Combination of ADAM17 knockdown with eplerenone is more effective than single therapy in ameliorating diabetic cardiomyopathy.

Background: The renin-angiotensin-aldosterone system (RAAS) members, especially Ang II and aldosterone, play key roles in the pathogenesis of diabetic cardiomyopathy (DCM). Angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers combined with aldosterone receptor antagonists (mineralocorticoid receptor antagonists) have substantially improved clinical outcomes in patients with DCM. However, the use of the combination has been limited due to its high risk of inducing hyperkalemia. Methods: Type 1 diabetes was induced in 8-week-old male C57BL/6J mice by intraperitoneal injection of streptozotocin at a dose of 55 mg/kg for 5 consecutive days. Adeno-associated virus 9-mediated short-hairpin RNA (shRNA) was used to knock down the expression of ADAM17 in mice hearts. Eplerenone was administered via gavage at 200 mg/kg daily for 4 weeks. Primary cardiac fibroblasts were exposed to high glucose (HG) in vitro for 24 h to examine the cardiac fibroblasts to myofibroblasts transformation (CMT). Results: Cardiac collagen deposition and CMT increased in diabetic mice, leading to cardiac fibrosis and dysfunction. In addition, ADAM17 expression and activity increased in the hearts of diabetic mice. ADAM17 inhibition and eplerenone treatment both improved diabetes-induced cardiac fibrosis, cardiac hypertrophy and cardiac dysfunction, ADAM17 deficiency combined with eplerenone further reduced the effects of cardiac fibrosis, cardiac hypertrophy and cardiac dysfunction compared with single therapy in vivo. High-glucose stimulation promotes CMT in vitro and leads to increased ADAM17 expression and activity. ADAM17 knockdown and eplerenone pretreatment can reduce the CMT of fibroblasts that is induced by high glucose levels by inhibiting TGFß1/Smad3 activation; the combination of the two can further reduce CMT compared with single therapy in vitro. Conclusion: Our findings indicated that ADAM17 knockout could improve diabetes-induced cardiac dysfunction and remodeling through the inhibition of RAAS overactivation when combined with eplerenone treatment, which reduced TGF-ß1/Smad3 pathway activation-mediated CMT. The combined intervention of ADAM17 deficiency and eplerenone therapy provided additional cardiac protection compared with a single therapy alone without disturbing potassium level. Therefore, the combination of ADAM17 inhibition and eplerenone is a potential therapeutic strategy for human DCM.

Comparison of seven surrogate insulin resistance indexes for prediction of incident coronary heart disease risk: a 10-year prospective cohort study.

Background: There were seven novel and easily accessed insulin resistance (IR) surrogates established, including the Chinese visceral adiposity index (CVAI), the visceral adiposity index (VAI), lipid accumulation product (LAP), triglyceride glucose (TyG) index, TyG-body mass index (TyG-BMI), TyG-waist circumference (TyG-WC) and TyG-waist to height ratio (TyG-WHtR). We aimed to explore the association between the seven IR surrogates and incident coronary heart disease (CHD), and to compare their predictive powers among Chinese population. Methods: This is a 10-year prospective cohort study conducted in China including 6393 participants without cardiovascular disease (CVD) at baseline. We developed Cox regression analyses to examine the association of IR surrogates with CHD (hazard ratio [HR], 95% confidence intervals [CI]). Moreover, the receiver operating characteristic (ROC) curve was performed to compare the predictive values of these indexes for incident CHD by the areas under the ROC curve (AUC). Results: During a median follow-up period of 10.25 years, 246 individuals newly developed CHD. Significant associations of the IR surrogates (excepted for VAI) with incident CHD were found in our study after fully adjustment, and the fifth quintile HRs (95% CIs) for incident CHD were respectively 2.055(1.216-3.473), 1.446(0.948-2.205), 1.753(1.099-2.795), 2.013(1.214-3.339), 3.169(1.926-5.214), 2.275(1.391-3.719) and 2.309(1.419-3.759) for CVAI, VAI, LAP, TyG, TyG-BMI, TyG-WC and TyG-WHtR, compared with quintile 1. Furthermore, CVAI showed maximum predictive capacity for CHD among these seven IR surrogates with the largest AUC: 0.632(0.597,0.667). Conclusion: The seven IR surrogates (excepted for VAI) were independently associated with higher prevalence of CHD, among which CVAI is the most powerful predictor for CHD incidence in Chinese populations.

