenic growth factor via up-regulating hypoxia-inducible factor 1α in human dermal fibroblasts.

Numerous studies on the application of low temperature plasma (LTP) have produced impressive results, including antimicrobial, antitumor, and wound healing effects. Although LTP research has branched out to include medical applications, the detailed effects and working mechanisms of LTP on wound healing have not been fully investigated. Here, we investigated the potential effect of inducing growth factor after exposure to LTP and demonstrated the increased expression of angiogenic growth factor mediated by LTP-induced HIF1α expression in primary cultured human dermal fibroblasts. In cell viability assays, fibroblast viability was reduced 6 h and 24 h after LTP treatment for only 5 min, and pre-treating with NAC, a ROS scavenger, prevented cell loss. Fibroblast migration significantly increased at 6 h and 24 h in scratch wound healing assays, the expression of cytokines significantly changed, and regulatory growth factors were induced at 6 h and 24 h after exposure to LTP in RT-PCR or ELISAs. Specifically, LTP treatment significantly induced the expression of HIF1α, an upstream regulator of angiogenesis. Pre-treatment with the inhibitor CAY10585 abolished HIF1α expression and prevented LTP-induced angiogenic growth factor production according to immunoblotting, immunocytochemistry, and ELISA results. Taken together, our results provide information on the molecular mechanism by which LTP application may promote angiogenesis and will aid in developing methods to improve wound healing.

Modification of Catalyst Surface from Interaction Between Catalysts and Dielectric Barrier Discharge Plasma.

This paper describes modification of catalyst surface from interaction between catalysts and dielectric barrier discharge (DBD) plasma. Ru/γ­Al2O3 catalyst was exposed to DBD plasma for CO2 methanation and CH4 direct conversion reactions. Parameters related to the modification of catalyst surface were investigated by SEM and EDS analysis.

Low temperature activation of CO removal by O3-assisted catalysis.

Catalytic CO oxidation was activated at low temperature by injecting O3 as an additive. It was empirically confirmed that CO removal rate was dramatically enhanced by supplying a small amount of O3, and the reaction temperature was almost half that required for CO oxidation when using a catalyst only. By optimizing the concentration of O3, catalytic CO oxidation could be achieved within 1 min at low operational temperature. The removal rate of CO was sensitive to the concentration of O3, and a deduced reaction mechanism is discussed to explain how catalytic CO oxidation is activated but subsequently deactivated at higher O3 concentration. Moreover, the presence of C3H8 and C3H6 were considered to evaluate the effects of each gas on the enhancement of CO removal rate by O3. Finally, the rate of CO removal was evaluated with increasing O3 concentration for practical applications such as the cold-start problem in automobile engines.

Anticancer effects of different seaweeds on human colon and breast cancers.

Seafoods and seaweeds represent some of the most important reservoirs of new therapeutic compounds for humans. Seaweed has been shown to have several biological activities, including anticancer activity. This review focuses on colorectal and breast cancers, which are major causes of cancer-related mortality in men and women. It also describes various compounds extracted from a range of seaweeds that have been shown to eradicate or slow the progression of cancer. Fucoidan extracted from the brown algae Fucus spp. has shown activity against both colorectal and breast cancers. Furthermore, we review the mechanisms through which these compounds can induce apoptosis in vitro and in vivo. By considering the ability of compounds present in seaweeds to act against colorectal and breast cancers, this review highlights the potential use of seaweeds as anticancer agents.

Cartilage regeneration using transforming growth factor-beta 3-loaded injectable crosslinked hyaluronic acid hydrogel.

Cartilage defects can be difficult to heal, potentially leading to complications such as osteoarthritis. Recently, a tissue engineering approach that uses scaffolds and growth factors has been proposed to regenerate new cartilage tissues. Herein, we investigated the application of hyaluronic acid (HA) gel loaded with transforming growth factor-beta 3 (TGF-ß3) for enhanced cartilage regeneration. We assessed the clinical conditions required to efficiently enhance the ability of the modified HA gel to repair defective cartilage. Based on our findings, the prepared HA gel exhibited good physicochemical and mechanical properties and was non-toxic and non-inflammatory. Moreover, HA gel-loaded TGF-ß3 (HAT) had improved biocompatibility and promoted the synthesis of cartilage-specific matrix and collagen, further improving its ability to repair defects. The application of HAT resulted in an initial burst release of HA, which degraded slowly in vivo. Finally, HAT combined with microfracture-inducing bone marrow stem cells could significantly improve the cartilage microenvironment and regeneration of cartilage defects. Our results indicate that HA is a suitable material for developing growth factor carriers, whereas HAT is a promising candidate for cartilage regeneration. Furthermore, this differentiated strategy provides a rapid and effective clinical approach for next-generation cartilage regeneration.

