Exposure to cadmium and lead is associated with diabetic kidney disease in diabetic patients.

BACKGROUND: Cadmium (Cd) and lead (Pb) exhibit nephrotoxic activity and may accelerate kidney disease complications in diabetic patients, but studies investigating the relation to diabetic kidney disease (DKD) have been limited. We aimed to examine the associations of Cd and Pb with DKD in diabetic patients. METHODS: 3763 adults with blood metal measurements and 1604 adults with urinary ones who were diabetic from National Health and Nutrition Examination Survey (NHANES) 2007-2016 were involved. Multivariate logistic regression models were used to analyze the associations of blood Cd (BCd), blood Pb (BPb), urinary Cd (UCd), and urinary Pb (UPb) with DKD. RESULTS: BPb, BCd, and UCd levels were higher among participants with DKD than diabetics without nephropathy, but UPb performed the opposite result. BPb and UCd were significantly associated with DKD in the adjusted models (aOR, 1.17 (1.06, 1.29);1.52 (1.06, 2.02)). Participants in the 2nd and 3rd tertiles of BPb and BCd levels had higher odds of DKD, with a significant trend across tertiles, respectively (all P-trend < 0.005). Multiplication interaction was also identified for BPb and BCd (P for interaction = 0.044). CONCLUSION: BPb, BCd, and UCd were positively associated with the risk of DKD among diabetic patients. Furthermore, there were the dose-response relationship and multiplication interaction in the associations of BPb, BCd with DKD.

Associations between dietary magnesium intake and hypertension, diabetes, and hyperlipidemia.

Hypertension, diabetes, and hyperlipidemia significantly impact chronic diseases and mortality. Magnesium is an essential nutrient for maintaining critical physiological functions, and magnesium deficiency is often associated with adverse health outcomes. In a cross-sectional study of US adults, we aimed to explore dietary magnesium intake and its association with the prevalence of hypertension, diabetes, and hyperlipidemia in US adults over 20 years of age in NHANES 2007-2018. We obtained data on 24,171 samples of hypertension, 9950 samples of diabetes, and 12,149 samples of hyperlipidemia. We used multivariable logistic regression models adjusted for multiple sociodemographic, anthropometric, and lifestyle factors, with participants subdivided into five groups based on quintiles of daily dietary magnesium. After adjusting for the major lifestyle and dietary variables, an independent and significant inverse relationship between dietary magnesium and hypertension, diabetes, and hyperlipidemia was observed. Compared with the lowest quintile of magnesium intake, the prevalence of hypertension, diabetes, and hyperlipidemia was significantly reduced in the highest magnesium quintile. The OR of hypertension in the highest quintile was 0.66 (95% CI: 0.51-0.87; P trend < 0.001), the OR of diabetes was 0.56 (95% CI: 0.39-0.81; P trend < 0.001), and the OR of hyperlipidemia was 0.68 (95% confidence interval: 0.53-0.86; P trend = 0.007). In the subgroup analysis, most of the inverse relationships persisted. Our findings highlight the potential of magnesium-rich foods to prevent hypertension, diabetes, and hyperlipidemia in US adults. This article summarizes and discuss recent findings on: 1) A high dietary magnesium intake was associated with a lower prevalence of hypertension; 2) An inverse relationship between dietary magnesium with diabetes hyperlipidemia; 3) Monitoring and management of magnesium was important.

Exploring the molecular mechanism underlying the psoriasis and T2D by using microarray data analysis.

Although a large number of evidence has identified that psoriasis is significantly correlated with type 2 diabetes (T2D), the common molecular mechanism of its occurrence remains unclear. Our study aims to further elucidate the mechanism of the occurrence of this complication. We obtained the gene expression data of psoriasis (GSE30999) and T2D (GSE28829) from the Gene Expression Omnibus (GEO) dataset. Then the common differentially expressed genes (DEGs) of T2D and psoriasis were identified. After that, we performed three types of analyses about these DEGs, including functional enrichment analysis, protein-protein interaction (PPI) network and module manufacture, hub genes identification and co-expression analysis. 132 common DEGs (14 upregulated genes and 118 downregulated genes) were identified for subsequent a series of analyses. Function enrichment analysis demonstrated that Rap1 signaling pathway, PI3K-Akt signaling pathway, and cGMP-PKG signaling pathway may play a significant role in pathogenesis of psoriasis and T2D. Finally, 3 important hub genes were selected by utilizing cytoHubba, including SNRPN, GNAS, IGF2. Our work reveals the potential common signaling pathways of psoriasis and T2D. These Hub genes and common signaling pathways provide insights for further investigation of molecular mechanism about psoriasis and T2D.

