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The continuous emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants led to a rapid decline in protection efficacy and neutralizing titers even after three doses of COVID-19 vaccines. Here, we report an open-labeled Phase I clinical trial of a modified mRNA vaccine (SYS6006) as a fourth-dose booster in healthy adults. Eighteen eligible participants, who had completed three doses of inactivated COVID-19 vaccines, received a fourth boosting dose of SYS6006-20 μg. Eighteen convalescent COVID-19 patients were enrolled for the collection of serum samples as a comparator of immunogenicity. The primary endpoint of this trial was titers of anti-receptor binding domain of spike glycoprotein (RBD) antibodies of the Omicron strain (BA.2 and BA.4/5) in serum; titers of neutralizing antibodies against pseudovirus of the Omicron strain (BA.2 and BA.4/5). The secondary endpoint was the incidence of adverse events within 30 days after the boosting. The exploratory endpoint was the cellular immune responses (interferon gamma, IFN-γ). This trial was registered with the Chinese Clinical Trial Registry website. No serious adverse events were reported within 30 days after vaccination. No Grade 3 fever or serious adverse event was reported in the SYS6006 group. Notably, SYS6006 elicited higher titers and longer increases in anti-RBD antibodies and neutralizing antibodies (>90 days) compared with the convalescent group (P < 0.0001) against Omicron strain (BA.2 and BA.4/5). Besides, higher positive spots of T-cell-secreting IFN-γ were observed in the SYS6006 group than those in the convalescent group (P < 0.05). These data demonstrated that SYS6006 was well tolerated and highly immunogenic, generating a stronger and more durable immune response against different variants of SARS-CoV-2.

Baicalein is a biologically important flavonoid in extracted from the Scutellaria baicalensis Georgi, which can effectively inhibit the influenza virus. This study aimed to analyze the safety and pharmacokinetic (PK) characteristics of baicalein tablets in healthy Chinese subjects and provide more information for phase II clinical trials. In this multiple‐ascending‐dose placebo‐controlled trial, 36 healthy subjects were randomized to receive 200, 400, and 600 mg of baicalein tablet or placebo once daily on day 1 and day 10, 3 times daily on days 4–9. All groups were intended to produce safety and tolerability outcomes (lowest dose first). Blood and urine samples were collected from subjects in the 600 mg group for baicalein PK analysis. Our study had shown that Baicalein tablet was generally safe and well‐tolerated. All adverse events were mild and resolved without any intervention except one case of fever reported in the 600 mg group, which was considered as moderate but not related with baicalein as judged by the investigator. Oral baicalein tablets were rapidly absorbed with peak plasma levels being reached within 2 h after multiple administration. The highest urinary excretion of baicalein and its metabolites peaked in 2 h, followed by 12 h, with a double peak trend.

Single-ion-conducting polymer electrolytes are attractive to use in lithium batteries as the transference number of the lithium cation approaches unity. This helps prevent concentration gradients a...

Objective This paper aims to investigate whether machine learning (ML) can be used to predict the state of pulmonary hypertension (PH), including pre-capillary and post-capillary, from echocardiographic data.Methods Two hundred and seventy-five patients with PH who underwent both echocardiography and right heart catheterization were included in the study. Mean pulmonary artery pressure, pulmonary artery wedge pressure measured by right heart catheterization were used as criteria for judging pre-capillary PH and post-capillary PH. Thirteen echocardiographic indicators were used to predict whether the PH was pre-capillary or post-capillary. Nine ML models were used to make predictions. Accuracy was used as the primary reference standard, and the performance of classification model is observed in conjunction with area under curve (AUC), specificity (Sp), sensitivity (Se), Positive Prediction Value (PPV), Negative Prediction Value (NPV), Positive Likelihood Ratio (PLR) and Negative Likelihood Ratio (NLR) and other assessment protocols.Results By comparing the accuracy (ACC), recall rate (Recall) and other model effect evaluation index of the classification under the nine ML models, it can be found that the ML model can effectively identify the pre-capillary PH and the post-capillary PH. LogitBoost performed best in nine ML models (ACC=0.87, Recall=0.83, F1score=0.85, AUC=0.87, Se=0.90, NPV=0.88, PPV=0.87, PLR=8.61 and NLR=0.18, AUC=0.83), it showed good results in identification of the pre-capillary PH (ACC=0.83, Recall=0.87, F-score=0.85); Post-vascular PH (ACC=0.90, Recall=0.88, F-score=0.89). Decision Tree (ACC=0.75, Recall=0.77, F1score=0.78, AUC=0.75, Se=0.72, NPV=0.78, PPV=0.77, PLR=3.66 and NLR=0.29, AUC=0.79) performed worst, and the accuracy of the other seven models was greater than 0.82.Conclusion The classification results of the nine ML models in this paper indicate that the ML method can effectively identify the pre-capillary PH and post-capillary PH from echocardiographic data. Compared with medical diagnosis, ML methods can distinguish between pre-capillary PH and the post-capillary PH under non-invasive conditions.

In this work, we report methods to quantify and minimize the interfacial resistance for Li ion transport, Rinterface, between a model polymer electrolyte, poly(ethylene oxide) + LiCF3SO3 (PE), and a model Li+-conducting ceramic electrolyte, LICGC from Ohara Corporation. By constructing a PE–ceramic–PE trilayer cell, we found Rinterface to be very large, 1.2 kΩ·cm2 at 30 °C, accounting for 66% of the total trilayer cell resistance. When dimethyl carbonate, a loose-binding solvent of Li+, was introduced into the trilayer, Rinterface decreased to essentially zero. As a result, a composite electrolyte with carbonate plasticizers wherein 40 vol % ceramic particles were dispersed in the polymer showed extraordinary room-temperature conductivity of approximately 10–4 S/cm, 3 orders of magnitude higher than that of the dry composite electrolyte. This discovery can be used as guidance in designing composite electrolytes to achieve synergistic effects.

