Triglyceride-glucose Index as a Valuable Marker to Predict Severity of Coronary Artery Disease: A Retrospective Cohort Study.

BACKGROUND AND AIMS: The diagnostic standard of coronary artery disease (CAD) is coronary angiography (CAG). Since CAG is an invasive procedure underscores the need for identifying non-invasive, effective, and innovative biomarkers. Our study aimed to retrospectively analyze hematological markers for predicting the severity of CAD. METHODS AND RESULTS: Case data were collected from 195 CAD patients admitted to the hospital for CAG. According to Gensini score, patients were divided into mild, moderate, and severe CAD groups. Blood indexes and predictive efficacy of the triglyceride-glucose (TyG) index were retrospectively analyzed. Among 195 CAD patients, 81 had mild CAD, 60 had moderate CAD, and 54 had severe CAD. Sex, fast blood glucose (FBG), TyG index, and high-sensitivity C-reactive protein (hs-CRP) significantly differed among the three groups. The TyG index demonstrated higher values in patients with moderate (9.07[8.62-9.44]) and severe (8.98[8.46-9.45]) CAD compared to those with mild CAD (8.75[8.49-9.14]). The AUC of the TyG index was 0.615 (95% confidence interval (CI): 0.536-0.694, P =.004), with a cut-off value of 8.997, specificity of 0.704, and sensitivity of 0.535. Logistics analysis showed the risk of moderate and severe CAD with an odds ratio (OR) value of 2.595 (95% CI: 1.199-5.619, adjusted P = .016) following regrouping by the TyG index optimal cut-off value of 8.997. The TyG index combined with FBG and hs-CRP had an elevated AUC value, significantly higher than other combinations (P = .011 and 0.02, respectively). CONCLUSIONS: The severity of CAD is positively correlated with an increased TyG index value. A combination of TyG, FBG, and hs-CRP has demonstrated improved diagnostic efficiency, suggesting its potential as a novel indicator for predicting and diagnosing CAD progression.

A supramolecular cucurbit[8]uril-based rotaxane chemosensor for the optical tryptophan detection in human serum and urine.

Sensing small biomolecules in biofluids remains challenging for many optical chemosensors based on supramolecular host-guest interactions due to adverse interplays with salts, proteins, and other biofluid components. Instead of following the established strategy of developing alternative synthetic binders with improved affinities and selectivity, we report a molecular engineering approach that addresses this biofluid challenge. Here we introduce a cucurbit[8]uril-based rotaxane chemosensor feasible for sensing the health-relevant biomarker tryptophan at physiologically relevant concentrations, even in protein- and lipid-containing human blood serum and urine. Moreover, this chemosensor enables emission-based high-throughput screening in a microwell plate format and can be used for label-free enzymatic reaction monitoring and chirality sensing. Printed sensor chips with surface-immobilized rotaxane-microarrays are used for fluorescence microscopy imaging of tryptophan. Our system overcomes the limitations of current supramolecular host-guest chemosensors and will foster future applications of supramolecular sensors for molecular diagnostics.

A multiplexed phospholipid membrane platform for curvature sensitive protein screening.

The curvature of lipid membranes plays a key role in many relevant biological processes such as membrane trafficking, vesicular budding and host-virus interactions. In vitro studies on the membrane curvature of simplified biomimetic models in the nanometer range are challenging, due to their complicated nanofabrication processes. In this work, we propose a simple and low-cost platform for curvature sensitive protein screening, prepared through scanning probe lithography (SPL) methods, where lipid bilayer patches of different compositions can be multiplexed onto substrate areas with tailored local curvature. The curvature is imposed by anchoring nanoparticles of the desired size to the substrate prior to lithography. As a proof of principle, we demonstrate that a positive curvature membrane sensitive protein derived from the BAR domain of Nadrin2 binds selectively to lipid patches patterned on substrate areas coated with 100 nm nanoparticles. The platform opens up a path for screening curvature-dependent protein-membrane interaction studies by providing a flexible and easy to prepare substrate with control over lipid composition and membrane curvature.

Rapid Capture of Cancer Extracellular Vesicles by Lipid Patch Microarrays.

Extracellular vesicles (EVs) contain various bioactive molecules such as DNA, RNA, and proteins, and play a key role in the regulation of cancer progression. Furthermore, cancer-associated EVs carry specific biomarkers and can be used in liquid biopsy for cancer detection. However, it is still technically challenging and time consuming to detect or isolate cancer-associated EVs from complex biofluids (e.g., blood). Here, a novel EV-capture strategy based on dip-pen nanolithography generated microarrays of supported lipid membranes is presented. These arrays carry specific antibodies recognizing EV- and cancer-specific surface biomarkers, enabling highly selective and efficient capture. Importantly, it is shown that the nucleic acid cargo of captured EVs is retained on the lipid array, providing the potential for downstream analysis. Finally, the feasibility of EV capture from patient sera is demonstrated. The demonstrated platform offers rapid capture, high specificity, and sensitivity, with only a small need in analyte volume and without additional purification steps. The platform is applied in context of cancer-associated EVs, but it can easily be adapted to other diagnostic EV targets by use of corresponding antibodies.

α-Cyclodextrins Polyrotaxane Loading Silver Sulfadiazine.

As a drug carrier, polyrotaxane (PR) has been used for targeted delivery and sustained release of drugs, whereas silver sulfadiazine (SD-Ag) is an emerging antibiotic agent. PR was synthesized by the use of α-cyclodextrin (CD) and poly(ethylene glycol) (PEG), and a specific antibacterial material (PR-(SD-Ag)) was then prepared by loading SD-Ag onto PR with different mass ratios. The loading capacity and the encapsulation efficiency were 90% at a mass ratio of 1:1 of PR and SD-Ag. SD-Ag was released stably and slowly within 6 d in vitro, and its cumulative release reached more than 85%. The mechanism of PR loading SD-Ag might be that SD-Ag attached to the edge of α-CD through hydrogen bonding. PR-(SD-Ag) showed a higher light stability than SD-Ag and held excellent antibacterial properties against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus).