Adaptive Neural Backstepping Terminal Sliding Mode Control of a DC-DC Buck Converter.

In this paper, an adaptive backstepping terminal sliding mode control (ABTSMC) method based on a double hidden layer recurrent neural network (DHLRNN) is proposed for a DC-DC buck converter. The DHLRNN is utilized to approximate and compensate for the system uncertainty. On the basis of backstepping control, a terminal sliding mode control (TSMC) is introduced to ensure the finite-time convergence of the tracking error. The effectiveness of the composite control method is verified on a converter prototype in different test conditions. The experimental comparison results demonstrate the proposed control method has better steady-state performance and faster transient response.

Xanthine oxidase, a therapeutic target of realgar for non-small cell lung cancer.

Background: The effects of realgar against non-small cell lung cancer (NSCLC) have been massively studied, but the direct therapeutic targets of realgar remain unclear. This study aimed to identify the molecular targets of realgar against NSCLC and explore their therapeutic mechanisms based on a network pharmacology approach and experimental validations. Methods: The BATMAN-TCM and Digsee databases were used to predict realgar targets and NSCLC-related genes, respectively. A protein-protein interaction network was constructed for each gene set, and the overlapping genes were identified as potential targets of realgar against NSCLC. The correlation between potential targets and NSCLC was analyzed using The Cancer Genome Atlas and International Cancer Genome Consortium databases, and the key target was validated by in-silico and in-vitro experiments. Results: Twenty-three overlapping genes, including xanthine oxidase (XO), were identified as potential targets of realgar against NSCLC. XO was selected as the key target for validation, as it was found to be upregulated in NSCLC tumor tissue, which correlated with poor overall survival. A possible interaction between realgar and XO was revealed by molecular docking which was further validated experimentally. Realgar treatment suppressed the activity of XO in NSCLC cells, as demonstrated by the unchanged XO protein levels. Finally, the mechanism of action of XO as a target against NSCLC through the cell-cell junction organization pathway was investigated. Conclusions: Overall, this study proposes a potential molecular mechanism illustrating that XO is a target of realgar against NSCLC and highlights the usefulness of XO as a therapeutic target for NSCLC.

Non-autofluorescence Detection of H5N1 Virus Using Photochemical Aptamer Sensors Based on Persistent Luminescent Nanoparticles.

Fluorescence sensing is limited in practical applications owing to multiple autofluorescent substances in complex biological samples such as serum. In this paper, the luminescence decay effect of persistent luminescent nanoparticles (PLNPs) was used to avoid the interference of autofluorescence in complex biological samples, and a non-autofluorescence molecularly imprinted polymer aptamer sensor (MIP-aptasensor) was designed to detect H5N1 virus. The proposed MIP-aptasensor consists of a magnetic MIP and aptamer-functionalized persistent luminescent nanoparticle Zn2GeO4:Mn2+-H5N1 aptamer (ZGO-H5N1 Apt). Upon simultaneous recognition of H5N1 virus, strong persistent luminescent signal changes were produced. Using the unique luminescent characteristics of PLNPs and the high selectivity of imprinted polymers and aptamers, the designed MIP-aptasensor effectively eliminates the autofluorescence background interference of serum samples and realizes the non-autofluorescence detection of H5N1 virus with high sensitivity (a limit of detection of 0.0128 HAU mL-1, 1.16 fM) and selectivity (the imprinting factor for the target H5N1 virus was 6.72). This tool provides a strategy for the design of sensors and their application in complex biological samples.

Effects of macrophages on the proliferation and cardiac differentiation of human induced pluripotent stem cells.

