Chemical Analysis of the Gallium Surface in a Physiologic Buffer.

Gallium and its alloys have been regarded as one of the promising materials for flexible bioelectronics due to their liquid-like mechanical properties, excellent electrical property, and low toxicity. Although many studies have fabricated bioelectronics from gallium-based liquid metals, gallium surface chemistry in physiologic conditions is rarely investigated. Here, we investigated the chemical change of the gallium surface in a physiologic buffer at 37 °C over 45 days. The gallium ion concentration and pH measurement indicated that the oxidation and corrosion progressed more rapidly in the physiological buffer than in air. Also, the release of gallium ions and protons followed a square root of time growth. Various spectroscopic techniques were used to measure the chemical composition change on the gallium surface. The FT-IR study indicated that the GaOOH-rich gallium surface produced Ga3+ and OH- ions. The XPS study indicated the oxide layer formation within 5 days, and then the contamination layer was deposited over time, which includes different ions and organic materials derived from the physiologic buffer. This study provides a detailed chemical analysis of the gallium surface in a physiological buffer. These fundamental studies would be a cornerstone for understanding the complex interaction between the gallium surface and the biological environment.

Highly conductive thermoresponsive silver nanowire PNIPAM nanocomposite for reversible electrical switch.

Highly conductive nanocomposite hydrogels have been challenging to produce due to their high water volumes inhibiting the incorporation of an essential amount of conductive nanofillers. Furthermore, the most common fillers used, typically for easy integration, display small aspect ratios. Thus, the formation of interparticle pathways for electronic travel is limited, resulting in low conductivities. Here, we introduce ultralong silver nanowires (ULAgNWs) into a thermoresponsive, volume changing PNIPAM gel to form a nanocomposite that shows switchable electronic performance. The produced nanocomposite surpasses other PNIPAM nanocomposites by expressing the largest electrical switch ratio and the highest peak conductivity. The PNIPAM matrix possesses an interconnected microporous structure that offers a spacious network for the dispersion of nanowires while still maintaining a high volume switch ratio and excellent elastic behavior under extreme compression cycles (98% compression). The ULAgNWs significantly enhance the probability of more numerous connections forming during shrinking cycles. The high swellability displayed by the PNIPAM gel provides the ability to separate the embedded nanowires by many lengths. Together, they form a nanocomposite that can thermo-modulate its electrical properties. Moreover, the conductive PNIPAM maintains the electrical switch of 4.3-4.4 orders of magnitude with thermo-responsive cycles. Because of their high electrical conductivity and outstanding elastic behavior, these stimuli-responsive nanocomposite hydrogels may expand the prospects for conductive hydrogel applications and provide greater performance in their applications.

Simultaneous measurement of neurite and neural body mass accumulation via quantitative phase imaging.

Measurement of neuron behavior is crucial for studying neural development and evaluating the impact of potential therapies on neural regeneration. Conventional approaches to imaging neuronal behavior require labeling and do not separately quantify the growth processes that underlie neural regeneration. In this paper we demonstrate the use of quantitative phase imaging (QPI) as a label-free, quantitative measurement of neuron behavior in vitro. By combining QPI with image processing, our method separately measures the mass accumulation rates of soma and neurites. Additionally, the data provided by QPI can be used to separately measure the processes of maturation and formation of neurites. Overall, our approach has the potential to greatly simplify conventional neurite outgrowth measurements, while providing key data on the resources used to produce neurites during neural development.

Silicon Nanoribbon pH Sensors Protected by a Barrier Membrane with Carbon Nanotube Porins.

Limited biocompatibility and fouling propensity can restrict real-world applications of a large variety of biosensors. Biological systems are adept at protecting and separating vital components of biological machinery with semipermeable membranes that often contain defined pores and gates to restrict transmembrane transport only to specific species. Here we use a similar approach for creating fouling-resistant pH sensors. We integrate silicon nanoribbon transistor sensors with an antifouling lipid bilayer coating that contains proton-permeable carbon nanotube porin (CNTP) channels and demonstrate robust pH detection in a variety of complex biological fluids.

A multitask clustering approach for single-cell RNA-seq analysis in Recessive Dystrophic Epidermolysis Bullosa.

