Essential Active Components Research Articles

Uporedno spektrofotometrijsko određivanje 3-hidroksiflavona bazirano na kompleksima cinka i aluminijuma i njihovi antioksidatni profili

Flavonoids, as plant-derived compounds, were essential active components in traditional medicine for centuries. Their potential or confirmed effects include antiviral, antimutagenic, antiinflammatory, antibacterial, vasodilatory, and anticancer properties. The promotion of a plantbased diet, along with the benefits of consuming flavonoids, has recently become increasingly attractive. 3-Hydroxyflavone (3HF) is the structural spine of flavonols, an important subgroup of flavonoids. Although 3HF itself does not exist in plants per se, it exerts many of its effects because of its characteristics that allow it to prevent free radical generation. This work is focused on the characterization of 3HF complexes with zinc(II) and aluminium(III) ions (Zn-3HF and Al-3HF, respectively). Besides this, a simple, fast, and low-priced spectrophotometric method for 3HF determination, with very low LOD and LOQ, based on Zn-3HF and Al-3HF formation, was established. A slight advantage is given to the modification with Al3+ ion on pH 4.91, due to very low LOD and LOQ values of 1.83×10-7 molL-1 , and 5.50×10-7 molL-1 , respectively, and a high correlation coefficient, R =0.99986. Furthermore, the antioxidant ability of Zn-3HF, Al-3HF, and parent 3HF was examined by the ABTS and DPPH tests. They brought the Zn-3HF complex to the fore as a potential antioxidative agent.

Exploring the Mechanism of Brucea Javanica against Ovarian Cancer based on Network Pharmacology and the Influence of Luteolin on the PI3K/AKT Pathway.

Ovarian cancer (OC) is a commonly diagnosed female cancer around the world. The Chinese herbal medicine Brucea Javanica has an anti-cancer effect. However, there is no relevant report on whether Brucea Javanica is effective in treating OC, and the corresponding mechanism is also unknown. This study was projected to excavate the active components and underpinned molecular mechanisms of Brucea Javanica in treating ovarian cancer (OC) through network pharmacology combined with in vitro experiments. The essential active components of Brucea Javanica were selected using the TCMSP database. The OC-related targets were selected by GeneCards, intersecting targets were obtained by Venn Diagram. The core targets were obtained through the PPI network and Cytoscape, and the key pathway was gained through GO and KEGG enrichment analyses. Meanwhile, docking conformation was observed as reflected by molecular docking. MTT, colony formation assay and flow cytometer (FCM) analysis were performed to determine cell proliferation and apoptosis, respectively. Finally, Levels of various signaling proteins were evaluated by western blotting. Luteolin, β-sitosterol and their corresponding targets were selected as the essential active components of Brucea Javanica. 76 intersecting targets were obtained by Venn Diagram. TP53, AKT1, and TNF were obtained through the PPI network and Cytoscape, and the key pathway PI3K/AKT was gained through GO and KEGG enrichment analyses. A good docking conformation was observed between luteolin and AKT1. Luteolin could hinder A2780 cell proliferation, induce cell apoptosis and enhance the inhibition of the PI3K/AKT pathway. It was verified in vitro that luteolin could hinder OC cell proliferation and activate the PI3K/AKT pathway to lead to apoptosis.

Regulation of phospholipid peroxidation signaling by a traditional Chinese medicine formula for coronary heart disease