Solid state electrolytes are a promising alternative to flammable liquid electrolytes for high-energy lithium battery applications. In this work polymer-ceramic composite electrolyte membrane with high ceramic loading (greater than 60 vol%) is fabricated using a model polymer electrolyte poly(ethylene oxide) + lithium trifluoromethane sulfonate and a lithium-conducting ceramic powder. The effects of processing methods, choice of plasticizer and varying composition on ionic conductivity of the composite electrolyte are thoroughly investigated. The physical, structural and thermal properties of the composites are exhaustively characterized. We demonstrate that aqueous spray coating followed by hot pressing is a scalable and inexpensive technique to obtain composite membranes that are amazingly dense and uniform. The ionic conductivity of composites fabricated using this protocol is at least one order of magnitude higher than those made by dry milling and solution casting. The introduction of tetraethylene glycol dimethyl ether further increases the ionic conductivity. The composite electrolyte's interfacial compatibility with metallic lithium and good cyclability is verified by constructing lithium symmetrical cells. A remarkable Li+ transference number of 0.79 is discovered for the composite electrolyte.

Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is an important disease in Canada. The worldwide genetic structure of Pst populations have been characterized, excluding Canada. Here, we elucidated the genetic structure of the western Canadian Pst population using molecular markers, revealing the presence of four divergent lineages with predominantly clonal structure. In the worldwide context, two previously reported lineages were identified: PstS0 (22%), representing an old Northwestern-European and PstS1 (35%), an invasive warm-temperature adapted. Additionally, two new, unreported lineages, PstPr (9%) and PstS1-related (35%), were detected, which produced more telia than other lineages and had double the number of unique recombination events. The PstPr was a recent invasion, and likely evolved in a diverse, recombinant population as it was closely related to the PstS5, PstS7/Warrior, PstS8/Kranich, and PstS9 lineages originating from sexually recombining populations in the centre of diversity. The DNA methylation analysis revealed DNA-methyltransferase1-homologs, providing compelling evidence for epigenetic regulation and as a first report, an average of ∼5%, 5hmC in the Puccinia epigenome merits further investigation. The divergent lineages in the Canadian Pst population with the potential for genetic recombination, as well as epigenetic regulation needs consideration in the context of pathogen adaptation and management.

Recombinant glucagon-like peptide-1 receptor agonist (rE-4) is a glucagon-like peptide-1 receptor agonist, which has the same amino acid sequence to exenatide, except for the C-terminal deamidated. This study assessed the pharmacokinetics and preliminary pharmacodynamics of rE-4, following single and multiple subcutaneous injections in Chinese patients with type 2 diabetes mellitus (T2DM). In the randomized, open-label study, Chinese patients with T2DM (n = 36) were randomly assigned to three groups of rE-4 (n = 12), rE-4 with metformin (n = 12) and exenatide (n = 12, as the control group) for 12 weeks. rE-4 and exenatide were administered by subcutaneous injection in the abdomen, and metformin was given by oral administration. Patients received rE-4 or exenatide 5 μg twice a day for the first 4 weeks and adjusted the dose of rE-4 or exenatide to 10 μg twice a day at day 29 for the following 8 weeks, if their glycated albumin (GA) values were still greater than 17%. We evaluated pharmacokinetic parameters of rE-4 and exenatide, fasting plasma glucose (FPG), 2-h postprandial blood glucose (PG2 h), glycosylated hemoglobin (HbA1c) and body weight at designated time points. Thirty-six patients were enrolled, and 29 subjects finished the study. rE-4 was absorbed quickly with a median peak-reaching time (t max) of 0.8–1.5 h and eliminated rapidly with a median terminal half-life (t 1/2z) of 1.6–1.9 h. The exposure of rE-4 increased in an approximately dose-proportional method without accumulation. rE-4 10 μg twice a day could reduce FPG (~2.29 mmol/L), PG2 h (~6.00 mmol/L), HbA1c (~1.19%) and body weight (~0.48 kg) from baseline to 12 weeks, with no statistical significance compared with exenatide (FPG: ~1.88 mmol/L; PG2 h: ~6.66 mmol/L; HbA1c: ~1.13%; body weight: ~0.47 kg) and rE-4 with metformin (FPG: ~2.33 mmol/L; PG2 h: ~6.51 mmol/L; HbA1c: ~0.84%; body weight: ~1.16 kg) (p > 0.05). rE-4 twice a day has a pharmacokinetic profile similar to exenatide and rE-4 with metformin after single and multiple doses in Chinese patients with T2DM. Also, rE-4 could improve glycemic control effectively. NCT01342042.

Ethnopharmacological relevance Scutellaria baicalensis (Huang-Qin in Chinese) is a dry root of the perennial herb Scutellaria baicalensis Georgi, which has been used extensively in current prescriptions. Scutellaria baicalensis is an herb high in flavonoids, and baicalein is the one flavonoid found in the highest amount in Scutellaria baicalensis. Aim of the study Influenza virus could cause mild respiratory tract illness to severe pneumonia and even death. Baicalein has been proved to be one of the effective components against the influenza virus. However, there have been few reports on human trials of baicalein. The purpose of this study was to evaluate the safety of baicalein in vivo and analyze its pharmacokinetic characteristics. Materials and methods Three randomized studies were conducted to evaluate the pharmacokinetics (PK), safety, tolerability, and food effects of baicalein tablets. In the 7-month single-dose safety study, 60 subjects were enrolled and randomized to receive 100–800 mg baicalein tablets or placebo. In the single-dose PK study, 40 subjects were enrolled and randomized to receive 200 mg, 400 mg, 600 mg, 800 mg baicalein tablets. In the study of food effect on PK of baicalein, an additional 10 subjects were enrolled in the 400 mg group, this part of the trial lasted for 7 months. Blood and urine samples for PK analysis were collected at a pre-specified time. PK properties in both fasted and fed states were evaluated, as well as safety and tolerability. Results Among the 80 subjects who were evaluable for the single-dose safety and tolerability, 56 adverse events (AEs) were observed in 32/80 subjects, of which 49 events were from 28/68 subjects in baicalein group and 7 events were from 4/12 subjects in placebo group. All AEs were mild and resolved without any medical intervention. The most common AEs were elevated high-sensitivity C-reactive protein (hs-CRP) level and high triglycerides. After a single administration of baicalein tablets (200 mg, 400 mg, 600 mg, or 800 mg), Cmax were 280.44, 628.80, 845.20, 489.55 ng/mL; AUC0-∞ were 2035.57, 2939.31, 4494.88, and 3754.43 h*ng/mL, respectively. And t1/2z ranged from 7.80 to 14.91 h. The exposure of baicalein and its metabolites increased in a less than dose-proportional manner. Conclusion Baicalein tablets within the studied dose range were safe and well-tolerated in healthy Chinese subjects with no serious or severe adverse effects. Further investigation will be needed to assess the safety and efficacy in the target patients.

