Nonlinear relationship between untraditional lipid parameters and the risk of prediabetes: a large retrospective study based on Chinese adults.

BACKGROUND: Abnormal lipid metabolism poses a risk for prediabetes. However, research on lipid parameters used to predict the risk of prediabetes is scarce, and the significance of traditional and untraditional lipid parameters remains unexplored in prediabetes. This study aimed to comprehensively evaluate the association between 12 lipid parameters and prediabetes and their diagnostic value. METHODS: This cross-sectional study included data from 100,309 Chinese adults with normal baseline blood glucose levels. New onset of prediabetes was the outcome of concern. Untraditional lipid parameters were derived from traditional lipid parameters. Multivariate logistic regression and smooth curve fitting were used to examine the nonlinear relationship between lipid parameters and prediabetes. A two-piecewise linear regression model was used to identify the critical points of lipid parameters influencing the risk of prediabetes. The areas under the receiver operating characteristic curve estimated the predictive value of the lipid parameters. RESULTS: A total of 12,352 participants (12.31%) were newly diagnosed with prediabetes. Following adjustments for confounding covariables, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol were negatively correlated with prediabetes risk. Conversely, total cholesterol, triglyceride (TG), lipoprotein combine index (LCI), atherogenic index of plasma (AIP), non-HDL-C, atherogenic coefficient, Castelli's index-I, remnant cholesterol (RC), and RC/HDL-C ratio displayed positive correlations. In younger adults, females, individuals with a family history of diabetes, and non-obese individuals, LCI, TG, and AIP exhibited higher predictive values for the onset of prediabetes compared to other lipid profiles. CONCLUSION: Nonlinear associations were observed between untraditional lipid parameters and the risk of prediabetes. The predictive value of untraditional lipid parameters for prediabetes surpassed that of traditional lipid parameters, with LCI emerging as the most effective predictor for prediabetes.

Polymer-DNA Carriers Co-Deliver Photosensitizer and siRNA for Light-Promoted Gene Transfection and Hypoxia-Relieved Photodynamic Therapy.

Photochemical internalization is an efficient strategy relying on photodynamic reactions to promote siRNA endosomal escape for the success of RNA-interference gene regulation, which makes gene-photodynamic combined therapy highly synergistic and efficient. However, it is still desired to explore capable carriers to improve the delivery efficiency of the immiscible siRNA and organic photosensitizers simultaneously. Herein, we employ a micellar nanostructure (PSNA) self-assembled from polymer-DNA molecular chimeras to fulfill this task. PSNA can plentifully load photosensitizers in its hydrophobic core simply by the nanoprecipitation method. Moreover, it can organize siRNA self-assembly by the densely packed DNA shell, which leads to a higher loading capacity than the typical electrostatic condensation method. The experimental results prove that this PSNA carrier can greatly facilitate siRNA escape from the endosome/lysosome and enhance transfection. Accordingly, the PSNA-administrated therapy exhibits a significantly improved anti-tumor efficacy owing to the highly efficient co-delivery capability.

Natural Mediterranean Spotted Fever Foci, Qingdao, China.

We sequenced DNA from spleens of rodents captured in rural areas of Qingdao, East China, during 2013-2015. We found 1 Apodemus agrarius mouse infected with Rickettsia conorii, indicating a natural Mediterranean spotted fever foci exists in East China and that the range of R. conorii could be expanding.

Light-Harvesting Fluorescent Spherical Nucleic Acids Self-Assembled from a DNA-Grafted Conjugated Polymer for Amplified Detection of Nucleic Acids.

The ultralow concentration of nucleic acids in complex biological samples requires fluorescence probes with high specificity and sensitivity. Herein, a new kind of spherical nucleic acids (SNAs) is developed by using fluorescent π-conjugated polymers (FCPs) as a light-harvesting antenna to enhance the signal transduction of nucleic acid detection. Specifically, amphiphilic DNA-grafted FCPs are synthesized and self-assemble into FCP-SNA structures. Tuning the hydrophobicity of the graft copolymer can adjust the size and light-harvesting capability of the FCP-SNAs. We observe that more efficient signal amplification occurs in larger FCP-SNAs, as more chromophores are involved, and the energy transfer can go beyond the Förster radius. Accordingly, the optimized FCP-SNA shows an antenna effect of up to 37-fold signal amplification and the limit of detection down to 1.7 pM in microRNA detection. Consequently, the FCP-SNA is applied to amplified in situ nucleic acid detecting and imaging at the single-cell level.

Molecular Dynamics Simulation Study of Aluminum-Copper Alloys' Anisotropy under Different Loading Conditions and Different Crystal Orientations.

