Speciation and Reactivity Control of Cu-Oxo Clusters via Extraframework Al in Mordenite for Methane Oxidation.

The stoichiometric conversion of methane to methanol by Cu-exchanged zeolites can be brought to highest yields by the presence of extraframework Al and high CH4 chemical potentials. Combining theory and experiments, the differences in chemical reactivity of monometallic Cu-oxo and bimetallic Cu-Al-oxo nanoclusters stabilized in zeolite mordenite (MOR) are investigated. Cu-L3 edge X-ray absorption near-edge structure (XANES), infrared (IR), and ultraviolet-visible (UV-vis) spectroscopies, in combination with CH4 oxidation activity tests, support the presence of two types of active clusters in MOR and allow quantification of the relative proportions of each type in dependence of the Cu concentration. Ab initio molecular dynamics (MD) calculations and thermodynamic analyses indicate that the superior performance of materials enriched in Cu-Al-oxo clusters is related to the activity of two µ-oxo bridges in the cluster. Replacing H2O with ethanol in the product extraction step led to the formation of ethyl methyl ether, expanding this way the applicability of these materials for the activation and functionalization of CH4. We show that competition between different ion-exchanged metal-oxo structures during the synthesis of Cu-exchanged zeolites determines the formation of active species, and this provides guidelines for the synthesis of highly active materials for CH4 activation and functionalization.

Importance of Methane Chemical Potential for Its Conversion to Methanol on Cu-Exchanged Mordenite.

Copper-oxo clusters exchanged in zeolite mordenite are active in the stoichiometric conversion of methane to methanol at low temperatures. Here, we show an unprecedented methanol yield per Cu of 0.6, with a 90-95 % selectivity, on a MOR solely containing [Cu3 (µ-O)3 ]2+ active sites. DFT calculations, spectroscopic characterization and kinetic analysis show that increasing the chemical potential of methane enables the utilization of two µ-oxo bridge oxygen out of the three available in the tricopper-oxo cluster structure. Methanol and methoxy groups are stabilized in parallel, leading to methanol desorption in the presence of water.

Importance of Methane Chemical Potential for Its Conversion to Methanol on Cu-exchanged Mordenite.

Invited for the cover of this issue is the collaborative team of researchers from TU Munich, PNNL and TU Delft. Read the full text of the article at 10.1002/chem.202000772.

Micro-/nanofluidic device for tunable generation of a concentration gradient: application to Caenorhabditis elegans chemotaxis.

In this study, we propose a novel micro-/nanofluidic device that can generate a chemical concentration gradient using a parallel nanochannel as gradient generator. This device is easy to fabricate, showing high reproducibility. Its main feature is the multiple-nanochannel-based gradient generator, which permits the diffusion of small molecules and tunably generates concentration gradients. The nanopattern for the nanochannels can be rapidly and easily fabricated by wrinkling a diamond-like carbon thin film which is deposited on a polydimethylsiloxane substrate; the generation of the concentration gradient can be adjusted by controlling the dimensions of the nanochannels. The developed gradient generator is embedded into a microfluidic device to study chemotaxis in the nematode Caenorhabditis elegans, which has a highly developed chemosensory system and can detect a wide variety of chemical molecules. This device shows good performance for rapid analysis of C. elegans chemotaxis under sodium chloride stimuli.

Effects of various extracellular matrix proteins on the growth of HL-1 cardiomyocytes.

We present the physical and biochemical effects of extracellular matrixes (ECMs) on HL-1 cardiomyocytes. ECMs play major roles in cell growth, adhesion and the maintenance of native cell functions. We investigated the effects of 6 different cell culture systems: 5 different ECM-treated surfaces (fibronectin, laminin, collagen I, gelatin and a gelatin/fibronectin mixture) and 1 nontreated surface. Surface morphology was scanned and analyzed using atomic force microscopy in order to investigate the physical effects of ECMs. The attachment, growth, viability, proliferation and phenotype of the cells were analyzed using phase-contrast microscopy and immunocytochemistry to elucidate the biochemical effects of ECMs. Our study provides basic information for understanding cell-ECM interactions and should be utilized in future cardiac cell research and tissue engineering.

