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A robust all-solid-state potentiometric microsensor using carbon nanotube fibers was designed. The ion-selective microelectrodes provide a simple and versatile tool for real-time monitoring of the calcification process by Bacillus subtilis biofilms.

Bioelectronic sensors that report charge changes of a biomolecule upon target binding enable direct and sensitive analyte detection but remain a major challenge for potentiometric measurement, mainly due to Debye Length limitations and the need for molecular-level platforms. Here, we report on a magneto-controlled potentiometric method to directly and sensitively measure the target-binding induced charge change of DNA aptamers assembled on magnetic beads using a polymeric membrane potentiometric ion sensor. The potentiometric responses of the negatively charged aptamer, serving as a receptor and reporter, were dynamically controlled and modulated by applying a magnetic field. Based on a potentiometric array, this non-equilibrium measurement technique combined with deep learning algorithms allows for rapidly and reliably classifying and quantifying diverse small molecules using antibiotics as models. This potentiometric strategy opens new modalities for sensing applications.

A knowledge graph is defined as a collection of interlinked descriptions of concepts, relationships, entities and events. Medical knowledge graphs have been the most recent advances in technology, therapy and medicine. Nowadays, a number of specific uses and applications rely on knowledge graphs. The application of the knowledge graph, another form of artificial intelligence (AI) in cardiology and cardiovascular medicine, is a new concept, and only a few studies have been carried out on this particular aspect. In this brief literature review, the use and importance of disease-specific knowledge graphs in exploring various aspects of Kawasaki disease were described. A vision of individualized knowledge graphs (iKGs) in cardiovascular medicine was also discussed. Such iKGs would be based on a modern informatics platform of exchange and inquiry that could comprehensively integrate biologic knowledge with medical histories and health outcomes of individual patients. This could transform how clinicians and scientists discover, communicate and apply new knowledge. In addition, we also described how a study based on the comprehensive longitudinal evaluation of dietary factors associated with acute myocardial infarction and fatal coronary heart disease used a knowledge graph to show the dietary factors associated with cardiovascular diseases in Nurses' Health Study data. To conclude, in this fast-developing world, medical knowledge graphs have emerged as attractive methods of data storage and hypothesis generation. They could be a major and effective tool in cardiology and cardiovascular medicine and play an important role in reaching effective clinical decisions during treatment and management of patients in the cardiology department.

Sarcopenia is defined as a progressive and generalized muscle disorder that involves accelerated loss of muscle mass and impaired function. It is believed to influence the ability to carry out daily activities, muscle strength, and physical capacity in the elderly. Studies have shown that sarcopenia has been implicated as both a cause and a consequence of diabetes mellitus. In this analysis, we aimed to systematically show the impact of exercise intervention as a therapy for patients with diabetes mellitus and sarcopenia.Electronic databases, including PubMed, EMBASE, Web of Science, and the Cochrane database, were searched from November to December 2021 for publications based on exercise intervention in patients with sarcopenia. After the selection of studies for this analysis, patients with diabetes mellitus were retrieved. Since dichotomous data including mean and standard deviation were reported, weighted mean difference (MD) with 95% confidence intervals (CI) were used to represent the data following analysis.A total of 431 participants with diabetes mellitus and sarcopenia were included in this meta-analysis. A statistical analysis was carried out on patients with diabetes mellitus who were assigned to the exercise intervention group. Our analysis showed that "sit-to-stand test" and "timed up and go" were significantly in favor of exercise intervention: MD -1.57, 95% confidence interval (CI) -2.26 to -0.87 (P = 0.0001) versus MD -0.61, 95% CI -1.21 to -0.01 (P = 0.05), respectively. Handgrip strength, walking speed and leg strength were also assessed. Another statistical analysis was carried out, this time on patients with diabetes mellitus and sarcopenia who were not assigned to an exercise intervention. The results showed no significant difference among sit-to-stand test, timed up and go, handgrip strength, and leg strength.Exercise intervention significantly improved the time taken to stand up from a sitting position, and to "stand up and go" in patients with diabetes mellitus and sarcopenia. Therefore, exercise intervention should be considered a relevant therapy for such patients.

Four hydrogen bond-based macrocyclic and tripodal neutral receptors with increasing conformational complementarity with sulfate were used for the first time as ionophores to develop polymeric membrane sulfate-selective electrodes. Optimizing the membrane composition such as ionophores, lipophilic additives, and plasticizers yielded ISEs which showed Nernstian response to sulfate with the best selectivity so far and improved detection limits (a slope of -29.8 mV/dec in the linear range of 1 X 10(-6) -1 x 10(-1 )M with a detection limit of 5 x 10(-7) M), which led to the success of the determination of sulfate in drinking water samples and neomycine tablets. The anion-ionophore complex constants in the membrane phase were determined and correlated with the selectivity sequence of the ISEs. Studies on the influence of pH of the sample solution demonstrated that the developed ISEs can be operated in a wide pH range of 3-8 with fast response and rapid (in 1 min) and long lifetime. The success of these ionophores represents a feasible strategy for overcoming the "Hofmeister series" by employing a combination of complementarity and hydrogen bonds.

Background This case report presents a patient diagnosed with sick sinus syndrome who was successfully treated with permanent His-bundle pacing (PHBP). Case presentation A 36-year-old man was transferred to our hospital due to recurrent syncope. He was diagnosed with sick sinus syndrome based on the 24-h Holter and a history of syncope. He was admitted to hospital and successfully treated with PHBP. The postoperative examination showed that the pacing rhythm, pacemaker pacing and perception function were normal. He was discharged without any complications after a successful pacemaker implantation. Conclusions We described a case in which PHBP may become an optimal approach to the management of patients with sick sinus syndrome. Right ventricular pacing has been attempted with inconsistent efficacy outcomes. HBP provides a promising alternative pacing option that might provide symptom resolution to patients with sick sinus syndrome.