Single-cell RNA sequencing (scRNA-seq) has been widely applied to discover new cell types by detecting sub-populations in a heterogeneous group of cells. Since scRNA-seq experiments have lower read coverage/tag counts and introduce more technical biases compared to bulk RNA-seq experiments, the limited number of sampled cells combined with the experimental biases and other dataset specific variations presents a challenge to cross-dataset analysis and discovery of relevant biological variations across multiple cell populations. In this paper, we introduce a method of variance-driven multitask clustering of single-cell RNA-seq data (scVDMC) that utilizes multiple single-cell populations from biological replicates or different samples. scVDMC clusters single cells in multiple scRNA-seq experiments of similar cell types and markers but varying expression patterns such that the scRNA-seq data are better integrated than typical pooled analyses which only increase the sample size. By controlling the variance among the cell clusters within each dataset and across all the datasets, scVDMC detects cell sub-populations in each individual experiment with shared cell-type markers but varying cluster centers among all the experiments. Applied to two real scRNA-seq datasets with several replicates and one large-scale droplet-based dataset on three patient samples, scVDMC more accurately detected cell populations and known cell markers than pooled clustering and other recently proposed scRNA-seq clustering methods. In the case study applied to in-house Recessive Dystrophic Epidermolysis Bullosa (RDEB) scRNA-seq data, scVDMC revealed several new cell types and unknown markers validated by flow cytometry. MATLAB/Octave code available at https://github.com/kuanglab/scVDMC.

An improved procedure to implement NSGA-III in coordinate waste management for urban agglomeration.

With the growth of urbanization in countries globally, large cities have often formed clusters of urban agglomerations in metropolitan areas. The coordinated management of regional solid waste produced by such urban agglomeration poses a typical high-dimensional, multi-objective optimization issue. This paper aims to introduce a procedure to implement the third-generation genetic algorithm (NSGA-III), an established multi-objective genetic algorithm based on non-dominated sorting mechanisms, for the purpose of evaluating environmental and economic benefits simultaneously while seeking the optimal solutions for coordinated management among multiple recycling centres. In this study, two series of scenarios were abstracted from scrap tire recycling, representing linear calculation and nonlinear calculation cases separately. Several improvements were made to the originally published NSGA-III procedure that solve the problem of non-convergence for hypervolumes of the output. Through comparisons of calculation results, an improved procedure is suggested and shown to have improved performance.

Global analysis of canola genes targeted by SHORT HYPOCOTYL UNDER BLUE 1 during endosperm and embryo development.

Seed development in dicots includes early endosperm proliferation followed by growth of the embryo to replace the endosperm. Endosperm proliferation in dicots not only provides nutrient supplies for subsequent embryo development but also enforces a space limitation, influencing final seed size. Overexpression of Arabidopsis SHORT HYPOCOTYL UNDER BLUE1::uidA (SHB1:uidA) in canola produces large seeds. We performed global analysis of the canola genes that were expressed and influenced by SHB1 during early endosperm proliferation at 8 days after pollination (DAP) and late embryo development at 13 DAP. Overexpression of SHB1 altered the expression of 973 genes at 8 DAP and 1035 genes at 13 DAP. We also surveyed the global SHB1 association sites, and merging of these sites with the RNA sequencing data identified a set of canola genes targeted by SHB1. The 8-DAP list includes positive and negative genes that influence endosperm proliferation and are homologous to Arabidopsis MINI3, IKU2, SHB1, AGL62, FIE and AP2. We revealed a major role for SHB1 in canola endosperm development based on the dynamics of SHB1-altered gene expression, the magnitude of SHB1 chromatin immunoprecipitation enrichment and the over-representation of eight regulatory genes for endosperm development. Our studies focus on an important agronomic trait in a major crop for global agriculture. The datasets on stage-specific and SHB1-induced gene expression and genes targeted by SHB1 also provide a useful resource in the field of endosperm development and seed size engineering. Our practices in an allotetraploid species will impact similar studies in other crop species.

HRB2 and BBX21 interaction modulates Arabidopsis ABI5 locus and stomatal aperture.

