CD8+ T and NK cells characterized by upregulation of NPEPPS and ABHD17A are associated with the co-occurrence of type 2 diabetes and coronary artery disease.

Background: Coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) are closely related. The function of immunocytes in the pathogenesis of CAD and T2DM has not been extensively studied. The quantitative bioinformatics analysis of the public RNA sequencing database was applied to study the key genes that mediate both CAD and T2DM. The biological characteristics of associated key genes and mechanism of CD8+ T and NK cells in CAD and T2DM are our research focus. Methods: With expression profiles of GSE66360 and GSE78721 from the Gene Expression Omnibus (GEO) database, we identified core modules associated with gene co-expression relationships and up-regulated genes in CAD and T2DM using Weighted Gene Co-expression Network Analysis (WGCNA) and the 'limma' software package. The enriched pathways of the candidate hub genes were then explored using GO, KEGG and GSEA in conjunction with the immune gene set (from the MSigDB database). A diagnostic model was constructed using logistic regression analysis composed of candidate hub genes in CAD and T2DM. Univariate Cox regression analysis revealed hazard ratios (HRs), 95% confidence intervals (CIs), and p-values for candidate hub genes in diagnostic model, while CIBERSORT and immune infiltration were used to assess the immune microenvironment. Finally, monocytes from peripheral blood samples and their immune cell ratios were analyzed by flow cytometry to validate our findings. Results: Sixteen candidate hub genes were identified as being correlated with immune infiltration. Univariate Cox regression analysis revealed that NPEPPS and ABHD17A were highly correlated with the diagnosis of CAD and T2DM. The results indicate that CD8+ T cells (p = 0.04) and NKbright cells (p = 3.7e-3) are significantly higher in healthy controls than in individuals with CAD or CAD combined with T2DM. The bioinformatics results on immune infiltration were well validated by flow cytometry. Conclusions: A series of bioinformatics studies have shown ABHD17A and NPEPPS as key genes for the co-occurrence of CAD and T2DM. Our study highlights the important effect of CD8+ T and NK cells in the pathogenesis of both diseases, indicating that they may serve as viable targets for diagnosis and therapeutic intervention.

Design and fabrication of wearable electronic textiles using twisted fiber-based threads.

Mono-dimensional fiber-based electronics can effectively address the growing demand for improved wearable electronic devices because of their exceptional flexibility and stretchability. For practical applications, functional fiber electronic devices need to be integrated into more powerful and versatile systems to execute complex tasks that cannot be completed by single-fiber devices. Existing techniques, such as printing and sintering, reduce the flexibility and cause low connection strength of fiber-based electronic devices because of the high curvature of the fiber. Here, we outline a twisting fabrication process for fiber electrodes, which can be woven into functional threads and integrated within textiles. The design of the twisted thread structure for fiber devices ensures stable interfacing and good flexibility, while the textile structure features easily accessible, interlaced points for efficient circuit connections. Electronic textiles can be customized to act as displays, health monitors and power sources. We detail three main fabrication sections, including the fabrication of the fiber electrodes, their twisting into electronic threads and their assembly into functional textile-based devices. The procedures require ~10 d and are easily reproducible by researchers with expertise in fabricating energy and electronic devices.

DNMT1-mediated NR3C1 DNA methylation enables transcription activation of connexin40 and augments angiogenesis during colorectal cancer progression.

Colorectal cancer (CRC) continues to be a major contributor to cancer-related mortality. Connexin 40 (CX40) is one of the major gap junction proteins with the capacity in regulating cell-to-cell communication and angiogenesis. This study investigates its role in angiogenesis in CRC and explores the regulatory mechanism. Aberrant high CX40 expression was detected in tumor tissues, which was associated with a poor prognosis in CRC patients. Elevated CX40 expression was detected in CRC cell lines as well. Conditioned medium of SW620 and HT29 cell lines was used to induce angiogenesis of human umbilical vein endothelial cells (HUVECs). CX40 knockdown in CRC cells reduced angiogenesis and mobility of HUVECs and blocked CRC cell proliferation, mobility, and survival. Following bioinformatics predictions, we validated by chromatin immunoprecipitation and luciferase assays that nuclear receptor subfamily 3 group C member 1 (NR3C1), which was poorly expressed in CRC samples, suppressed CX40 transcription. The poor NR3C1 expression was attributive to DNA hypermethylation induced by DNA methyltransferase 1 (DNMT1). Restoration of NR3C1 suppressed the pro-angiogenic effect, proliferation and survival, and tumorigenic activity of CRC cells, which were, however, rescued by CX40 upregulation. Collectively, this study demonstrates that transcription activation of CX40 upon DNMT1-mediated NR3C1 DNA methylation potentiates angiogenesis in CRC.