Effectiveness of manual therapy and cervical spine stretching exercises on pain and disability in myofascial temporomandibular disorders accompanied by headaches: a single-center cohort study.

BACKGROUND: Previous studies have demonstrated a relationship between headaches and temporomandibular disorders (TMDs). Moreover, recent studies have shown functional, anatomical, and neurological associations between the temporomandibular joint (TMJ) and upper cervical spine. This study aimed to investigate the effectiveness of manual therapy and cervical spine stretching exercises for pain and disability in patients with myofascial TMDs accompanied by headaches. METHODS: Thirty-four patients recruited from Gyeryong Hospital with headaches and diagnosed with TMDs were randomly assigned to the experimental (n = 17) and control (n = 17) groups. Headache impact was assessed using the Korean Headache Impact Test-6. Masseter myofascial pain was measured using the visual analog scale, and TMJ pressure pain threshold levels were evaluated using an algometer. Neck pain intensity was assessed using the numerical rating scale. Once per week for 10 weeks, the experimental group received cervical spine-focused manual therapy and stretching exercises alongside conservative physical therapy, and the control group received conservative physical therapy alone. Patients were evaluated at baseline and 5 and 10 weeks post-intervention. RESULTS: After the intervention, the experimental group exhibited significant reductions in the cervical kyphotic angle, Korean Headache Impact Assessment score, neck pain intensity, TMJ pain pressure threshold, Neck Disability Index score, and Jaw Functional Limitation Scale level compared with the control group (p < 0.01). CONCLUSION: Manual therapy and stretching exercises could help resolve TMDs accompanied by headaches through biomechanical changes in the cervical spine. These findings may guide protocols and clinical trials involving manual therapy that align morphological structures.

Concurrent Validity of GAITRite and the 10-m Walk Test to Measure Gait Speed in Adults with Chronic Ankle Instability.

Since there are many different assessments related to gait speed, it is important to determine the concurrent validity of each measure so that they can be used interchangeably. Our study aimed to investigate the concurrent validity of gait speed measured by the 10 m walk test (10 MWT) and the gold standard gait analysis system, the GAITRite system, for people with chronic ankle instability (CAI). For 16 people with CAI, 4 evaluations of the 10 MWT and 4 evaluations of the GAITRite system were performed (a comfortable gait speed for 2 evaluations; a maximal gait speed for 2 evaluations). We used intraclass correlations [ICC (2,1), absolute agreement] and Bland−Altman plots to analyze the relationship between the gait speed of the two measures. The absolute agreement between the 10 MWT and the GAITRite system is at the comfortable gait speed [ICC = 0.66; p < 0.001)], and the maximal gait speed [ICC = 0.68; p < 0.001)] showed fair to good agreement. Both gait speeds had a proportional bias; the limit of agreement (LOA) was large (0.50 at the comfortable gait speed and 0.60 at the maximal gait speed). Regression-based Bland−Altman plots were created for the comfortable gait speed (R2 = 0.54, p < 0.001) and the maximal gait speed (R2 = 0.78, p < 0.001). The regression-based LOA ranged from 0.45 to 0.66 m/s for the comfortable gait speed and 1.09 to 1.37 m/s for the maximal gait speed. Our study suggests that it is undesirable to mix the 10 MWT and the GAITRite system gait speed measurements in people with CAI. Each measure should not be recorded by the same evaluation tool and referenced to normative data.

Influence of Self-Esteem of Middle School Students for Mental Care on Academic Achievement: Based on the Mediation Effect of GRIT and Academic Enthusiasm.

The purpose of this study is to identify how self-esteem of middle school students for mental care influences their academic achievement and to verify the mediation effect of GRIT on academic enthusiasm. Data of 2590 first graders in middle school from the Kora Children and Youth Panel Survey 2019 was used to support this study. Data analysis was performed by using SPSS21.0, AMOS22.0, and PROCESS macro program. The results are as follows. Comparison of the model fits of each full mediation model and partial mediation model with χ2 showed that the full mediation model was more suitable for this study. In more detail, the influence of self-esteem on GRIT and the influence of GRIT on academic enthusiasm were significantly positive. Lastly, the study identified that there was a mediation effect between self-esteem and academic achievement through GRIT and academic enthusiasm. It indicates that self-esteem is the key to improve academic achievement and that specific programs should be supplemented in order to enhance self-esteem, GRIT, and academic enthusiasm.