There is an increasing body of evidence indicating the important roles of miRNAs in the progression of pituitary adenoma. Recent studies have shown decreased expression and tumor suppressive function of miR-448 in cancers; however, the clinical significance of miR-448 in pituitary adenoma has remained largely unknown. In our study, we found that miR-448 was down-regulated in pituitary adenoma tissues and cell lines. Overexpression of miR-448 significantly inhibited the proliferation and migration of pituitary adenoma cells. Increased cell apoptosis was also observed with overexpression of miR-448. To further understand the mechanisms behind the regulation of pituitary adenoma by miR-448 in, the targets of miR-448 were predicted using the bioinformatics tools. B cell lymphoma 2 (BCL2) was identified as a target of miR-448. MiR-448 bound the 3′-untranslated region (UTR) of BCL2 and inhibited the expression of BCL2 in pituitary adenoma cells. There was a consistent and significantly negative correlation between the level of miR-448 and BCL2 in pituitary adenoma tissues. When BCL2 was highly expressed, the inhibitory impact of miR-448 on the proliferation and apoptosis of pituitary adenoma cells was significantly inhibited. Collectively, our findings emphasize the significance of the miR-448–BCL2 axis in the development of pituitary adenoma, highlighting the potential therapeutic significance of miR-448 in pituitary adenoma.

We report here a general strategy to read out potentiometric signals via a photoelectrochemical method. The photocurrent at a working electrode coated with a ZnSe/r-GO composite can be modulated by a polymeric membrane ion-selective electrode that works as a reference electrode.

Recent studies have shown that RIP3/CaMK II plays a key role in myocardial ischemia-reperfusion injury; however, the role of RIP3/CaMK II-mediated cardiomyocyte necroptosis in CVB3-induced severe myocarditis has remained largely unknown. In this study, we found that KN-93(CaMK II–specific inhibitor) significantly reduced myocardial cell necrosis, improved cardiac function, and an improved survival curve. To further understand the mechanisms behind the regulation of necroptosis by RIP3/CaMK II, we added Ti(reactive oxygen species–specific inhibitor) in the model using the double-antibody sandwich immunoassay and BCA methods. After adding Ti, H2O2 content in the CVB3+KN-93+Ti group was slightly lower than that in the CVB3+KN-93 group. However, there was no obvious improvement of cardiac function or survival curve. Collectively, the RIP3/CaMK II pathway plays a significant role in cardiomyocyte death induced by viral infection. KN-93 blocks this pathway and may serve as a new therapeutic option for the treatment of severe viral myocarditis. The mechanism may occur through the direct inhibition of CaMK II and the indirect inhibition of reactive oxygen species.

The modulation of the ion-fluxes across a polymeric membrane is important for designing attractive methodologies. As an alternative to the commonly used dynamic electrochemistry approaches, light can be used as an external stimulus and provides a very convenient way to manipulate ions release and/or extraction into a polymeric membrane. Herein, we designed a solid-contact polymeric membrane ion-selective sensor that exhibits dynamic response by light irradiation at 375 nm. The electrode membrane contains a light-sensitive lipophilic salt (bis(4-tert-butylphenyl)iodonium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (R+-R-, BTDT-TFPB) instead of traditional ion exchanger. Under light illumination, the decomposition of the lipophilic cation makes the membrane with ion-exchange properties. The solid-contact ion-selective electrodes based on potentiometry and constant potential coulometry have been explored for direct ion sensing. Copper was selected as a mode analyte and can be determined at micromole levels. The proposed dynamic ion sensors show promise for on-demand ion sensing.

Achillinoside was isolated from methanol extract of Achillea alpina L., Asteraceae. The structure of the compound was characterized based on various spectrum data, including IR, HR-ESI-MS, 1D and 2D NMR. The cardiovascular protective effect of achillinoside was tested on H2O2-induced H9c2 cells. In our research, achillinoside could increase the cell viability dose-dependently in H2O2-induced H9c2 cells. In addition, the levels of caspase-3/9 cells were significantly decreased in H2O2 and achillinoside incubated H9c2 cells. Keywords: Achillinoside, Apoptosis inhibition, Spectroscopic analysis, H9c2 cells

Introduction Although aspirin (ASA) is the mainstay of treatment for the prevention of recurrent ischemic stroke, the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial showed ASA monotherapy to be inferior to clopidogrel in preventing recurrent adverse cardiovascular outcomes in patients with high cardiac risks. Here, we aimed to systematically compare ASA versus clopidogrel monotherapy for the treatment of patients with stable coronary artery disease (CAD). Methods Electronic databases were searched and studies were included if they compared ASA versus clopidogrel monotherapy for the treatment of patients with CAD and they reported adverse clinical outcomes. The latest version of RevMan software (version 5.3) was used as the statistical tool for the data analysis. Odds ratios (OR) and 95% confidence intervals (CI) were generated to interpret the data. Results A total number of 5497 patients (from years 2003 to 2011) were treated with ASA monotherapy, whereas 2544 patients were treated with clopidogrel monotherapy. Results of this analysis showed no significant difference in composite endpoints (cardiovascular death, myocardial infarction, and stroke) (OR 0.99, 95% CI 0.47–2.10; P = 0.98), all-cause mortality (OR 1.05, 95% CI 0.82–1.33; P = 0.71), cardiac death (OR 0.89, 95% CI 0.17–4.74; P = 0.89, myocardial infarction (OR 0.84, 95% CI 0.52–1.36; P = 0.48), stroke (OR 1.26, 95% CI 0.39–4.06; P = 0.70), and bleeding defined by the Bleeding Academic Research Consortium (BARC [grade 3 or above]) (OR 1.28, 95% CI 0.78–2.12; P = 0.33). Conclusion This analysis did not show any significant difference in all-cause mortality, cardiac death, myocardial infarction, stroke, and BARC grade 3 or above among CAD patients who were treated with either ASA or clopidogrel monotherapy. However, as a result of the limited data, this hypothesis should be confirmed in other major trials.