Optimizing retrieval spaces of bio-optical models for remote sensing of ocean color.

We investigated the optimal number of independent parameters required to accurately represent spectral remote sensing reflectances (R rs) by performing principal component analysis on quality controlled in situ and synthetic R rs data. We found that retrieval algorithms should be able to retrieve no more than four free parameters from R rs spectra for most ocean waters. In addition, we evaluated the performance of five different bio-optical models with different numbers of free parameters for the direct inversion of in-water inherent optical properties (IOPs) from in situ and synthetic R rs data. The multi-parameter models showed similar performances regardless of the number of parameters. Considering the computational cost associated with larger parameter spaces, we recommend bio-optical models with three free parameters for the use of IOP or joint retrieval algorithms.

Low temperature synthesis of carbon dots in microfluidic chip and their application for sensing cefquinome residues in milk.

In this study, the N-doped carbon dots were continuously synthesized by a facile microfluidic strategy at 90 °C, and their quantum yields reached 19.2%. The characteristics of the obtained carbon dots could be real-time monitored in order to synthesize carbon dots with specific properties. By incorporating the carbon dots into a well-established enzymatic cascade amplification system, an inner filter effect-based fluorescence immunoassay was set up for ultrasensitive detection of cefquinome residues in milk samples. The developed fluorescence immunoassay provided a low detection limit of 0.78 ng/mL, which satisfied the maximum residue limit set by authorities. The fluorescence immunoassay had an 50% inhibition concentration of 0.19 ng/mL against cefquinome and showed a good linear relationship from 0.013 ng/mL to 1.52 ng/mL. While, the average recovery values ranged from 77.8% to 107.8% in spiked milk samples, with relative standard deviations ranging from 6.8% to 10.9%. Compared with conventional methods, the microfluidic chip was more flexible on carbon dots synthesis and the developed fluorescence immunoassay was more sensitive and eco-friendlier for ultra-trace cefquinome residue analysis.

Activity-balanced GLP-1/GDF15 dual agonist reduces body weight and metabolic disorder in mice and non-human primates.

Obesity is a considerable health concern with limited pharmacotherapy options of low efficacy. Here, we develop a GLP-1/GDF15 fusion protein and explore its weight-lowering potential in animals. The molecule, QL1005, is engineered via fusing GLP-1 and GDF15 analogs by a peptide linker and conjugating it to a fatty acid for time-action extension. In vitro, the potency of QL1005 is superior to the GLP-1 analog semaglutide. In obese mice, QL1005 induces reductions in body weight, food intake, insulin, fasting glucose, and triglycerides. Notably, these metabolic effects come as a result of activities emanating from both GLP-1 and GDF15, in an individual pathway-balanced fashion. In a cynomolgus monkey model of obesity, QL1005 reduces body weight, food intake, insulin, and glucose in a dose-dependent manner with limited incidence of GI side effects. Altogether, this long-acting, dual GLP-1/GDF15 molecule demonstrates the promise of poly-pharmaceutical approaches in metabolic drug discovery and development.

Aggregation-induced emission luminogens-encoded microspheres preparation and flow-through immunoaffinity chromatographic assay development for microcystin-LR analysis.

Despite decades of efforts, we are faced with the daunting task of on-site ultratrace environmental toxins detecting, especially the microcystins caused by water bloom. In this work, a novel fluorescent microsphere-based flow-through immunoaffinity chromatographic assay has been designed for detecting ultratrace microcystin-LR in water and aquatic products. The aggregation-induced emission luminogens were encapsulated into fluorescent microspheres to ensure microcystin-LR quantitation with a whole analytical time of less than 30 min. Furthermore, the colorimetric images were captured and quantitatively analyzed, which offered a limit of detection at 0.217 pg/mL and a limit of quantitation at 0.362 pg/mL in water and aquatic muscle samples. The developed immunoassays provide average recovery ranging from 79.1 % to 95.7 %, with relative standard deviations less than 13.4 %. Thus, the validated flow-through immunoaffinity chromatographic assay is an easy-to-use alternative for on-site screening of microcystin-LR in water and aquatic samples at picogram levels.

In-situ construction of fluorescent probes for hydrogen peroxide detection in mitochondria and lysosomes with on-demand modular assembling and double turn-on features.

