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Mg alloys are promising biodegradable orthopedic implants in the future. However, poor corrosion resistance and biocompatibility limit their wide applications. In this study, a pure Mg–Al layered double hydroxide (Mg–Al LDH) film on AZ31 was prepared through combining hydrofluoric acid pretreatment and hydrothermal treatment. Electrochemical analysis and the immersion test suggested that the as-prepared Mg–Al LDH-coated sample exhibited significantly enhanced corrosion resistance. The in vitro cell culture revealed that the Mg–Al LDH film was favorable for the alkaline phosphatase activity, collagen secretion, and osteogenesis-related gene expression of MC3T3-E1. Furthermore, the LDH-coated sample was beneficial for the migration, vascular endothelial growth factor secretion, and angiogenesis-related gene expression of human umbilical vein endothelial cells. The subcutaneous implantation test demonstrated that the Mg–Al LDH film could protect the substrate from corrosion and induce milder inflammation. The femur implantation demonstrated that the Mg–Al LDH sample showed better bone regeneration and osseointegration than bare AZ31. In summary, the as-prepared pure Mg–Al LDH film is able to enhance the in vitro and in vivo performances of AZ31, indicating a promising application in the orthopedic field.

Fingerprints consist of unique patterns of skin ridges and valleys, and are commonly described by three levels of feature details. Most fingerprint identification systems rely on matching only firs...

We report a new DNA nanostructure, an extended 1-dimensional composite built for the first time out of structurally robust yet conveniently disassembled DNA triple helices, interspersed with short stretches of G-quadruplexes. These "TQ Hybrid" 1-dimensional nanostructures require potassium ions and modestly acidic pH for their formation and are easily disassembled by changes to either of these requirements. We initially prepared and characterized a "monomeric" TQ Hybrid tile; followed by "sticky" TQs tiles, incorporating unique guanine-only sticky ends, that enable efficient self-assembly via G-quartet formation of nanostructures >150 nm in length, as seen with atomic force microscopy and transmission electron microscopy. We anticipate that such DNA TQ Hybrid structures will find unique and varied application as communication modules within larger nanostructures, and as sensors, logic gates, as well as in other aspects of DNA nanotechnology.

Superhydrophobic coatings have tremendous potential for applications in different fields and have been achieved commonly by increasing nanoscale roughness and lowering surface tension. Limited by the availability of either ideal nano-structural templates or simple fabrication procedures, the search of superhydrophobic coatings that are easy to manufacture and are robust in real-life applications remains challenging for both academia and industry. Herein, we report an unconventional protocol based on a single-step, stoichiometrically controlled reaction of long-chain organosilanes with water, which creates micro- to nano-scale hierarchical siloxane aggregates dispersible in industrial solvents (as the coating mixture). Excellent superhydrophobicity (ultrahigh water contact angle >170° and ultralow sliding angle, Artificial superhydrophobic coatings that are simple to prepare and practical to use are sought after. Here, the authors create versatile, complete-waterproof coatings based on a single-step, stoichiometrically controlled reaction of organosilanes with water.

Cu2ZnSnS4 (CZTS) is a promising thin-film solar cell material consisting of earth-abundant and nontoxic elements. Yet there exists a fundamental bottleneck that hinders the performance of the devic...

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening clinical conditions predominantly arising from uncontrolled inflammatory reactions. It has been found that the administration of astaxanthin (AST) can exert protective effects against lipopolysaccharide (LPS)-induced ALI; however, the robust genetic signatures underlying LPS induction and AST treatment remain obscure. Here we performed a statistical meta-analysis of five publicly available gene expression datasets from LPS-induced ALI mouse models, conducted RNA-sequencing (RNA-seq) to screen differentially expressed genes (DEGs) in response to LPS administration and AST treatment, and integrative analysis to determine robust genetic signatures associated with LPS-induced ALI onset and AST administration. Both the meta-analyses and our experimental data identified a total of 198 DEGs in response to LPS administration, and 11 core DEGs (Timp1, Ly6i, Cxcl13, Irf7, Cxcl5, Ccl7, Isg15, Saa3, Saa1, Tgtp1, and Gbp11) were identified to be associated with AST therapeutic effects. Further, the 11 core DEGs were verified by quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC), and functional enrichment analysis revealed that these genes are primarily associated with neutrophils and chemokines. Collectively, these findings unearthed the robust genetic signatures underlying LPS administration and the molecular targets of AST for ameliorating ALI/ARDS which provide directions for further research.