Blue light triggers the opening of stomata in the morning to allow CO2 uptake and water loss through transpiration. During the day, plants may experience periodic drought and accumulate abscisic acid (ABA). ABA antagonizes blue light signalling through phosphatidic acid and reduces stomatal aperture. This study reveals a molecular mechanism by which two light signalling proteins interact to repress ABA signalling in the control of stomatal aperture. A hypersensitive to red and blue 2 (hrb2) mutant has a defective ATP-dependent chromatin-remodelling factor, PKL, in the chromodomain/helicase/DNA binding family. HRB2 enhances the light-induced expression of a B-box transcription factor gene, BBX21. BBX21 binds a T/G box in the ABI5 promoter and recruits HRB2 to modulate the chromatin structure at the ABI5 locus. Mutation in either HRB2 or BBX21 led to reduced water loss and ABA hypersensitivity. This hypersensitivity to ABA was well explained by the enhanced expression of the ABA signalling gene ABI5 in both mutants. Indeed, stomatal aperture was significantly reduced by ABI5 overexpression in the absence or presence of ABA under monochromatic light conditions. Overall, we present a regulatory loop in which two light signalling proteins repress ABA signalling to sustain gas exchange when plants experience periodic drought.

TGF-ß1-induced epithelial-mesenchymal transition in lung cancer cells involves upregulation of miR-9 and downregulation of its target, E-cadherin.

BACKGROUND: TGF-ß1 plays an important role in the epithelial-mesenchymal transition (EMT) of epithelial cancers, including non-small cell lung cancer (NSCLC). While the full underlying mechanism remains unclear, miR-9 is known to play a critical role in the regulation of NSCLC cell invasion. We tested whether miR-9 targets E-cadherin and thus affects TGF-ß1-induced EMT in NSCLC cells by assessing the expression levels of miR-9 and E-cadherin for NSCLC patients and then verifying the targeting of E-cadherin by miR-9 using the dual luciferase reporter system. RESULTS: MiR-9 was significantly upregulated in NSCLC tissues compared with its level in adjacent normal tissues. The expression of E-cadherin in NSCLC tissues was significantly decreased. In addition, we found that TGF-ß1 significantly upregulated the expression of miR-9 and downregulated the expression of E-cadherin. E-cadherin was confirmed as a direct target gene of miR-9. Using an miR-9 inhibitor reversed the TGF-ß1-mediated inhibition of E-cadherin expression and upregulation of the mesenchymal marker α-SMA. TGF-ß1 significantly induced cell invasion, and this effect was significantly inhibited by miR-9 inhibitors. CONCLUSIONS: TGF-ß1 induced EMT in NSCLC cells by upregulating miR-9 and downregulating miR-9's target, E-cadherin.

SubPatCNV: approximate subspace pattern mining for mapping copy-number variations.

BACKGROUND: Many DNA copy-number variations (CNVs) are known to lead to phenotypic variations and pathogenesis. While CNVs are often only common in a small number of samples in the studied population or patient cohort, previous work has not focused on customized identification of CNV regions that only exhibit in subsets of samples with advanced data mining techniques to reliably answer questions such as "Which are all the chromosomal fragments showing nearly identical deletions or insertions in more than 30% of the individuals?". RESULTS: We introduce a tool for mining CNV subspace patterns, namely SubPatCNV, which is capable of identifying all aberrant CNV regions specific to arbitrary sample subsets larger than a support threshold. By design, SubPatCNV is the implementation of a variation of approximate association pattern mining algorithm under a spatial constraint on the positional CNV probe features. In benchmark test, SubPatCNV was applied to identify population specific germline CNVs from four populations of HapMap samples. In experiments on the TCGA ovarian cancer dataset, SubPatCNV discovered many large aberrant CNV events in patient subgroups, and reported regions enriched with cancer relevant genes. In both HapMap data and TCGA data, it was observed that SubPatCNV employs approximate pattern mining to more effectively identify CNV subspace patterns that are consistent within a subgroup from high-density array data. CONCLUSIONS: SubPatCNV available through http://sourceforge.net/projects/subpatcnv/ is a unique scalable open-source software tool that provides the flexibility of identifying CNV regions specific to sample subgroups of different sizes from high-density CNV array data.

Chiral plasmonic nanostructures on achiral nanopillars.