In this work, the properties of univalent, that is, Li+, Na+, NH4+, and TEA+ form perfluorosulfonate (PFSA) membranes are studied and compared to the properties of H+ form materials. Properties of these polymer membranes including water uptake, density and conductivity, were investigated for membranes exposed to various water activity levels. The water uptake by the membranes decreased in the order H+ > Li+ > Na+ > NH4+ > TEA+, the same order as the hydration enthalpy (absolute values) of cations. Conductivity values did not strictly follow this order, indicating the importance of different factors besides the hydration level. The partial molar volume of water is derived from the density data as a function of water content for the various membrane forms. This provides further insight into the water, cation, and polymer interactions. Factors that contribute to the conductivity of these membranes include the size of cations, the electrostatic attraction between cations and sulfonate group, and the ion-dipole and hydrogen bonding interactions between cations and water. NH4+ transport is surprisingly high given the low water uptake in NH4+ form membranes. We attribute this to the ability of this ion to develop hydrogen bonded structures that helps to overcome electrostatic interactions with sulfonates. Pulsed-field gradient (PFG) nuclear magnetic resonance (NMR) was used to measure the diffusion coefficient of water in the membranes. FT-IR spectroscopy is employed to probe cation interactions with water and sulfonate sites in the polymer. Overall, the results reflect a competition between the strong electrostatic interaction between cation and sulfonate versus hydration and hydrogen bonding which vary with cation type.

L-3-n-butylphthalide (L-NBP) is a naturally occurring antioxidant, which can be used for the treatment of acute ischemic stroke and vascular dementia. This study evaluated the safety, tolerability and pharmacokinetics of L-NBP tablets in healthy Chinese volunteers. This was a single-center, randomized, double-blind, placebo-controlled, single- and multiple-dose study. Subjects were assigned to receive a single dose of L-NBP tablet at either 80, 160, 320, or 480 mg (n=40), or multiple doses of 160 mg twice daily for 7 days (n=12). Plasma samples were analyzed with LC-MS/MS. Pharmacokinetic parameters of L-NBP were calculated using non-compartmental analysis with WinNonlin software. Statistical analysis was performed using SPSS software. All adverse events (AEs) were mild and of limited duration; AEs in this study occurred less frequently and more mildly than AEs listed for the DL-NBP soft capsule. No serious adverse event (SAE), death or withdrawal from the study was observed. In the single-dose study, Cmax was reached at about 1 h, and the mean t1/2 was approximately 13.76 h. Area under curve (AUC) and Cmax increased with dose escalation, but dose proportionality was not observed over the range of 160 to 480 mg. In the multiple-dose study, the steady-state was reached within 3 days with slight accumulation. In summary, the L-NBP tablet was well tolerated in healthy Chinese subjects. Slight accumulation appeared after repeated doses. L-3-n-butilftalida (L-NMP) é um antioxidante natural, que pode ser utilizado para o tratamento do acidente isquêmico agudo e demência vascular. Este estudo avaliou segurança, tolerância e farmacocinética de comprimidos de L-NBP em chineses voluntários sadios. Este foi um estudo monocêntrico, randomizado, duplo cego, com controle por placebo e doses única e múltipla. Os indivíduos receberam dose única de comprimido de L-NBP de 80, 160, 320 ou 480 mg (n=40) e doses múltiplas de 160 mg duas vezes ao dia, por sete dias (n=12). Amostras de plasma foram analisadas com LC-MS/MS. Os parâmetros farmacocinéticos do L-NBP foram calculados utilizando análise não compartimental, com o programa WinNonlin. A análise estatística foi realizada utilizando-se o programa SPSS. Todos os eventos adversos (EAs) foram moderados e de duração limitada. EAs nesse estudo ocorreram menos frequentemente e mais moderadamente do que os EAs relacionados para cápsulas moles de DL-NBP. Não se observaram eventos adversos graves (EAG), morte ou abandono do estudo. Com dose única, atingiu-se o Cmax em cerca de 1 hora e o t1/2 médio foi de, aproximadamente, 13,76 h. A área sob a curva (ASC) e o Cmax aumentaram com o aumento da dose, mas não se observou proporcionalidade na faixa acima de 160 a 480 mg. No estudo de dose múltipla, o equilíbrio foi alcançado em três dias, com pequeno acúmulo. Em resumo, o comprimido de L-NMP foi bem tolerado em indivíduos chineses saudáveis. O acúmulo pequeno apareceu após doses repetidas.

Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is an important disease in Canada. The worldwide genetic structure of Pst populations have been characterized, excluding Canada. Here, we elucidated the genetic structure of the western Canadian Pst population using molecular markers, revealing the presence of four divergent lineages with predominantly clonal structure. In the worldwide context, two previously reported lineages were identified: PstS0 (22%), representing an old Northwestern-European and PstS1 (35%), an invasive warm-temperature adapted. Additionally, two new, unreported lineages, PstPr (9%) and PstS1-related (35%), were detected, which produced more telia than other lineages and had double the number of unique recombination events. The PstPr was a recent invasion, and likely evolved in a diverse, recombinant population as it was closely related to the PstS5, PstS7/Warrior, PstS8/Kranich, and PstS9 lineages originating from sexually recombining populations in the centre of diversity. The DNA methylation analysis revealed DNA-methyltransferase1-homologs, providing compelling evidence for epigenetic regulation and as a first report, an average of ∼5%, 5hmC in the Puccinia epigenome merits further investigation. The divergent lineages in the Canadian Pst population with the potential for genetic recombination, as well as epigenetic regulation needs consideration in the context of pathogen adaptation and management.