Prevalence, characteristics and significant predictors for cardiovascular disease of patients with preserved ratio impaired spirometry: A 10-year prospective cohort study in China.

BACKGROUND AND OBJECTIVE: Patients with preserved ratio impaired spirometry (PRIsm) have higher incidence rate of cardiovascular disease (CVD). However, few studies focused on PRIsm in China. We determined the prevalence and characteristics of patients with PRIsm in Chinese population. We also aimed to investigate the significant predictive factors of CVD in PRIsm patients. METHODS: In total, 6994 subjects aged from 35 to 70 years old and free of CVD at baseline were categorized into normal (n = 3895), PRIsm (the ratio of forced expired volume in the first second (FEV1) to forced vital capacity (FVC) ≥0.7 and FEV1 <80 % predicted; n = 1997) and obstructive spirometry (FEV1:FVC<0.7; n = 1102). Cox proportional hazards multivariable regression was performed to investigate how baseline characteristics impact CVD incidence. RESULTS: In participants with PRIsm, men had a 0.68-fold higher risk of CVD incidence than women (HR, 1.68; 95%CI, 1.09-2.59; p = 0.020). Our study showed that the rate of CVD incidence increased by 6.0 % with every year's increase in age (HR, 1.06; 95%CI, 1.04-1.09; p < 0.001). A 0.1 increase in FEV1/FVC was significantly associated with a 23.0 % decrease in CVD incidence (HR, 0.77; 95%CI, 0.61-0.97; p = 0.028). Family history of CVD greatly increased the risk of cardiovascular disease incidence (HR, 1.83; 95%CI, 1.18-2.83; p = 0.007). Higher BMI was also a significant risk factor of CVD incidence (HR, 1.06; 95%CI, 1.01-1.10; p = 0.013). CONCLUSION: The prevalence of PRIsm in China was high. PRIsm subjects should be monitored carefully, especially for the older, male, those with higher BMI, lower FEV1/FVC and family history of CVD.

Triglyceride-glucose index in the prediction of adverse cardiovascular events in patients without diabetes mellitus after coronary artery bypass grafting: a multicenter retrospective cohort study.

BACKGROUND: The triglyceride-glucose (TyG) index has been evaluated as a reliable surrogate for insulin resistance (IR) and has been proven to be a predictor of poor outcomes in patients with cardiovascular diseases. However, data are lacking on the relationship of the TyG index with prognosis in nondiabetic patients who underwent coronary artery bypass grafting (CABG). Thus, the purpose of our current study was to investigate the potential value of the TyG index as a prognostic indicator in patients without diabetes mellitus (DM) after CABG. METHODS: This multicenter, retrospective cohort study involving 830 nondiabetic patients after CABG from 3 tertiary public hospitals from 2014 to 2018. Kaplan-Meier survival curve analysis was conducted followed by the log-rank test. Cox proportional hazards regression models were used to explore the association between the TyG index and major adverse cardiovascular events (MACEs). The incremental predictive power of the TyG index was evaluated with C-statistics, continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: An incrementally higher TyG index was associated with an increasingly higher cumulative incidence of MACEs (log-rank test, p < 0.001). The hazard ratio (95% CI) of MACEs was 2.22 (1.46-3.38) in tertile 3 of the TyG index and 1.38 (1.18-1.62) per SD increase in the TyG index. The addition of the TyG index yielded a significant improvement in the global performance of the baseline model [C-statistic increased from 0.656 to 0.680, p < 0.001; continuous NRI (95% CI) 0.269 (0.100-0.438), p = 0.002; IDI (95% CI) 0.014 (0.003-0.025), p = 0.014]. CONCLUSIONS: The TyG index may be an independent factor for predicting adverse cardiovascular events in nondiabetic patients after CABG.

Photoelectrochemical biosensor based on SiW12@CdS quantum dots for the highly sensitive detection of HPV 16 DNA.