Chirality of plasmonic films can be strongly enhanced by three-dimensional (3D) out-of-plane geometries. The complexity of lithographic methods currently used to produce such structures and other methods utilizing chiral templates impose limitations on spectral windows of chiroptical effects, the size of substrates, and hence, further research on chiral plasmonics. Here we demonstrate 3D chiral plasmonic nanostructures (CPNs) with high optical activity in the visible spectral range based on initially achiral nanopillars from ZnO. We made asymmetric gold nanoshells on the nanopillars by vacuum evaporation at different inclination and rotation angles to achieve controlled symmetry breaking and obtained both left- and right-rotating isomers. The attribution of chiral optical effects to monolithic enantiomers made in this process was confirmed by theoretical calculations based on their geometry established from scanning electron microscope (SEM) images. The chirality of the nanoshells is retained upon the release from the substrate into a stable dispersion. Deviation of the incident angle of light from normal results in increase of polarization rotation and chiral g-factor as high as -0.3. This general approach for preparation of abiological nanoscale chiral materials can be extended to other out-of plane 3D nanostructures. The large area films made on achiral nanopillars are convenient for sensors, optical devices, and catalysis.

The complexity of coffee and its impact on metabolism.

Coffee is one of the three most consumed beverages in the world. It is made by first roasting coffee beans and then grinding and boiling or steeping the roasted beans in water (brewing). The process of roasting and brewing produces a complex mix of bioactive compounds which include methylxanthines (caffeine, theobromine, theophylline), diterpenes, chlorogenic acid, trigonelline, flavonoids and hydroxycinnamic acid. In the body these compounds may be metabolized to produce other bioactive compounds. For example, caffeine is primarily (80%) broken down by demethylation to produce paraxanthine. In the post ingestion period levels of paraxanthine may be higher than caffeine due to its slower elimination. Hence, while paraxanthine is not found in coffee itself, it has many of the same properties of caffeine and may be a major contributor to its metabolic effects. The impacts of caffeine and paraxanthine on metabolism relate to their impact on adenosine receptors (notably the A2A receptor). It has been known for almost 100 years that intake of coffee stimulates metabolism by between 5 and 20% for at least 3 hours. About half of the increase in metabolic rate after drinking coffee is due to caffeine and derivatives, but the source of the other half is unclear. There are large differences in the response to the same amount of coffee in different individuals, which may be related to caffeine clearance rates, effects of other unknown pathways, genetic polymorphism, age, sex and body composition.

Role of TRIM59 in regulating PPM1A in the pathogenesis of silicosis and the intervention effect of tanshinone IIA.

This study examines the involvement of TRIM59 in silica-induced pulmonary fibrosis and explores the therapeutic efficacy of Tanshinone IIA (Tan IIA). In vivo experiments conducted on rats with silica-induced pulmonary fibrosis unveiled an increase in TRIM59 levels and a decrease in PPM1A levels. Subsequent investigations using in vitro silicosis cell models demonstrated that modulation of TRIM59 expression significantly impacts silicosis fibrosis, influencing the levels of PPM1A and activation of the Smad2/3 signaling pathway. Immunofluorescence and co-immunoprecipitation assays confirmed the interaction between TRIM59 and PPM1A in fibroblasts, wherein TRIM59 facilitated the degradation of PPM1A protein via proteasomal and ubiquitin-mediated pathways. Furthermore, employing a rat model of silica-induced pulmonary fibrosis, Tan IIA exhibited efficacy in mitigating lung tissue damage and fibrosis. Immunohistochemical analysis validated the upregulation of TRIM59 and downregulation of PPM1A in silica-induced pulmonary fibrosis, which Tan IIA alleviated. In vitro studies elucidated the mechanism by which Tan IIA regulates the Smad2/3 signaling pathway through TRIM59-mediated modulation of PPM1A. Treatment with Tan IIA in silica-induced fibrosis cell models resulted in concentration-dependent reductions in fibrotic markers and attenuation of relevant protein expressions. Tan IIA intervention in silica-induced fibrosis cell models mitigated the TRIM59-induced upregulation of fibrotic markers and enhanced PPM1A expression, thereby partially reversing Smad2/3 activation. Overall, the findings indicate that while overexpression of TRIM59 may activate the Smads pathway by suppressing PPM1A expression, treatment with Tan IIA holds promise in counteracting these effects by inhibiting TRIM59 expression.