Surface-directed engineering of tissue anisotropy in microphysiological models of musculoskeletal tissue.

Here, we present an approach to model and adapt the mechanical regulation of morphogenesis that uses contractile cells as sculptors of engineered tissue anisotropy in vitro. Our method uses heterobifunctional cross-linkers to create mechanical boundary constraints that guide surface-directed sculpting of cell-laden extracellular matrix hydrogel constructs. Using this approach, we engineered linearly aligned tissues with structural and mechanical anisotropy. A multiscale in silico model of the sculpting process was developed to reveal that cell contractility increases as a function of principal stress polarization in anisotropic tissues. We also show that the anisotropic biophysical microenvironment of linearly aligned tissues potentiates soluble factor-mediated tenogenic and myogenic differentiation of mesenchymal stem cells. The application of our method is demonstrated by (i) skeletal muscle arrays to screen therapeutic modulators of acute oxidative injury and (ii) a 3D microphysiological model of lung cancer cachexia to study inflammatory and oxidative muscle injury induced by tumor-derived signals.

Activity of Cu-Al-Oxo Extra-Framework Clusters for Selective Methane Oxidation on Cu-Exchanged Zeolites.

Cu-zeolites are able to directly convert methane to methanol via a three-step process using O2 as oxidant. Among the different zeolite topologies, Cu-exchanged mordenite (MOR) shows the highest methanol yields, attributed to a preferential formation of active Cu-oxo species in its 8-MR pores. The presence of extra-framework or partially detached Al species entrained in the micropores of MOR leads to the formation of nearly homotopic redox active Cu-Al-oxo nanoclusters with the ability to activate CH4. Studies of the activity of these sites together with characterization by 27Al NMR and IR spectroscopy leads to the conclusion that the active species are located in the 8-MR side pockets of MOR, and it consists of two Cu ions and one Al linked by O. This Cu-Al-oxo cluster shows an activity per Cu in methane oxidation significantly higher than of any previously reported active Cu-oxo species. In order to determine unambiguously the structure of the active Cu-Al-oxo cluster, we combine experimental XANES of Cu K- and L-edges, Cu K-edge HERFD-XANES, and Cu K-edge EXAFS with TDDFT and AIMD-assisted simulations. Our results provide evidence of a [Cu2AlO3]2+ cluster exchanged on MOR Al pairs that is able to oxidize up to two methane molecules per cluster at ambient pressure.

Risk factors of postoperative remote intracerebral hemorrhage after craniotomy for ruptured cerebral aneurysms.

OBJECTIVE: We aimed to identify the relation between perioperative cerebrospinal fluid (CSF) drain through lumbar drainage (LD) and development of postoperative (POP) remote intracerebral hemorrhage (rICH) in craniotomy to treat ruptured intracranial aneurysms. METHODS: We retrospectively reviewed consecutive patients who underwent craniotomy for ruptured cerebral aneurysms at the authors' institution between 1998 and 2004. We subsequently compared the incidence and characteristics of POP rICH between the patients who had a perioperative LD and those who did not. All statistical analyses were conducted using the software package SPSS 19.0 (SPSS Inc., Chicago, IL, USA). A p value of <0.05 was considered statistically significant. RESULTS: We enrolled 688 patients, of which 80 patients (11.6%) received perioperative LD, and 608 did not. LD and non-LD groups were comparable because although clinical characteristics of the two groups were significantly different considering history of hypertension, timing of surgery, and closed system negative pressure suction drain (SD) placement, none of these three variables was an independent risk factor associated with POP rICH in multivariate analysis. POP rICH incidence was significantly higher in the LD goup (12.5%) than non-LD group (0.8%) (p=0.000) in univariate analysis. LD placement was the only independent risk factor associated with the development of rICH in multivariate logistic regression analysis. CONCLUSIONS: POP rICH incidence was significantly higher in patients who were managed with perioperative LD than in those who did not. LD insertion in craniotomy for ruptured intracranial aneurysm, should be closely monitored to address the occurrence of POP rICH.