A highly sensitive biosensor for detecting HPV 16 DNA was prepared based on Keggin-type polyoxometalate (SiW12)-grafted CdS quantum dots (SiW12@CdS QDs) and colloidal gold nanoparticles (Au NPs), which exhibited remarkable selectivity and sensitivity upon target DNA detection because of its excellent photoelectrochemical (PEC) response. Here, an enhanced photoelectronic response ability was achieved with the strong association of SiW12@CdS QDs by polyoxometalate modification, which was developed through a convenient hydrothermal process. Furthermore, on Au NP-modified indium tin oxide slides, a multiple-site tripodal DNA walker sensing platform coupled with T7 exonuclease was successfully fabricated with SiW12@CdS QDs/NP DNA as a probe for detecting HPV 16 DNA. Due to the remarkable conductivity of Au NPs, the photosensitivity of the as-prepared biosensor was improved in an I3-/I- solution and avoided the use of other regents toxic to living organisms. Finally, under optimized conditions, the as-prepared biosensor protocol demonstrated wide linear ranges (15-130 nM), with a limit of detection of 0.8 nM and high selectivity, stability, and reproducibility. Moreover, the proposed PEC biosensor platform offers a reliable pathway for detecting other biological molecules with nano-functional materials.

Photoelectrochemical biosensor based on CdS quantum dots anchored h-BN nanosheets and tripodal DNA walker for sensitive detection of miRNA-141.

Herein, a high-sensitivity photoelectrochemical (PEC) biosensor was developed based on CdS quantum dots (QDs) sensitized porous hexagonal boron nitride (h-BN) nanosheets (NSs) and the multiple sites tripodal DNA walker (TDW) formed by catalytic hairpin assembly (CHA). Noticeably, the porous structure of h-BN NSs gives it a lasting gift of large specific surface areas and extensive active reaction sites, which makes it possible to be employed as photoelectric substrate material. The h-BN/CdS QDs composite material promotes the transmission of photogenerated electrons and holes, the outstanding photoelectric conversion efficiency. Meanwhile, the CHA-formed TDWs triggered by miRNA-141 moved on track strand-functionalized electrode, so that a large number of alkaline phosphatase (ALP) was immobilized on the electrode surface and further in situ catalyzed ascorbic acid 2-phosphate (AAP) to produce ascorbic acid (AA) as the electron donor. As the result of the decisive influence of electron donor on PEC biosensor, the sensitive detection of miRNA-141 was realized. The proposed PEC biosensor displayed an excellent linear relationship ranging from 1 fM to 100 nM with a detection limit of 0.73 fM, providing a powerful strategy for early clinical diagnosis and biomedical research.

Polyoxometalate-based nanocomposites for antitumor and antibacterial applications.

Polyoxometalates (POMs), as emerging inorganic metal oxides, have been shown to have significant biological activity and great medicinal value. Nowadays, biologically active POM-based organic-inorganic hybrid materials have become the next generation of antibacterial and anticancer drugs because of their customizable molecular structures related to their highly enhanced antitumor activity and reduced toxicity to healthy cells. In this review, the current developed strategies with POM-based materials for the purpose of antibacterial and anticancer activities from different action principles inducing cell death and hyperpolarization, cell plasma membrane destruction, interference with bacterial respiratory chain and inhibiting bacterial growth are overviewed. Moreover, specific interactions between POM-based materials and biomolecules are highlighted for a better understanding of their antibacterial and anticancer mechanisms. POMs have great promise as next-generation antibacterial and anticancer drugs, and this review will provide a valuable systematic reference for the further development of POM-based nanomaterials.

Light-Induced Efficient Hydroxylation of Benzene to Phenol by Quinolinium and Polyoxovanadate-Based Supramolecular Catalysts.

Direct Hydroxylation of benzene to phenol with high yield and selectivity has been the goal of phenol industrial production. Photocatalysis can serve as a competitive method to realize the hydroxylation of benzene to phenol owing to its cost-effective and environmental friendliness, however it is still a forbidding challenge to obtain good yield, high selectivity and high atom availability meanwhile. Here we show a series of supramolecular catalysts based on alkoxohexavanadate anions and quinolinium ions for the photocatalytic hydroxylation of benzene to phenol under UV irradiation. We demonstrate that polyoxoalkoxovanadates can serve as efficient catalysts which can not only stabilize quinolinium radicals but also reuse H2 O2 produced by quinolinium ions under light irradiation to obtain excellent synergistic effect, including competitive good yield (50.1 %), high selectivity (>99 %) and high atom availability.

Polyoxometalate-Based Photoactive Hybrid: Uncover the First Crystal Structure of Covalently Linked Hexavanadate-Porphyrin Molecule.

