Association of plasma advanced glycation end-products and their soluble receptor with type 2 diabetes among Chinese adults.

AIMS: Population-based evidence regarding circulating advanced glycation end-products (AGEs) and the risk of type 2 diabetes (T2D) is conflicting and insufficient. We aimed to examine the association of plasma AGEs and plasma soluble receptors for AGEs (sRAGE) with T2D. MATERIALS AND METHODS: We conducted a hospital-based case-control study including 1072 pairs (53.9 ± 9.7 years, 56.0% male) of newly diagnosed T2D and age- and sex-matched controls. We further performed a nested case-control study within an ongoing prospective cohort consisting of 127 incident T2D cases and 381 well-matched controls (62.2 ± 5.1 years, 71.7% male). Plasma AGEs were detected using liquid chromatography-tandem mass spectrometry, and plasma sRAGE was measured by enzyme-linked immunosorbent assay. Conditional logistic regression was used to evaluate the association of plasma AGEs and sRAGE concentrations with T2D. RESULTS: Higher plasma AGEs and lower sRAGE concentrations were associated with higher odds of T2D. The multivariable-adjusted odds ratios of T2D comparing the highest with the lowest quartile levels were 3.28 (95% CI: 2.14, 5.02) for plasma AGEs and 0.25 (95% CI: 0.16, 0.39) for plasma sRAGE. Participants in the highest quartile of plasma AGEs and the lowest quartile of sRAGE concentrations had the greatest odds of T2D. The positive association of AGEs and inverse association of sRAGE with T2D risk was confirmed in the replication-nested case-control study. CONCLUSIONS: Increased circulating AGEs and decreased sRAGE concentrations were associated with elevated T2D risk. Our findings may have implications for the strategies of T2D prevention and management.

Manipulating Cation-π Interactions of Reader Proteins in Living Cells with Genetic Code Expansion.

Despite tremendous success in understanding the chemical nature and the importance of cation-π interactions in a range of biological processes, particularly in epigenetic regulation, the design and synthesis of stronger cation-π interactions in living cells remain largely elusive. Here, we design several electron-rich Trp derivatives and incorporate them into histone methylation reader domains to enhance the affinity of the reader domains for histone methylation marks via cation-π interactions in living cells. We show that this site-specific Trp replacement strategy is generally applicable for the engineering of high-affinity reader domains for the major histone H3 trimethylation marks, such as H3K4me3, H3K9me3, H3K27me3, and H3K36me3, with high specificity. Furthermore, we demonstrate that engineered reader domains can serve as powerful tools for the enrichment and imaging of histone methylation, as well as for capturing the protein interactome at chromatin marks in living cells. Therefore, our study paves the way for the design of enhanced cation-π interactions in reader proteins in living cells for various biological applications.

Investigation of mitochondrial targeting ability of sydnones and sydnonimines and mitochondria-targeted delivery of celecoxib.

Mitochondria are considered to be a promising target in cancer diagnosis and therapeutics. Recently, sydnone and sydnonimine, as mesoionic bioorthogonal reagents, have been used in cell labeling and drug delivery. Here we investigated the mitochondrial targeting ability of sydnones and sydnonimines for the first time. Experimental results show that sydnone and sydnonimine themselves have high mitochondrial distribution. However, the introduction of a phenyl group into the C4 position of sydnone dramatically decreases the mitochondrial affinity. In addition, we took advantage of mitochondrial targeting ability and click-and-release reaction of sydnonimine to evaluate anticancer activities of in-mitochondria delivery of celecoxib against HeLa and HepG2 cells, indicating that celecoxib-induced cancer cell death may not involve mitochondria-related pathway.

Causal associations between hand grip strength and pulmonary function: a two-sample Mendelian randomization study.