Intravesical instillation-based mTOR-STAT3 dual targeting for bladder cancer treatment.

BACKGROUND: Recent intravesical administration of adenoviral vectors, either as a single injection or in combination with immune checkpoint inhibitors, exemplified by cretostimogene grenadenorepvec and nadofaragene firadenovec, has demonstrated remarkable efficacy in clinical trials for non-muscle invasive bladder cancer. Despite their ability to induce an enhanced immune reaction within the lesion, the intracellular survival signaling of cancer cells has not been thoroughly addressed. METHODS: An analysis of the prognostic data revealed a high probability of therapeutic efficacy with simultaneous inhibition of mTOR and STAT3. Considering the challenges of limited pharmaco-accessibility to the bladder due to its pathophysiological structure and the partially undruggable nature of target molecules, we designed a dual siRNA system targeting both mRNAs. Subsequently, this dual siRNA system was encoded into the adenovirus 5/3 (Ad 5/3) to enhance in vivo delivery efficiency. RESULTS: Gene-targeting efficacy was assessed using cells isolated from xenografted tumors using a single-cell analysis system. Our strategy demonstrated a balanced downregulation of mTOR and STAT3 at the single-cell resolution, both in vitro and in vivo. This approach reduced tumor growth in bladder cancer xenograft and orthotopic animal experiments. In addition, increased infiltration of CD8+ T cells was observed in a humanized mouse model. We provided helpful and safe tissue distribution data for intravesical therapy of siRNAs coding adenoviruses. CONCLUSIONS: The bi-specific siRNA strategy, encapsulated in an adenovirus, could be a promising tool to augment cancer treatment efficacy and overcome conventional therapy limitations associated with "undruggability." Hence, we propose that dual targeting of mTOR and STAT3 is an advantageous strategy for intravesical therapy using adenoviruses.

Transcriptome-based deep learning analysis identifies drug candidates targeting protein synthesis and autophagy for the treatment of muscle wasting disorder.

Sarcopenia, the progressive decline in skeletal muscle mass and function, is observed in various conditions, including cancer and aging. The complex molecular biology of sarcopenia has posed challenges for the development of FDA-approved medications, which have mainly focused on dietary supplementation. Targeting a single gene may not be sufficient to address the broad range of processes involved in muscle loss. This study analyzed the gene expression signatures associated with cancer formation and 5-FU chemotherapy-induced muscle wasting. Our findings suggest that dimenhydrinate, a combination of 8-chlorotheophylline and diphenhydramine, is a potential therapeutic for sarcopenia. In vitro experiments demonstrated that dimenhydrinate promotes muscle progenitor cell proliferation through the phosphorylation of Nrf2 by 8-chlorotheophylline and promotes myotube formation through diphenhydramine-induced autophagy. Furthermore, in various in vivo sarcopenia models, dimenhydrinate induced rapid muscle tissue regeneration. It improved muscle regeneration in animals with Duchenne muscular dystrophy (DMD) and facilitated muscle and fat recovery in animals with chemotherapy-induced sarcopenia. As an FDA-approved drug, dimenhydrinate could be applied for sarcopenia treatment after a relatively short development period, providing hope for individuals suffering from this debilitating condition.

Plasma-assisted combustion technology for NOx reduction in industrial burners.

Stronger regulations on nitrogen oxide (NOx) production have recently promoted the creation of a diverse array of technologies for NOx reduction, particularly within the combustion process, where reduction is least expensive. In this paper, we discuss a new combustion technology that can reduce NOx emissions within industrial burners to single-digit parts per million levels without employing exhaust gas recirculation or other NOx reduction mechanisms. This new technology uses a simple modification of commercial burners, such that they are able to perform plasma-assisted staged combustion without altering the outer configuration of the commercial reference burner. We embedded the first-stage combustor within the head of the commercial reference burner, where it operated as a reformer that could host a partial oxidation process, producing hydrogen-rich reformate or synthesis gas product. The resulting hydrogen-rich flow then ignited and stabilized the combustion flame apart from the burner rim. Ultimately, the enhanced mixing and removal of hot spots with a widened flame area acted as the main mechanisms of NOx reduction. Because this plasma burner acted as a low NOx burner and was able to reduce NOx by more than half compared to the commercial reference burner, this methodology offers important cost-effective possibilities for NOx reduction in industrial applications.