BackgroundPhospholipid peroxidation signaling was recently revealed as a novel pathological mechanism of coronary heart disease (CHD), and small molecules involved in this redox-metabolic pathway are suggested as the potential anti-CHD drugs. Danlou Tablet (DLT), a famous traditional Chinese medicine (TCM) formula characterized by multi-component and multi-target regulation, is widely used in the clinical treatment of CHD by regulating lipid metabolism. However, little information is available addressing the corresponding pharmacological mechanisms and associated active components of DLT. PurposeTo study whether phospholipid peroxidation involves a novel mechanism of DLT for the therapeutic effect of CHD and to explain the essential active components. MethodsFirstly, the HPLC fingerprint was constructed to ensure the controllability of the quality of DLT. Then, a CHD animal model with the characteristics of lipid disorder and myocardial ischemia was established by a high-fat diet (HFD) combined with left anterior descending coronary artery (LAD) ligation. The therapeutic effect of DLT was further evaluated based on the results of the rat survival rate, cardiac function, cardiac histopathology, and myocardial ischemia indicators. Correspondingly, whether DLT can regulate the key indicators (ALOX15, GPX4, MDA, GSH, and NADPH) of the phospholipid peroxidation pathway was investigated, and Alox15−/− mice have been applied to confirm the mechanism of DLT. Finally, the target-mediated characterization strategy based on ALOX15, including the integration of in vivo component characterization, network pharmacology, molecular docking analysis, and activity verification, has been further implemented to reveal the key bio-active components in DLT. ResultsIn this study, a high-fat diet (HFD) combined with left anterior descending coronary artery (LAD) ligation was utilized to generate a CHD model, and DLT significantly improved the cardiac dysfunction and reduced the myocardial cell death susceptibility. Further results revealed that DLT reversed the protein expression of ALOX15 and GPX4, the key proteins of phospholipid peroxidation pathways, which subsequently influenced the parameters of phospholipid peroxidation (MDA, GSH, and NADPH). The ALOX15 knockout transgenic animal model confirmed that Alox15−/− mice lost their cardioprotective effects with DLT, suggesting that DLT exerted therapeutic effects on CHD by regulating ALOX15-mediated phospholipid peroxidation. Finally, the target-mediated characterization strategy identified that daidzein is an active component in DLT against CHD by modulating ALOX15. ConclusionInnovatively, ALOX15-mediated phospholipid peroxidation was identified as one of the critical mechanisms of DLT exerting cardioprotective effects. Our findings elucidate a novel mechanism of DLT and provide some new drug evaluation targets and therapeutic strategies for CHD.

Elucidating reaction pathways occurring in CO2 hydrogenation over Fe-based catalysts

A detailed experimental analysis of reaction pathways proceeding in CO2 hydrogenation over Fe-based catalysts was performed. The catalytic activity was measured at different degrees of conversion and used to analyze the production/consumption rates of reagents and products along the catalyst bed. It was demonstrated that except for the reverse water gas shift reaction and the subsequent hydrogenation of CO via Fischer-Tropsch (FT) mechanism, additional routes of hydrocarbon formation from CO2 exist in the CO2 hydrogenation. One of them is the methanation reaction which takes place over all studied catalysts. Another one is a direct pathway of C2+ hydrocarbon formation from CO2 that plays a significant role at least for some catalysts. In this route, iron carbides may be responsible for hydrogenating CO2 into C2+ hydrocarbons. Based on these results, the concept of requiring iron oxides as an essential active component for catalyzing the RWGS reaction in CO2-FT should be reviewed.

Analyzing network pharmacology and molecular docking to clarify Duhuo Jisheng decoction potential mechanism of osteoarthritis mitigation

As a classic remedy for treating Osteoarthritis (OA), Duhuo Jisheng decoction has successfully treated countless patients. Nevertheless, its specific mechanism is unknown. This study explored the active constituents of Duhuo Jisheng decoction and the potential molecular mechanisms for treating OA using a Network Pharmacology approaches. Screening active components and corresponding targets of Duhuo parasite decoction by traditional Chinese medicine systems pharmacology database and analysis platform database. Combining the following databases yielded OA disease targets: GeneCards, DrugBank, PharmGkb, Online Mendelian Inheritance in Man, and therapeutic target database. The interaction analysis of the herb-active ingredient-core target network and protein-protein interaction protein network was constructed by STRING platform and Cytoscape software. Gene ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were carried out. PyMOL and other software were used to verify the molecular docking between the essential active components and the core target. 262 active ingredients were screened, and their main components were quercetin, kaempferol, wogonin, baicalein, and beta-carotene. 108 intersection targets of disease and drug were identified, and their main components were RELA, FOS, STAT3, MAPK14, MAPK1, JUN, and ESR1. Gene ontology analysis showed that the key targets were mainly involved in biological processes such as response to lipopolysaccharide, response to xenobiotic stimulus, and response to nutrient levels. The results of Kyoto Encyclopedia of Genes and Genomes analysis show that the signal pathways include the AGE - RAGE signaling pathway, IL - 17 signaling pathway, TNF signaling pathway, and Toll - like receptor signaling pathway. Molecular docking showed that the main active components of Duhuo parasitic decoction had a good bonding activity with the key targets in treating OA. Duhuo Jisheng decoction can reduce the immune-inflammatory reaction, inhibit apoptosis of chondrocytes, strengthen proliferation and repair of chondrocytes and reduce the inflammatory response in a multi-component-multi-target-multi-pathway way to play a role in the treatment of OA.