In-situ FTIR is a successful tool to study water absorption and interactions within the Perfluorsulfonate Ion Exchange Membrane (PFSA)(1–4). The versatility of the technique can reveal in-depth information related to proton transport in PFSA, including proton dissociation and solvation. Another desirable feature is that experiments under controlled water content(λ) is also possible. Studies of PFSA membranes equilibrated with different λ was fundamental to understand membrane behavior(5). The volatile nature of acetonitrile and many organic solvents adds to the inaccuracy of many classic membrane characterization methods. To overcome this, techniques tailored for membrane incorporated with organic solvents are necessary. In this study, acetonitrile and lithiated PFSA were chosen to revisit the in-situ IR technique. The goal of this work is to examine acetonitrile’s role in membrane swelling and to create a ‘slow-motion picture’ of how acetonitrile molecules behave upon being imbibed into the membrane, especially at low λ. The vibrational signal of cyanide group (~2250 cm-1)does not overlap with other signals from the membrane and is known to respond to dipole interactions by shifting to higher wavenumber(6). This feature makes an acetonitrile-swollen system an even more favorable candidate for in-situ IR study compared to its aqueous counterpart. For studying proton transport in membrane, initial water buildup in membrane yields a weak and broad signal, making the already obscure -OH stretching region even more complicated to analyze. Without interference from hydrogen bonding, lithium ion solvation with cyanide can be clearly observed. Coupled with monitoring -SO3- area, it is totally feasible to simultaneously see both cation dissociation from membrane (Fig.1A) and cation solvation in solvent (Fig.1B) in a real-time manner to compare with fully swollen state. Acknowledgement We gratefully acknowledge the support of this work by the U.S. Department of Energy, Office of Electricity Delivery and Energy Reliability (Dr. Imre Gyuk). We also thank 3M for providing membranes. References Elabd YA, Baschetti MG, Barbari TA. Time-resolved Fourier transform infrared/attenuated total reflection spectroscopy for the measurement of molecular diffusion in polymers. J Polym Sci Part B Polym Phys. 2003;41(22):2794–807. Hallinan DT, Elabd YA. Diffusion of Water in Nafion Using Time-Resolved Fourier Transform Infrared−Attenuated Total Reflectance Spectroscopy. J Phys Chem B. 2009 ;113(13):4257–66. Hallinan DT, Elabd YA. Diffusion and Sorption of Methanol and Water in Nafion Using Time-Resolved Fourier Transform Infrared−Attenuated Total Reflectance Spectroscopy. J Phys Chem B. 2007 ;111(46):13221–30. Kunimatsu K, Bae B, Miyatake K, Uchida H, Watanabe M. ATR-FTIR Study of Water in Nafion Membrane Combined with Proton Conductivity Measurements during Hydration/Dehydration Cycle. J Phys Chem B. 2011 21;115(15):4315–21. Zawodzinski TA, Derouin C, Radzinski S, Sherman RJ, Smith VT, Springer TE, et al. Water Uptake by and Transport Through Nafion® 117 Membranes. J Electrochem Soc. 1993 ;140(4):1041–7. Barthel J, Buchner R, Wismeth E. FTIR Spectroscopy of Ion Solvation of LiClO4 and LiSCN in Acetonitrile, Benzonitrile, and Propylene Carbonate. J Solut Chem. 2000 ;29(10):937–54. Figure.1A: SO stretching shift due to solvation; Figure.1B: Normalized CN stretching area upon acetonitrile buildup in the membrane. Blue dashline indicates corresponding fully swollen state. Figure 1

In redox flow batteries, capacity fade upon cycling is often attributed to the effects of cross-over through membranes. However, capacity fade is sometimes observed in situations in which flow is stopped. Also, one common measure of cross-over that is described in the literature is the decline in open circuit voltage in a cell. There is a need for a more complete and coherent description of these phenomena and their interrelationship. In this talk, we will build for our extensive data base of measurements of transport properties of membranes, interactions underlying these properties, cell data and some new approaches to begin to build this picture. Acknowledgement We gratefully acknowledge the support of this work by the U.S. Department of Energy, Office of Electricity Delivery and Energy Reliability (Dr. Imre Gyuk). We also thank 3M for providing membranes.

From aqueous to non-aqueous redox flow batteries, the general membrane properties are unchanged: electronically isolating anolyte and catholyte and allowing conductance through the membrane to keep charge balance. However, on top of the high cost(1), existing membranes for non-aqueous flow battery inherit the natural disadvantage of non-hydrogen-bonding transport compared to all-vanadium redox system while leaving the door wide open for redox species to pass through. Crossover-induced capacity fade remains one of the most challenging problems for non-aqueous flow battery(2). Efforts have been made to address the issue. For example, composite membranes(3), crosslinking(4) and size exclusion approaches (5) have all been used. Herein, we use Perfluorsulfonate Ion Exchange Membrane (PFSA) as a benchmark to study the crossover behavior in non-aqueous system. For membranes swollen with non-aqueous solvents, tetraalkylammonium cations in the membrane have outperform lithium ion in terms of ionic conductivity(6). However, a large volume of swelling is observed in our study and also in literature(3). In fact, our previous vibrational data suggested that only a small portion of the organic solvent in the membrane participates in solvation of cations, leaving a substantial portion of the solvent molecules as potential carriers to dissolve and transport redox species across the membrane(7). The solvent mediated process, crossover of redox species through PFSA will be presented from a fundamental, interaction-oriented perspective. In-depth understanding of interactions among redox species, solvent and membrane are obtained by combining various spectroscopic measurements with transport measurements. This understanding is crucially necessary to shed light on future membrane design exclusive for non-aqueous flow batteries. Acknowledgement We gratefully acknowledge the support of this work by the U.S. Department of Energy, Office of Electricity Delivery and Energy Reliability (Dr. Imre Gyuk). We also thank 3M for providing membranes. References Darling RM, Gallagher KG, Kowalski JA, Ha S, Brushett FR. Pathways to low-cost electrochemical energy storage: a comparison of aqueous and nonaqueous flow batteries. Energy Environ Sci. 2014;7(11):3459–77. Su L, Darling RM, Gallagher KG, Xie W, Thelen JL, Badel AF, et al. An Investigation of the Ionic Conductivity and Species Crossover of Lithiated Nafion 117 in Nonaqueous Electrolytes. J Electrochem Soc. 2016;163(1):A5253–62. Bamgbopa MO, Almheiri S. Influence of solvents on species crossover and capacity decay in non-aqueous vanadium redox flow batteries: Characterization of acetonitrile and 1, 3 dioxolane solvent mixture. J Power Sources. 2017 Feb 28;342:371–81. Li Y, Sniekers J, Malaquias JC, Van Goethem C, Binnemans K, Fransaer J, et al. Crosslinked anion exchange membranes prepared from poly(phenylene oxide) (PPO) for non-aqueous redox flow batteries. J Power Sources. 2018;378:338–44. Hendriks KH, Robinson SG, Braten MN, Sevov CS, Helms BA, Sigman MS, et al. High-Performance Oligomeric Catholytes for Effective Macromolecular Separation in Nonaqueous Redox Flow Batteries. ACS Cent Sci. 2018;4(2):189–96. Escalante-García IL, Wainright JS, Thompson LT, Savinell RF. Performance of a Non-Aqueous Vanadium Acetylacetonate Prototype Redox Flow Battery: Examination of Separators and Capacity Decay. J Electrochem Soc. 2015;162(3):A363–72. Lou K, Peng J, Tang Z, Zawodzinski TA. Solvation of Perfluorsulfonate Ion Exchange Membrane in Non-Aqueous Solvents. Meet Abstr. 2018;MA2018-01(30):1760–1760.