The commonly used aluminum-copper alloys in industry are mainly rolled plates and extruded or drawn bars. The aluminum-copper alloys' anisotropy generated in the manufacturing process is unfavorable for subsequent applications. Its underlying mechanism shall be interpreted from a microscopic perspective. This paper conducted the loading simulation on Al-4%Cu alloy crystals at the microscopic scale with molecular dynamics technology. Uniaxial tension and compression loading were carried out along three orientations: X-<1¯12>, Y-<11¯1>, and Z-<110>. It analyzes the micro-mechanisms that affect the performance changes of aluminum-copper alloys through the combination of stress-strain curves and different organizational analysis approaches. As shown by the results, the elastic modulus and yield strength are the highest under tension along the <11¯1> direction. Such is the case for the reasons below: The close-packed plane of atoms ensures large atomic binding forces. In addition, the Stair-rod dislocation forms a Lomer-Cottrell dislocation lock, which has a strengthening effect on the material. The elastic modulus and yield strength are the smallest under tension along the <110> direction, and the periodic arrangement of HCP atom stacking faults serves as the main deformation mechanism. This is because the atomic arrangement on the <110> plane is relatively loose, which tends to cause atomic misalignment. When compressed in different directions, the plastic deformation mechanism is mainly dominated by dislocations and stacking faults. When compressed along the <110> direction, it has a relatively high dislocation density and the maximum yield strength. That should be attributed to the facts below. As the atomic arrangement of the <110> plane itself was not dense originally, compression loading would cause an increasingly tighter arrangement. In such a case, the stress could only be released through dislocations. This research aims to provide a reference for optimizing the processing technology and preparation methods of aluminum-copper alloy materials.

Identifying metabolic dysfunction-associated steatotic liver disease in patients with hypertension and pre-hypertension: An interpretable machine learning approach.

Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the most prevalent liver diseases and is associated with pre-hypertension and hypertension. Our research aims to develop interpretable machine learning (ML) models to accurately identify MASLD in hypertensive and pre-hypertensive populations. Methods: The dataset for 4722 hypertensive and pre-hypertensive patients is from subjects in the NAGALA study. Six ML models, including the decision tree, K-nearest neighbor, gradient boosting, naive Bayes, support vector machine, and random forest (RF) models, were used in this study. The optimal model was constructed according to the performances of models evaluated by K-fold cross-validation (k = 5), the area under the receiver operating characteristic curve (AUC), average precision (AP), accuracy, sensitivity, specificity, and F1. Shapley additive explanation (SHAP) values were employed for both global and local interpretation of the model results. Results: The prevalence of MASLD in hypertensive and pre-hypertensive patients was 44.3% (362 cases) and 28.3% (1107 cases), respectively. The RF model outperformed the other five models with an AUC of 0.889, AP of 0.800, accuracy of 0.819, sensitivity of 0.816, specificity of 0.821, and F1 of 0.729. According to the SHAP analysis, the top five important features were alanine aminotransferase, body mass index, waist circumference, high-density lipoprotein cholesterol, and total cholesterol. Further analysis of the feature selection in the RF model revealed that incorporating all features leads to optimal model performance. Conclusions: ML algorithms, especially RF algorithm, improve the accuracy of MASLD identification, and the global and local interpretation of the RF model results enables us to intuitively understand how various features affect the chances of MASLD in patients with hypertension and pre-hypertension.

TG2 participates in pulmonary vascular remodelling by regulating the senescence of pulmonary artery smooth muscle cells.

Pulmonary hypertension (PH) is a severe cardiovascular disease characterised by pulmonary vascular remodelling. The pivotal role of cellular senescence in vascular remodelling has been acknowledged. Transglutaminase type 2 (TG2), a calcium-dependent enzyme, is intricately linked to both cellular senescence and PH. However, the precise mechanisms underlying the involvement of TG2 in PH remain unclear. In this study, we explored the expression of TG2 and the cellular senescence marker p16INK4a in the pulmonary vasculature of mice with PH induced by hypoxia combined with SU5416. Our findings revealed upregulation of both TG2 and p16INK4a expression in the pulmonary vasculature of PH mice. Additionally, a notable increase in TG2 expression was observed in senescent pulmonary artery smooth muscle cells (PASMC). To delve deeper, we employed proteomic sequencing to reveal seven genes associated with cellular senescence, with a subsequent focus on MAPK14. Our investigation revealed that TG2 regulates senescence in PASMC by modulating the phosphorylation levels of MAPK14. Additionally, in the context of hypoxia combined with SU5416, our observations revealed a noteworthy reduction in both pulmonary vascular remodelling and senescent manifestations in smooth muscle-specific TG2 knockout mice compared with their wild-type counterparts. In summary, our findings indicate that TG2 deficiency lowers the senescence levels of PASMC by inhibiting the activity of MAPK14. This inhibition of senescence in the pulmonary vasculature of PH mice helps to decelerate the progression of pulmonary vascular remodelling and consequently hinders the onset and development of PH.