Potentiometric microelectrodes are regarded as promising probes for ion sensing when only limited sample volumes are available. In this work, an all-solid-state ion-selective microelectrode (ISμE) has been developed by coating ionophore-based ion-selective membrane on a poly(3,4-ethylenedioxythiophene)-poly(sodium 4-styrenesulfonate) modified gold wire with a diameter of 14 μm for detection of copper. Under the optimized conditions, the proposed all-solid-state Cu2+-ISμE shows a Nernst response toward Cu2+ in 0.5 M NaCl in the range from 2.5 × 10−7 to 2.5 × 10−4 M with a detection limit of 4.0 × 10−8 M. Additionally, the Cu2+-ISμE has been used for monitoring the vertical distribution profile of Cu2+ in coastal sediment pore water with a small volume (e.g., 300 μL). The results agree well with those obtained by anodic stripping voltammetry, which indicates that the proposed potentiometric technique based on the all-solid-state ISμE is promising for detection of Cu2+ in coastal sediment pore water. The method for the preparation of the ISμE can be extended to detect other heavy metal ions in sediments by using different ion-selective membranes.

Calcium is closely related to the oceanic biosphere and carbonate system. Potentiometry based on a calcium-selective electrode (Ca-ISE) represents a promising tool for detection of calcium ion activities in seawater. This technique, however, generally is limited by the low sensitivity for the inherent Nernstian response (i.e. ca 30 mV/dec). A current pulse based ion-selective electrode with enhanced sensitivity for chronopotentiometric measurements of calcium in seawater is proposed. The Ca2+-selective membrane containing lipophilic salt ETH 500 instead of traditional ion-exchanger is galvanostatically controlled. An applied constant cathodic current pulse can leads to the extraction of the calcium ions into the membrane to produce a chronopotential response, which shows a stable and reproducible super-Nernstian response in a narrow calcium activity range. The super-Nernstian region of the electrode depends on not only the the magnitude and duration of the applied current pulse but also the interfering ions. Under optimal conditions, the proposed Ca-ISE exhibits a super-Nernstian response between the calcium concentrations of 10−2.5–10−1.5 M with a slope of ca 80 mV/dec. The current pulse based Ca-ISE has been applied to determination of calcium in seawater with satisfactory results.

Four Lewis acidic organo-antimony(V) compounds with strong binding affinity to fluoride were used for the first time as ionophores to fabricate polymeric membrane fluoride-selective electrodes. Improved detection limits and significant anti-Hofmeister selectivity could be achieved by optimizing ionophores, lipophilic additives, and plasticizers. Membrane electrodes fabricated with tetrakis-(pentafluorophenyl)stibonium (ionophore 2) performed best in detection limit, sensitivity, and selectivity. Optimal performance was obtained by fluoride with a slope of -59.5 mV/decade in the linear range of 1 × 10-5 to 4 × 10-2 M and a detection limit of 5 × 10-6 M. Studies on the influence of sample solution pH demonstrate that the best pH for fluoride determination is pH 3.0. All of the electrodes studied respond rapidly (in 1 min) in different concentrations of fluoride solutions. The anion-ionophore complex constants in the membrane phase determined using the segmented sandwich membrane method correlate well with the solution-phase binding data and determined selectivity sequence of the ion-selective electrodes. The possibility of real life application of the optimized electrodes was assessed by determination of fluoride concentrations in tap water.

A signal amplification strategy based on the horseradish peroxidase catalyzed polymerization of dopamine on a polymeric ion-selective membrane surface is proposed for the sensitive chronopotentiometric detection of an aptamer–target binding event.

Atherosclerosis is the leading cause of morbidity and mortality worldwide. The underlying pathogenesis involves multiple metabolic disorders, endothelial dysfunction and a maladaptive immune response, and leads to chronic arterial wall inflammation. Numerous normal physiological activities exhibit daily rhythmicity, including energy metabolism, vascular function and inflammatory immunoreactions, and disrupted or misaligned circadian rhythms may promote the progression of atherosclerosis. However, the association between the circadian rhythm and atherosclerosis remains to be fully elucidated. In the present review, the effects of the circadian rhythm on atherosclerosis progression are discussed.

We report here the concept of a magnetically controlled extraction of hydrophilic bioreceptors into polymeric membranes for bioassays. The potentiometric assay relies on the intrinsic charges of an antimicrobial peptide and its unique recognition abilities, which can eliminate the probe labeling and indicator addition. The target binding event could effectively prevent the extraction of the peptide into the polymeric membrane doped with an ion exchanger, thus resulting in a potential change. The potentiometric response properties of the peptide assembled on magnetic beads can be dynamically controlled and modulated by applying a magnetic field. Staphylococcus aureus, as a model of food-borne pathogens, was measured at levels down to 10 CFU mL-1 . Based on this sensing strategy, a potentiometric array was developed for the pattern recognition of bacteria. The proposed general platform can be used for potentiometric biosensing using other hydrophilic bioreceptors.