A new method of solid phase extraction (SPE), using crosslinked carboxymethyl starch as adsorbent, combined with direct slurry sampling graphite furnace atomic absorption spectrometry (ss-GFAAS) has been developed for the high sensitive determination of lead in water samples. The SPE adsorbent loaded with the analyte was made in to slurry with the assistance of Triton X-100. The slurry was directly injected into the graphite furnace for the determination of lead. Variables such as the pH, sample volume, and amount of Crosslinked Carboxymethyl Starch (CCMS) were investigated. The detection limit (3σ) was 0.082 μg L-1 and the RSD was 4.9% (n = 11, c = 1.0 mg L-1) for Pb(II). The enrichment factor was 100 at a sample volume of 100 mL. The proposed method has been applied to the determination of lead in environmental water reference materials and two water samples with satisfied results.

e19503Background: PLM60 is a novel liposomal pegylated nanoparticle formulation of conventional mitoxantrone (cMI) that showed improved PK properties, good tolerability, and potential efficacy vers...

As a typical single ion conductor, the perfluorsulfonate (PFSA) ion exchange membrane performance predominantly relies on the interactions amongst cation, sulfonate group and solvent. Such solvation information is crucial to the performance of electrochemical devices. The well-studied interaction between water and proton exchange membranes paved the way for the development of fuel cells and redox flow batteries (1–3). The emerging non-aqueous redox flow battery (NARFB) features alkyl or organic cations. Given the overall inferior performance of NARFBs to aqueous systems, it is important to try to find paths to improve the conductance of the membrane. Despite this and its importance in determining conductivity, the understanding of PFSA cation solvation in non-aqueous solvent is limited so far. We previously reported the surprisingly high ionic conductivity of bulky tetraalkylammonium cations in organic solvents compared to conventional alkyl cations(4). To further investigate the fundamental aspects of cation solvation, we applied different characterization techniques to build connections between ionic conductivity and cation-solvent interaction. Ion mobility data will be discussed in light of solvent uptake. As an example, Figure. 1 shows the relationship between the degree of solvation and relative quantity of deuterated acetonitrile solvating tetrabutylammonium (TBA) form 825EW 3M PFSA. The degree of solvation was derived from solvation signal picked up from carbon-13 NMR on cyanide carbon of deuterated acetonitrile. The degree of solvation increased accordingly with the amount of solvent until it reaches saturation when excess solvent molecules would not participate in the solvation. The respective diffusion coefficients from NMR pulsed gradient diffusion experiments on cations were also presented. A clear signal corresponding to solvent molecules involved in solvation is captured by FTIR and this will also be analyzed as a function of composition and ion type. Acknowledgement We gratefully acknowledge the support of this work by the U.S. Department of Energy, Office of Electricity Delivery and Energy Reliability (Dr. Imre Gyuk). We also thank 3M for providing membranes. References Vishnyakov A, Neimark AV. Molecular Simulation Study of Nafion Membrane Solvation in Water and Methanol. J Phys Chem B. 2000;104(18):4471–8. Bontha JR, Pintauro PN. Water orientation and ion solvation effects during multicomponent salt partitioning in a Nafion cation exchange membrane. Chem Eng Sci. 1994;49(23):3835–51. Zawodzinski TA, Derouin C, Radzinski S, Sherman RJ, Smith VT, Springer TE, et al. Water Uptake by and Transport Through Nafion® 117 Membranes. J Electrochem Soc. 1993;140(4):1041–7. Lou K, Peng J, Tang Z, Fujimoto C, Zawodzinski TA. Investigation of Ionic Conductivity, Uptake and Cation Diffusion of Perfluorsulfonate and Sulfonated Block Copolymer Ion Exchange Membrane in Non-Aqueous Solvents. Meet Abstr. 2017;MA2017-01(2):166–166. Figure 1. Degree of solvated CN vs relative acetonitrile quantity of TBA+ form 825EW 3M membrane in deuterated Acetonitrile. Figure 1