Network Pharmacology and Molecular Docking-Based Mechanism Study to Reveal Antihypertensive Effect of Gedan Jiangya Decoction

Primary hypertension is understood as a disease with diverse etiology, a complicated pathological mechanism, and progressive changes. Gedan Jiangya Decoction (GJD), with the patent publication number CN114246896A, was designed to treat primary hypertension. It contains six botanical drugs; however, the underlying mechanism is uncertain. We utilized network pharmacology to predict the active components, targets, and signaling pathways of GJD in the treatment of primary hypertension. We also investigated the potential molecular mechanism using molecular docking and animal experiments. The Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), the Protein Database (UniProt), and a literature review were used to identify the active components and related targets of GJD's pharmacological effects. The GeneCards, Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), and DrugBank databases were utilized to identify hypertension-related targets. Based on a Venn diagram of designed intersection targets, 214 intersection targets were obtained and 35 key targets for the treatment of hypertension were determined using the STRING data platform and Cytoscape software. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of key targets revealed that the relevant molecular action pathways of GJD in the treatment of hypertension include the Toll-like receptor, MAPK, PI3K-Akt, and renin-angiotensin signaling pathways. A GJD active ingredient-key target-pathway connection diagram was created using Cytoscape software, and 11 essential active components were selected. Molecular docking was then used to verify the binding activity of key targets and key active ingredients in GJD to treat primary hypertension. The results of this study indicate that AGTR1, AKT1 with puerarin, EDNRA with tanshinone IIA, MAPK14 with daidzein, MAPK8 with ursolic acid, and CHRM2 with cryptotanshinone had high binding activity to the targets with active components, whereas AGTR1 was selected as target genes verified by our experiment. HPLC was utilized to identify the five active ingredients. Experiments in high-salt rats demonstrated that GJD might decrease the expression of AGTR1 in the kidney and thoracic aorta while increasing the expression of eNOS by preventing the activation of the renin-angiotensin pathway, thereby reducing lowering systolic and diastolic blood pressure.

Research progress on chemical constituents and pharmacological activities of Morus alba

Morus alba, a traditional economic crop, is also a significant medicinal plant. The branches(Mori Ramulus), leaves(Mori Folium), roots and barks(Mori Cortex), and fruits(Mori Fructus) of M. alba are rich in chemical components, such as alkaloids, flavonoids, flavanols, anthocyanins, benzofurans, phenolic acids, and polysaccharides, and possess hypoglycemic, hypolipidemic, anti-inflammatory, anti-tumor, anti-microbial, liver protective, immunoregulatory, and other pharmacological activities. This study analyzed the sources, classification, and functions of the main chemical components in M. alba and systematically summarized the latest research results of essential active components in M. alba and their pharmacological effects to provide references for in-depth research and further development as well as utilization of active components in M. alba.

Insulin-Mimic Components in Acer truncatum Leaves: Bio-Guided Isolation, Annual Variance Profiling and Regulating Pathway Investigated by Omics.

Insulin mimic can promote transporting glucose to muscle tissue and accelerate glucose consumption. It is commonly occurring in many functional foods or traditional medicines. Anti-diabetes molecules from food sources are highly safe and suitable for long-term use to prevent early diabetes. The leaves of Acer truncatum was found glucose uptake promotion in our phenotypic screening. However, its bioactive components and mechanism are still unclear. We collected leaves from trees of different ages (2, 3, 4, 7 and 11 years old) and profiled the ingredients by LC-MS/MS. The essential active component (myricitrin) was acquired following bio-guide on a whole organism Zebrafish (Danio rerio). Its content in the leaves was not affected by tree ages. Therefore, myricitrin can serve as a quality mark for functional foods derived from A. truncatum leaves. The transcriptomic and metabolomic analysis in Zebrafish explored the differentially expressed genes and metabolites. Based on joint-pathway enrichment and qRT-PCR verification, the critical bioactive component myricitrin was found to affect toll-like receptors signaling pathways to regulate glucose uptake. Our findings disclosed a bioactive marker (myricitrin) in A. truncatum leaves and explored its regulation mechanism, which rationalized the anti-diabetes function of the herbal food.