Introduction Cardiovascular mortality is a major concern for patients with type 2 diabetes mellitus (T2DM). Insulin therapy significantly contributes to a high rate of death in these patients. We have performed a meta-analysis comparing cardiac and non-cardiac-related mortality following percutaneous coronary intervention (PCI) in a sample of patients with insulin-treated type 2 diabetes mellitus (ITDM). Methods Studies were included in the meta-analysis if: (1) they were trials or cohort studies involving patients with T2DM post-PCI; (2) the outcomes in ITDM were separately reported; and (3) they reported cardiac death and non-cardiac death among their clinical endpoints. ITDM patients with any degree of coronary artery disease were included. The analysis was carried out using RevMan version 5.3 software, and data were reported with odds ratios (OR) and 95% confidence intervals (CI) as the main parameters. Results A total of 4072 participants with ITDM were included, of whom 1658 participants and 2414 participants were extracted from randomized controlled trials and observational cohorts, respectively. Analysis of all data showed that death due to cardiac causes was significantly higher in patients with ITDM (OR 2.16, 95% CI 1.79–2.59; P = 0.00001). At 1 year of follow-up, cardiac death was still significantly higher compared to non-cardiac death (OR 2.39, 95% CI 1.47–3.88; P = 0.0004), and this result did not change with a longer follow-up period (3–5 years) (OR 2.09, 95% CI 1.70–2.56; P = 0.00001). Death due to cardiac causes was still significantly higher in the subpopulations of patients with everolimus-eluting stents (OR 2.31, 95% CI 1.26–4.26; P = 0.007), paclitaxel-eluting stents (OR 2.36, 95% CI 1.63–3.39; P = 0.00001), sirolimus-eluting stents (OR 2.11, 95% CI 1.67–2.67; P = 0.00001), and zotarolimus-eluting stents (OR 2.12, 95% CI 1.11–4.05; P = 0.02), respectively. Conclusions Mortality due to cardiac causes was significantly higher than that due to non-cardiac causes in patients with ITDM who had undergone PCI. The same conclusion could be drawn from analyses focused on different follow-up periods, types of coronary stents, and type of study data used.

Solid-state potentiometric sensors based on surface charge change are well-established tools for measuring ions and biological species. However, their use for detection of small molecules with high sensitivity and good selectivity is still elusive. In this work, a novel potentiometric aptasensing platform for small molecules is presented, using bisphenol A (BPA) as a model. The proposed sensor can be prepared by layer-by-layer assembling of carboxylated multiwall carbon nanotubes, poly(diallyldimethylammonium chloride) (polycation), and aptamer (polyanion) on the electrode surface. The presence of BPA induces the conformational change and detachment of the aptamer at the surface of the modified electrode, which leads to a variation of the surface charge (negative to positive) and therefore a potential change. The introduction of polyions can cause substantial charge change on the electrode surface, thus improving the sensitivity of the sensor. The morphology and electron-transfer properties of the electrode have been characterized. Under optimum conditions, the present sensor shows a stable response to BPA in the concentration range from 3.2 × 10−8 to 1.0 × 10−6 M with a detection limit of 1.0 × 10−8 M. The proposed methodology can be used for sensitive potentiometric sensing of other small molecules involved in aptamer/target binding events.

The Toll-like receptor 4 (TLR4) signal pathway- induced inflammation is considered to be a crucial link to myocardial ischemia reperfusion injury (MIRI). Our previous study proved that radioprotective 105 kDa protein (RP105), a negative regulator of TLR4, performed a protective role in MIRI by anti-apoptosis approach. However, the mechanism of RP105 cardioprotection of anti-inflammation is still unclear. This study aimed to explore the underlying mechanism of RP105 anti-inflammation effect in MIRI. We established a rat model of MIRI induced by ligation of the left anterior descending coronary artery for 30 min followed by 2 h reperfusion. Animals were pre-infected with Ad-EGFP-RP105, Ad-EGFP or saline at the apex of the heart. All rats were sacrificed to collect blood samples and myocardial tissue and assessed by immunofluorescence, blood biochemical analysis, Evans blue/triphenyltetrazolium chloride (TTC), hematoxylin and eosin (H&E) staining, enzyme-linked immuno sorbent assay (ELISA), western blot analysis, quantitative PCR and electrophoretic mobility shift assay (EMSA). RP105 overexpression with adenovirus vectors reduced serum myocardial enzyme (CK-MB and LDH) activities, decreased myocardial infarct size, mitigated inflammatory factors interferon-β and tumor necrosis factor-α during MIRI. We also found that Ad-RP105 group exerted distinct repression of TLR4/TRIF signal pathway related proteins and mRNAs (TRIF, TBK-1, IRF3 and p-IRF3) with a low transcriptional activity of IRF3. These findings first expounded that RP105 could alleviate the ischemia reperfusion induced inflammatory status in heart via inhibiting TLR4/TRIF signaling pathway and provided a theoretical foundation of RP105 gene in MIRI.

In the natural environment, organisms are frequently exposed to complex mixtures of pollutants. These pollutants usually enter organisms simultaneously, which leads to joint toxicological effects. With excellent adsorption properties, graphene nanomaterials can interact with other pollutants when they are released into the environment, which may affect the environmental behavior of these pollutants. The molecule structure of triphenyl phosphate (TPP) contains three benzene rings, which leads to that TPP interact with graphene easily. With the mass demand and production of graphene and TPP, it is of great significance to study the joint toxicological effects of graphene and TPP, which will provide theoretical basis and data support for ecological risk assessment. The cell membrane is an important barrier of organism to resist external environment. The environmental pollutants usually act on the cell membrane and then enter the cells to produce toxic effects. Studies have shown that graphene and its derivatives can damage cell membrane in the process of interaction. After entering the cell, graphene can bind with receptors and produce reactive oxygen species, which may have a more serious impact. The biological membrane consists of various phospholipids bilayer membrane structures. The interactions between graphene nanomaterials and biological membrane can be studied simply and effectively using the simple artificial biofilm model. The solid supported bilayer membrane is a kind of simulated biofilm which can be simply prepared, easily repeated and stably performed. At present, the electrochemical technology plays an important role in the characterization of the bilayer membrane supported on the metal surface, which has gained more and more applications in the study field of biofilm. The electrochemical impedance spectroscopy (EIS) can preliminary assess the membrane permeability, and can be used as sensitive detector to membrane structure change. Hence, the electrochemical methods can be used to study the interactions between small molecular contaminants and simulated biofilm. In this study, the ″frozen-blotted out″ method was adopted to construct covalent binding phospholipid bilayer on the gold electrode surface, thus forming simulation of biofilm, and the EIS was used to study the interactions between graphene/TPP and the simulated phospholipid bilayer. The results showed that graphene and TPP could reduce the impedance of the bilayer membrane modified gold electrode, which indicated that graphene and TPP could influence the permeability of cell membrane and damage the integrity of the simulated phospholipid bilayer. With the combined effects of graphene and TPP, the damage of simulated biomembrane was increased, suggesting a synergistic effect. The pollutants through the cell membrane may interact with large molecules such as DNA or protein in cells, these results can provide theoretical basis for evaluating the ecological risks of this kind of pollutants.