BACKGROUND: Macrophage phenotypes switch from proinflammatory (M1) to anti-inflammatory (M2) following myocardial injury. Implanted stem cells (e.g., induced pluripotent stem cells (iPSCs)) for cardiomyogenesis will inevitably contact the inflammatory environment at the myocardial infarction site. To understand how the macrophages affect the behavior of iPSCs, therefore, improve the therapeutic efficacy, we generated three macrophage subtypes and assessed their effects on the proliferation, cardiac differentiation, and maturation of iPSCs. METHODS: M0, M1, and M2 macrophages were polarized using cytokines, and their properties were confirmed by the expression of specific markers using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence. The effects of macrophages on iPSCs were studied using Transwell co-culture models. The proliferative ability of iPSCs was investigated by cell counting and CCK-8 assays. The cardiac differentiation ability of iPSCs was determined by the cardiomyocyte (CM) yield. The maturation of CM was analyzed by the expression of cardiac-specific genes using RT-qPCR, the sarcomere organization using immunofluorescence, and the mitochondrial function using oxidative respiration analysis. RESULTS: The data showed that the co-culture of iPSCs with M0, M1, or M2 macrophages significantly decreased iPSCs' proliferative ability. M2 macrophages did not affect the CM yield during the cardiac differentiation of iPSCs. Still, they promoted the maturation of CM by improving sarcomeric structures, increasing contractile- and ion transport-associated gene expression, and enhancing mitochondrial respiration. M0 macrophages did not significantly affect the cardiomyogenesis ability of iPSCs during co-culture. In contrast, co-culture with M1 macrophages significantly reduced the cardiac differentiation and maturation of iPSCs. CONCLUSIONS: M1- or M2-polarized macrophages play critical roles in the proliferation, cardiac differentiation, and maturation of iPSCs, providing knowledge to improve the outcomes of stem cell regeneration therapy. Video abstract.

Interfacial Nucleation Mechanism of Water-Soluble Ag-In-S Quantum Dots at Room Temperature and Their Visible Light Catalytic Performance.

A novel interfacial reaction nucleation mechanism for the preparation of water-soluble Ag-In-S quantum dots (AIS QDs) was proposed in which interfacial acid regulates the concentration of hydroxide ions outside the complex and sulfur sources attack cations at the interface of the complex, covalent bonds between cations and sulfur sources are formed at the interface of the complex, and the nucleation and growth of crystals is finished at room temperature. By bypassing the heating process normally necessary for crystal nucleation and growth, AIS QDs can be produced on a large scale under simple, mild conditions. At the same time, the characteristics of this mechanism enable AIS QDs to be directly synthesized in an organic pollutant solution. This study represents a significant advance in the mechanism of crystal synthesis and contributes to the photocatalytic decomposition of organic pollutants from theory to practice.

Preparation of a Water-Soluble ZnX Cd1-X S Quantum Dot Photocatalyst at Room Temperature Assisted by 3-Mercaptopropionic Acid.

An effective path to synthesize Znx Cd1-x S quantum dots (ZCS QDs) in aqueous phase at room temperature has remained relatively unexplored. Here, we developed a room-temperature, aqueous-phase approach to ZCS QDs, using 3-mercaptopropionic acid (MPA) to adjust the pH of the reaction precursor solution to regulate the competition between sulfur source and hydroxyl group, and realize the large-scale preparation of water-soluble ZCS QDs photocatalyst at room temperature. Without recombination with other materials, and only by regulating the ratio of pH, excess sulfur sources and Zn/Cd, the photocatalytic degradation of rhodamine B (RhB) can reach 98% within 1 min, showing high photocatalytic activity. ZCS QDs show high stability and recoverability, and are expected to be able to deal with organic pollutants on a large scale. This study provides a new idea for the preparation of other QDs at room temperature.

Release of Cellulose Nanocrystal Particles from Natural Rubber Latex Composites into Immersed Aqueous Media.