Mobile Apps to Improve Medication Adherence in Cardiovascular Disease: Systematic Review and Meta-analysis.

BackgroundAdherence rates of preventative medication for cardiovascular disease (CVD) have been reported as 57%, and approximately 9% of all CVD events in Europe are attributable to poor medication adherence. Mobile health technologies, particularly mobile apps, have the potential to improve medication adherence and clinical outcomes.ObjectiveThe objective of this study is to assess the effects of mobile health care apps on medication adherence and health-related outcomes in patients with CVD. This study also evaluates apps’ functionality and usability and the involvement of health care professionals in their use.MethodsElectronic databases (MEDLINE [Ovid], PubMed Central, Cochrane Library, CINAHL Plus, PsycINFO [Ovid], Embase [Ovid], and Google Scholar) were searched for randomized controlled trials (RCTs) to investigate app-based interventions aimed at improving medication adherence in patients with CVD. RCTs published in English from inception to January 2020 were reviewed. The Cochrane risk of bias tool was used to assess the included studies. Meta-analysis was performed for clinical outcomes and medication adherence, with meta-regression analysis used to evaluate the impact of app intervention duration on medication adherence.ResultsThis study included 16 RCTs published within the last 6 years. In total, 12 RCTs reported medication adherence as the primary outcome, which is the most commonly self-reported adherence. The duration of the interventions ranged from 1 to 12 months, and sample sizes ranged from 24 to 412. Medication adherence rates showed statistically significant improvements in 9 RCTs when compared with the control, and meta-analysis of the 6 RCTs reporting continuous data showed a significant overall effect in favor of the app intervention (mean difference 0.90, 95% CI 0.03-1.78) with a high statistical heterogeneity (I2=93.32%). Moreover, 9 RCTs assessed clinical outcomes and reported an improvement in systolic blood pressure, diastolic blood pressure, total cholesterol, and low-density lipoprotein cholesterol levels in the intervention arm. Meta-analysis of these clinical outcomes from 6 RCTs favored app interventions, but none were significant. In the 7 trials evaluating app usability, all were found to be acceptable. There was a great variation in the app characteristics. A total of 10 RCTs involved health care professionals, mainly physicians and nurses, in the app-based interventions. The apps had mixed functionality: 2 used education, 7 delivered reminders, and 7 provided reminders in combination with educational support.ConclusionsApps tended to increase medication adherence, but interventions varied widely in design, content, and delivery. Apps have an acceptable degree of usability; yet the app characteristics conferring usability and effectiveness are ill-defined. Future large-scale studies should focus on identifying the essential active components of successful apps.Trial RegistrationPROSPERO International Prospective Register of Systematic Reviews CRD42019121385; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=121385

Perdisulfate-assisted advanced oxidation of 2,4-dichlorophenol by bio-inspired iron encapsulated biochar catalyst

To improve advanced oxidation processes (AOPs), bio-inspired iron-encapsulated biochar (bio-inspired Fe⨀BC) catalysts with superior performance were prepared from iron-rich biomass of Iris sibirica L. using a pyrolysis method under anaerobic condition. The obtained compounds were used as catalysts to activate perdisulfate (PDS) and then degradate 2,4-dichlorophenol (2,4-DCP), and synthetic iron-laden biochar (synthetic Fe-BC) was used for comparison. The highest removal rate of 2,4-DCP was 98.35%, with 37.03% of this being distinguished as the contribution of micro-electrolysis, greater than the contribution of adsorption (32.81%) or advanced oxidation (28.51%). The high performance of micro-electrolysis could be attributable to the formation of Fe (Iron, syn) and austenite (CFe15.1) with strong electron carrier at 700 °C. During micro-electrolysis, Fe2+ and electrons were gradually released and then used as essential active components to enhance the AOPs. The slow-releasing Fe2+ (K = 0.0048) also inhibited the overconsumption of PDS (K = −0.00056). Furthermore, the electrons donated from Fe⨀BC-4 were able to activate PDS directly. The electrons were enriched by the porous structure of Fe⨀BC-4, and the formation of the COFe bond in the π-electron system could also accelerate the electron transfer to activate PDS. Similar reactive oxygen species (ROS) were identified during the micro-electrolysis and AOPs, leading to similar degradation pathways. The higher does concentration of O2− generated during micro-electrolysis than during the AOPs also led to a greater dechlorination effect.