Rapid, sensitive and reliable Escherichia coli (E. coli) detection and identification are critically important to protect public health. Here, we describe a magneto-controlled potentiometric assay for specific detection of E. coli cells by making use of the E. coli outer-membrane protease T (OmpT). OmpT is an endopeptidase that specifically cleaves peptide at dibasic sites. A rationally designed peptide serving as both OmpT substrate and potentiometric signal reporter was immobilized on magnetic beads. The rapid accumulation and extraction of peptide-functionalized magnetic beads on a polymeric membrane doped with an ion exchanger can be achieved using a magnetic force. The magnetic-field-assisted extraction of the peptide into the polymeric membrane ion-sensitive sensor, as confirmed by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy, can lead to a rapid, stable and reproducible potential change. OmpT is capable of cleaving the positively charged peptide on the magnetic beads, thus resulting in charge density change. The change in charge density and subsequently the potential change can be readily detected and used for quantification of E. coli at levels down to 5.0 × 103 CFU mL−1. This work provides a versatile, rapid and reliable potentiometric method for E. coli detection.

In this study, we investigated the roles of RIP1/RIP3 mediated cardiomyocyte necroptosis in CVB3-induced acute myocarditis. Serum concentrations of creatinine kinase (CK), CK-MB, and cardiac troponin I were detected using a Hitachi Automatic Biochemical Analyzer in a mouse model of acute VMC. Histological changes in cardiac tissue were observed by light microscope and expression levels of RIP1/RIP3 in the cardiac tissue were detected via Western blot and immunohistochemistry. The data showed that RIP1/RIP3 was highly expressed in cardiomyocytes in the acute VMC mouse model and that the necroptosis pathway specific blocker, Nec-1, dramatically reduced the myocardial damage by downregulating the expression of RIP1/RIP3. These findings provide evidence that necroptosis plays a significant role in cardiomyocyte death and it is a major pathway for cell death in acute VMC. Blocking the necroptosis pathway may serve as a new therapeutic option for the treatment of acute viral myocarditis.

Using sensors to quantify clinically relevant biological species has emerged as a fascinating research field due to their potential to revolutionize clinical diagnosis and therapeutic monitoring. Taking advantage of the wide utility in clinical analysis and low cost of potentiometric ion sensors, we demonstrate a method to use such ion sensors to quantify bioanalytes without chemical labels. This is achieved by combination of chronopotentiometry with a mussel-inspired surface imprinting technique. The biomimetic sensing method is based on a blocking mechanism by which the recognition reaction between the surface imprinted polymer and a bioanalyte can block the current-induced ion transfer of an indicator ion, thus causing a potential change. The present method offers high sensitivity and excellent selectivity for detection of biological analytes. As models, trypsin and yeast cells can be measured at levels down to 0.03 U mL−1 and 50 CFU mL−1, respectively.

This work demonstrates a paper-based microfluidic sampling and separation platform that allows potentiometric sensing of chloride ions in presence of strongly interfering salicylate ions using a solid-contact ion-selective electrode as a detector. The device was composed of two pieces of paper with different shapes and pore sizes. A “T” shaped filter paper with a pore size of 12–25 μm was used as the detection zone. A filter paper with a pore size of 2.0 μm was modified with a complexing agent (Fe 3+ ) and served as the separation zone. The two pieces of the paper were joined together just like a jigsaw. A solid-contact Cl − −selective electrode and a reference electrode were gently pressed onto the detection zone to create a direct contact between the electrodes and the solution absorbed in the paper. Utilizing the possibility to form stable complexes between Fe 3+ and salicylate, the proposed platform enables the separation of salicylate and detection of chloride. This system offers a convenient platform for both sampling and separation of ions, in which sample pretreatment procedures can be simplified or avoided.

Wetland-estuarine-marine environments are typical oxic/anoxic transition zones and have complex water flow-paths within the zone of mixing where freshwater interacts with ocean water. Little is known about the impact of this interaction on bacterial community structures or the relationship between bacterial community and geochemical factors in such transitional mixing environments. Hence, we investigated the distribution patterns and diversity in bacterial communities in the Yellow River estuary-coastal wetland-Bohai Sea transition zone by analyzing 39 samples from 13 ordered sites. High-throughput sequencing of the 16S rRNA gene revealed significant shifts in diversity and distribution of bacterial community in sediments from the Yellow River estuary to the Bohai Sea. Yellow River sediment was dominated by hydrogen-, nitrogen-, and iron-cycling bacteria, such as Hydrogenophaga, Nitrospira, Pseudomonas, and Thiobacillus. The coastal wetland had a haloduric community associated with different functions, such as Planctomyces, Marinobacter, Halomonas, Salinivibrio, and Salinibacter. The Bohai Sea sediment had a higher relative abundance of Lutimonas, Desulfococcus, Photobacterium, Propionigenium, and Vibrio. Spatial variation in bacterial community was correlated with pH, salinity and sulfate (SO42-) concentration in such coastal environments. The major bacterial taxa were significantly different across the wetland, estuary, and coastal marine ecosystems, indicating substantial spatial heterogeneity among the three ecosystems. Statistical analysis revealed strong links between variation in bacterial community structure and ecosystem type. Our results demonstrate the importance of geographic and geochemical factors in structuring the bacterial community in natural environments.