The characterization of perfluorsulfonate and sulfonated block copolymer ion exchange membranes is well established in aqueous systems. While many of these membranes have been proved to have favorable conductivity and stability in multiple applications(1,2), similar studies are hardly found for membranes in non-aqueous systems. Although some characterization results on non-aqueous system have been published(3), a complete understanding how sulfonated ion exchange membranes behave in organic solvents is lacking. The largest range of existing methods is mostly dedicated to probing aqueous systems. In light of emerging applications, especially in nonaqueous redox flow batteries (NARFBs), it is certainly desirable to combine various techniques beyond simply conductivity in hope of elucidating some of the membrane properties in non-aqueous system. A series of protocols is being developed to characterize some fundamental membrane properties. A four-point cell conductivity configuration was adopted to minimize artifacts (4). Swelling behavior was studied to complement conductivity data. In Figure 1, while the 3Mion-825EW membranes in TEA+ form overall showed higher conductivity than the Li+ form membranes. Acetonitrile soaked-TEA form membranes exhibited a 9-fold boost. This is consistent with relatively high performance of NARFBs using this electrolyte. To reveal fundamental aspects of this performance, other means of characterization are certainly necessary to look into cation/membrane/solvent matches. Fourier transform infrared spectroscopy (FTIR) was utilized to examine membranes exchanged with different cations (li+, Na+, TEA+ ,etc) so the interaction between the cation and membrane, as well as between the solvent and the membrane can be better understood. Measuring the relaxation time (T1) of cations and solvents by NMR has been an effective way to unravel the local diffusion kinetics for cation exchange membranes(5). Cation pulsed gradient diffusion experiments by NMR were carried out to further clarify the long-range transport. These data will help us explicate the correlation between the cation behavior/vibrational bonding and macroscopic properties. On top of indicating good cation/membrane/solvent matches, a more complete and precise understanding of membrane behavior in non-aqueous system is the goal of the study. The behavior of several different membrane types will be discussed. Acknowledgement We gratefully acknowledge the support of this work by the U.S. Department of Energy, Office of Electricity Delivery and Energy Reliability (Dr. Imre Gyuk). We also thank 3M for providing membranes. References 1. Yeager HL, Steck A. Cation and Water Diffusion in Nafion Ion Exchange Membranes: Influence of Polymer Structure. J Electrochem Soc. 1981;128(9):1880–4. 2. Tang Z, Lawton JS, Sun C-N, Chen J, Bright MI, Jones AM, et al. Characterization of Sulfonated Diels-Alder Poly(phenylene) Membranes for Electrolyte Separators in Vanadium Redox Flow Batteries. J Electrochem Soc. 2014;161(12):A1860–8. 3. Doyle M, Lewittes ME, Roelofs MG, Perusich SA, Lowrey RE. Relationship between Ionic Conductivity of Perfluorinated Ionomeric Membranes and Nonaqueous Solvent Properties. J Membr Sci. 2001;184(2):257–73. 4. Cahan BD, Wainright JS. AC Impedance Investigations of Proton Conduction in NafionTM. J Electrochem Soc. 1993 Dec 1;140(12):L185–6. 5. Zawodzinski TA, Neeman M, Sillerud LO, Gottesfeld S. Determination of Water Diffusion Coefficients in Perfluorosulfonate Ionomeric Membranes. J Phys Chem. 1991;95(15):6040–4. Figure 1

A binuclear ruthenium(II) dimer (BiRD) bridged by an alkene linker was synthesized that was labile to reactive oxygen species generated by another photosensitizer. Compared to the monomeric Ru(II) complex, the BiRD had attenuated fluorescence and singlet oxygen production which could be restored by a longer-wavelength photosensitizer. This two-step amplification strategy demonstrates proof-of-principal for photosensitization chain-reactions.

Objective: To study the gene expression of high metastatic human ovarian carcinoma cell line (HO-8910PM) and to screen for novel metastasis- associated genes by cDNA microarray. Methods: The cDNA was retro-transcribed from equal quantity mRNA derived from tissues of highly metastatic ovarian carcinoma cell line and normal ovarian, and was labeled with Cy5 and Cy3 fluorescence as probes. The mixed probes were hybridized with BioDoor 4096 double dot human whole gene chip. The chip was scanned by scanArray 3000 laser scanner. The acquired image was analyzed by ImaGene 3.0 software. Results: By applying the cDNA microarray we found: A total of 323 genes whose expression level were 3 times higher or lower in HO-8910PM cell than normal ovarian epithelium cell were screened out, with 71 higher and 252 lower respectively. Among these 10 were new genes. 67 genes showed expression difference bigger than 6 times between HO-8910PM cell and normal ovarian epithelium cell, among these genes 12 were higher, 55 lower, and two new genes were found. Conclusion: cDNA microarray technique is effective in screening the differentially expressed genes between human ovarian cancer cell line (HO-8910PM) and normal ovarian epithelium cell. Using the cDNA microarray to analyze of human ovarian cancer cell line gene expression profile difference will help the gene diagnosis, treatment and protection.

Objective To test the hypothesis that insulin resistance of the spontaneously hypertensive rat (SHR) and adrenocorticotropin -hypertensive rat is related to a difference in the proportion of the functionally different, alternatively spliced exon 11 isoforms of the insulin receptor. Design We determined the proportions of mRNA for the exon 11+ and exon 11- isoforms in various tissues of SHR and Wistar-Kyoto rats aged 3, 6, 9 and 12 weeks, which span the pre-hypertensive phase through to established hypertension, as well as in Sprague-Dawley rats with adrenocorticotropin-induced hypertension and Sprague-Dawley controls. Methods Detection of mRNA involved a reverse-transcriptase polymerase chain reaction technique specific for each isoform and quantification was by slot and dot blot hybridization. Results Mean proportions of exon 11+ mRNA in SHR, Wistar-Kyoto rats, adrenocorticotropin-hypertensive rats and Sprague-Dawley control rats at each age were 95% for liver, 82% for adipose tissue, 77% for kidney, 66% for adrenal, 53% for heart, 26% for cerebral cortex, 23% for hypothalamus, and 3% for skeletal muscle. There was also no difference in concentration of total insulin receptor mRNA. Conclusions The absence of any difference in proportions of insulin receptor mRNA isoforms argues against the hypothesis that an alteration of differential splicing plays a role in the models of hypertension studied.