Cationized liposomal keto-mycolic acids isolated from Mycobacterium bovis bacillus Calmette-Guérin induce antitumor immunity in a syngeneic murine bladder cancer model.

Intravesical therapy using Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the most established cancer immunotherapy for bladder cancer. However, its underlying mechanisms are unknown. Mycolic acid (MA), the most abundant lipid of the BCG cell wall, is suspected to be one of the essential active components of this immunogenicity. Here, we developed cationic liposomes incorporating three subclasses (α, keto, and methoxy) of MA purified separately from BCG, using the dendron-bearing lipid D22. The cationic liposomes using D22 were efficiently taken up by the murine bladder cancer cell line MB49 in vitro, but the non-cationic liposomes were not. Lip-kMA, a cationic liposome containing keto-MA, presented strong antitumor activity in two murine syngeneic graft models using the murine bladder cancer cell lines MB49 and MBT-2 in comparison to both Lip-aMA and Lip-mMA, which contained α-MA and methoxy-MA, respectively. Interestingly, Lip-kMA(D12), which was made of D12 instead of D22, did not exhibit antitumor activity in the murine syngeneic graft model using MB49 cells, although it was successfully taken up by MB49 cells in vitro. Histologically, compared to the number of infiltrating CD4 lymphocytes, the number of CD8 lymphocytes was higher in the tumors treated with Lip-kMA. Antitumor effects of Lip-kMA were not observed in nude mice, whereas weak but significant effects were observed in beige mice with natural killer activity deficiency. Thus, a cationized liposome containing keto-MA derived from BCG induced in vivo antitumor immunity. These findings will provide new insights into lipid immunogenicity and the underlying mechanisms of BCG immunotherapy.

Oxidative degradation of polyamines by serum supplement causes cytotoxicity on cultured cells

Serum is a common supplement for cell culture due to it containing the essential active components for the growth and maintenance of cells. However, the knowledges of the active components in serum are incomplete. Apart from the direct influence of serum components on cultured cells, the reaction of serum components with tested drugs cannot be ignored, which usually results in the false conclusion on the activity of the tested drugs. Here we report the toxicity effect of polyamines (spermidine and spermine) on cultured cells, especially on drug-resistant cancer cell lines, which resulted from the oxidative degradation of polyamines by amine oxidases in serum supplement. Upon adding spermidine or spermine, high concentration of H2O2, an enzyme oxidation product of polyamines, was generated in culture media containing ruminant serum, such as fetal bovine serum (FBS), calf serum, bovine serum, goat serum or horse serum, but not in the media containing human serum. Drug-resistant cancer cell lines showed much higher sensitivity to the oxidation products of polyamines (H2O2 and acrolein) than their wild cell lines, which was due to their low antioxidative capacity.

Antitumor effect of cationic liposome incorporating keto-mycolic acid from Mycobacterium bovis bacillus Calmette-Guérin in mouse model.

461 Background: Intravesical instillation of live bacillus Calmette-Guérin (BCG) is an established immunotherapy for non-muscle invasive bladder cancer. However, development of non-infectious agents has been expected, because there are several problems due to instillation of live bacteria. BCG cell wall skeleton is known to stimulate host immune system, but the mechanism is still unknown. Mycolic acid (MA), which consist of three subclasses (α, keto, methoxy), is the most abundant lipid component of BCG cell wall and is expected to be one of essential active components. Objective: In order to identify active component from BCG cell wall and develop non-infectious BCG-derived immunotherapy, anti-tumor activities of cationic liposomes incorporating each subclass of MA were assessed using mouse syngeneic graft model. Methods: Heat killed packed cells of M. bovis BCG Tokyo 172 were fully hydrolyzed and MA was obtained. MA was separated to three subclasses by thin layer chromatography. Cationic and hydrophilic liposomes incorporating each subclass of MA were prepared. C57BL/6 mice were subcutaneously inoculated with a mixture of MB49 cells and PBS or liposome with/without MA followed by additional injection of PBS or liposome. Tumor growth was monitored. Infiltration of CD4/8 lymphocytes was examined by immunostaining. Results: Cationic liposomes were internalized into cytoplasm of MB49 cells, a mouse bladder cancer cell line. Cell proliferation was not affected by liposome incorporating MA. Tumor growth was significantly suppressed in mice treated with keto MA-liposome (vs PBS, p = 0.007), but not in mice treated withα-or methoxy-MA liposomes. Number of infiltrating CD8 lymphocytes was higher in tumor treated with keto MA-liposome than control. Antitumor effect of keto MA-liposome disappeared in nude mouse, while the effect existed in beige mouse with NK activity deficiency (vs PBS, p = 0.045). Conclusions: Keto MA-liposome showed the strongest antitumor effects in mouse model among three subclasses. T cell immunity may contribute to those effects.