Combination of plasma with a honeycomb-structured catalyst for automobile exhaust treatment.

To activate a catalyst efficiently at low temperature by plasma for environmental control, we developed a hybrid reactor that combines plasma with a honeycomb-structured catalyst in a practical manner. The reactor developed generated stable cold plasma at atmospheric pressure because of the dielectric and conductive nature of the honeycomb catalyst by consuming low amounts of power. In this reactor, the applied voltage and temperature determined the balance between the oxidation and adsorption by the plasma and catalyst. The synergistic reaction of the plasma and catalyst was more effective at low temperatures, resulting in a reduction in a lowered light-off temperature.

Electron Microscopic Study in the Rat Model of Electrically Injured Myelopathy: Preliminary Report.

Objective: The patient with electrically injured myelopathy showed mild motor weakness without somatosensory pathway abnormalities. Few reports have been reported on the pathophysiological mechanisms of electrically injured myelopathy, and there is controversy about the exact pathological causes. This study aimed to investigate the ultrastructural changes in the electron microscopic findings of electrical spinal cord injury. Methods: Nine rats were used in this study. We performed 7 electrical shocks (frequency, 120 Hz; pulse width, 0.9 ms; duration, 3 seconds; current, 99 mA) using an electroconvulsive therapy (ECT) apparatus (57800 ECT unit; UGO BASILE). We used one ear and one contralateral hind limb as entry and exit sites, respectively. We only enrolled rats with hind limb weakness and performed electron microscopy evaluations of the spinal cord on the first day and 4 weeks after injury. Results: On the first day after injury, an electron microscopic examination showed a directly damaged area that appeared to be torn as physical damage, damaged myelin sheath, vacuolated axons in the myelin sheath, swollen Golgi apparatus, and injured mitochondria. Looking at changes in motor and sensory nerves, the sensory neurons showed recovered mitochondria and Golgi apparatus 4 weeks after injury; however, motor neurons still showed injured mitochondria, swollen Golgi apparatus, and endoplasmic reticulum. Conclusion: This study showed that recovery from ultrastructural injury was more rapid in sensory neurons than in motor neurons.

Accelerating bone regeneration using poly(lactic-co-glycolic acid)/hydroxyapatite scaffolds containing duck feet-derived collagen.

Collagen, with low antigenicity and excellent cell adhesion, is a biomaterial mainly used for regenerating bone, cartilage, and skin, owing to its biocompatibility and biodegradability. Results from a previous study confirmed that a scaffold mixed with duck feet-derived collagen (DC) and Poly(lactic-co-glycolic acid) (PLGA) reduced inflammatory reaction and increased bone regeneration. To develop an optimal bone substitute we included hydroxyapatite (HAp), a key osteoconductive material, in a DC and PLGA mixture. We fabricated 0, 10, 20, 40, 60, and 80 wt% DC/PLGA/HAp scaffolds and studied their potential for bone tissue engineering. Characteristic analysis of the scaffold and seeding of rabbit bone marrow mesenchymal stem cells (rBMSCs) on the scaffold were conducted to investigate cell proliferation, osteogenic differentiation, and bone formation. We confirmed that increasing DC concentration not only improved the compressive strength of the DC/PLGA/HAp scaffold but also cell proliferation and osteogenic differentiation. It was found through comparison with previous studies that including HAp in the scaffold also promotes osteogenic differentiation. Our study thus shows through in vivo results that the 80 wt% DC/PLGA/HAp scaffold promotes bone mineralization and collagen deposition while reducing the inflammatory response. Hence, 80 wt% DC/PLGA/HAp has excellent potential as a biomaterial for bone regeneration applications.

Anti-apoptotic Splicing Variant of AIMP2 Recover Mutant SOD1-Induced Neuronal Cell Death.