Micro-interfacial behavior of antibiotic-resistant bacteria and antibiotic resistance genes in the soil environment: A review.

Overutilization and misuse of antibiotics in recent decades markedly intensified the rapid proliferation and diffusion of antibiotic resistance genes (ARGs) within the environment, thereby elevating ARGs to the status of a global public health crisis. Recognizing that soil acts as a critical reservoir for ARGs, environmental researchers have made great progress in exploring the sources, distribution, and spread of ARGs in soil. However, the microscopic state and micro-interfacial behavior of ARGs in soil remains inadequately understood. In this study, we reviewed the micro-interfacial behaviors of antibiotic-resistant bacteria (ARB) in soil and porous media, predominantly including migration-deposition, adsorption, and biofilm formation. Meanwhile, adsorption, proliferation, and degradation were identified as the primary micro-interfacial behaviors of ARGs in the soil, with component of soil serving as significant determinant. Our work contributes to the further comprehension of the microstates and processes of ARB and ARGs in the soil environments and offers a theoretical foundation for managing and mitigating the risks associated with ARG contamination.

Trypsin Encapsulation in the Zeolitic Imidazolate Framework for Low-Molecular Weight Protein Analysis with High Selectivity and Efficiency.

Low-molecular weight proteins (LWPs) are important sources of biological information in biomarkers, signaling molecules, and pathology. However, the separation and analysis of LWPs in complex biological samples are challenging, mainly due to their low abundance and the complex sample pretreatment procedure. Herein, trypsin modified by poly(acrylic acid) (PAA) was encapsulated by a zeolitic imidazolate framework (ZIF-L). Mesopores were formed on the ZIF-L with the introduction of PAA. An alternative strategy for separation and pretreatment of LWPs was developed based on the prepared ZIF-L-encapsulated trypsin with adjustable pore size. The mesoporous structure of the prepared materials selectively excluded high-molecular weight proteins from the reaction system, allowing LWPs to enter the pores and react with the internal trypsin, resulting in an improved separation efficiency. The hydrophobicity of the ZIF-L simplified the digestion process by inducing significant structural changes in substrate proteins. In addition, the enzymatic activity was significantly enhanced by the developed encapsulation method that maintained the enzyme conformation, allowed low mass transfer resistance, and possessed a high enzyme-to-substrate ratio. As a result, the ZIF-L-encapsulated trypsin can achieve highly selective separation, valid denaturation, and efficient digestion of LWPs in a short time by simply mixing with substrate proteins, greatly simplifying the separation and pretreatment process of the traditional hydrolysis method. The prepared materials and the developed strategy demonstrated an excellent size-selective assay performance in model protein mixtures, showing great potential in the application of proteomics analysis.

Dual-functionalized two-dimensional metal-organic framework composite with highly hydrophilicity for effective enrichment of glycopeptides.

Protein glycosylation research is currently focused on the development of various functionalized materials that can effectively enrich the levels of glycopeptides in samples. However, most of these materials possess limited glycopeptide-specific recognition sites because of large steric hindrance, unsuitable mass transfer kinetics, and relatively low surface areas. Herein, a highly hydrophilic two-dimensional (2-D) metal-organic framework (MOF) nanosheet modified with glutathione (GSH) and l-cysteine (l-Cys) (denoted as Zr-Fc MOF@Au@GC) has been synthesized for efficient glycopeptide enrichment. Using this composite material, 39 and 44 glycopeptides from horseradish peroxidase (HRP) and human serum immunoglobulin G (IgG) digests were detected, respectively, which represents a higher efficiency for glycopeptide enrichment from model glycoprotein digests than has been previously reported. The material Zr-Fc MOF@Au@GC exhibited ultra-high sensitivity (0.1 fmol/µL), excellent selectivity (weight ratio of HRP tryptic digest to bovine serum albumin (BSA) tryptic digest = 1:2000), good binding capacity (200 mg/g), satisfactory reusability, and long-term storage capacity. In addition, 655 glycopeptides corresponding to 366 glycoproteins were identified from human serum samples. To the best of our knowledge, this is the largest number of glycoproteins detected in human serum samples to date. These results indicated that Zr-Fc MOF@Au@GC has the potential to be used for the enrichment of glycopeptides in biological samples and the analysis of protein glycosylation.