Otophylloside B Protects Against A\u03b2 Toxicity in Caenorhabditis elegans Models of Alzheimer\u2019s Disease

Alzheimer’s disease (AD) is a major public health concern worldwide and the few drugs currently available only treat the symptoms. Hence, there is a strong need to find more effective anti-AD agents. Cynanchum otophyllum is a traditional Chinese medicine for treating epilepsy, and otophylloside B (Ot B), isolated from C. otophyllum, is the essential active component. Having previously identified anti-aging effects of Ot B, we evaluated Ot B for AD prevention in C. elegans models of AD and found that Ot B extended lifespan, increased heat stress-resistance, delayed body paralysis, and increased the chemotaxis response. Collectively, these results indicated that Ot B protects against Aβ toxicity. Further mechanistic studies revealed that Ot B decreased Aβ deposition by decreasing the expression of Aβ at the mRNA level. Genetic analyses showed that Ot B mediated its effects by increasing the activity of heat shock transcription factor (HSF) by upregulating the expression of hsf-1 and its target genes, hsp-12.6, hsp-16.2 and hsp-70. Ot B also increased the expression of sod-3 by partially activating DAF-16, while SKN-1 was not essential in Ot B-mediated protection against Aβ toxicity.Graphical

A Retrospective Study on Qualitative Assessment of Copper Content in Oral Leukoplakia, Submucous Fibrosis and Squamous Cell Carcinoma with Rhodamine Stain

Background: Trace elements are required in small concentrations as essential active components of biological enzyme systems. They are in the form of metalloenzymes and copper is one such component. Copper metabolism is profoundly altered in neoplastic disease. Copper plays an important role in tumor angiogenesis especially in early stages and is also necessary for endothelial cell activation. Copper content in tissues of oral leukoplakia (OL), oral submucous fibrosis (OSMF), and oral squamous cell carcinoma (OSCC) has not been studied extensively. Hence, we attempted this retrospective study to analyze copper content in the tissues by using rhodamine stain for better understanding of pathogenesis. Aim and Objectives: To evaluate and compare the copper content and its depth of penetration in tissue sections of diagnosed cases of oral precancer and cancer by using rhodamine staining method. Materials and Methods: This retrospective analytical study was conducted on histologically diagnosed 10 cases each of OL, OSMF, and OSCC. Ten cases of normal mucosa served as control. The selected cases were subjected to staining with rhodamine for qualitative analysis of copper content. Results: Paired t-test showed a significant increase in copper content in the study group (P = 0.516) as compared to control group. Krushall–Wallis non-parametric test showed higher mean value of copper content in cases of OSMF (2.00) than the cases of OL (1.20) and OSCC (1.70). Conclusion: Copper content by rhodamine staining technique was found to be higher in OSMF than OL and OSCC this staining technique can be used as a prognostic indicator for assessment of disease progression.