Soil denitrification rates and the roles Mn(II) and Fe(II) played as alternative electron donors were investigated by performing anoxic incubation experiments, using agricultural soils from Guangxi Autonomous Region, South China. The dynamic of Mn(II) and Fe(II), electron contributions of Mn(II) and Fe(II) to denitrification, potential denitrification capacity, and gaseous-N composition were investigated. The results indicated that Mn(II) and Fe(II) act as electron donors during the denitrification of paddy soils with high Mn and Fe contents. Coupling of denitrification and Fe(II) oxidation and coupling of denitrification and Mn(II) oxidation was found in paddy soils from the villages of Xialei. The maximum electron contributions of Mn(II) and Fe(II) to denitrification were similar, both reaching 18%, although the total Mn content was lower than the total Fe content. On the contrary, the roles and contributions of Mn(II) and Fe(II) to denitrification in soils from upland fields were not proved, even though all the studied agricultural soils had high Mn and Fe contents. The results suggested that Mn(II) is an important but previously ignored electron donor for denitrification and that Mn(II) plays a vital role in denitrification in paddy soils.

Nitrate pollution in water environments is a ubiquitous problem. Solid-phase denitrification (SPD) is a technology that has attracted in recent years increasing attention due to its significant advantage suitability over the aqueous-based denitrification for

It is important to pursue more effective and environmentally friendly methods of termite control. Nitenpyram has achieved good control effect in some insects. Herein, we evaluated the effect of nitenpyram (10, 20, 40, 80 and 160 ppm) in conjunction with two kinds of the block (clay and sand) on the survival, body water content, food consumption, tunneling behavior, microbial infectivity and three behavior patterns (corpse-burying behavior, cannibalism behavior, and particle transport behavior) of the termite Reticulitermes flaviceps. We found that the 10–160 ppm concentration nitenpyram significantly inhibited the survival, food consumption, particle transport behavior, corpse-burying behavior, cannibalism behavior, and tunneling behavior of the termites. The survival of R. flaviceps decreased with the increase of the concentration of nitenpyram, and the survival was the lowest at 160 ppm. Still, there was no significant difference in the conditions with concentrations of 80 and 160 ppm. Therefore, the 80 ppm concentration of nitenpyram in combination with pathogenic microorganisms may have great potential values in termite control.

Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC), the representative reaction of modern “click chemistry”, has been broadly employed in organic synthesis, bio-labeling, and surface functionalizat...

Conventional DNA constructs with integrated aptamer motifs usually undergo “global-scale” conformational and associated conductivity switches in response to specific ligand binding, which can be ex...

Background We aimed to identify metabolic biomarkers and investigate the metabolic alterations in relation to primary open-angle glaucoma (POAG) and cataract in human aqueous humor. Methods Sixteen POAG patients undergoing surgical treatments and 24 patients undergoing cataract surgeries were included in this case-control study. We performed the metabolomic analysis of aqueous humor samples using a non-targeted gas chromatography coupled to time-of-flight mass spectrometer. The area under the receiver operating characteristic curve (AUC) was computed to assess the discrimination capacities of each metabolite marker. Databases including the Kyoto Encyclopedia of Genes and Genomes (KEGG) and MetaboAnalyst were utilized to search for the potential pathways of metabolites. Results Aqueous humor metabolomic profiles could well distinguish POAG from controls. Fourteen metabolic biomarkers were identified as potential aqueous humor biomarkers for POAG, yielding AUC values from 0.62 to 0.86. In pathway analysis, Biotin metabolism was highly impacted, implying that these metabolic markers play important roles in the regulation of this pathway. Conclusions This study identified valuable metabolic biomarkers and pathways that may facilitate an improved understanding of the POAG pathogenesis. The finding holds translational value in the development of new therapeutic measures for POAG.