Investigation of wound healing process guided by nano-scale topographic patterns integrated within a microfluidic system.

When living tissues are injured, they undergo a sequential process of homeostasis, inflammation, proliferation and maturation, which is called wound healing. The working mechanism of wound healing has not been wholly understood due to its complex environments with various mechanical and chemical factors. In this study, we propose a novel in vitro wound healing model using a microfluidic system that can manipulate the topography of the wound bed. The topography of the extracellular matrix (ECM) in the wound bed is one of the most important mechanical properties for rapid and effective wound healing. We focused our work on the topographical factor which is one of crucial mechanical cues in wound healing process by using various nano-patterns on the cell attachment surface. First, we analyzed the cell morphology and dynamic cellular behaviors of NIH-3T3 fibroblasts on the nano-patterned surface. Their morphology and dynamic behaviors were investigated for relevance with regard to the recovery function. Second, we developed a highly reproducible and inexpensive research platform for wound formation and the wound healing process by combining the nano-patterned surface and a microfluidic channel. The effect of topography on wound recovery performance was analyzed. This in vitro wound healing research platform will provide well-controlled topographic cue of wound bed and contribute to the study on the fundamental mechanism of wound healing.

Hypoxic Physiological Environments in a Gas-Regulated Microfluidic Device.

Hypoxic environment is known as one of the critical factors in various physiological/pathological processes. It is imperative to recapitulate oxygen level in microscale for human physiology/pathology induced by hypoxia. Herein, we propose an oxygen-regulating system that can be applied to in vitro tissue models. We fabricated a microdevice with a gas-permeable membrane, allowing oxygen diffusion without direct contact to cells. We verified the formation of oxygen level less than 2% O2 concentration inside the device through computational simulation and experiments. H9c2 heart myoblasts were exposed to hypoxic condition in the device, and their cell viability were investigated. We anticipate that our system will be integrated with a platform to study hypoxia-induced human physiology and pathology as an efficient oxygen-regulating system.

Measuring perceived effects of drinking an extract of basidiomycetes Agaricus blazei Murill: a survey of Japanese consumers with cancer.

BACKGROUND: To survey cancer patients who consume an extract of the Basidiomycetes Agaricus blazei Murill mushroom (Sen-Sei-Ro) to measure their self-assessment of its effects and to develop an instrument for use in future randomized trials. METHODS: We designed, translated and mailed a survey to 2,346 Japanese consumers of Sen-Sei-Ro self-designated as cancer patients. The survey assessed consumer demographics, cancer history, Sen-Sei-Ro consumption, and its perceived effects. We performed exploratory psychometric analyses to identify distinct, multi-item scales that could summarize perceptions of effects. RESULTS: We received completed questionnaires from 782 (33%) of the sampled Sen-Sei-Ro consumers with a cancer history. Respondents represented a broad range of cancer patients familiar with Sen-Sei-Ro. Nearly all had begun consumption after their cancer diagnosis. These consumers expressed consistently positive views, though not extremely so, with more benefit reported for more abstract benefits such as emotional and physical well-being than relief of specific symptoms. We identified two conceptually and empirically distinct and internally consistent summary scales measuring Sen-Sei-Ro consumers' perceptions of its effects, Relief of Symptoms and Functional Well-being (Cronbach's alpha: Relief of Symptoms, alpha = .74; Functional Well-Being, alpha = .91). CONCLUSION: Respondents to our survey of Sen-Sei-Ro consumers with cancer reported favorable perceived effects from its use. Our instrument, when further validated, may be a useful outcome in trials assessing this and other complementary and alternative medicine (CAM) substances in cancer patients.

Synthetic anion transporters that bear a terminal ethynyl group.

Cl(-) transporters that bear a terminal ethynyl group were synthesized; they consist of non-pyrrolic hydrogen bond motifs such as phenolic OH, amide NH, and triazole CH. The ethynyl group of these non-pyrrolic analogs plays an important role in chloride efflux and they exhibit no significant cytotoxic activity.