Due to the diverse H2O2 distribution in organelles, fluorescent probes were usually required to be prepared separately, which limited the convenience and practicability. Herein, we reported a flexible strategy to in-situ construct H2O2 fluorescent probes in different organelles. A tetrazine fused probe TP was developed with rapid click reaction capacity and sensitive H2O2 response. When treated with H2O2, the turn-on fluorescence was effectively quenched by the tetrazine part. Only after click reaction with dienophiles, the fluorescence resumed. In application, cells were firstly treated with triphenylphosphorus tagged norbornene (TPP-NB) to label mitochondria, which was followed by the introduction of probe TP to trigger click reaction. The in-situ constructed probe P1 served as a local H2O2 sensor. In a similar way, probe P2 was in-situ constructed in lysosomes via probe TP and morpholine tagged norbornene (MP-NB). With this on-demand modular assembling and double turn-on features, our strategy to construct fluorescent probes presented high flexibility and anti-interference performance, which was expected to inspired more applications in biological studies.

A biocompatible ratiometric fluorescent nanoprobe for intracellular hydrogen sulfide accurate detection based on rare earth nanoparticle.

Hydrogen sulfide (H2S) is an important signal molecule involved in intracellular activities. To understand the role of H2S in cellular physiological and pathological process, the development of sensitive and selective methods, especially biocompatible assays, for efficient monitoring the level of H2S is necessary. Herein, we modified novel rare earth element europium (EU) based fluorescent nanospheres with azide (-N3) based sensor to construct an ingenious ratiometric fluorescent nanoprobe EU-N3. This nanoprobe showed excellent water solubility and high biocompatibility for intracellular H2S accurate detection. Nanoprobe EU-N3 had two obvious emission peaks, the green fluorescence peak at 540 nm increased according to the increasing of H2S concentration and the red fluorescence peak at 616 nm was stable as ratiometric reference. The fluorescence intensity ratio (I540/I616) displayed good linear response (R = 0.99136) in H2S range of 0.5 âˆ¼ 30 µM. The analytes response assay demonstrated that the nanoprobe EU-N3 possessed a better specificity for H2S, compared with other 9 anions and 3 cations. The cell viability assay indicated the nanoprobe EU-N3 had an excellent biocompatibility. The cell imaging showed that the proposed nanoprobe could be applied for detecting the intracellular H2S changes accurately in live cells. Such nanoprobe provided a safe and accurate strategy for intracellular H2S detection, which is helpful for the real-time H2S visualization in the live cell activities.

The Antiviral Effects of Jasminin via Endogenous TNF-α and the Underlying TNF-α-Inducing Action.

Previous studies have reported that recombinant tumor necrosis factor (TNF)-α has powerful antiviral activity but severe systematic side effects. Jasminin is a common bioactive component found in Chinese herbal medicine beverage "Jasmine Tea". Here, we report that jasminin-induced endogenous TNF-α showed antiviral activity in vitro. The underlying TNF-α-inducing action of jasminin was also investigated in RAW264.7 cells. The level of endogenous TNF-α stimulated by jasminin was first analyzed by an enzyme-linked immunosorbent assay (ELISA) from the cell culture supernatant of RAW264.7 cells. The supernatants were then collected to investigate the potential antiviral effect against herpes simplex virus 1 (HSV-1). The antiviral effects of jasminin alone or its supernatants were evaluated by a plaque reduction assay. The potential activation of the PI3K-Akt pathway, three main mitogen-activated protein kinases (MAPKs), and nuclear factor (NF)-κB signaling pathways that induce TNF-α production were also investigated. Jasminin induces TNF-α protein expression in RAW264.7 cells without additional stimuli 10-fold more than the control. No significant up-expression of type I, II, and III interferons; interleukins 2 and 10; nor TNF-ß were observed by the jasminin stimuli. The supernatants, containing jasminin-induced-TNF-α, showed antiviral activity against HSV-1. The jasminin-stimulated cells caused the simultaneous activation of the Akt, MAPKs, and NF-κB signal pathways. Furthermore, the pretreatment of the cells with the Akt, MAPKs, and NF-κB inhibitors effectively suppressed jasminin-induced TNF-α production. Our research provides evidence that endogenous TNF-α can be used as a strategy to encounter viral infections. Additionally, the Akt, MAPKs, and NF-κB signaling pathways are involved in the TNF-α synthesis that induced by jasminin.

Instantaneous photosynthetically available radiation models for ocean waters using neural networks.