In terms of how the signal varies in response to increased concentration of an analyte, sensors can be classified as either "signal-on" or "signal-off" format. While both types hold potentials to be sensitive, selective, and reusable, in many situations "signal-on" sensors are preferred for their low background signal and better selectivity. In this study, with the detection of lysozyme using its DNA aptamer as a trial system, for the first time we demonstrated that such an aptamer-based electrochemical biosensor can be converted from intrinsically "signal-off" to "signal-on" with the aid of a DNA exonuclease. The fact that the stepwise cleavage of antilysozyme aptamer catalyzed by Exonuclease I (Exo I) is entirely inhibited upon binding lysozyme leads to the selective removal of unbound DNA probes (thiolate anti-lysozyme DNA aptamer strands immobilized on gold electrode) upon the introduction of Exo I to the sensor. With the aid of electrostatically bound redox cations ([Ru(NH3)6]3+), we were able to quantitate the number of aptamer strands that are bound with lysozymes via conventional cyclic voltammetry (CV) measurements. We demonstrated that Exo I-assisted signal-on conversion protocol not only improves the sensing performance (10 times better limit of detection) but also promises a versatile strategy for DNA-based biosensor design, i.e., it can be readily adapted to other aptamer-protein binding systems (thrombin, as another example).

Previously, we demonstrated that treatment with gefitinib combined with pemetrexed plus carboplatin chemotherapy improved progression-free survival (PFS) compared to gefitinib or chemotherapy alone in lung adenocarcinoma patients with sensitizing EGFR mutations. In the present study, we updated the long-term overall survival (OS) of the combination therapy and the gefitinib groups. Furthermore, the possible mechanisms underlying the effects of combination therapy were investigated. Lung adenocarcinoma patients harboring sensitizing EGFR mutations received either gefitinib plus chemotherapy (n = 40) or gefitinib alone (n = 41), and long-term survival was assessed. The pharmacological interaction between gefitinib and pemetrexed was evaluated in the PC-9 lung adenocarcinoma cell line using a colorimetric assay for assessing cell metabolic activity (MTT assay). The influence of combined treatment with gefitinib plus pemetrexed on gene expression profiles and signaling pathways was investigated using microarrays and Ingenuity Pathway Analysis (IPA). On the last day of follow-up (28 September 2018), 30 (75.0%) patients in the combination group and 35 (85.4%) patients in the gefitinib group had died. The 2-year and 3-year survival rates of the combination versus gefitinib were 85.0% versus 56.1% (P = 0.004) and 52.5% versus 24.4% (P = 0.009), respectively. The median OS was 37.9 months (95% CI: 17.3–58.6) for the combination group and 25.8 months (95% CI: 19.2–32.3) for the gefitinib group (HR = 0.56, 95% CI: 0.34–0.91, P = 0.02). A synergistic inhibitory effect between gefitinib and pemetrexed was observed in the lung adenocarcinoma cell line PC-9. Furthermore, widespread gene expression changes and critical signaling pathways such as AKT signaling were identified, which might be responsible for the synergism seen with the combination treatment. Combined treatment with gefitinib plus pemetrexed resulted in improved OS over gefitinib alone. A synergistic inhibitory effect between gefitinib and pemetrexed was observed on lung adenocarcinoma cell growth. Gene expression profile analysis revealed potential signaling pathways, including AKT signaling, contributing to the synergism. NCT02148380.

Colorimetric assays have drawn increasing research interest with respect to the quantitative detection of hydrogen peroxide (H2O2) based on artificial enzymes because of their advantages with respe...

We have discovered herein that commonly used laboratory glass microfiber filters can be functionalized as background-free superhydrophobic substrates for quantitative fluorometric assays. In particular, glass microfiber filters (Whatman GF/A) can be treated with low-concentration (20 mM) methyltrichlorosilane/toluene solution to be superhydrophobic (water contact angle >150°) in less than 5 min; the modified glass microfiber filter can be readily patterned with UV/ozone irradiation to create hydrophilic reaction zones on the otherwise superhydrophobic substrate. Compared with traditional cellulose filter paper, the glass microfiber filter has extremely low fluorescence background, which makes it an excellent substrate for preparing quantitative fluorometric assays. In conjunction with smartphone imaging and color analysis, we have showcased a copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC)-based fluorometric assay for copper quantitation on these patterned, superhydrophobic glass microfiber filter substrates. Both the limit of detection and linear response range are comparable with the standard spectrophotometric quantitation in solution and commercial copper detection kits, which augments the application potential of superhydrophobic glass microfiber filters as ideal (e.g., background-free) substrates for the preparation of multiplex microassays and other advanced microanalytical devices based on fluorescence readout.