A major constituent of green tea, EGCG, inhibits the growth of a human cervical cancer cell line, CaSki cells, through apoptosis, G(1) arrest, and regulation of gene expression.

A constituent of green tea, (-)-epigallocatechin-3-gallate (EGCG) has been known to possess antiproliferative properties. In this study, we investigated the anticancer effects of EGCG in human papillomavirus (HPV)-16 associated cervical cancer cell line, CaSki cells. The growth inhibitory mechanism(s) and regulation of gene expression by EGCG were also evaluated. EGCG showed growth inhibitory effects in CaSki cells in a dose-dependent fashion, with an inhibitory dose (ID)(50) of approximately 35 microM. When CaSki cells were further tested for EGCG-induced apoptosis, apoptotic cells were significantly observed after 24 h at 100 microM EGCG. In contrast, an insignificant induction of apoptotic cells was observed at 35 microM EGCG. However, cell cycles at the G1 phase were arrested at 35 microM EGCG, suggesting that cell cycle arrests might precede apoptosis. When CaSki cells were tested for their gene expression using 384 cDNA microarray, an alteration in the gene expression was observed by EGCG treatment. EGCG downregulated the expression of 16 genes over time more than twofold. In contrast, EGCG upregulated the expression of four genes more than twofold, suggesting a possible gene regulatory role of EGCG. This data supports that EGCG can inhibit cervical cancer cell growth through induction of apoptosis and cell cycle arrest as well as regulation of gene expression in vitro. Furthermore, in vivo antitumor effects of EGCG were also observed. Thus, EGCG likely provides an additional option for a new and potential drug approach for cervical cancer patients.

Comparison of effects of As2O3 and As4O6 on cell growth inhibition and gene expression profiles by cDNA microarray analysis in SiHa cells.

An arsenical compound, As2O3 has been reported to be effective for treating acute leukemia and induce apoptosis in many different tumor cell types. In this study we designed a novel arsenical compound, As4O6, and compared its ability to induce cell growth inhibition as well as gene expression profiles along with As2O3 in HPV16 infected SiHa cervical cancer cells. Both As2O3 and As4O6 induced apoptosis in SiHa cells, as determined by a DNA ladder formation. As4O6 was more effective in suppressing the growth of SiHa cells in vitro, as compared to As2O3. To further compare gene expression profiles between these two drugs, we used a 384 cDNA microarray system. The gene expression profiles were also classified into the Gene Ontology (GO) to investigate apoptosis-related cellular processes. In the case of As2O3, 41 genes were up- or down-regulated at least 2-fold, as compared to non-treatment, whereas, 65 genes were up- or down-regulated by As4O6 treatment. In particular, 27 genes were commonly regulated by both arsenic compounds. The GO analysis also indicated that down-regulation of cell-regulatory functions, such as cell cycle, protein kinase activity and DNA repair, induces an anti-tumor effect. Taken together, these data support that As4O6 could be more effective than As2O3 in inhibiting the growth of HPV16 infected cervical cancer cells. This appears to be mediated through a unique but overlapping regulatory mechanism(s), suggesting that the regulated genes and cellular processes could be used for a new potential drug approach for treating cervical cancer in clinical settings.

Two potent competitive inhibitors discriminating alpha-glucosidase family I from family II.

The inhibition kinetics for isoacarbose (a pseudotetrasaccharide, IsoAca) and acarviosine-glucose (pseudotrisaccharide, AcvGlc), both of which are derivatives of acarbose, were investigated with various types of alpha-glucosidases obtained from microorganisms, plants, and insects. IsoAca and AcvGlc, competitive inhibitors, allowed classification of alpha-glucosidases into two groups. Enzymes of the first group were strongly inhibited by AcvGlc and weakly by IsoAca, in which the K(i) values of AcvGlc (0.35-3.0 microM) were 21- to 440-fold smaller than those of IsoAca. However, the second group of enzymes showed similar K(i) values, ranging from 1.6 to 8.0 microM for both compounds. This classification for alpha-glucosidases is in total agreement with that based on the similarity of their amino acid sequences (family I and family II). This indicated that the alpha-glucosidase families I and II could be clearly distinguished based on their inhibition kinetic data for IsoAca and AcvGlc. The two groups of alpha-glucosidases seemed to recognize distinctively the extra reducing-terminal glucose unit in IsoAca.