Polyoxometalates (POMs)-porphyrin hybrids can serve as multifunctional materials with fascinating photocatalytic and photovoltaic properties. However, most previous POM-porphyrin hybrids are synthesized relied on electrostatic interactions to form ion pairs, which is not stable enough and subject to leaching and poor electronic communication. To our knowledge, no specific crystalline structure of direct covalently tris-functionalized POM-porphyrin hybrids has been identified. Herein, we discover an unprecedented polyoxometalates (POMs)-based photoresponsive cluster, {V6O13[ZnC61H58N5O4]2}2- (denoted as V6-Zn-2Por), which can be synthesized by covalently grafting two tris-functionalized Zn-porphyrin ligands onto Lindqvist-type hexavanadate cluster using decavanadates (TBA)3[H3V10O28] (denoted as V10, TBA = tetrabutylammonium cation) as precursor. Additionally, using tetraphenyl phosphonium as counterion, for the first time, a high-quality single crystal structure of the hybrid hexavanadate-porphyrin molecule is uncovered. Interestingly, the fluorescence emission spectra show that the fluorescence intensity of the organic-inorganic hybrid is partly quenched compared to pristine porphyrins, indicating possible energy/electron transfer between POMs cluster and porphyrin under light irradiation. Their UV-vis diffuse reflectance spectra show an extended absorption in the visible-light range. Finally, the as-prepared photoresponsive hexavanadate-porphyrin molecule is proved to exhibit effective photocatalytic activity toward removal of rhodamine B (an organic dye) under visible-light illumination.

Guest Controlled Pillar[5]arene and Polyoxometalate Based Two-Dimensional Nanostructures toward Reversible Iodine Capture.

The two-dimensional (2D) nanostructures comprised of polyoxometalate based building blocks are of great value in nanoarchitectures, which have unique properties and widespread potential applications, but it is still challenging in mature preparation. Herein a new strategy to build Cr(III) centered Anderson type polyoxometalate 2D nanostructures based on the modulation of host-guest interaction between cationic pillar[5]arenes and sodium dodecyl sulfonate (SDS) in aqueous media was exploited in this work. Through regulating stoichiometry of SDS, the morphology of assemblies vary from nanobones to 2D nanosheets. The fine assembled structure was discovered by combined 1H NMR, SAXS, and element analyses. The nanomaterials can be used as adsorbents for I2 in various solutions, including n-hexane, cyclohexane, water, and chloroform, where the polyoxometalates play a key role in the effective adsorption of iodine since they can expand the interspace between pillar[5]arenes in the as-prepared nanostructure. Furthermore, such adsorbents are easily regenerated and reused as iodine can be released spontaneously from nanobones@I2 and nanosheets@I2 solids when being immersed in dimethyl sulfoxide.

Highly practical and efficient preparation of aldehydes and ketones from aerobic oxidation of alcohols with an inorganic-ligand supported iodine catalyst.

Herein, we divulge an efficient protocol for aerobic oxidation of alcohols with an inorganic-ligand supported iodine catalyst, (NH4)5[IMo6O24]. The catalyst system is compatible with a wide range of groups and exhibits high selectivity, and shows excellent stability and reusability, thus serving as a potentially greener alternative to the classical transformations.

Anderson-Type Polyoxometalates Functionalized by Tetrathiafulvalene Groups: Synthesis, Electrochemical Studies, and NLO Properties.

Three polyoxometalates (POMs) functionalized by tetrathiafulvalene (TTF) molecules have been synthesized by a coupling reaction between the Anderson-type POMs [MnMo6O18{(OCH2)3CNH2}2]3- or [AlMo6O18(OH)3{(OCH2)3CNH2}]3- and the TTF carboxylic acid derivative (MeS)3TTF(S-CH2-CO2H). The monofunctionalized TTF-AlMo6 POM contains one TTF group covalently grafted on an Al Anderson platform. The symmetrical TTF-MnMo6-TTF POM possesses two TTF groups grafted on each side of a Mn Anderson derivative while the asymmetrical TTF-MnMo6-SP POM contains a TTF and a spiropyran groups. These three trianionic species have been characterized by elemental analysis, 1H and 13C NMR, FT-IR spectroscopy, ESI-MS spectrometry, and single-crystal X-ray diffraction (for TTF-MnMo6-TTF). In the solid state, the grafted TTF molecules of TTF-MnMo6-TTF POMs interact via S···S and π···π interactions and form chains. The electrochemical properties of the complexes reflect the contributions of both the inorganic POM and the TTF moieties. Despite adsorption of the oxidized hybrid species on the Pt grid working electrode, UV-vis-NIR spectroelectrochemical investigations evidence peaks characteristic of the oxidation of the TTF units. Finally, hyper-Rayleigh scattering (HRS) measurements show that the three novel TTF derivatives exhibit ß values between 20 and 37 × 10-30 esu. Moreover it is observed that the oxidation of the TTF moieties by Fe3+ ions increases the NLO response. These values are in the order of magnitude of that found for the well-known 4-dimethylamino- N-methyl-4-stilbazolium (DAS+) cation (ß = 60 × 10-30 esu).