To find potential alkaline-earth metal-doped aromatic superconductors and clarify the origin of superconductivity in metal-doped phenanthrene (PHN) systems, we have systematically investigated the crystal and electronic structures of bivalent metal (Mg, Ca, Sr and Ba)-doped PHNs by first-principles calculations. The results show that only Ba1.5PHN can satisfy the conditions of both thermodynamic stability and metallization. We predicted that Ba1.5PHN is superconducting with the critical temperature of 5.3 K. Based on the metal atomic radius and electronegativity and combined with monovalent metal- and trivalent metal-doped PHNs, the relations among charge transfer, metallization, and superconductivity were analyzed. The results indicate that the electronegativity of the metal element rather than the atomic radius is predominant in the charge transfer and superconductivity of metal-doped phenanthrene.

Herein, we describe a benchtop protocol to create superhydrophobic polydimethylsiloxane (PDMS) via nanocontact molding of polycarbonate (PC) that was crystallized by controlled solvent treatment. The crystallized PC chains rearrange into a network of spherulites (spherical semicrystalline domains); the overall surface is rough on the micrometer-scale, while the spherulites themselves consist of nanoscale features. It was confirmed via conventional spectroscopic and high-resolution microscopic investigation that such hierarchical roughness is key to the development of superhydrophobic PC and the substantial enhancement upon PDMS molding. Thus, the prepared PDMS surface has excellent superhydrophobicity with an optimized contact angle of 172 ± 1° and a sliding angle of

The macrocyclic cucurbit[7]uril (CB[7]) host has exhibited great application potential as a pharmaceutical excipient due to its versatile abilities to modulate the chemical/physical properties of drug molecules (guests) and to control their in vivo delivery and release (upon complexation). The formation of stable CB[7]@drug complexes is the prerequisite for these promising applications; we report herein a general assay strategy to quantitate the complexation based on competitive binding with surface-immobilized redox guests in conjunction with conventional electrochemical techniques (e.g., cyclic voltammetry). Particularly, by incubating a mixture of CB[7] and a drug molecule with ferrocene (Fc)-terminated self-assembled monolayers (SAMs) on gold, the competitive host@guest binding between the CB[7]@drug complex formed in solution and the CB[7]@Fc complex formed on surface can be quantified with direct cyclic voltammetry measurements. On the basis of the known concentrations of CB[7]/drug and electrochemically determined surface densities of free/complexed Fc groups, the formation constant of CB[7]@drug complex can be determined. With several drug molecules as examples, we have demonstrated the capability of this method for quantitative studies of the formation of supramolecular excipient@drug complexes that are of interest in pharmaceutical and biomedical sciences. More importantly, this work promises a general assay strategy that allows electrochemical quantitation of a wide range of electro-inactive analytes based on the competitive supramolecular host@guest binding at redox-tagged molecular interfaces.

Efficient synthesis of cyclic polymers has received much attention in polymer chemistry field. Although photochemical cycloaddition of terminal π-bonded units provides a plausible way toward cyclic polymerization, it remains challenging to avoid side reactions by manipulating the reaction selectivity. Herein supramolecular confinement has been developed as a promising strategy to address this issue, by introducing highly directional hydrogen bonds to the photo-reactive cyanostilbenes. The cyanostilbenes units on both ends of a telechelic macromonomer are orientationally aligned with high local concentrations, yielding [2+2] photo-cycloaddition products upon 430 nm light irradiation. It leads to the formation of cyclic polymers in the self-assembled state, in stark contrast to Z-E isomerization of cyanostilbenes in the monomeric state. Overall, supramolecular confinement effect exemplified in the current study provides new avenues toward cyclic topological polymers with high synthetic efficiency.

The development of high-performance recyclable polymers represents a circular plastics economy to address the urgent issues of plastic sustainability. Herein, we design a series of biobased seven-membered-ring esters containing aromatic and aliphatic moieties. Ring-opening polymerization studies showed that they readily polymerize with excellent activity (TOF up to 2.1 × 105 h-1) at room temperature and produce polymers with high molecular weight (Mn up to 438 kg/mol). The variety of functionalities allows us to investigate the substitution effect on polymerizability/recyclability of monomers and properties of polymers (such as Tgs from -1 to 79 °C). Remarkably, a stereocomplexed P(M2) exhibited significantly increased Tm and crystallization rate. More importantly, product P(M)s were capable of depolymerizing into their monomers in solution or bulk with high efficiency, thus establishing their circular life cycle.