Current paper-based potentiometric ion-sensing platforms are planar devices used for clinically relevant ions. These devices, however, have not been designed for the potentiometric biosensing of proteins or small molecule analytes. A three-dimensional origami paper-based device, in which a solid-contact ion-selective electrode is integrated with an all-solid-state reference electrode, is described for the first time. The device is made by impregnation of paper with appropriate bioreceptors and reporting reagents on different zones. By folding and unfolding the paper structures, versatile potentiometric bioassays can be performed. A USB-controlled miniaturized electrochemical detector can be used for simple and in situ measurements. Using butyrylcholinesterase as a model enzyme, the device has been successfully applied to the detection of enzyme activities and organophosphate pesticides involved in the enzymatic system as inhibitors. The proposed 3D origami paper device allows the potentiometric biosensing of proteins and small molecules in a simple, portable, and cost-effective way.

Previous studies have reported that microRNA-22 (miR-22) may be implicated in ischemia-reperfusion (I/R)-induced myocardial injury. Our previously published data also demonstrated that miR-22 may protect against myocardial I/R injury via anti-apoptosis in rats by targeting cAMP response element-binding protein binding protein (CBP). However, the specific function of miR-22 in myocardial I/R injury is far from fully elucidated. The present study was designed to investigate another cardioprotective signaling mechanism of miR-22 in myocardial I/R injury. A total of 40 adult male Sprague-Dawley rats were randomly divided into four equal groups (n=10): Sham, myocardial I/R, myocardial I/R with adenovirus expressing scramble miRNA (Ad-Scramble) and myocardial I/R with adenovirus expressing miR-22 (Ad-miR-22) groups. Besides the Sham operation group, the remaining three groups were artificially afflicted with coronary occlusion for 30 min and subsequently reperfused for 4 h. A light microscope was used to observe structural changes in the myocardium; reverse transcription polymerase chain reaction was used to measure the miR-22 mRNA expression level; the myocardial infarct size was analyzed by the Evans Blue/triphenyltetrazolium chloride double-staining; and p38 mitogen-activated protein kinase (MAPK), CBP, c-Jun-activator protein (AP)-1 and phospho (p)-c-Jun-AP-1 expression protein levels were detected by a western blot. Furthermore, ELISA was used to measure the levels of TNF-α and IL-6 in the myocardium. The results demonstrated that adenovirus-mediated miR-22 overexpression markedly reduced p38 MAPK, CBP, c-Jun-AP-1, p-c-Jun-AP-1 expression levels concomitant with an improvement in myocardial injury, including smaller infarct size, reduced release of creatine kinase, lactate dehydrogenase and proinflammation mediators (tumor necrosis factor-α and interleukin-6). These findings suggest that miR-22 has a protective effect on myocardial I/R injury. This protection mechanism, at least in part, is due to its anti-inflammatory function via the suppression of the p38 MAPK/CBP/c-Jun-AP-1 signaling pathway.

Methods for in-situ measurements of heavy metal ions in coastal sediment pore water to elucidate fine-scale biogeochemical and environmental processes are highly required but have rarely been reported. In this work, an all-solid-state lead-selective microelectrode (Pb2+-ISμE) based on a poly(3,4-ethylenedioxythiophene)-poly(sodium 4-styrenesulfonate) (PEDOT/PSS) modified gold wire with a diameter of 14 μm has been fabricated. The proposed Pb2+-ISμE is capable of in-situ measurement of Pb2+ in coastal sediment pore water at millimeter depth intervals. The Pb2+-ISμE shows a Nernstian response for Pb2+ within the activity range of 2.1 × 10−9-2.1 × 10−4 M (S = 28.1 ± 1.3 mV/dec, R2 = 0.998) in 0.5 M NaCl, and the detection limit is 6.4 × 10−10 M. By lowering the microelectrode into a coastal sediment core with a micro-manipulator, the proposed Pb2+-ISμE allows the direct measurement of the vertical distribution profile of Pb2+ in the pore water. The in-situ measurement of Pb2+ using the microsensor could avoid the problems of sample handling. Moreover, the detection system can be extended to assess the vertical distribution profiles of other heavy metal ions in sediment pore water by using different ion-selective microelectrodes.

Uncoupling protein 2 (UCP2), located in the mitochondrial inner membrane, is a predominant isoform of UCP that expressed in the heart and other tissues of human and rodent tissues. Nevertheless, its functional role during myocardial ischemia/reperfusion (I/R) is not entirely understood. Ischemic preconditioning (IPC) remarkably improved postischemic functional recovery followed by reduced lactate dehydrogenase (LDH) release with simultaneous upregulation of UCP2 in perfused myocardium. We then investigated the role of UCP2 in IPC-afforded cardioprotective effects on myocardial I/R injury with adenovirus-mediated in vivo UCP2 overexpression (AdUCP2) and knockdown (AdshUCP2). IPC-induced protective effects were mimicked by UCP2 overexpression, while which were abolished with silencing UCP2. Mechanistically, UCP2 overexpression significantly reinforced I/R-induced mitochondrial autophagy (mitophagy), as measured by biochemical hallmarks of mitochondrial autophagy. Moreover, primary cardiomyocytes infected with AdUCP2 increased simulated ischemia/reperfusion (sI/R)-induced mitophagy and therefore reversed impaired mitochondrial function. Finally, suppression of mitophagy with mdivi-1 in cultured cardiomyocytes abolished UCP2-afforded protective effect on sI/R-induced mitochondrial dysfunction and cell death. Our data identify a critical role for UCP2 against myocardial I/R injury through preventing the mitochondrial dysfunction through reinforcing mitophagy. Our findings reveal novel mechanisms of UCP2 in the cardioprotective effects during myocardial I/R.