A disposable simultaneous electrochemical sensor array based on a molecularly imprinted film at a NH2-graphene modified screen-printed electrode for determination of psychotropic drugs.

A disposable simultaneous electrochemical sensor array based on a molecularly imprinted film with a screen-printed electrode (SPE) has been developed for the detection of psychotropic drugs. A molecularly imprinted film (MIF) was synthesized by electro-polymerization using methcathinone and cathinone as the templates and pyrrole (py) as the monomer. Scanning electron microscopy (SEM) was employed to characterize the surface morphology of the MIF. The conductivity of the SPE was improved by the NH2-graphene (NG). The surface feature of the modified electrode was characterized by cyclic voltammetry (CV) and an electrochemical impedance method. The proposed sensor array was tested by differential pulse voltammetry. Several important parameters controlling the performance of the molecularly imprinted sensor array were investigated and optimized. Under the optimal conditions, this multiplexed immunoassay method showed wide linear ranges over 3 orders of magnitude with the detection limits (S/N = 3) down to 3.3 and 8.9 pg mL(-1) for methcathinone and cathinone, respectively. This disposable simultaneous electrochemical sensor array was successfully employed to detect methcathinone and cathinone in practical serum samples. The disposable simultaneous strategy avoided crosstalk and the need of deoxygenation for the electrochemical sensor, thus, provided a promising potential in clinical applications.

A novel high selectivity chemiluminescence sensor for fenvalerate based on double-sided hollow molecularly imprinted materials.

Novel fenvalerate double-sided hollow molecularly imprinted microspheres (fenvalerate-DHMIMs) were fabricated by in situ polymerization with the help of mesoporous silica microspheres (MSMs) in this paper for the very first time. Scanning electron microscope was employed to characterize the surface morphology of the fenvalerate-DHMIMs. Taking advantage of the quenching effect of fenvalerate on the luminol-H(2)O(2)-NaOH chemiluminescence system, a new model was established to determine fenvalerate by a highly selective flow injection chemiluminescence method. The traditional flow-through cell was replaced by a novel Y-shaped column. The chemiluminescence intensity was linear with fenvalerate concentration over the range of 5.0 × 10(-8) to 2.0 × 10(-5) g mL(-1) and the detection limit was 2.2 × 10(-8) g mL(-1). The relative standard deviation (RSD) for the determination of 2.0 × 10(-6) g mL(-1) fenvalerate was 1.4% (n = 11). The proposed method was applied to the determination of fenvalerate in real samples with satisfactory results.

A disposable electrochemical immunosensor based on carbon screen-printed electrodes for the detection of prostate specific antigen.

A novel screen-printed electrode (SPEs) on sheets of vegetable parchment was prepared. The obtained SPEs were stable, convenient, inexpensive and suitable for large-area screen-printing. With these SPEs, we explored the fabrication of a novel, disposable and highly sensitive electro-analytical immunosensor using graphene nanosheets (GS) and horseradish peroxidase (HRP)-labeled signal antibody functionalized with gold nanoparticles (HRP-Ab(2)/Au NPs). GS was used to increase the conductivity and stability of this immunosensor due to its fast electron transportation and good biocompatibility. Au NPs could not only provide a large surface area for the immobilization of HRP-Ab(2) but also enhance the electroreduction between HRP and H(2)O(2) to amplify the electrochemical signal on the sandwich immuno-complexes modified SPEs. The proposed SPEs were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and electrochemical methods involving cyclic voltammetry (CV), and electrochemical impedence method. Using prostate specific antigen (PSA) as a model analyte, this immunosensor showed a wide linear range over 6 orders of magnitude with the minimum value down to 2 pg mL(-1). In addition, this immunosensor could avoid the need of deoxygenation for the electrochemical immunoassay. Thus, it provided a promising potential in clinical applications.

Electrochemical immunoassay on a 3D microfluidic paper-based device.

A high-throughput, simple, fast, low-cost and sensitive paper-based electrochemical immunodevice has been demonstrated based on a functionalized 3D paper-based device for point-of-care diagnosis.