The effect of additional etching and curing mechanism of composite resin on the dentin bond strength.

PURPOSE: The aim of this study was to evaluate the effects of additional acid etching and curing mechanism (light-curing or self-curing) of a composite resin on the dentin bond strength and compatibility of one-step self-etching adhesives. MATERIALS AND METHODS: Sixteen human permanent molars were randomly divided into eight groups according to the adhesives used (All-Bond Universal: ABU, Clearfil S3 Bond: CS3), additional acid etching (additional acid etching performed: EO, no additional acid etching performed: EX), and composite resins (Filtek Z-250: Z250, Clearfil FII New Bond: CFNB). Group 1: ABU-EO-Z250, Group 2: ABU-EO-CFNB, Group 3: ABU-EX-Z250, Group 4: ABU-EX-CFNB, Group 5: CS3-EO-Z250, Group 6: CS3-EO-CFNB, Group 7: CS3-EX-Z250, Group 8: CS3-EX-CFNB. After bonding procedures, composite resins were built up on dentin surfaces. After 24-hour water storage, the teeth were sectioned to make 10 specimens for each group. The microtensile bond strength test was performed using a microtensile testing machine. The failure mode of the fractured specimens was examined by means of an optical microscope at ×20 magnification. The data was analyzed using a one-way ANOVA and Scheffe's post-hoc test (α=.05). RESULTS: Additional etching groups showed significantly higher values than the no additional etching group when using All-Bond Universal. The light-cured composite resin groups showed significantly higher values than the self-cured composite resin groups in the Clearfil S3 Bond. CONCLUSION: The additional acid etching is beneficial for the dentin bond strength when using low acidic one-step self-etch adhesives, and low acidic one-step self-etch adhesives are compatible with self-cured composite resin. The acidity of the one-step self-etch adhesives is an influencing factor in terms of the dentin bonding strength and incompatibility with a self-cured composite resin.

Activity of green tea polyphenol epigallocatechin-3-gallate against ovarian carcinoma cell lines.

PURPOSE: A constituent of green tea, (-)-epigallocatechin-3-gallate (EGCG), is known to possess anti-cancer properties. In this study, the time-course of the anticancer effects of EGCG on human ovarian cancer cells were investigated to provide insights into the molecular-level understanding of the growth suppression mechanism involved in EGCG-mediated apoptosis and cell cycle arrest. MATERIALS AND METHODS: Three human ovarian cancer cell lines (p53 negative, SKOV-3 cells; mutant type p53, OVCAR-3 cells; and wild type p53, PA-1 cells) were used. The effect of EGCG treatment was studied via a cell count assay, cell cycle analysis, FACS, Western blot and macroarray assay. RESULTS: EGCG exerts a significant role in suppressing ovarian cancer cell growth, showed dose dependent growth inhibitory effects in each cell line and induced apoptosis and cell cycle arrest. The cell cycle was arrested at the G1 phase by EGCG in SKOV-3 and OVCAR-3 cells. In contrast, the cell cycle was arrested in the G1/S phase in PA-1 cells. EGCG differentially regulated the expression of genes and proteins (Bax, p21, Retinoblastoma, cyclin D1, CDK4 and Bcl-X(L)) more than 2 fold, showing a possible gene regulatory role for EGCG. The continual expression in p21WAF1 suggests that EGCG acts in the same way with p53 proteins to facilitate apoptosis after EGCG treatment. Bax, PCNA and Bcl-X are also important in EGCG-mediated apoptosis. In contrast, CDK4 and Rb are not important in ovarian cancer cell growth inhibition. CONCLUSION: EGCG can inhibit ovarian cancer cell growth through the induction of apoptosis and cell cycle arrest, as well as in the regulation of cell cycle related proteins. Therefore, EGCG-mediated apoptosis could be applied to an advanced strategy in the development of a potential drug against ovarian cancer.