Instantaneous photosynthetically available radiation (IPAR) at the ocean surface and its vertical profile below the surface play a critical role in models to calculate net primary productivity of marine phytoplankton. In this work, we report two IPAR prediction models based on the neural network (NN) approach, one for open ocean and the other for coastal waters. These models are trained, validated, and tested using a large volume of synthetic datasets for open ocean and coastal waters simulated by a radiative transfer model. Our NN models are designed to predict IPAR under a large range of atmospheric and oceanic conditions. The NN models can compute the subsurface IPAR profile very accurately up to the euphotic zone depth. The root mean square errors associated with the diffuse attenuation coefficient of IPAR are less than 0.011m-1 and 0.036m-1 for open ocean and coastal waters, respectively. The performance of the NN models is better than presently available semi-analytical models, with significant superiority in coastal waters.

Elucidating the surface compositions of Pd@PtnL core-shell nanocrystals through catalytic reactions and spectroscopy probes.

The catalytic behaviors or properties of bimetallic catalysts are highly dependent on the surface composition, but it has been a grand challenge to acquire such information. In this work, we employ Pd@PtnL core-shell nanocrystals with an octahedral shape and tunable Pt shell thickness as a model system to elucidate their surface compositions using catalytic reactions based upon the selective hydrogenation of butadiene and acetylene. Our results indicate that the surface of the core-shell nanocrystals changed from Pt-rich to Pd-rich when they were subjected to calcination under oxygen, a critical step involved in the preparation of many industrial catalysts. The inside-out migration can be attributed to both atomic interdiffusion and the oxidation of Pd atoms during the calcination process. The changes in surface composition were further confirmed using infrared and X-ray photoelectron spectroscopy. This work offers insightful guidance for the development and optimization of bimetallic catalysts toward various reactions.

Construction of Inverse Metal-Zeolite Interfaces via Area-Selective Atomic Layer Deposition.

The spatial confinement at metal-zeolite interfaces offers a powerful knob to steer the selectivity of chemical reactions on metal catalysts. However, encapsulating metal catalysts into small-pore zeolites remains a challenging task. Here, we demonstrate an inverse design of metal-zeolite interfaces, "metal-on-zeolite," constructed by area-selective atomic layer deposition. This inverse design bypasses the intrinsic synthetic issues associated with metal encapsulation, offering a potential solution for the fabrication of task-specific metal-zeolite interfaces for desired catalytic applications. Infrared spectroscopy and several probe reactions confirmed the spatial confinement effects at the inverse metal-zeolite interfaces.

Role of hypothalamic MAPK/ERK signaling and central action of FGF1 in diabetes remission.

The capacity of the brain to elicit sustained remission of hyperglycemia in rodent models of type 2 diabetes following intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1) is well established. Here, we show that following icv FGF1 injection, hypothalamic signaling by extracellular signal-regulated kinases 1 and 2 (ERK1/2), members of the mitogen-activated protein kinase (MAPK) family, is induced for at least 24 h. Further, we show that this prolonged response is required for the sustained antidiabetic action of FGF1 since it is abolished by sustained (but not acute) pharmacologic blockade of hypothalamic MAPK/ERK signaling. We also demonstrate that FGF1 R50E, a FGF1 mutant that activates FGF receptors but induces only transient hypothalamic MAPK/ERK signaling, fails to mimic the sustained glucose lowering induced by FGF1. These data identify sustained activation of hypothalamic MAPK/ERK signaling as playing an essential role in the mechanism underlying diabetes remission induced by icv FGF1 administration.

PAF enhances cancer stem cell properties via ß-catenin signaling in hepatocellular carcinoma.

Increasing proofs have declared that liver cancer stem cells (CSCs) are the main contributors to tumor initiation, metastasis, therapy resistance, and recurrence of hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying CSCs regulation remain largely unclear. Recently, PCNA-associated factor (PAF) was identified to play a key role in maintaining breast cancer cell stemness, but its role in liver cancer stem cells has not been declared yet. Herein, we found that both mRNA and protein expression levels of PAF were significantly higher in HCC tissues and cell lines than normal controls. CSC-enriched hepatoma spheres displayed an increase in PAF expression compared to monolayer-cultured cells. Both loss-of-function and gain-of-function experiments revealed that PAF enhanced sphere formation and the percentage of CD133+ or EpCAM+ cells in HCCLM3 and Huh7 cells. In the xenograft HCC tumor model, tumor initiation rates and tumor growth were suppressed by knockdown of PAF. Mechanistically, PAF can amplify the self-renewal of liver CSCs by activating ß-catenin signaling. Taken together, our results demonstrate that PAF plays a crucial role in maintaining the hepatoma cell stemness by ß-catenin signaling.Abbreviations: CSCs: cancer stem cells; HCC: hepatocellular carcinoma; PAF: pCNA-associated factor.

Fabrication of plasmonic cotton gauze-Ag composite as versatile SERS substrate for detection of pesticides residue.