A highly conductive, robust, self-healable, and thermally responsive liquid metal-based hydrogel for reversible electrical switches.

This study introduces a thermally responsive smart hydrogel with enhanced electrical properties achieved through volume switching. This advancement was realized by incorporating multiscale liquid metal particles (LMPs) into the PNIPAM hydrogel during polymerization, using their inherent elasticity and conductivity when deswelled. Unlike traditional conductive additives, LMPs endow the PNIPAM hydrogel with a remarkably consistent volume switching ratio, significantly enhancing electrical switching. This is attributed to the minimal nucleation effect of LMPs during polymerization and their liquid-like behavior, like vacancies in the polymeric hydrogel under compression. The PNIPAM/LMP hydrogel exhibits the highest electrical switching, with an unprecedented switch of 6.1 orders of magnitude. Even after repeated swelling/deswelling cycles that merge some LMPs and increase the conductivity when swelled, the hydrogel consistently maintains an electrical switch exceeding 4.5 orders of magnitude, which is still the highest record to date. Comprehensive measurements reveal that the hydrogel possesses robust mechanical properties, a tissue-like compression modulus, biocompatibility, and self-healing capabilities. These features make the PNIPAM/LMP hydrogel an ideal candidate for long-term implantable bioelectronics, offering a solution to the mechanical mismatch with dynamic human tissues.

Ultrasmall implantable composite microelectrodes with bioactive surfaces for chronic neural interfaces.

Implantable neural microelectrodes that can record extracellular biopotentials from small, targeted groups of neurons are critical for neuroscience research and emerging clinical applications including brain-controlled prosthetic devices. The crucial material-dependent problem is developing microelectrodes that record neural activity from the same neurons for years with high fidelity and reliability. Here, we report the development of an integrated composite electrode consisting of a carbon-fibre core, a poly(p-xylylene)-based thin-film coating that acts as a dielectric barrier and that is functionalized to control intrinsic biological processes, and a poly(thiophene)-based recording pad. The resulting implants are an order of magnitude smaller than traditional recording electrodes, and more mechanically compliant with brain tissue. They were found to elicit much reduced chronic reactive tissue responses and enabled single-neuron recording in acute and early chronic experiments in rats. This technology, taking advantage of new composites, makes possible highly selective and stealthy neural interface devices towards realizing long-lasting implants.

Layered nanocomposites from gold nanoparticles for neural prosthetic devices.

Treatments of neurological diseases, diagnostics of brain malfunctions, and the realization of brain-computer interfaces require ultrasmall electrodes that are "invisible" to resident immune cells. Functional electrodes smaller than 50 µm are impossible to produce with traditional materials due to high interfacial impedance at the characteristic frequency of neural activity and insufficient charge storage capacity. The problem can be resolved by using gold nanoparticle nanocomposites. Careful comparison indicates that layer-by-layer assembled films from Au NPs provide more than 3-fold improvement in interfacial impedance and 1 order of magnitude increase in charge storage capacity. Prototypes of microelectrodes could be made using traditional photolithography. Integration of unique nanocomposite materials with microfabrication techniques opens the door for practical realization of the ultrasmall implantable electrodes. Further improvement of electrical properties is expected when using special shapes of gold nanoparticles.

Polyphyllin I induces apoptosis and autophagy in temozolomide-resistant glioma via modulation of NRF2 and MAPK-signaling activation.

Glioma is the most prevailing main malignant neoplasm of the central nervous system with a miserable prognosis. Temozolomide is the first-line chemotherapy drug for glioma, but its drug resistance reduces temozolomide's clinical efficacy and becomes the principal cause of the failure of glioma chemotherapy. Polyphyllin I (PPI), an active component in Rhizoma Paridis, demonstrates favorable therapeutic actions in diverse malignant neoplasms. Its effect on temozolomide-resistant glioma, however, has not yet been characterized. Here, we demonstrated that polyphyllin I inhibited the proliferation of temozolomide-resistant glioma cell in a concentration-dependent manner. Further, we found that polyphyllin I had a direct effect on temozolomide-resistant glioma tumor cells and promote reactive oxygen species (ROS)-dependent apoptosis and autophagy via mitogen-activated protein kinase (MAPK)-signaling (p38-JNK) pathway. Mechanistically, we showed that polyphyllin I downregulate the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway, indicating that polyphyllin I may be an expected therapeutic strategy for patients with temozolomide-resistant gliomas.