Although a couple of studies have reported that mutant superoxide dismutase 1 (SOD1), one of the causative genes of familial amyotrophic lateral, interacts physically with lysyl-tRNA synthetase (KARS1) by a gain of function, there is limited evidence regarding the detailed mechanism about how the interaction leads to neuronal cell death. Our results indicated that the aminoacyl-tRNA synthetase-interacting multi-functional protein 2 (AIMP2) mediated cell death upon the interplay between mutant SOD1 and KARS1 in ALS. Binding of mutant SOD1 with KARS1 led to the release of AIMP2 from its original binding partner KARS1, and the free form of AIMP2 induced TRAF2 degradation followed by TNF-α-induced cell death. We also suggest a therapeutic application that overexpression of DX2, the exon 2-deleted antagonistic splicing variant of AIMP2 (AIMP2-DX2), reduced neuronal cell death in the ALS mouse model. Expression of DX2 suppressed TRAF2 degradation and TNF-α-induced cell death by competing mode of action against full-length AIMP2. Motor neuron differentiated form iPSC showed a resistance in neuronal cell death after DX2 administration. Further, intrathecal administration of DX2-coding adeno-associated virus (AAV) improved locomotive activity and survival in a mutant SOD1-induced ALS mouse model. Taken together, these results indicated that DX2 could prolong life span and delay the ALS symptoms through compensation in neuronal inflammation.

Neogenin inhibits HJV secretion and regulates BMP-induced hepcidin expression and iron homeostasis.

Neogenin, a deleted in colorectal cancer (DCC) family member, has been identified as a receptor for the neuronal axon guidance cues netrins and repulsive guidance molecules repulsive guidance molecules (RGM). RGMc, also called hemojuvelin (HJV), is essential for iron homeostasis. Here we provide evidence that neogenin plays a critical role in iron homeostasis by regulation of HJV secretion and bone morphogenetic protein (BMP) signaling. Livers of neogenin mutant mice exhibit iron overload, low levels of hepcidin, and reduced BMP signaling. Mutant hepatocytes in vitro show impaired BMP2 induction of Smad1/5/8 phosphorylation and hepcidin expression. Neogenin is expressed in liver cells in a reciprocal pattern to that of hepcidin, suggesting that neogenin functions in a cell nonautonomous manner. Further studies demonstrate that neogenin may stabilize HJV, a glycosylphosphatidylinositol-anchored protein that interacts with neogenin and suppresses its secretion. Taken together, our results lead the hypothesis that neogenin regulates iron homeostasis via inhibiting secretion of HJV, an inhibitor of BMP signaling, to enhance BMP signaling and hepcidin expression. These results reveal a novel mechanism underlying neogenin regulation of HJV-BMP signaling.

Optimal timing to evaluate prediagnostic baseline erectile function in patients undergoing robot-assisted radical prostatectomy.

INTRODUCTION: Accurate assessment of prediagnostic baseline erectile function (EF) is crucial when evaluating postoperative changes of EF in patients undergoing bilateral nerve sparing robot-assisted laparoscopic radical prostatectomy (RLRP). Because score domains of the International Index of Erectile Function-5 (IIEF-5) can be affected by factors such as recall intervals and psychological stress or discomfort due to cancer diagnosis and treatment, it is important to assess the prediagnostic baseline EF at appropriate times. AIM: To determine optimal timing to evaluate prediagnostic baseline EF in patients undergoing bilateral nerve sparing RLRP. METHODS: Between March 2009 and February 2010, 54 patients ranging in age from 48 to 74 years were asked to complete IIEF-5 questionnaires before prostate biopsy, 1 day before RLRP, and 1 month after RLRP to assess preoperative baseline EF. MAIN OUTCOME MEASURES: Differences in the mean scores of IIEF-5 were analyzed using paired t-tests. The strengths of the linear relationships among the three IIEF-5 scores were quantified using Pearson's correlation coefficient. An interrator agreement analysis in distribution was performed using the kappa statistic to determine the degree of agreement among the IIEF-5 scores. RESULTS: The mean IIEF-5 score before RLRP was significantly higher than the mean IIEF-5 score before prostate biopsy (P < 0.001). There was no significant difference between the mean IIEF-5 scores before prostate biopsy and 1 month following RLRP (P = 0.931). Scores of the IIEF-5 taken before prostate biopsy and 1 month following RLRP showed substantial agreement (kappa = 0.712), whereas scores of the IIEF-5 taken before prostate biopsy and before RLRP showed lower agreement (kappa = 0.325). CONCLUSION: To more accurately assess the prediagnostic baseline EF in patients with localized prostate cancer, the IIEF-5 questionnaire should be administered before prostate biopsy rather than before RLRP as cancer diagnosis-related symptoms and depression can affect IIEF-5 scores.

Is it suitable to eliminate bone scan for prostate cancer patients with PSA ≤ 20 ng/mL?