The ability to provide biomolecular recognition with a fluorescence readout has made molecular beacons useful in various medical and biological applications. Combined with photodynamic therapy photosensitizers, photodynamic molecular beacons hold potential as new tools for not only disease diagnosis, but therapy as well. In this chapter, we focus on classic and emerging nucleic acid-based molecular beacon design considerations. Designs based on the original stem-and-loop structure have been expanded, and these concepts have direct applicability for conversion into photodynamic molecular beacons.

Abstract To determine responses in renin gene expression in different tissues of two-kidney, one clip hypertensive Sprague-Dawley rats and the effect of NaCl loading, we developed a novel, highly sensitive quantitative polymerase chain reaction technique and measured renin mRNA at 19 and 40 days after clipping. Basal renin mRNA concentrations were 1575±127 fg/μg total RNA in kidney, 52±7 in hypothalamus, 7.9±0.7 in adrenal, and 4.7±0.5 in atria. In two-kidney, one clip rats, renin mRNA in the clipped kidney was increased 5.4-fold ( P =.00001) and 2.3-fold ( P =.001) on each respective day after clipping and in the unclipped kidney was decreased by 27% ( P =.01) and 38% ( P =.04). In adrenal, 3.9-fold ( P =.004) and 1.7-fold ( P =.02) increases were seen on days 19 and 40, respectively, and a decrease of 57% ( P =.02) was found in a hypothalamic block at day 19 but not at day 40. The decrease in hypothalamus was abolished by 1% oral NaCl, which reduced renin mRNA by 37% in the clipped kidney and by 30% in the adrenal but did not lead to any change in the unclipped kidney or hypothalamus at day 40. Hypothalamic renin mRNA was also decreased by enalapril compared with increases of sixfold to ninefold in other tissues. In conclusion, we have quantified a decrease in hypothalamic renin mRNA in two-kidney, one clip rats 19 days after clipping that can be abolished by NaCl loading, whereas in the adrenal, renin mRNA was increased. Similar relative tissue-specific changes were also seen in enalapril-treated rats.

The present study examined polymorphisms of genes that might be involved in the onset of essential hypertension (HT). These included the (i) growth hormone gene (GH1), whose locus has recently been linked to elevated blood pressure (BP) in the stroke-prone SHR, although recent sib-pair analysis of a polymorphism near the human chorionic somatomammotropin gene (a member of the GH cluster) was unable to show linkage with HT; (ii) renal kallikrein gene (KLK1); and (iii) atrial natriuretic factor gene (ANF), where a primary defect in production or activity of kallikrein or ANF could cause NaCl retention and vasoconstriction. Association analyses were conducted to compare restriction fragment length polymorphisms (RFLPs) of each gene in 85 HT and 95 normotensive (NT) Caucasian subjects whose parents had a similar BP status at age ≥50 years. The frequency of the minor allele of (i) a RsaI RFLP in the promoter of GH1, amplified from leukocyte DNA by the polymerase chain reaction, was 0.15 in the HT group and 0.14 in the NT group (X2=0.34, P=0.55); (ii) a TagI RFLP for KLK1 was 0.035 in the HT group and 0.015 in the NT group (X2=1.5, P=0.21); and (iii) a XhoI RFLP for ANF was 0.50 in HTs and 0.46 in NTs (X2=0.20, P=0.65). Studies of HT pedigrees found one family in which the ANF locus and HT were not linked, owing to an obligate recombinant. The present data thus provide no evidence for involvement of the growth hormone, renal kallikrein, nor ANF gene in the causation of essential hypertension. (Hypertens Res 1993; 16: 113-120)

Angiotensin I-converting enzyme (ACE) is responsible for production of angiotensin II and breakdown of kinins, leading to increased blood pressure (BP). Furthermore, ACE inhibitors are effective antihypertensive agents. A 287 bp insertion/deletion polymorphism in intron 16 of the ACE gene (ACE) was examined by PCR in a cross-sectional study of 80 hypertensive (HT) and 93 normotensive (NT) subjects whose parents had a similar BP status at age greater than or equal to 50. The frequency of the insertion allele was 0.56 in HTs and 0.41 in NTs, and the difference between observed alleles in all subjects in each group was significant (chi 2 = 7.6, P less than 0.01). The data thus provide evidence in favour of an association of HT with a polymorphism at the ACE locus (17q23), so implicating this locus, and possibly a genetic variant of ACE itself, in human essential hypertension.

To investigate the clinical and pathological characteristics, treatment, and The data of 12 patients prognosis of synchronous primary cancer of the endometrium and ovary. Methods with synchronous primary cancer of the endometrium and ovary were retrospectively reviewed . Results Eight patients had the same histological type of endometrioid carcinoma in both uterus and ovary, 4 patients had different histological types in uterus and ovary. Synchronous primary cancer of the endometrium and ovary was difficult to be dignosed preoperatively. All ovarian tumors were small with an average diameter of 7 cm. Infertility was common among these patients(40.7%). Most of them had early stage I lesion (66.7%). endometrioid carcinomas was the main pathologic type (66.7%). All patients were treated surgically followed by chemotherapy with a 3-year survival rate of 66.7% (8/12).Synchronous primary endometrium and ovary cancer is a specific kind of tumor different from either the primary endometrium carcinoma or ovary carcinoma, and usually can be detected in early stage with a good prognosis.

Abstract —Administration of adrenocorticotropic hormone (ACTH) leads to the development of hypertension. Because glucocorticoids can affect the nitric oxide system at several sites, the present study tested the hypothesis that nitric oxide synthase (NOS) expression may be altered in ACTH-induced and corticosterone-induced hypertension in the rat. This was addressed by measuring Nos1 , Nos2 , and Nos3 mRNA in the kidney, adrenal gland, heart, and hypothalamus of 16 ACTH-treated and 16 vehicle-treated rats as well as in 10 corticosterone-treated and 10 control rats. In addition, in situ hybridization and immunohistochemistry were used to confirm changes by detection of Nos in RNA and NOS protein in tissues. Systolic blood pressure of ACTH and corticosterone rats was elevated (165±6 and 162±11 mm Hg; P Nos isoform mRNA was measured by reverse transcriptase-polymerase chain reaction technique. In ACTH rats, mRNA for Nos2 was reduced in renal cortex by 58±5% and in medulla by 68±7%; for Nos3 , mRNA reductions of 59±6% and 51±11% were seen ( P Nos2 mRNA decreased in cortex by 68±5% and in medulla by 62±6%; Nos3 mRNA by 50±8% in cortex, and Nos1 by 29±7% in medulla (all P Nos2 mRNA in adrenal of ACTH rats (corrected P Nos2 and Nos3 expression in the kidney. Such changes are consistent with a role in hypertension for ACTH and corticosterone.

