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Reliable determination of binding kinetics and affinity of DNA hybridization and single-base mismatches plays an essential role in systems biology, personalized and precision medicine. The standard tools are optical-based sensors that are difficult to operate in low cost and to miniaturize for high-throughput measurement. Biosensors based on nanowire field-effect transistors have been developed, but reliable and cost-effective fabrication remains a challenge. Here, we demonstrate that a graphene single-crystal domain patterned into multiple channels can measure time- and concentration-dependent DNA hybridization kinetics and affinity reliably and sensitively, with a detection limit of 10 pM for DNA. It can distinguish single-base mutations quantitatively in real time. An analytical model is developed to estimate probe density, efficiency of hybridization and the maximum sensor response. The results suggest a promising future for cost-effective, high-throughput screening of drug candidates, genetic variations and disease biomarkers by using an integrated, miniaturized, all-electrical multiplexed, graphene-based DNA array. Monitoring DNA binding and single-base mismatches accurately in real time is difficult, especially for miniaturized devices. Here the authors report a graphene field-effect transistor array capable of reliably measuring DNA hybridization kinetics and affinity at the picomolar level.

Advanced Glycation End Products (AGEs) are the molecular mediators that contribute to the progression of diabetic complications. However, there is a paucity of research on effective AGEs inhibitors and strategies for blocking the AGEs-RAGE pathway. To solve the problem, we synthesized polymetformin (PL), which for the first time proved the ability to inhibit AGEs formation and block the AGEs-RAGE pathway to protect the vascular from being damaged. Based on gene ontology (GO) analysis and Kegg enrichment, we found that PL could antagonize AGEs. Molecular docking and dynamics analyses showed that PL formed stable structures with AGEs through electrostatic interactions and hydrogen bonding. PL treatment altered AGEs structures have been proven in FT-IR results. The study discovered that PL interacted with AGEs via both non-covalent and covalent modifications, altering AGEs’ binding sites and antagonizing the AGEs-RAGE pathway. Immunofluorescence assays indicated lower levels of RAGE, IL-1β, and TNFα, while ROS assays demonstrated lower ROS levels, highlighting PL’s inhibitory effects and biocompatibility. Our work underscores PL’s potential to treat diabetic complications by elucidating its mechanism of action against the AGEs-RAGE pathway and inflammatory factors for the first time. This research provides insights for managing chronic illnesses linked to the AGEs-RAGE pathway beyond diabetes complications.

Background Adult full-thickness cutaneous wound repair suffers from an imbalanced immune response, leading to nonfunctional reconstructed tissue and fibrosis. Although various treatments have been reported, the immune-mediated tissue regeneration driven by biomaterial offers an attractive regenerative strategy for damaged tissue repair. Methods In this research, we investigated a specific bone marrow-derived mesenchymal stem cell (BMSC) sheet that was induced by the Traditional Chinese Medicine curcumin (CS-C) and its immunomodulatory effects on wound repair. Comparisons were made with the BMSC sheet induced without curcumin (CS-N) and control (saline). Results In vitro cultured BMSC sheets (CS-C) showed that curcumin promoted the proliferation of BMSCs and modified the features of produced extracellular matrix (ECM) secreted by BMSCs, especially the contents of ECM structural proteins such as fibronectin (FN) and collagen I and III, as well as the ratio of collagen III/I. Two-photon fluorescence (TPF) and second-harmonic generation (SHG) imaging of mouse implantation revealed superior engraftment of BMSCs, maintained for 35 days in the CS-C group. Most importantly, CS-C created a favorable immune microenvironment. The chemokine stromal cell-derived factor 1 (SDF1) was abundantly produced by CS-C, thus facilitating a mass migration of leukocytes from which significantly increased expression of signature T H 1 cells (interferon gamma) and M1 macrophages (tumor necrosis factor alpha) genes were confirmed at 7 days post-operation. The number of T H 1 cells and associated pro-inflammatory M1 macrophages subsequently decreased sharply after 14 days post-operation, suggesting a rapid type I immune regression. Furthermore, the CS-C group showed an increased trend towards M2 macrophage polarization in the early phase. CS-C led to an epidermal thickness and collagen deposition that was closer to that of normal skin. Conclusions Curcumin has a good regulatory effect on BMSCs and this promising CS-C biomaterial creates a pro-regenerative immune microenvironment for cutaneous wound healing.

Background/Aims: Bone marrow Mesenchymal stem cells (MSCs) are promising for promoting cutaneous wound healing through reinforcing cellular processes. We evaluated the effect of GFP-tagged MSCs transplantation on skin regeneration in excisional wounds in mice. Methods: MSCs from GFP-labeled transgenic mice were co-cultured with acellular dermal matrix (ADM) scaffolds, and MSC-ADM scaffolds were transplanted into surgical skin wounds of BALB/c mice. After implantation, the survival and behavior of MSCs were examined by second harmonic generation and two-photon excitation fluorescence imaging, western blotting and DNA amplification and sequencing. Results: GFP-tagged MSCs were retained inside the regenerating skin until day 14 post-transplantation. Alpha-smooth muscle actin (α-SMA) and vimentin (VIM) were detected at 3, 5, 7, and 14 days post-transplantation by immunofluorescence double labeling. Although the GFP + /α-SMA + - and GFP + /VIM + -cell numbers decreased gradually with healing time, α-SMA + - and VIM + -cell numbers significantly increased, most of them were endogenous functional cells which were related to angiogenesis and collagen fiber structural remodeling. Conclusion: Therefore, in the initial stage of wound healing, transplanted MSCs differentiated into functional cells and played paracrine roles to recruit more endogenous cells for tissue remodeling. With the disappearance of exogenous cells, endogenous cells were responsible for the latter stage of cutaneous wound healing.