Conventional potentiometric ion sensors that rely on a specific ion carrier in a polymeric membrane can hardly achieve multianalyte detection. Inspired by the remarkable ability of built-in logic gate sensors for multianalyte detection, herein we report a potentiometric aptasensing platform based on a G-quadruplex/hemin DNAzyme and logic gate operations for determination of two analytes using a single membrane electrode. A bifunctional probe with two aptamer units and a signal reporter oligonucleotide with a DNAzyme sequence are assembled on the magnetic beads to form a DNA hybrid structure. The "OR" and "INHIBIT" logic functions can be performed by using the two aptamers and their targets as inputs, and using the chronopotentiometric response based on the G-quadruplex/hemin DNAzyme-H2O2-mediated oxidation of 3,3',5,5'-tetramethylbenzidine as output. Kanamycin and oxytetracycline, as commonly used antibiotics, have been employed as the models and successfully measured.

We report here on paper-supported thin sample layer voltammetry for the determination of ions. To achieve this goal, a simple setup for the coupling of a commercially available electrode to a silver rod electrode was designed and evaluated for paper-supported thin-layer voltammetry. Linear scan ion transfer voltammetry was explored here for ion-selective membranes doped with an ionophore. The ion-transfer processes and electrochemical behaviors of the system are here evaluated and confirmed by numerical simulation. In the proof-of-concept experiments described, the ions tetrabutylammonium chloride (TBA+) and potassium (K+) were studied as model analytes at membranes without and with ionophore, respectively. A linear relationship from 0.1 mM to 1.0 mM K+ was obtained between the charge and ion concentration. The coexistence of background sodium ions did not give appreciable interference, but the background wave was not completely isolated from the analyte wave, as also confirmed by the model. The methodology was successfully demonstrated for determination of K+ in mineral water. It is anticipated that this paper-supported thin-layer detection approach may provide an attractive readout protocol for disposable paper-based analytical devices as the methodology does not place strict demands on reference electrode performance.

Peptide-based sandwich assays are promising tools in molecular detection, but may be restricted by the availability of “pairs” of affinity peptides. Herein, a new potentiometric sandwich assay for bacteria based on peptide pairs derived from an antimicrobial peptide (AMP) ligand is demonstrated. As a model, the original AMP with a well-defined structure for Listeria monocytogenes (LM) can be split into two fragments to serve as the peptide pairs for the sandwich assay. The recognition and binding of the short peptide pairs to the target can be verified by circular dichroism, flow cytometry, fluorometry, and optical microscopy. The potentiometric magnetic bead-based sandwich assay is designed by using horseradish peroxidase as a label. The enzyme can catalyze the oxidation of 3,3′,5,5′-tetramethylbenzidine with H2O2 to induce a potential change on a polymeric membrane ion-selective electrode. Under optimal conditions, the concentration of LM can be determined potentiometrically in a linear range of 1.0 × 1...

Pituitary tumors are generally intracranial neoplasms with high incidence and mortality rates. The investigation of novel factors involved in the tumorigenesis of pituitary tumors and the characterization of the underlying molecular mechanisms is urgently required for the diagnosis and treatment of pituitary tumors. Accumulating evidence has indicated that microRNAs (miRs) serve important roles in the initiation and progression of cancer. The present study found that miR‑1 was significantly downregulated in pituitary tumor tissues upon reverse transcription‑quantitative polymerase chain reaction analysis. Decreased expression of miR‑1 was associated with the progression and worse prognosis of patients with pituitary tumors. The MTT assay showed that overexpression of miR‑1 significantly suppressed proliferation. Highly expressed miR‑1 promoted the apoptosis of pituitary tumor cells upon fluorescence‑activated cell sorting analysis. Further molecular study revealed that glucose‑6‑phosphate dehydrogenase (G6PD), the first and rate‑limiting enzyme of the pentose phosphate pathway (PPP), was one of the targets of miR‑1. Western blot assays showed that overexpression of miR‑1 significantly decreased the protein level of G6PD in pituitary tumor cells without changing the mRNA level of G6PD. Consequently, oxidative PPP flux analysis revealed that suppression of G6PD by miR‑1 decreased the production of nicotinamide adenine dinucleotide phosphate and the glycolysis of pituitary cancer cells. Restoration of the expression of G6PD significantly reversed the inhibitory effect of miR‑1 on the PPP and the growth of pituitary tumor cells. Collectively, the present results uncovered the critical involvement of miR‑1 in pituitary tumors, indicating that miR‑1 is a potential therapeutic target for the treatment of pituitary tumors.

We report here on the development of a chronopotentiometric assay for microcystin-LR based on enzymatic inhibition. The inhibition of protein phosphatase by microcystin-LR can be sensed potentiometrically by using 4-nitrophenyl phosphate as an enzyme substrate. A solid-contact ion-selective electrode (ISE) with poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) as a transduction layer has been designed for potentiometric biosensing using the pulsed galvanastatic technique. By applying an anodic current, the enzymatic generated p-nitrophenol can be extracted into the polymeric membrane with tetradodecylammonium tetrakis(4-chlorophenyl)-borate to produce the chronopotentiometric signal. Meanwhile, a controlled voltage was applied to refresh the membrane for multiple consecutive measurements. The proposed potentiometric assay showed a linear response for microcystin-LR in the range 1-100 mu g/L with a detection limit of 0.5 mu g/L (3 sigma). We believe that the proposed method can be employed for sensitive, rapid and reliable determination of analytes involved in enzyme inhibition. (C) 2016 Elsevier B.V. All rights reserved.