Plasmonic cotton gauze-Ag composite were fabricated through a simple, instant and cost-effective way, in which the Ag NPs were immobilized on the surface of cotton gauze through in-situ growth process. The in-situ growth of Ag NPs was started from electroless-immobilized Ag seeds on the surface of cotton fiber, which could form numerous hot spots for SERS compared with current method. The cotton gauze-Ag composite was employed as versatile substrate in surface-enhanced Raman scattering (SERS) spectroscopy. The plasmonic cotton gauze-Ag exhibited excellent uniformity, temporal stability and enhanced effect for SERS measurement. The detection limit of P-aminothiopheno (PATP) was 10-8 M. Furthermore, the plasmonic cotton gauze-Ag composite presented excellent flexibility and adsorption capability, which enable to adsorb and detect pesticide residue from irregular surface of cucumber directly by simple swabbing process, the detection limit could achieve 0.1 ppm. The cotton gauze-Ag composite also shown excellent selectivity is SERS sensing. The fabrication method could be simply extended to other cellulose compound, such as absorbent cotton, paper and even for natural fibers. This study proposed a new method for fabricating the cost-effective, eco-friendly and flexible SERS substrates.

Atmospheric correction over the ocean for hyperspectral radiometers using multi-angle polarimetric retrievals.

We developed a fast and accurate polynomial based atmospheric correction (POLYAC) algorithm for hyperspectral radiometric measurements, which parameterizes the atmospheric path radiances using aerosol properties retrieved from co-located multi-wavelength multi-angle polarimeter (MAP) measurements. This algorithm has been applied to co-located spectrometer for planetary exploration (SPEX) airborne and research scanning polarimeter (RSP) measurements, where SPEX airborne was used as a proxy of hyperspectral radiometers, and RSP as the MAP. The hyperspectral remote sensing reflectance obtained from POLYAC is accurate when compared to Aerosol Robotic Network (AERONET), and Visible Infrared Imaging Radiometer Suite (VIIRS) ocean color products. POLYAC provides a robust alternative atmospheric correction algorithm for hyperspectral or multi-spectral radiometric measurements for scenes involving coastal oceans and/or absorbing aerosols, where traditional atmospheric correction algorithms are less reliable.

Large-area display textiles integrated with functional systems.

Displays are basic building blocks of modern electronics1,2. Integrating displays into textiles offers exciting opportunities for smart electronic textiles-the ultimate goal of wearable technology, poised to change the way in which we interact with electronic devices3-6. Display textiles serve to bridge human-machine interactions7-9, offering, for instance, a real-time communication tool for individuals with voice or speech difficulties. Electronic textiles capable of communicating10, sensing11,12 and supplying electricity13,14 have been reported previously. However, textiles with functional, large-area displays have not yet been achieved, because it is challenging to obtain small illuminating units that are both durable and easy to assemble over a wide area. Here we report a 6-metre-long, 25-centimetre-wide display textile containing 5 × 105 electroluminescent units spaced approximately 800 micrometres apart. Weaving conductive weft and luminescent warp fibres forms micrometre-scale electroluminescent units at the weft-warp contact points. The brightness between electroluminescent units deviates by less than 8 per cent and remains stable even when the textile is bent, stretched or pressed. Our display textile is flexible and breathable and withstands repeated machine-washing, making it suitable for practical applications. We show that an integrated textile system consisting of display, keyboard and power supply can serve as a communication tool, demonstrating the system's potential within the 'internet of things' in various areas, including healthcare. Our approach unifies the fabrication and function of electronic devices with textiles, and we expect that woven-fibre materials will shape the next generation of electronics.

Highly Selective Olefin Production from CO2 Hydrogenation on Iron Catalysts: A Subtle Synergy between Manganese and Sodium Additives.

Mn and Na additives have been widely studied to improve the efficiency of CO2 hydrogenation to valuable olefins on Fe catalysts, but their effects on the catalytic properties and mechanism are still under vigorous debate. This study shows that Fe-based catalysts with moderate Mn and Na contents are highly selective for CO2 hydrogenation to olefins, together with low selectivities for both CO and CH4 and much improved space-time olefin yields compared to state-of-the-art catalysts. Combined kinetic assessment and quasi in situ characterizations further unveil that the sole presence of Mn suppresses the activity of Fe catalysts because of the close contact between Fe and Mn, whereas the introduction of Na mediates the Fe-Mn interaction and provides strong basic sites. This subtle synergy between Na and Mn sheds light on the importance of the interplay of multiple additives that could bring an enabling strategy to improve catalytic activity and selectivity.