In the current study, we focused on the preparation of nanocomposite films of natural rubber latex-cellulose nanocrystals (NR/CNCs) and investigated the release of CNCs from those materials into aqueous solutions. The obtained nanocomposite films were well characterized for further understanding of the release mechanism; as the intermolecular interactions between the two components were studied by Fourier-transform infrared spectroscopy, the morphology was studied with scanning electron microscopy, and nanostructures were analyzed by tensile and dynamic mechanical testing. The release behavior of CNCs from the NR/CNCs nanocomposite films was studied by a fluorescent labeling technique, and the release process in various media was modeled by first-order kinetics. Higher contents of CNCs in the nanocomposite films and a relatively acidic or alkaline medium facilitated the release process, while higher ionic strength of the media could hamper the release of CNCs from the nanocomposite films. In this study, our objective was to transport CNC particles from NR/CNC composites into immersed media to be used beneficially in biomedical applications. Nevertheless, in other surroundings, the release of CNCs or any other nanoparticles from composite materials may not be desirable. Hence, this study also provides a protocol to investigate the release of nanoparticles from a host matrix into the surrounding media and also promotes a rethinking of the nanoparticle release issue from composites to the environment.

The metabolic pathways of polyhydroxyalkanoates and exopolysaccharides synthesized by Haloferax mediterranei in response to elevated salinity.

How polymer synthesis is mobilized or activated as a biological response of Haloferax mediterranei against hypertonic conditions remains largely unexplored. This study investigated the protein expression of H. mediterranei in response to high salinity by using isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis. The microbes were harvested at end of fermentation at the NaCl salinity of 75 and 250 g L-1. Among the identified 2123 proteins, 170 proteins were differentially expressed. Gene ontology annotation revealed that the highest number of proteins was annotated in biological process category, which was responsible for metabolic process, cellular component and catalytic activity. Differentially expressed proteins were belonged to the class of response to stimulus as well as catalytic activity and binding. Under high salinity conditions, three pathways were established as key responses of PHA and EPS production to hypertonic pressure. Two overexpressed proteins, beta-ketoacyl-ACP reductase and 3-hydroxyacyl-CoA dehydrogenase, enhanced the synthesis of PHAs. The serine-pyruvate transaminase and serine-glyoxylate transaminase were upregulated, thereby increasing the conversion of glucose to PHA. Downregulated levels of sulfate-adenylyl transferase and adenylyl-sulfate kinase could cause diminished EPS synthesis. This study could contribute to better understanding of the proteomic mechanisms of the synthesized polymers in defending against salt stress. SIGNIFICANCE: Haloferax mediterranei, a family member of halophilic archaea, is well known for its fermentative production of poly-ß-hydroxyalkanoates (PHAs). PHAs are natural polymers that exhibit great potential in a wide range of applications such as a good alternative to petroleum-based plastics and the biocompatible material. For decades, the functional role of PHAs synthesized by H. mediterranei is deemed to be carbon and energy reservations. The finding proved that differential production of PHA and EPS in H. mediterranei exposed to elevated salinity was caused by differential protein expression. This is the first report on how PHA and EPS synthesized by H. mediterranei is mobilized as the response of increased salinity, contributing to the understanding of halophilic archaea's response to hypertonic stress and the precise control of fermentation production. Despite its advantages as a PHA cell factory, H. mediterranei synthesized EPS simultaneously, thereby lowering the maximum yield of PHA production. Overall, salinity can be used as a vital microbial fermentation parameter to obtain the highest harvest of PHA, as well as the lowest EPS synthesis in industrial fermentation.

Practical interrogation scheme for the abrupt taper Mach-Zehnder interferometer refractive index sensor.

A practical interrogation scheme of a refractive index (RI) sensing system based on the abrupt fiber taper Mach-Zehnder interferometer sensor is designed, implemented, and demonstrated by experiment. The broadband light source and optical spectrum analyzer in the conventional design are replaced by two single-wavelength laser diodes modulated by a periodical square waveform and a simple photodetector (PD), which can significantly lower the cost and lead to easier integration. The photocurrent of the PD output signal is used as the indicator of the surrounding RI. Automatic data acquisition and processing is realized by LabVIEW programming. The experiment proves the feasibility of the new scheme and shows a high sensitivity (2371 mV/RIU) and high stability.

Cu-Cd-Zn-S/ZnS core/shell quantum dot/polyvinyl alcohol flexible films for white light-emitting diodes.