SUMMARY 1. There are two functionally different isoforms of the insulin receptor in humans and rats. We hypothesized that a change in their relative proportion could be of relevance to insulin resistance in hypertension. 2. A reverse-transcriptase polymerase chain reaction technique was established for the detection of mRNA for the exon 11+ and exon 11—isoforms and the proportion of each was determined in 3, 6, 9 and 12 week old spontaneously hypertensive rats and Wistar-Kyoto rats, as well as adrenocorticotrophin (ACTH)-induced hypertensive rats and controls. 3. The proportion of the exon 11+ form (∼95%) and exon 11—form (∼5%) was similar in the liver of all rats studied. 4. We conclude that there is no change in insulin receptor isoform expression in the liver in the models of hypertension studied.

TiO2 nanotube arrays (NTAs) on transparent conducting oxides (TCO) have attracted great attention due to the potential application in dye-sensitized solar cells (DSCs). Here, we introduce the template-assisted process for direct fabrication of aligned TiO2 NTAs on TCO substrates, involving layer-by-layer adsorption and reaction (LBL-AR) assembled TiO2 coating on ZnO nanorods (NR). Key factors of the fabrication process on the microstructures of TiO2 NTAs are analyzed, and the geometry effects of TiO2 NTAs on the performance and electron transport properties of DSCs are investigated by using electrochemical impedance spectra (EIS). An efficiency of 4.25% (under AM1.5 irradiation, 100 mW cm−2) is obtained from N719 sensitized 20 μm thick TiO2 NTAs with a wall thickness of 20 nm, with Jsc = 8.2 mA cm−2, Voc = 0.81 V and FF = 63%.

Sample preparation is an important step in the detection of viral DNA by the polymerase chain reaction (PCR) technique. The method used should achieve release of cellular DNA with the minimum of manipulation steps so as to reduce the possibility of contamination. The present report demonstrates that either microwaving or 20 min of boiling in the heating block of a thermal cycler lead to satisfactory results in the detection by PCR of human papillomavirus in cervicovaginal epithelial cell specimens obtained by lavage. Since each of these methods uses only one step the possibility of contamination is greatly reduced compared to the widely used proteins K/nonionic detergent extraction procedure.

OBJECTIVE The aim of the present study was to use a highly sensitive, polymerase chain reaction (PCR) technique to examine the controversial question of renin gene expression in the heart and to determine whether expression in cardiac tissue can be stimulated. DESIGN The study involved female Wistar rats fed either a normal-sodium diet or a low-sodium diet, together with an angiotensin I converting enzyme inhibitor, enalapril, orally for 1 week. METHODS RNA was extracted from atrium, ventricle, kidney (positive control) and submandibular gland (negative control) and, after reverse transcription into complementary DNA, was used in a 35-cycle PCR. Reaction products were visualized after electrophoresis by ethidium bromide staining and hybridization probing with [32P]-labelled target oligonucleotide. RESULTS Atrial RNA from sodium-replete rats gave little or no renin messenger (m)RNA PCR product on ethidium bromide-stained gels. After DNA transfer, followed by hybridization probing and extended autoradiography, a faint band was seen. In sharp contrast, atrial extracts from sodium-depleted enalapril-treated rats displayed a pronounced band of hybridization, corresponding in size to that expected for renin mRNA. No band was seen for ventricle. CONCLUSION The present PCR study has shown that in the normal sodium-replete rat, atrial tissue has only very low renin gene expression, but that after a low-sodium diet + treatment with enalapril, expression is switched on in atrium. Ventricular tissue does not express the renin gene in either state.

Highly crystalline organic superlattice has great potential for providing innovative function in organic devices. With studies of the structure and fundamental electronical properties, we have demonstrated the phathalocynine organic superlattice, which is a structure composed of periodically alternating crystalline layers of H2Pc and F16CuPc. A periodical crystal structure and electronic structure appear in this organic superlattice system. High density of mobile electrons and holes distribute periodically in F16CuPc and H2Pc layers, respectively, leading to a significant change in intrinsic properties of organic semiconductors.

SUMMARY 1. Renin mRNA is present in the kidney and, in lower concentrations, in many extrarenal tissues and serves as an index of renin gene activity, as well as potential renin or prorenin synthesis in cell populations within those tissues. Unfortunately the quantity can be very low. 2. A new, highly sensitive technique is described for detection of renin mRNA that involves the enzyme Taq polymerase for both reverse transcription of renin mRNA into renin cDNA and for amplification of the 769–1099 nucleotide segment by the polymerase chain reaction (PCR), all of which involves a single reaction mixture. 3. In this way renin mRNA was detected in kidney and several extrarenal tissues as a PCR product of ∼330 base pairs on agarose gels by ethidium-bromide staining or hybridization probing. The region of renin mRNA chosen for amplification spanned several intron sites in the coding sequence so that the presence of amplicants derived from genomic DNA could be readily discriminated, as a band of ∼1.5 kilobases. 4. Thus single-step PCR offers a powerful new approach to detection of renin mRNA.

We studied the charge transport in organic heterojunction films consisting of copper phthalocyanine (CuPc) and copper hexadecafluorophthalocyanine (F16CuPc). The heterojunction effect between CuPc and F16CuPc induced high-density carriers at both sides of heterojunction. The Hall effect was observed at room temperature, which demonstrated the existence of free carriers and their delocalized transport under heterojunction effect. The Hall mobility of 1.2cm2∕Vs for holes and 2.4cm2∕Vs for electrons indicated that the transport capability of the heterojunction films is comparable to single crystals. The transport process was further explained by the multiple trap-and-release model according to the temperature dependence of conduction.