Purpose: To investigate the clinical significance of macular estimated retinal ganglion cell (mRGC) and estimated retinal ganglion cell (eRGC) in the diagnosis and staging of glaucoma.Methods: This is a cross-section study. All enrolled subjects underwent standard automated perimetry (SAP) and optical coherence tomography (OCT) examination. Swedish Interactive Threshold Algorithm (SITA)-FAST detection strategy and 24-2, 10-2 detection programs were employed in SAP assessment. The visual-field parameters and OCT parameters were calculated according to three formulas to obtain the eRGC and mRGC1 or mRGC2. The efficiency of eRGC, mRGC1, and mRGC2 estimates for the staging of glaucoma was compared. The sensitivity and specificity of each parameter for diagnosis of glaucoma were analyzed using the receiver operating characteristic (ROC) curve.Results: A total of 119 eyes were included in the analysis. Compared with the healthy controls, eRGC, mRGC1, and mRGC2 estimates were significantly decreased in patients with glaucoma. As glaucoma progressed, eRGC, mRGC1, and mRGC2 estimates were gradually reduced. In preperimetric glaucoma, mRGC1, mRGC2, and eRGC were reduced by 13.2, 14.5, and 18%, respectively. In the mild stage of glaucoma, mRGC1, mRGC2, and eRGC were reduced by 28, 34, and 38%, respectively. In the advanced stage of glaucoma, mRGC1, mRGC2, and eRGC were reduced by 81, 85, and 92% respectively. The proportion of retinal ganglion cell (RGC) loss in the macula was close to that outside the macula. The specificity at 95% gave a sensitivity of 95.51, 86.52, and 87.64% for eRGC, mRGC1, and mRGC2, respectively. The sensitivity of structural parameters macular ganglion cell complex thickness and retinal nerve fiber layer (RNFL) were 98.88 and 95.51%, respectively. The sensitivity of functional parameters mean deviation (24-2) and visual field index (VFI) were 80.90 and 73.03%, respectively. The area under ROC curve of mRGC1, mRGC2, and eRGC were 0.982, 0.972, and 0.995 (P < 0.0001), respectively.Conclusion: Estimated retinal ganglion cell, mRGC1, and mRGC2 provide value to the staging of glaucoma and better diagnostic performance. Macular RGC estimatesthat integration of both structural and functional damages in macular may serve as a sensitive indicator for assessing macular damage in glaucoma and are of importance for the diagnosis and progression management of glaucoma.

Heme oxygenase-1 (HO-1) has been reported to be upregulated following renal ischemia-reperfusion injury (IRI) and plays a key cytoprotective role; however, the underlying molecular mechanisms of its protective effects remain poorly understood. In the present study, in order to further elucidate the molecular mechanisms underlying the cytoprotective role of HO-1 in renal IRI, HO-1+/+ and HO-1+/− mice were subjected to renal ischemia and subsequent reperfusion followed by the analysis of blood urea nitrogen (BUN) and serum creatinine (SCr) levels, the severity of histological changes, HO-1 and vascular cell adhesion molecule-1 (VCAM-1) protein expression, the mRNA expression of inflammatory factors and the effects of VCAM-1 blockade. The results of the present study demonstrated that the upregulated expression levels of VCAM-1 in HO-1+/− mice during IRI increased the extent of renal tissue damage and activated the inflammatory response. These effects were subsequently reversed following infusion with an anti-VCAM-1 antibody. In addition, the upregulated expression of VCAM-1 in mouse glomerulus vascular endothelial cells isolated from HO-1+/− mice increased the adhesion and migration of neutrophils, effects which were also reversed upon incubation with an anti-VCAM-1 antibody. These results indicated that HO-1 knockdown may upregulate the expression of VCAM-1 during renal IRI, resulting in increased neutrophil recruitment and the activation of the inflammatory response, thereby exacerbating renal IRI. The present study thus highlights the regulatory mechanisms of HO-1 in renal IRI and provides a potential target for the clinical treatment of IRI following renal transplantation.