BACKGROUND: Several observational studies have reported an association between hand grip strength (HGS) and pulmonary function (PF). However, causality is unclear. To investigate whether HGS and PF are causally associated, we performed Mendelian randomization (MR) analyses. METHODS: We identified 110 independent single nucleotide polymorphisms (SNPs) for right-hand grip strength (RHGS) and 103 independent SNPs for left-hand grip strength (LHGS) at the genome-wide significant threshold (P < 5 × 10-8) from MRC-IEU Consortium and evaluated these related to PF. MR estimates were calculated using the inverse-variance weighted (IVW) method and multiple sensitivity analyses were further performed. RESULTS: Genetical liability to HGS was positively causally associated with forced vital capacity (FVC) and forced expiratory volume in one second (FEV1), but not with FEV1/FVC. In addition, there was positive causal association between RHGS and FVC (OR=1.519; 95% CI, 1.418-1.627; P=8.96E-33), and FEV1 (OR=1.486; 95% CI, 1.390-1.589; P=3.19E-31); and positive causal association between LHGS and FVC (OR=1.464; 95% CI, 1.385-1.548; P=2.83E-41) and FEV1 (OR=1.419; 95% CI, 1.340-1.502; P=3.19E-33). Nevertheless, no associations were observed between RHGS and FEV1/FVC (OR=0.998; 95% CI, 0.902-1.103; P=9.62E-01) and between LHGS and FEV1/FVC (OR=0.966; 95% CI, 0.861-1.083; P=5.52E-01). Similar results were shown in several sensitivity analyses. CONCLUSION: Our study provides support at the genetic level that HGS is positively causally associated with FVC and FEV1, but not with FEV1/FVC. Interventions for HGS in PF impairment deserve further exploration as potential indicators of PF assessment.

Study on the Wetting and Permeation Properties of Bio-Oil as Bitumen Rejuvenator.

In order to explore the diffusion and regeneration of bio-oil in aged bitumen, waste cooking oil (WCO), waste wood oil (WWO) and straw liquefied residue oil (SLRO) were selected in this paper. According to the surface wetting theory, the contact angle is obtained by combining laboratory experiments with molecular dynamics (MD) simulation, and the wetting parameters are calculated to evaluate the wetting behavior of bio-oil. The experimental phenomena of the wetting process and the main factors driving wetting are further analyzed. A permeation experiment is designed to obtain the permeation fusion layer (PFL). If the crossover modulus of PFLs changes compared with that of the aged bitumen, it is determined that the bio-oil penetrates the corresponding fusion layer. The results show that the motion of bio-oil included spreading and shrinking processes, and a precursor film played a pivotal role in the transportation of nanodroplets. Higher surface tension, lower viscosity and cohesion can effectively promote the wettability of bio-oil. A higher temperature and a longer permeation time are conducive to the permeation of bio-oil in aged bitumen. WCO with the strongest wettability has the weakest permeability, while WWO has superior permeability and can activate the macromolecules' surface activity, but its wettability is relatively weak. It is necessary to further modify WCO and WWO to be suitable rejuvenators.

Fluorogenic sydnonimine probes for orthogonal labeling.

A FRET-based fluorescence turn-on probe is designed, which employs a sydnonimine as the linker to match specific fluorophore and quencher pairs and releases the fluorescence after the "click-and-release" reaction. Furthermore, we realized selective fluorescence labeling by exploiting the mutual orthogonality between sydnonimine-DIBAC and tetrazine-1,3-Cp cycloaddition pairs.

Long short-term memory network of machine learning for compensating temperature error of a fiber optic gyroscope independent of the temperature sensor.

We present an artificial intelligence compensation method for temperature error of a fiber optic gyroscope (FOG). The difference from the existing methods is that the compensation model finally determined by this method only uses the FOG's data to complete the regression prediction of the temperature error and eliminate the dependency on the temperature sensor. In the experimental stage, the proposed method performs temperature experiments with three varying trends of temperature heating, holding, and cooling and obtains sufficient output data sets of the FOG. Taking the output time series of the FOG as the input sample and based on the long short-term memory network of machine learning, the training, validation, and test of the model are completed. From the two perspectives of network learning ability and the improvement degree of the FOG's performance, four indicators, including root mean square error, error cumulative distribution function, FOG bias stability, and Allan variance analysis are selected to evaluate the performance of the compensation model comprehensively. Compared with the existing methods using temperature information for prediction and compensation, the results show that the error compensation method without temperature information proposed can effectively improve the accuracy of the FOG and reduce the complexity of the compensation system. The work can also provide technical references for error compensation of other sensors.

High-Quality Conjugated Polymers Achieving Ultra-Trace Detection of Cr2O72- in Agricultural Products.

In view of that conjugated polymers (CPs) are an attractive option for constructing high-sensitive Cr2O72- sensors but suffer from lacking a general design strategy, we first proposed a rational structure design of CPs to tailor their sensing properties while validating the structure-to-performance correlation. Short side chains decorated with N and O atoms as recognition groups were instructed into fluorene to obtain monomers Fmoc-Ala-OH and Fmoc-Thr-OH. Additionally, their polymers P(Fmoc-Ala-OH) and P(Fmoc-Thr-OH) were obtained through electrochemical polymerization. P(Fmoc-Ala-OH) and P(Fmoc-Thr-OH) with high polymerization degrees have an excellent selectivity towards Cr2O72- in comparison to other cations and anions. Additionally, their limit of detection could achieve 1.98 fM and 3.72 fM, respectively. Especially, they could realize the trace detection of Cr2O72- in agricultural products (red bean, black bean, and millet). All these results indicate that short side chains decorated with N and O atoms functionalizing polyfluorene enables the ultra-trace detection of Cr2O72-. Additionally, the design strategy will spark new ideas for the construction of highly selective and sensitive Cr2O72- sensors.