In this paper, we generated polarization-independent ring-Airy beams by designing metasurfaces that can realize modulations of both phase and amplitude. In numerical simulation, such metasurfaces are designed by placing subwavelength rectangular slits in Au film uniformly. Two orthogonal types of slits, with orientation angles of 45 and −45 degrees, are used to obtain the binary phase profile in the light transmitted from the metasurface under illumination with either right circular polarization (RCP) or left circular polarization (LCP). This satisfies the phase required for Airy beam generation. Meanwhile, the difference between the phase profile under RCP illumination and that under LCP illumination is right 2π, which can be regarded as the same. This makes the metasurface available to generate Airy beams regardless of incident polarization. We also analyzed the auto-focusing, self-healing, and frequency-response properties of the generated Airy beams with different parameters. This work opens up more opportunities for applications of Airy beams.

Mesenchymal stem cells (MSCs) had been reported as a novel therapeutic strategy for non-healing diabetic cutaneous wound mainly by promoting the formation of extracellular matrix (ECM) and neovasculature. Collagen regeneration is one of the key processes of ECM remodeling in wound healing. Accordingly, rapid assessment of the collagen content in a noninvasive manner can promptly provide objective evaluation for MSC therapy of cutaneous wound healing and strength evidence to adjust therapeutic regimen. In the present study, noninvasive Raman microspectroscopy was used for tracing the regeneration status of collagen during diabetic wound healing with MSCs. Wound tissues of normal mice, diabetic mice, and MSC-treated diabetic mice were subjected to Masson trichrome staining assay and submitted to spectroscopic analysis by Raman microspectroscopy after wounding 7, 14, and 21 days. Masson trichrome staining demonstrated that there was more collagen deposition in diabetic + MSCs group relative to diabetic group. The relative intensity of Raman collagen peak positions at 937, 1004, 1321, 1452, and 1662 cm −1 increased in MSC-treated diabetic group compared to diabetic group, although normal mice group had the highest relative intensity of collagen peak bands. Correlation analysis suggested that the spectral bands had a high positive correlation with the collagen intensity detected by Masson trichrome staining in wound tissues of three groups. Our results demonstrate that Raman microspectroscopy has potential application in rapidly and quantitatively assessing diabetic wound healing with MSCs by monitoring collagen variation, which may provide a novel method for the study of skin regeneration.

There is still no suitable mice model that can completely mimic the human fulminant hepatitis, which sets a block for drug effect evaluation and mechanism researching of human fulminant hepatitis. The aim of this study was to establish an animal model able to mimic the main features of human fulminant hepatitis. Dimethylnitrosamine (DMN) was peritoneally injected to mice for liver injury induction. Serum biochemicals, and Prothrombin Time were tested, and Prothrombin activity was calculated, the liver tissue pathological changes were evaluated via macroscopic view observation, HE staining, immunochemical staining, and electron microscopy observation. The mRNA levels of TNF-a, Fas, and IL-1beta were tested with quantitative PCR assay. The serum levels of both ALT and AST were elevated significantly and showed a high plateau. Liver pathological changes were progressed before 48 hours post DMN injection and then started to restore. The mRNA and protein expression levels of TNF-α and IL-1β were significantly elevated. The PT started to extend from 36 hours and PTA was lower than 40% from then on. This kind of DMN induced mice liver injury is similar to human fulminant hepatitis in main features. This work provided a mice model which could mimic human fulminant hepatitis, and could be valuable for fulminant hepatitis mechanism research and liver protection drug evaluation.

Interstellar H sub(2)O and OH masers associated with massive star-forming regions can be classified into three morphological types: isolated H sub(2)O masers; isolated OH masers; and spatially overlapping OH/H sub(2)O maser groups. In a large sample of star-forming regions the total number of maser groups of each type is approximately equal. In order to account for these statistics we propose a pumping scheme based on a broadband radiative pump which produces inverted populations of both OH and H sub(2)O masers by a process involving predissociation and dissociation of H sub(2)O. This scheme overcomes some drawbacks of earlier radiative pumping models, and may account for the association of OH and H sub(2)O masers in massive star forming regions.

Interstellar H^sub 2^O and OH masers associated with massive star-forming regions can be classified into three morphological types: isolated H^sub 2^O masers; isolated OH masers; and spatially overlapping OH/H^sub 2^O maser groups. In a large sample of star-forming regions the total number of maser groups of each type is approximately equal. In order to account for these statistics we propose a pumping scheme based on a broadband radiative pump which produces inverted populations of both OH and H^sub 2^O masers by a process involving predissociation and dissociation of H^sub 2^O. This scheme overcomes some drawbacks of earlier radiative pumping models, and may account for the association of OH and H^sub 2^O masers in massive star forming regions.[PUBLICATION ABSTRACT]

An accessible model for interstellar OH/H sub(2)O maser associations is presented. It can be classified into radiative pumping model. It can close the dynamical cycle of H sub(2)O and OH species, and can give an interpretation on interstellar OH/H sub(2)O associations. A reasonable scheme for both regeneration and destruction of interstellar H sub(2)O and OH molecules is argued. Our model has overcome the defects of former radiative models, and is compatible with astronomical conditions. It is shown that the rotational population of H sub(2)O and OH in these regions is much less affected by collisions than by radiation. Some experiments have confirmed our proposal.