Antioxidative 0-dimensional nanodrugs overcome obstacles in AKI antioxidant therapy.

Acute kidney injury (AKI) is a commonly encountered syndrome associated with various aetiologies and pathophysiological processes leading to enormous health risks and economic losses. In the absence of specific drugs to treat AKI, hemodialysis remains the primary clinical treatment for AKI patients. The revelation of the pathology opens new horizons for antioxidant therapy in the treatment of AKI. However, small molecule antioxidant drugs and common nanozymes have failed to challenge AKI due to their unsatisfactory drug properties and renal physiological barriers. 0-Dimensional (0D) antioxidant nanodrugs stand out at this time thanks to their small size and high performance. Recently, a number of research studies have been carried out around 0D nanodrugs for alleviating AKI, and their multi-antioxidant enzyme mimetic activities, smooth glomerular filtration barrier permeability and excellent biocompatibility have been investigated. Here, we comprehensively summarize recent advances in 0D nanodrugs for AKI antioxidant therapy. We classify these representative studies into three categories according to the characteristics of 0D nanomaterials, namely ultra-small metal nanodots, inorganic non-metallic quantum dots and polymer nanodots. We focus on the antioxidant mechanisms and their distribution in vivo in each inspiring work, and the purpose and ingenuity of each design are rigorously captured and described. Finally, we provide our reflections and prospects for 0D antioxidant nanodrugs in AKI treatment. This mini review provides unique insights and valuable clues in the design of 0D nanodrugs and other kidney absorbable drugs.

Conductive Polymer Enabled Biostable Liquid Metal Electrodes for Bioelectronic Applications.

Gallium (Ga)-based liquid metal materials have emerged as a promising material platform for soft bioelectronics. Unfortunately, Ga has limited biostability and electrochemical performance under physiological conditions, which can hinder the implementation of its use in bioelectronic devices. Here, an effective conductive polymer deposition strategy on the liquid metal surface to improve the biostability and electrochemical performance of Ga-based liquid metals for use under physiological conditions is demonstrated. The conductive polymer [poly(3,4-ethylene dioxythiophene):tetrafluoroborate]-modified liquid metal surface significantly outperforms the liquid metal.based electrode in mechanical, biological, and electrochemical studies. In vivo action potential recordings in behaving nonhuman primate and invertebrate models demonstrate the feasibility of using liquid metal electrodes for high-performance neural recording applications. This is the first demonstration of single-unit neural recording using Ga-based liquid metal bioelectronic devices to date. The results determine that the electrochemical deposition of conductive polymer over liquid metal can improve the material properties of liquid metal electrodes for use under physiological conditions and open numerous design opportunities for next-generation liquid metal-based bioelectronics.

Camelina sativa Oil Treatment Alleviates Castor Oil-Induced Diarrhea in ICR Mice by Regulating Intestinal Flora Composition.

Diarrhea, occurring due to intestinal flora disturbance, is potentially lethal, and its current treatments have adverse effects such as constipation and vomiting. Camelina sativa oil (CSO) is a cooking ingredient and natural remedy used in several countries; however, its pharmacological effects on intestinal health remain unknown. Here, we explored the CSO treatment effects on intestinal flora in male ICR mice with castor oil-induced diarrhea. The rate and degree of loose stools, the diarrhea index, serum inflammatory indices, fecal short-chain fatty acids (SCFAs), and the diversity and abundance of intestinal flora were measured. Castor oil-administered mice experienced diarrhea, reduced intestinal flora diversity and fecal SCFAs concentrations, altered intestinal flora composition, and increased serum proinflammatory indices. In contrast, CSO treatment relieved diarrhea, improved intestinal flora composition, and increased the relative abundance of Lactobacillus and Lachnospiraceae. Additionally, CSO significantly increased the concentrations of fecal propionic acid, valeric acid, isovaleric acid, and serum sIgA, while it reduced those of serum interleukin-17. These findings suggest that CSO could be a promising preventive agent against diarrhea.