PURPOSE: We evaluated the relationship between bone metastasis (BM) and clinical or pathological variables, including the serum prostate-specific antigen (PSA) concentration. METHODS: This retrospective study included 579 consecutive patients with newly diagnosed prostate cancer (Pca) who underwent a bone scan study at our institution between 2002 and 2010. We used receiver operating characteristics curves to evaluate accuracy of bone metastasis between serum PSA 10 and 20 ng/mL. RESULTS: A positive bone scan result was found in 83 men (14.3%) with PCa. However, 27 men (4.6%) with serum PSA between 10 and 20 ng/mL, 29/579 men (5.0%) with GS ≤ 7, and 21/83 (25.3%) with serum PSA ≤ 20 ng/mL and Gleason score (GS) ≤ 7 had positive bone scans. In the logistic regression analyses, clinical T stage (odds ratio [OR] = 3.26; 95% CI, 2.29-4.33; P = 0.021), GS (OR = 3.41; 95% CI, 2.91-4.63; P = 0.019), and serum PSA (OR = 8.37; 95% CI, 3.91-19.21; P < 0.001) were predictive factors of detecting the BM. When the serum PSA concentration ≤20 ng/mL and GS ≤ 7, AUC value of bone scans for the detection of BM was 0.640 (P = 0.020; 95% CI, 0.563-0.717). With serum PSA at 10 ng/mL and GS ≤ 7, the AUC values of bone scans were 0.828 (P < 0.001; 95% CI, 0.773-0.883). CONCLUSIONS: Bone scans might be necessary in men with serum PSA between 10 and 20 ng/mL. New guidelines for eliminating bone scans in patients with newly diagnosed Pca are needed, especially in Asians.

Retrograde regulation of motoneuron differentiation by muscle beta-catenin.

Synapse formation requires proper interaction between pre- and postsynaptic cells. In anterograde signaling, neurons release factors to guide postsynaptic differentiation. However, less is known about how postsynaptic targets retrogradely regulate presynaptic differentiation or function. We found that muscle-specific conditional knockout of beta-catenin (Ctnnb1, also known as beta-cat) in mice caused both morphologic and functional defects in motoneuron terminals of neuromuscular junctions (NMJs). In the absence of muscle beta-catenin, acetylcholine receptor clusters were increased in size and distributed throughout a wider region. Primary nerve branches were mislocated, whereas secondary or intramuscular nerve branches were elongated and reduced in number. Both spontaneous and evoked neurotransmitter release was reduced at the mutant NMJs. Furthermore, short-term plasticity and calcium sensitivity of neurotransmitter release were compromised in beta-catenin-deficient muscle. In contrast, the NMJ was normal in morphology and function in motoneuron-specific beta-catenin-deficient mice. Taken together, these observations indicate a role for muscle beta-catenin in presynaptic differentiation and function, identifying a previously unknown retrograde signaling in the synapse formation and synaptic plasticity.

Post-Cross-Linking of Collagen Hydrogels by Carboxymethylated Polyrotaxanes for Simultaneously Improving Mechanical Strength and Cell Proliferation.

To improve the mechanical properties of collagen hydrogels, which are widely utilized as biomaterials, post-cross-linking of collagen hydrogels was performed using polyrotaxane (PRX) as a cross-linker. Herein, carboxymethyl group-modified PRXs (CMPRs) composed of carboxymethylated α-cyclodextrins (α-CDs) threaded along poly(ethylene glycol) (PEG) capped with bulky stoppers were used to cross-link via reaction with the amino groups in the collagen. Four series of CMPRs with different α-CD threading ratios and axle PEG molecular weights were used for the post-cross-linking of the collagen hydrogels to verify the optimal CMPR chemical compositions. The post-cross-linking of the collagen hydrogels with CMPRs improved the swelling ratios and mechanical properties, such as viscoelasticity and tensile strength. Among the tested CMPRs, CMPRs with an axle PEG molecular weight of 35,000 (PEG35k) resulted in better mechanical properties than CMPRs with a PEG10k axis. Additionally, the cell adhesion and proliferation were greatly improved on the surface of the collagen hydrogels post-cross-linked with CMPRs with the PEG35k axle. These findings suggest that the molecular weight of an axle polymer in CMPRs is a more important parameter than the α-CD threading ratios. Accordingly, the post-cross-linking of hydrogels with PRXs is promising for improving the mechanical properties and biomaterial functions of collagen hydrogels.