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A variety of studies have demonstrated the role of lipocalin 2 (LCN2) in both diabetes and neurological disorders. Nevertheless, the relationship between LCN2 and diabetic peripheral neuropathy (DPN) needs to be elucidated in humans. Therefore, this study aimed to investigate the association of LCN2 with DPN in type 2 diabetes (T2D). A total of 207 participants with T2D and 40 participants with normal glucose tolerance (NGT) were included in this study. All participants were classified into DPN group and non-DPN (NDPN) group based on the Toronto Clinical Neuropathy Scoring (TCNS). Demographic and biochemical parameters were measured. Serum LCN2 levels were determined using an ELISA technique. Serum LCN2 levels in NGT group were lower than those in either DPN group (P = 0.000) or NDPN group (P = 0.043), while serum LCN2 levels in DPN group were higher than NDPN group (P = 0.001). Moreover, serum LCN2 levels positively correlated to TCNS scores, which reflects neuropathy severity (r = 0.438, P = 0.000). Multivariate stepwise regression analysis showed that BMI, triglycerides, and diastolic pressure were independently associated with serum LCN2 in DPN. Additionally, logistic regression analysis demonstrated that LCN2 (odds ratio (OR) = 1.009) and diabetes duration (OR = 1.058) were independently associated with the occurrence of DPN in T2D. Our report reveals the association of serum LCN2 with DPN in T2D. LCN2 might be used to evaluate DPN severity and serve a role in the pathogenesis of DPN.

Endothelial metabolism is a promising target for vascular functional regulation and disease therapy. Glucose is the primary fuel for endothelial metabolism, supporting ATP generation and endothelial cell survival. Multiple studies have discussed the role of endothelial glucose catabolism, such as glycolysis and oxidative phosphorylation, in vascular functional remodeling. However, the role of the first gatekeepers of endothelial glucose utilization, glucose transporters, in the vasculature has long been neglected. Here, this review summarizes glucose transporter studies in vascular research. We mainly focus on GLUT1 and GLUT3 because they are the most critical glucose transporters responsible for most endothelial glucose uptake. Some interesting topics are also discussed, intending to provide directions for endothelial glucose transporter research in the future.

The volumetric bar-chart microfluidic chips (V-Chips) driven by chemical reaction-generated gas provide a promising platform for point-of-care (POC) visual biomarker quantitation. However, multiple limitations are encountered in conventional V-Chips, such as costly and complex chip fabrication, complicated assembly, and imprecise controllability of gas production. Herein, we introduced nanomaterial-mediated photothermal effects to V-Chips, and for the first time developed a new type of V-Chip, photothermal bar-chart microfluidic chip (PT-Chip), for visual quantitative detection of biochemicals without any bulky and costly analytical instruments. Immunosensing signals were converted to visual readout signals via photothermal effects, the on-chip bar-chart movements, enabling quantitative biomarker detection on a low-cost polymer hybrid PT-Chip with on-chip scale rulers. Four different human serum samples containing prostate-specific antigen (PSA) as a model analyte were detected simultaneously using the PT-Chip, with the limit of detection of 2.1 ng/mL, meeting clinical diagnostic requirements. Although no conventional signal detectors were used, it achieved comparable detection sensitivity to absorbance measurements with a microplate reader. The PT-Chip was further validated by testing human whole blood without the color interference problem, demonstrating good analytical performance of our method even in complex matrixes and thus the potential to fill a gap in current clinical diagnostics that is incapable of testing whole blood. This new PT-Chip driven by nanomaterial-mediated photothermal effects opens a new horizon of microfluidic platforms for instrument-free diagnostics at the point of care.

Elevated retinol binding protein 4 levels are associated with atherosclerosis in diabetic rats via JAK2/STAT3 signaling pathway

Solving large-scale l1 minimization problem is very important and has attracted much attentions in recent years. In this paper, we present an efficient method for solving this problem. To this end, we first reformulate this problem as a nonnegative constrained minimization problem. Then we propose a modulus-based iterative method to solve the nonnegative constrained minimization problem. Convergence analysis and the choice of near optimal parameter are presented. Experimental results are given to illustrate feasibility and effectiveness of our proposed method.

A novel and recoverable platform of polyurethane (PU) sponge-supported Au nanoparticle catalyst was obtained by a water-based in-situ preparation process. The structure, chemical, and morphology properties of this platform were characterized by XRD, TGA, SEM, FT-IR, and XPS. The Au/PU sponge platform exhibited excellent catalytic performances in catalytic reductions of p-nitrophenol and o-nitroaniline at room temperature, and both catalytic reactions could be completed within 4.5 and 1.5 min, respectively. Furthermore, the strong interaction between Au nanoparticles and the PU sponge enabled the catalyst system to maintain a high catalytic efficiency after 5 recycling times, since the PU sponge reduced the trend of leaching and aggregation of Au nanoparticles. The unique nature of Au nanoparticles and the porous PU sponge along with their strong interaction resulted in a highly efficient, recoverable, and cost-effective multifunctional catalyst. The AuNP/Sponge nanocatalyst platform has great potential for wide environmental and other catalytic applications.