Redox Deposition of Nanoscale Metal Oxides on Carbon for Next-Generation Electrochemical Capacitors

Transition metal oxides that mix electronic and ionic conductivity are essential active components of many electrochemical charge-storage devices, ranging from primary alkaline cells to more advanced rechargeable Li-ion batteries. In these devices, charge storage occurs via cation-insertion/deinsertion mechanisms in conjunction with the reduction/oxidation of metal sites in the oxide. Batteries that incorporate such metal oxides are typically designed for high specific energy, but not necessarily for high specific power. Electrochemical capacitors (ECs), which are typically composed of symmetric high-surface-area carbon electrodes that store charge via double-layer capacitance, deliver their energy in time scales of seconds, but at much lower specific energy than batteries. The fast, reversible faradaic reactions (typically described as "pseudocapacitance") of particular nanoscale metal oxides (e.g., ruthenium and manganese oxides) provide a strategy for bridging the power/energy performance gap between batteries and conventional ECs. These processes enhance charge-storage capacity to boost specific energy, while maintaining the few-second timescale of the charge-discharge response of carbon-based ECs. In this Account, we describe three examples of redox-based deposition of EC-relevant metal oxides (MnO2, FeOx, and RuO2) and discuss their potential deployment in next-generation ECs that use aqueous electrolytes. To extract the maximum pseudocapacitance functionality of metal oxides, one must carefully consider how they are synthesized and subsequently integrated into practical electrode structures. Expressing the metal oxide in a nanoscale form often enhances electrochemical utilization (maximizing specific capacitance) and facilitates high-rate operation for both charge and discharge. The "wiring" of the metal oxide, in terms of both electron and ion transport, when fabricated into a practical electrode architecture, is also a critical design parameter for achieving characteristic EC charge-discharge timescales. For example, conductive carbon must often be combined with the poorly conductive metal oxides to provide long-range electron pathways through the electrode. However, the ad hoc mixing of discrete carbon and oxide powders into composite electrodes may not support optimal utilization or rate performance. As an alternative, nanoscale metal oxides of interest for ECs can be synthesized directly on the surfaces of nanostructured carbons, with the carbon surface acting as a sacrificial reductant when exposed to a solution-phase, oxidizing precursor of the desired metal oxide (e.g., MnO4(-) for MnO2). These redox deposition methods can be applied to advanced carbon nanoarchitectures with well-designed pore structures. These architectures promote effective electrolyte infiltration and ion transport to the nanoscale metal oxide domains within the electrode architecture, which further enhances high-rate operation.

Characterization of inactive components in conjugated equine estrogens

Objective: Premarin®, Conjugated Estrogens, United States Pharmacopeia (USP), is a pharmaceutical preparation that has been marketed since the 1940s. The conjugated estrogens found in Premarin® are derived from the urine of pregnant mares. The composition of equine-based estrogens has never been fully evaluated or characterized. Design: A complete estrogenic analysis has been undertaken to characterize the essential active components of conjugated equine estrogens (CEE) through the use of chemical analysis, chromatographic analysis, quantitation, and structure-function relationship analysis. Materials/Methods: The characterization was performed on several lots of Premarin® representing a spectrum of age, source and dosage forms (oral and injectable). The characterization process divided the multitudes of unique components into several classes: actives, concomitants, impurities, inconsistent components and insignificant components. Results: The comprehensive characterization provides sufficient scientific evidence that Premarin® contains ten essential active estrogenic components. The batches examined also contain numerous impurities, several of which are common urinary compounds. Many compounds are inconsistent components across batches and insignificant components that provide no proven pharmacological (estrogenic) activity for the treatment of conditions associated with menopause, including vasomotor symptoms. Conclusions: The comprehensive characterization provides sufficient scientific evidence that Premarin® contains high levels of several inactive components. Some of these impurities represent normal compounds usually found in the urine of horses. Supported by: Endeavor Pharmaceuticals, Inc., Wilmington, NC, USA.

Low Noise Junction Field Effect Transistors Exposed to Intense Ionizing Radiation

The low noise junction field effect transistor (JFET) is an essential active component in the input stages of low noise amplifiers. The changes in the characteristics of low noise JFETs have been studied after exposure to high doses of intense ionizing radiation as may be experienced in nuclear and space applications. The experimental results show that the source-drain current, transconductance and threshold voltage are only slightly degraded and that the gate junction leakage current and the noise voltage generated by the JFET both increase considerably, the latter especially at low frequencies. It is concluded from the results that JFETs should perform in low noise amplifiers provided the radiation dose does not exceed 10 Krad (Si), and that JFETs should be useable as active devices to very high doses if allowance is made for the degraded gate junction properties in specially designed circuits.