We present a facile route for the synthesis of water-soluble Cu-Cd-Zn-S/ZnS core/shell quantum dots (QDs) by simple pH regulation. The PL spectra of Cu-Cd-Zn-S/ZnS core/shell quantum dots can cover the whole visible light region in the case of only two ratios of Cu/Cd/Zn. The emission wavelength of Cu-Cd-Zn-S/ZnS QDs can be conveniently tuned from 474 to 515 and 548 to 629 nm by adjusting the pH value when the ratios of Cu/Cd/Zn are fixed at 1 : 5 : 80 and 1 : 5 : 10, respectively. It is worth noting that under the condition of a constant Cu/Cd/Zn ratio, the UV-vis absorption spectra do not change with the fluorescence spectra, indicating that the band gap of QDs remains unchanged during the change of pH value. The photoluminescence (PL) quantum yield of the as-prepared QDs with yellow emission is up to 76%. The QDs also show excellent chemical stability after the deposition of the ZnS shell. Luminescent and flexible films are fabricated by combining Cu-Cd-Zn-S QDs with polyvinyl alcohol (PVA). The QD/PVA flexible hybrid films are successfully applied on top of a conventional blue InGaN chip for remote-type warm-white LEDs. As-fabricated warm-white LEDs exhibit a higher color rendering index (CRI) of about 89.2 and a correlated color temperature (CCT) of 4308 K.

Flexible translucent chitosan-glycerin/QD nanocomposite glue for anti-counterfeiting films with strong adhesion and stability.

With the rapid development of commodity circulation, more attention has been paid to the anticounterfeiting technology of commodities, including stability, universality and ease of distinguishing. The authors report the use of gelatin-chitosan-glycerin/QD nanocomposite-functionalized glue for luminescent anti-counterfeiting labels. As the blend and plasticizer, the addition of chitosan and glycerin effectively improved the flexibility and formability of the gelatin-chitosan-glycerin/QD composite films, which show excellent mechanical properties, including high transparency, luminescence and flexibility, and they are easy to prepare on a large scale, providing certain reference values for new anticounterfeiting technology applying a variety of morphologies.

Positional effects on efficiency of CRISPR/Cas9-based transcriptional activation in rice plants.

The nuclease-dead Cas9 (dCas9) has been reprogrammed for transcriptional activation by fusing dCas9 to a transcriptional activation domain. In the presence of a guide RNA (gRNA), the dCas9 fusions specifically bind to regions of a promoter to activate transcription. Significant amount of effort has been directed toward the identification and optimization of the fusions of dCas9-activation domain, but very little is known about the impact of gRNA target positions within a promoter in plants on transcriptional activation efficiency. The dCas9-6TAL-VP128 system (dCas9-TV) has been optimized to activate transcription in plants. Here we use the dCas9-TV to activate transcription of OsWOX11 and OsYUC1, two genes that cause dramatic developmental phenotypes when overexpressed. We designed a series of gRNAs targeting the promoters of the two genes. We show that gRNAs that target regions within 350 bp upstream of the transcription start site were most effective in transcriptional activation. Moreover, we show that using two gRNAs that simultaneously target two discrete sites in a promoter can further enhance transcription. This work provides guidelines for designed transcriptional activation through CRISPR/dCas9 systems.

Carbon nanoparticle-protected RNA aptasensor for amplified fluorescent determination of theophylline in serum based on nuclease-aided signal amplification.

A carbon nanoparticle (CNP) and Cryonase-aided method that realizes the amplified fluorescent detection of theophylline was proposed. The amplification technique exploits distinct binding affinities of CNP towards the FAM-labeled theophylline RNA aptamer (aptasensor) and aptasensor/theophylline complex as well as the protection effect of CNP for absorbed aptasensor from enzymatic digestion by Cryonase. Upon the addition of theophylline, it forms an aptasensor/theophylline complex with a fluorescent dye-tagged aptasensor that is initially absorbed and quenched by CNP. The nuclease activity of Cryonase towards detached aptasensor probes is then activated, leading to efficient cleavage of aptasensor probes and separation of the fluorescent dye from the CNP surface. Theophylline that has been liberated can launch another reaction cycle, which ensures the sensitivity enhancement. A detection limit is achieved as high as 6.3 nM, which is 400-fold better than traditional strategies. The proposed sensing system also provides desired selectivity even in serum samples. The assay is simple, sensitive, selective, and universal, and has great promise for the design and application of aptasensors in the biological, chemical, and biomedical fields.