Immobilization of an antimicrobial peptide on silicon surface with stable activity by click chemistry.

Infections associated with biomedical implants and devices pose a serious clinical challenge in hospitals worldwide. Antimicrobial peptides (AMPs) have become a great prospect to inhibit this type of infection due to their broad-spectrum antimicrobial activity and low cytotoxicity. However, it is still a challenge to apply AMPs on the biomaterial surface as the activity of AMPs is sensitive to salt or enzyme. In the present study, we prepared a spacer molecule, poly[2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (polySBMA), on a model silicon surface via surface-initiated atom transfer radical polymerization (SI-ATRP). We then modified the antimicrobial peptide HHC36 (KRWWKWWRR) with l-propargylglycine (PraAMP) to improve its salt-tolerant activity and integrated PraAMP onto the spacer molecule using click chemistry. We employed X-ray photoelectron spectroscopy (XPS), contact angle goniometry, and atomic force microscopy (AFM) to confirm the success of the immobilization process. We also characterized the antimicrobial activity and stability of the surface with an antimicrobial assay. The results reveal that the modified surface exhibits good antimicrobial activity to inhibit 98.26% of E. coli, 83.72% of S. aureus, and 81.59% of P. aeruginosa. Furthermore, as compared to the control group without the polySBMA spacer, the modified surface improved its resistance to enzymolysis. An in vitro CCK-8 assay also illustrated that this surface showed negligible cytotoxicity to mouse bone mesenchymal stem cells.

Thermoresponsive Self-Assembled ß-Cyclodextrin-Modified Surface for Blood Purification.

For patients with liver failure, bilirubin (BR) is one of the endogenous toxins in their blood. Although blood purification can remove the bilirubin from the body in clinics, the detoxification system needs to be improved, and the cost needs to be decreased. In the present study, we developed a recyclable model surface that can strongly remove bilirubin. We first prepared adamantane (Ad) on a model gold surface by self-assembly. Then, we integrated the ß-cyclodextrin dimer (CDD) onto the surface with host-guest interactions between one of the CD cavities in the CDD and Ad. We characterized the surface with XPS, static contact angle measurements, and AFM. In addition, we employed QCM-D to characterize the preparation process as well as the detoxification of the surface. We demonstrated that this modified surface could strongly adsorb bilirubin through host-guest interactions between the CD cavities in the CDD and bilirubin and that the detoxification was improved 1.7 times (compared to the surface only with Ad). Interestingly, after characterization with QCM-D, this surface could be recycled due to the thermoresponsive property of the host-guest interaction between the CDD and Ad. After adsorbing the toxin and increasing the temperature to 45 °C, the CDD with bilirubin could be removed from the surface. Then, the refreshed surface with CDD could be prepared again at room temperature. This cycle could be repeated at least 3 times. Additionally, during each cycle, the modified surface exhibited good detoxification to bilirubin. This modified surface also showed strong resistance to plasma proteins, decreasing the adsorption of human serum albumin (HSA) and fibrinogen (Fg). An in vitro platelet adhesion assay showed that the adhesion of the platelets on the modified surface decreased and that the platelets were in an inactivated state. The hemolysis assay showed that this surface exhibited no hemolysis activity in the samples to red blood cells (RBCs). The CCK-8 assay showed that this surface had negligible cytotoxicity to L929 cells. This work has taken advantage of the host-guest self-assembly between ß-CD and BR/Ad for special recognizing adsorption, as well as the thermoresponse of ß-CD-Ad inclusion for recyclable application, and these results demonstrate that this technology has great potential for removing bilirubin and decreasing clinic costs.

Preparation of an antimicrobial surface by direct assembly of antimicrobial peptide with its surface binding activity.

Antimicrobial peptides (AMPs) are a broad prospect for clinical application against bacterial infections of biomaterials. However, a bottleneck exists as there is a lack of simple technology to prepare AMPs on biomaterials with sufficient activity, as the activity of AMP is dependent on the correct orientation on the biomaterial. In the present study, based on the conventional AMP (Tet213: KRWWKWWRRC) and surface binding peptide (SKHKGGKHKGGKHKG), we designed an Anchor-AMP that could be directly assembled onto the surface of the biomaterial and also showed excellent antimicrobial activity. By characterizing the surface using a quartz crystal microbalance with dissipation (QCM-D), contact angle, atom force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS), we found that Anchor-AMP could adsorb onto the titanium surface with a strong affinity. Different from Tet213 peptide, Anchor-AMP exhibits excellent antimicrobial activity on the titanium surface being able to inhibit 95.33% of Escherichia coli and 96.67% of Staphylococcus aureus after 2.5 h. The improved antimicrobial activity is a result of improved orientation of Anchor-AMP on the biomaterial compared to that of the Tet213 peptide. In addition, the antimicrobial activity of Anchor-AMP was active for more than 24 h. The CCK-8 assay illustrated that the modified titanium surface showed negligible cytotoxicity to bone marrow mesenchymal stem cells. The in vivo results showed that it exhibited excellent antimicrobial activity after 5 and 7 days, inhibiting 89.32% and 99.78% of S. aureus, respectively. We also demonstrated that Anchor-AMP could be applied on a variety of surfaces including gold (Au), polymethyl methacrylate (PMMA) and hydroxyapatite (HA) with strong affinity and good antimicrobial activity.