Metal- and Strain-Free Bioorthogonal Cycloaddition of o-Diones with Furan-2(3H)-one as Anionic Cycloaddend.

The development of new bioorthogonal reactions with mutual orthogonality to classic bioorthogonal reactions such as the strain-promoted azide-alkyne click reaction and the inverse-electron-demand Diels-Alder reaction is of great importance in providing chemical tools for multiplex labelling of live cells. Here we report the first anionic cycloaddend-promoted bioorthogonal cycloaddition reaction between phenanthrene-9,10-dione and furan-2(3H)-one derivatives, where the high polarity of water is exploited to stabilize the highly electron-rich anionic cycloaddend. The reaction is metal- and strain-free, which proceeds rapidly in aqueous solution and on live cells with a second-order rate constant up to 119 M-1 s-1 . The combined utilization of this reaction together with the two other widely used bioorthogonal reactions allows for mutually orthogonal labelling of three types of proteins or three groups of living cells in one batch without cross-talking. Such results highlight the great potential for multiplex labelling of different biomolecules in live cells.

Design and Development of a Bioorthogonal, Visualizable and Mitochondria-Targeted Hydrogen Sulfide (H2 S) Delivery System.

Hydrogen sulfide (H2 S) is an important endogenous gasotransmitter, but the targeted delivery and real-time feedback of exogenous H2 S are still challenging. With the aid of density functional theory (DFT) calculations, we designed a new 1,3-dithiolium-4-olate (DTO) compound, which can react with a strained alkyne via the 1,3-dipolar cycloaddition and the retro-Diels-Alder reaction to generate carbonyl sulfide (COS) as the precursor of H2 S, and a thiophene derivative with turn-on fluorescence. Moreover, the diphenylamino substituent in DTO greatly increases the mitochondrial targeting of this H2 S delivery system. Such a bioorthogonal click-and-release reaction has integrated three functions in one system for the first time: (1) in situ controllable H2 S release, (2) concomitant fluorescence response, and (3) mitochondria-targeted delivery. In addition, we investigated the mitochondrial membrane potential loss alleviation by using this system in H9c2 cells under oxidative stress.

Apelin ameliorated acute heart failure via inhibiting endoplasmic reticulum stress in rabbits.

This study aimed to investigate whether inhibition of endoplasmic reticulum stress (ERS) mediated the ameliorative effect of apelin on acute heart failure (AHF). Rabbit model of AHF was induced by sodium pentobarbital. Cardiac dysfunction and injury were detected in the rabbit models of AHF, including impaired hemodynamic parameters and increased levels of CK-MB and cTnI. Apelin treatment dramatically improved cardiac impairment caused by AHF. ERS, indexed by increased GRP78, CHOP, and cleaved-caspase12 protein levels, was simultaneously attenuated by apelin. Apelin also could ameliorate increased protein levels of cleaved-caspase3 and Bax, and improved decreased protein levels of Bcl-2. Two common ERS stimulators, tunicamycin (Tm) and dithiothreitol (DTT) blocked the ameliorative effect of apelin on AHF. Phosphorylated Akt levels increased after apelin treatment in the rabbit models of AHF. The Akt signaling inhibitors wortmannin and LY294002 could block the cardioprotective effect of apelin, which could be relieved by ERS inhibitor 4-phenyl butyric acid (4-PBA). The aforementioned beneficial effects of apelin could all be blocked by APJ receptor antagonist F13A. 4-PBA and SC79, an Akt activator, can restore the ameliorative effect of apelin on AHF blocked by F13A. Apelin treatment dramatically ameliorated cardiac impairment caused by AHF, which might be mediated by APJ/Akt/ERS signaling pathway. These results will shed new light on AHF therapy.

Fabrication of a biomimetic hydrogel actuator with rhythmic deformation driven by a pH oscillator.