Dysfunction of vascular smooth muscle cells (VSMCs) performs a key role in the pathogenesis of diabetic vascular disease. Recent studies have reported that microRNA-24 (miR-24) may be implicated in diabetes and atherosclerotic vascular diseases. This study was designed to explore the role of miR-24 on VSMC proliferation and migration under high glucose conditions mimicking diabetes, and reveal the underlying mechanism. VSMCs were isolated from rat thoracic aortas, treated with normal glucose (NG, 5.5mM) or high glucose (HG, 30mM) during an incubation period. Cell viability, proliferation and migration were detected by trypan blue staining, BrdU incorporation assay and transwell chamber assay. Gene and protein expression were analyzed by qRT-PCR and Western blot respectively. We also used electrophoretic mobility shift assay (EMSA) to detect nuclear factor kappaB (NF-κB) DNA binding. TNF-α and IL-6 levels were determined by enzyme-linked immunosorbent assay. The results showed that adenovirus-mediated miR-24 overexpression significantly inhibited HG-stimulated VSMC proliferation and migration. Meanwhile, high mobility group box-1 (HMGB1) as a target of miR-24, was also markedly suppressed after miR-24 transfection. Additionally, NF-κB nuclear translocation and DNA binding, TNF-α and IL-6 production were all decreased associated with the down-regulation of HMGB1. The above data indicated that miR-24 is a crucial regulator of high glucose-induced proliferation and migration in VSMCs, and suggests that elevation of miR-24 in vascular system may be a novel therapeutic strategy to prevent the development of diabetic atherosclerosis.

Background/Aims: Oxidative stress is strongly implicated in the pathogenesis of myocardial damage caused by ischemia reperfusion (I/R). Previous studies have confirmed that cardiac CD47 drives left ventricular heart failure. However, the role for CD47 in myocardial I/R injury (MIRI) has not previously been proposed. This study was designed to investigate whether down-regulation of CD47 using RNA interference (RNAi) technology can relieve inhibition of nitric oxide signaling and attenuate myocardial damage in a rat model of I/R. Methods: Male Sprague-Dawley rats (n = 40) were randomly allocated to four groups and pre-treated either with saline (Sham and I/R groups), or adenovirus expressing either control (Ad-EGFP-N) or CD47-targeting (Ad-EGFP-CD47) RNAi. After four days, the rat MIRI model was established by occluding the left anterior descending coronary artery for 30 min, followed by reperfusion for 3 h. Heart tissue was harvested and assessed by immunohistochemistry, western blot, and quantitative RT-PCR. Outcome measures included infarct size, myocardial enzyme (creatine kinase, creatine kinase-MB, and lactate dehydrogenase) levels in serum, markers of oxidative stress, and morphological changes to the myocardium. Results: Delivery of Ad-EGFP-CD47 RNAi into the myocardium remarkably decreased CD47 expression levels. Down-regulation of CD47 was significantly associated with reduced infarct size and serum levels of myocardial enzymes, increased activity of endothelial nitric oxide synthase, increased levels of nitric oxide, and decreased levels of oxidative stress. Conclusion: These data indicate that down-regulation of CD47 exerts a protective effect against MIRI, which may be attributable to attenuation of oxidative stress via activation of the eNOS/NO signaling pathway.

Potentiometry based on ion-selective electrodes (ISEs) has been injected with new vigor and gone through a renaissance with the improvements in the detection limits and selectivities of ISEs, the introduction of new materials, new sensing concepts (from conventional potentiometry to dynamic electrochemistry approaches), and deeper theoretical understanding and modelling of the potentiometric responses of ISEs. The new breakthroughs encourage innovations in ion sensing and biosensing applications. Moreover, with the introduction of new bioreceptors, such as enzymes, antibodies, aptamers, peptides, versatile sensing protocols have been designed for a broad range of different target molecules by using ISEs as powerful transducers. This paper reviews the recent trends in potentiometric biosensors. Their applications in biosensing of metal ions, small molecules, DNA, proteins, bacteria and toxicities have been discussed. This review provides the outlook of the potentiometric biosensing based on the integration of potentiometric ISEs with new materials and emerging techniques.

A polymeric membrane ion-selective electrode (ISE) is typically designed for the determination of one specific ion using a conventional method. In this work, we demonstrate a simple, versatile, and sensitive platform for simultaneous detection of two molecules with a single ISE. Under a series of periodic galvanostatic polarization, a solid-contact ISE without ion exchanger properties under zero-current conditions has been successfully used for simultaneous detection of two opposite charged ions with high sensitivity, good selectivity, and fast reversibility. By integration of biorecognition elements with the potentiometric measurement, highly sensitive and selective detection of a broad range of different molecular targets can be predicted. As a proof of concept, a potentiometric genosensor based on magnetic beads-enzyme sandwich assay has been designed for sensitive and selective detection of pathogenic bacteria Escherichia coli O157:H7 and Staphylococcus aureus. Under optimal conditions, two bacteria nucleic acid sequences can be detected simultaneously with high sensitivity and good selectivity by using a single solid-contact potentiometric ISE. The detection limits of Escherichia coli O157:H7 DNA and Staphylococcus aureus DNA are 120 and 54 fM (3σ), respectively. Because of its simplicity, this potentiometric technique based on ISE can be an attractive tool or detector to perform two analyte measurements.