Novel protein-lipid composite nanoparticles with an inner aqueous compartment as delivery systems of hydrophilic nutraceutical compounds.

Food protein and lipid based nanoparticles have attracted recent interest as a means of delivering nutraceuticals. Nanoparticle encapsulation of nutraceuticals faces challenges to overcome for it to be readily applied in the food industry, such as low encapsulation efficiency for hydrophilic compounds and poor stability once in the gastrointestinal tract. This research introduces a new protein-lipid composite nanoparticle with a three-layered structure (a barley protein layer, α-tocopherol layer and phospholipid layer) and an inner aqueous compartment to load hydrophilic nutraceuticals. This delivery system showed efficient encapsulation of vitamin B12 (69%) and controlled release behavior in simulated gastrointestinal media. An in vitro cell evaluation demonstrated that nanoparticles could internalize into Caco-2 cells via energy-dependent endocytosis and significantly increase the uptake and transport efficiency of vitamin B12 in this model. In vivo, the developed vitamin B12 loaded nanoparticle showed increased serum vitamin B12 levels upon oral administration and reduced the methylmalonic acid level more efficiently than the free form in rats. A 14-day in vivo toxicity study showed no evidence of toxicity in rats implying the safety of the developed nanoparticles in long term use. Overall, the results of this study show the great potential of the developed nanoparticles in increasing the absorption of vitamin B12 upon oral administration.

Mapping the mechanical gradient of human dentin-enamel-junction at different intratooth locations.

OBJECTIVES: The local structures and mechanical properties within tooth dentin-enamel-junction (DEJ) regions have been focused for numerous studies. The reported results, however, remain inconsistent particularly on the functional width and gradient architecture of the DEJ. The current study aims at systematically determining the mechanical gradient of the DEJ at different intratooth locations such that a clearer understanding on the tooth properties and the potential correlations with the tooth function could be obtained. METHODS: We re-examined how mechanical properties such as elastic modulus and hardness transitioned from those of dentin to those of enamel using combined static and dynamic nanoindentation mapping techniques. A new mapping method and associated image processing procedures were developed to improve the measurement accuracy and resolution. RESULTS: A thin, sigmoidally-transitioned interphase layer of the DEJ was identified with an accurate functional width of 2-3µm. The DEJ width and gradient architecture were found intratooth location-dependent, with the DEJ at the occlusal sites being wider and transitioning smoother than that at the cervical sites. Such different widths and architectures of the interphase layer at sites subjected to different types and magnitudes of loadings during mastication could promote more efficient stress transferring between enamel and dentin without compromising the overall stiffness of the tooth. SIGNIFICANCE: The presented study not only adds our understanding in the local mechanical properties within tooth DEJ regions, it could also further advance the development of DEJ-mimetic, functional gradient interphase for strong and ultra-durable jointing between dissimilar materials.

Enhanced emulsifying properties of wood-based cellulose nanocrystals as Pickering emulsion stabilizer.

Cellulose nanocrystals are hydrophilic nanomaterials, which limits their applications as interfacial compounds. Herein, we propose using modified wood-based cellulose nanocrystals as Pickering emulsion stabilizer. Wood cellulose was consecutively oxidized and modified with phenyltrimethylammonium chloride to create hydrophobic domains comprised of phenyl groups. These modified oxidized cellulose nanocrystals (m-O-CNCs) were homogeneous/electrostatically stable in water and they can stabilize O/W Pickering emulsions. The dispersed phase volume fraction (DPVF) of the Pickering emulsion was 0.7 at around 1.5g/L, whereas the tween-20 control needed a 13-fold greater concentration to have a similar DPVR. In addition, these m-O-CNC stabilized Pickering emulsions also showed good mechanical and thermal stability against centrifugation and heat, as well as size controllability. In terms of stability, size controllability, surfactant-free status, these m-O-CNCs possess superior and enhanced emulsifying properties. Future research for these new interfacial materials have potential in applications, for personal care, cosmetic and pharmaceutic industries.