A diversified and biocompatible rhythmic deformation (RD) system is successfully fabricated by coupling a heterogeneous hydrogel with a pH oscillator. By tailoring the geometry of the building blocks, a heterogeneous hydrogel actuator with diversity could be easily constructed through interfacial adhesion. Moreover, the RD behaviour can be regulated by the system temperature and actuator shape.

Progressive Increasing of Pt Nanoparticles with Multiple-Layered Manner inside Metal-Organic Frameworks for Enhanced Catalytic Activity.

Single-layered, double-layered, and triple-layered Pt nanoparticles with a well-defined arrangement were encapsulated inside metal-organic frameworks (MOFs) to investigate the catalytic performance influenced by the progressive increasing of Pt nanoparticles inside MOFs; the results show that the catalytic activity of the Pt-MOF hybrid catalysts increases progressively with the progressive increasing of the Pt nanoparticles inside MOFs. Progressive increasing of Pt nanoparticles with a multiple-layered manner inside MOFs provides a new route for designing well-organized hybrid catalysts of noble metal nanoparticles and MOFs with enhanced catalytic activity.

Inserting Pt Nanoparticles at the Designated Location inside Metal-Organic Frameworks for Promoted Catalytic Performance.

Metal-organic frameworks (MOFs)-supported noble metal nanoparticles (NMNPs) catalysts attract increasing attention due to their high durability and efficiency in catalytic reactions. In this work, Pt nanoparticles are inserted at the designated location inside MIL-100(Fe) to investigate the location-effect of NMNPs inside MOFs on the catalytic reaction. The comparison test on the reduction of p-nitrophenol suggests that the location of the Pt nanoparticles inside MIL-100(Fe) largely influences the catalytic performance and the Pt nanoparticles inside MIL-100(Fe) locate closer to the outer surface of the MIL-100(Fe), providing higher catalytic efficiency. Possible reasons are concluded as the location of the Pt nanoparticles inside MIL-100(Fe) dominates the reactants transport pathway and the loading amount of Pt nanoparticles.

Development and validation of a LC-MS/MS method for simultaneous determination of TQ-A3326 and its major metabolites in human plasma, urine and feces: application to pharmacokinetic assay.

TQ-A3326 has been developed as a new drug by modifying the structure of daclatasvir with deuterium. The pharmacokinetics (PK) of TQ-A3326 in human remains unclear. The aim of the present study was to establish a LC-MS/MS method to investigate preliminarily the PK characteristics of TQ-A3326 and its major metabolites in healthy Chinese volunteers. All volunteers were administrated TQ-A3326 (60 mg). Plasma, feces and urine samples were extracted through protein precipitation. A rapid and sensitive LC-MS/MS method was successfully developed and applied to assess the PK properties of TQ-A3326. The AUC0-t and Cmax were 39516.3 ± 10778.5, 1034.6 ± 452.9 and 71.0 ± 49.5 ng·h·mL-1, and 1411.2 ± 325.4, 52.9 ± 16.4 and 1.8 ± 0.5 ng·mL-1, respectively, for TQ-A3326, M2-D and M4-D. Feces were the predominant route of elimination of TQ-A3326. M2-D was an abundant metabolite in feces and urine, representing 23.72% and 0.24% of the dose, respectively. The measurements of TQ-A3326 and its active metabolites would help to better understand the predominant route of elimination of the prototype drug, and provide meaningful information for further investigation of the bioactive mechanism of TQ-A3326 and its clinical applications.

Power-Based Non-Intrusive Condition Monitoring for Terminal Device in Smart Grid.

As a critical component in the smart grid, the Distribution Terminal Unit (DTU) dynamically adjusts the running status of the entire smart grid based on the collected electrical parameters to ensure the safe and stable operation of the smart grid. However, as a real-time embedded device, DTU has not only resource constraints but also specific requirements on real-time performance, thus, the traditional anomaly detection method cannot be deployed. To detect the tamper of the program running on DTU, we proposed a power-based non-intrusive condition monitoring method that collects and analyzes the power consumption of DTU using power sensors and machine learning (ML) techniques, the feasibility of this approach is that the power consumption is closely related to the executing code in CPUs, that is when the execution code is tampered with, the power consumption changes accordingly. To validate this idea, we set up a testbed based on DTU and simulated four types of imperceptible attacks that change the code running in ARM and DSP processors, respectively. We generate representative features and select lightweight ML algorithms to detect these attacks. We finally implemented the detection system on the windows and ubuntu platform and validated its effectiveness. The results show that the detection accuracy is up to 99.98% in a non-intrusive and lightweight way.