Tuberculosis (TB), one of the deadliest infectious diseases, is caused by Mycobacterium tuberculosis (MTB) and remains a public health problem nowadays. Conventional MTB DNA detection methods require sophisticated infrastructure and well-trained personnel, which leads to increasing complexity and high cost for diagnostics and limits their wide accessibility in low-resource settings. To address these issues, we have developed a low-cost photothermal biosensing method for the quantitative genetic detection of pathogens such as MTB DNA on a paper hybrid device using a thermometer. First, DNA capture probes were simply immobilized on paper through a one-step surface modification process. After DNA sandwich hybridization, oligonucleotide-functionalized gold nanoparticles (AuNPs) were introduced on paper and then catalyzed the oxidation reaction of 3,3',5,5'-tetramethylbenzidine (TMB). The produced oxidized TMB, acting as a strong photothermal agent, was used for the photothermal biosensing of MTB DNA under 808 nm laser irradiation. Under optimal conditions, the on-chip quantitative detection of the target DNA was readily achieved using an inexpensive thermometer as a signal recorder. This method does not require any expensive analytical instrumentation but can achieve higher sensitivity and there are no color interference issues, compared to conventional colorimetric methods. The method was further validated by detecting genomic DNA with high specificity. To the best of our knowledge, this is the first photothermal biosensing strategy for quantitative nucleic acid analysis on microfluidics using a thermometer, which brings fresh inspirations on the development of simple, low-cost, and miniaturized photothermal diagnostic platforms for quantitative detection of a variety of diseases at the point of care.

Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are one of the main causes of the development of diabetic atherosclerotic process. The aim of our study was to assess the role of RBP4 in the proliferation and migration of VSMCs and the inhibitory effect of vitamin D on the mechanisms. In an in vivo experiment, rats were randomly classified into 6 groups: the control group, diabetic rats, diabetic atherosclerotic rats (diabetic rats intraperitoneally injected with RBP4), diabetic atherosclerotic rats treated with 0.075 μg kg-1 d-1 vitamin D, 0.15 μg kg-1 d-1 vitamin D and 0.3 μg kg-1 d-1 vitamin D. We found that the levels of JAK2, STAT3, cylinD1, and Bcl-2 were increased in diabetic atherosclerotic rats, and these increases were improved after vitamin D supplementation. Furthermore, to investigate the underlying molecular mechanisms, cells were cultured with glucose in the presence of RBP4 and the absence of RBP4, respectively, and vitamin D of different concentrations and different intervention times was simultaneously adopted. The proliferation and migration of VSMCs was enhanced and the levels of JAK2, STAT3, cyclinD1, and Bcl-2 were increased in the cells transfected with RBP4 overexpression plasmid. Moreover, vitamin D supplementation was detected to lower the expressions of JAK2, STAT3, cyclinD1, and Bcl-2 and inhibit the abnormal proliferation of VSMCs caused by the RBP4/JAK2/STAT3 signaling pathway. RBP4 can promote the proliferation and migration of VSMCs and contributes to the development of diabetic macroangiopathy via regulating the JAK2/STAT3 signaling pathway. This mechanism of RBP4 can be inhibited by vitamin D supplementation.

Paper-based microfluidic devices have undergone rapid development and offered a promising low-cost platform for disease diagnostics in poor-resource areas. Recently, paper-hybrid microfluidic devices have attracted much attention and been applied in various low-cost point-of-care testings, due to multiple merits derived from both paper and other substrates. This chapter summarizes the recent progress of low-cost paper and paper-hybrid microfluidic devices for rapid diagnostics of human diseases. The commonly used fabrication techniques are first introduced, and the applications of numerous paper and paper-hybrid microfluidic devices are then elaborated with an emphasis on rapid disease diagnostics in terms of the nature of biomolecules in three major categories, namely, protein-, gene-, and cell-based diagnostics. Both advantages and disadvantages of using these devices are discussed, followed by the perspectives for broad applications in low-cost diagnostics.

Type 2 diabetes mellitus (T2DM) is a metabolic disease with increasing prevalence and mortality year by year. The purpose of this study was to explore new therapeutic targets and candidate drugs for multitargets by single-cell RNA expression profile analysis, network pharmacology, and molecular docking. Single-cell RNA expression profiling of islet β cell samples between T2DM patients and nondiabetic controls was conducted to identify important subpopulations and the marker genes. The potential therapeutic targets of T2DM were identified by the overlap analysis of insulin-related genes and diabetes-related genes, the construction of protein-protein interaction network, and the molecular complex detection (MCODE) algorithm. The network distance method was employed to determine the potential drugs of the target. Molecular docking and molecular dynamic simulations were carried out using AutoDock Vina and Gromacs2019, respectively. Eleven cell clusters were identified by single-cell RNA sequencing (scRNA-seq) data, and three of them (C2, C8, and C10) showed significant differences between T2DM samples and normal samples. Eight genes from differential cell clusters were found from differential cell clusters to be associated with insulin activity and T2DM. The MCODE algorithm built six key subnetworks, with five of them correlating with inflammatory pathways and immune cell infiltration. Importantly, CCR5 was a gene within the key subnetworks and was differentially expressed between normal samples and T2DM samples, with the highest area under the ROC curve (AUC) of 82.5% for the diagnosis model. A total of 49 CCR5-related genes were screened, and DB05494 was identified as the most potential drug with the shortest distance to CCR5-related genes. Molecular docking illustrated that DB05494 stably bound with CCR5 (-8.0 kcal/mol) through multiple hydrogen bonds (LYS26, TYR37, TYR89, CYS178, and GLN280) and hydrophobic bonds (TRP86, PHE112, ILE198, TRP248, and TYR251). This study identified CCR5 as a potential therapeutic target and screened DB05494 as a potential drug for T2DM treatment.

Patients arrive in burn centers with many etiologies of burn incidence (such as scald, contact, flame, steam, etc.). Treatment of these injuries depends on the burn depth and surface area of these burns. Moreover, earlier diagnosis and treatment of these burns lead to better patient outcomes. In this study, we show that THz-TDS imaging with a neural network classification algorithm can reproducibly classify burns, independent of their etiology, with an ROC-AUC of 88% in a porcine model.