Oxone-Mediated Radical C-C Bond Acetmethylation/Arylation of Methylenecyclopropanes and Vinylcyclopropanes with α-Alkyl Ketones: Facile Access to Oxoalkyl-Substituted 3,4-Dihydronaphthalenes.

An efficient oxone-mediated radical carbon-carbon σ-bond acetmethylation/arylation of methylenecyclopropanes with α-C(sp3)-H bonds of ketones is described for the preparation of 2-(2-oxopropyl)-3,4-dihydronaphthalenes. This acetmethylation/arylation undergoes a series of α-C(sp3)-H bond activation, carbon-carbon double bond acetmethylation, carbon-carbon σ-bond cleavage, and cyclization with intramolecular aromatic ring. The experimental result indicates that the carbon-carbon σ-bond acetmethylation/arylation transformation contains a radical process. The difunctionalization method can also be applied to carbon-carbon σ-bond acetmethylation/arylation of vinylcyclopropanes with ketones. This strategy offers an efficient and convenient method for acetmethylation/arylation of a carbon-carbon σ-bond with a α-carbonyl radical and an aromatic carbon in one pot, building two new carbon-carbon bonds.

Encapsulating Pt Nanoparticles through Transforming Fe3O4 into MIL-100(Fe) for Well-Defined Fe3O4@Pt@MIL-100(Fe) Core-Shell Heterostructures with Promoting Catalytic Activity.

Metal-organic framework (MOF)-based magnetic Pt catalyst Fe3O4@Pt@MIL-100(Fe) core-shell heterostructures were prepared through transforming Fe3O4 into MIL-100(Fe) in benzene-1,3,5-tricarboxylic acid solution along with encapsulating the Pt nanoparticles successively adsorbed onto the surface of the Fe3O4 nanosphere and the continuously forming surfaces of the growing MIL-100(Fe) crystals. This method circumvented the obstacles, controlling the formation of metal nanoparticles (MNPs) inside MOFs or regulating growth of MOFs around the MNPs, for preparing an MNP-MOF composite catalyst. The obtained well-defined Fe3O4@Pt@MIL-100(Fe) core-shell heterostructure was shown promoting catalytic activity on the reduction of 4-nitrophenol due to the synergistic effect between the Pt nanoparticles and the MIL-100(Fe) shell and recycling convenience due to the rapid separation of the Fe3O4 core under an external magnetic field.

JamCatcher: A Mobile Jammer Localization Scheme for Advanced Metering Infrastructure in Smart Grid.

As the core component of the smart grid, advanced metering infrastructure (AMI) is responsible for automated billing, demand response, load forecasting, management, etc. The jamming attack poses a serious threat to the AMI communication networks, especially the neighborhood area network where wireless technologies are widely adopted to connect a tremendous amount of smart meters. An attacker can easily build a jammer using a software-defined radio and jam the wireless communications between smart meters and local controllers, causing failures of on-line monitoring and state estimation. Accurate jammer localization is the first step for defending AMIs against jamming attacks. In this paper, we propose JamCatcher, a mobile jammer localization scheme for defending the AMI. Unlike existing jammer localization schemes, which only consider stationary jammers and usually require a high density of anchor nodes, the proposed scheme utilizes a tracker and can localize a mobile jammer with sparse anchor nodes. The time delay of data transmission is also considered, and the jammer localization process is divided into two stages, i.e., far-field chasing stage and near-field capturing stage. Different localization algorithms are developed for each stage. The proposed method has been tested with data from both simulation and real-world experiment. The results demonstrate that JamCatcher outperforms existing jammer localization algorithms with a limited number of anchor nodes in the AMI scenario.

LESS: Link Estimation with Sparse Sampling in Intertidal WSNs.

Deploying wireless sensor networks (WSN) in the intertidal area is an effective approach for environmental monitoring. To sustain reliable data delivery in such a dynamic environment, a link quality estimation mechanism is crucial. However, our observations in two real WSN systems deployed in the intertidal areas reveal that link update in routing protocols often suffers from energy and bandwidth waste due to the frequent link quality measurement and updates. In this paper, we carefully investigate the network dynamics using real-world sensor network data and find it feasible to achieve accurate estimation of link quality using sparse sampling. We design and implement a compressive-sensing-based link quality estimation protocol, L E S S , which incorporates both spatial and temporal characteristics of the system to aid the link update in routing protocols. We evaluate L E S S in both real WSN systems and a large-scale simulation, and the results show that L E S S can reduce energy and bandwidth consumption by up to 50 % while still achieving more than 90 % link quality estimation accuracy.