Background Brain metastasis is an important cause of increased mortality in patients with non-small cell lung cancer (NSCLC). In brain metastasis, the blood–brain barrier (BBB) is frequently impaired, forming blood–tumor barrier (BTB). The efficacy of chemotherapy is usually very poor. However, the characteristics of BTB and the impacts of BTB on chemotherapeutic drug delivery remain unclear. The present study investigated the structure of BTB, as well as the distribution of routine clinical chemotherapeutic drugs in both brain and peripheral tumors. Methods Bioluminescent image was used to monitor the tumor load after intracranial injection of lung cancer Lewis cells in mice. The permeability of BBB and BTB was measured by fluorescent tracers of evans blue and fluorescein sodium. Transmission electron microscopy (TEM), immunohistochemistry and immunofluorescence were performed to analyze structural differences between BBB and BTB. The concentrations of chemotherapeutic drugs (gemcitabine, paclitaxel and pemetrexed) in tissues were assayed by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Results Brain metastases exhibited increased BTB permeability compared with normal BBB detected by fluorescence tracers. TEM showed abnormal blood vessels, damaged endothelial cells, thick basement membranes, impaired intercellular endothelial tight junctions, as well as increased fenestrae and pinocytotic vesicles in metastatic lesions. Immunohistochemistry and immunofluorescence revealed that astrocytes were distributed surrounded the blood vessels both in normal brain and the tumor border, but no astrocytes were found in the inner metastatic lesions. By LC-MS/MS analysis, gemcitabine showed higher permeability in brain metastases. Conclusions Brain metastases of lung cancer disrupted the structure of BBB, and this disruption was heterogeneous. Chemotherapeutic drugs can cross the BTB of brain metastases of lung cancer but have difficulty crossing the normal BBB. Among the three commonly used chemotherapy drugs, gemcitabine has the highest distribution in brain metastases. The permeability of chemotherapeutic agents is related to their molecular weight and liposolubility.

The diagnosis of liver damage induced by mushroom poisoning is still challenging. This study aims to screen the early biological indexes that could predict acute mushroom poisoning with liver damage. The patients with acute mushroom poisoning and liver damage admitted to The First Affiliated Hospital of Dalian Medical University，China from July 2007 to August 2017 were analyzed retrospectively. A total of 66 patients were enrolled in this study, with 44 and 22 patients in the liver injury group and liver failure group, respectively. Ten patients in the liver failure group died, with a mortality of 45.5% in this group. Multivariable Cox regression showed that the blood ammonia (NH3) and lactic acid (Lac) at the time of admission were independently associated with the in-hospital time to death for patients with liver failure induced by mushroom poisoning. Lactate and blood ammonia at the time of admission could be used to predict the prognosis of patients with acute mushroom poisoning and liver failure.

Objective The aim of this observational cohort study was to assess the effectiveness and safety of the IL-6-receptor inhibitor tocilizumab (TCZ) in Behçet’s syndrome (BS) with refractory arterial involvement. Methods Ten patients admitted to the Rheumatology and Immunology Department of Peking University People’s Hospital between January 2014 and December 2019 were enrolled. The enrolled patients met the BS international criteria and exhibited severe arterial impairments. Refractory arterio-BS was diagnosed based on objective vascular symptoms unexplainable by other known illnesses, and resistance to traditional immunosuppressants and glucocorticoids after 12 weeks. Patients received 8 mg/kg TCZ infusions every 4 weeks for ≥24 weeks, with simultaneous continuation of immunosuppressants and glucocorticoids. Clinical and imaging data were assessed before and after TCZ treatment. Results The enrolled patients were men aged 44.3 (10.5) years; the median disease duration was 186.5 (45.7) months, and the average age of arterial impairment onset was 38.7 (12.9) years. The following trends were observed: improvement and maintenance of symptoms after the 26.8 (7.2)-month follow-up, n = 9; complete remission, n = 6; partial response, n = 3; immunosuppressant dose reduction, n = 4; radiologic improvement of arterial lesions, n = 4; and TCZ discontinuation owing to enlarged abdominal aortic aneurysm relapse, n = 1. The average daily glucocorticoid dose reduced from 54.5 (20.6) to 8.3 (3.6) mg/d (P Conclusion TCZ proved to be safe and effective for refractory arterial lesions in BS, with a steroid- and immunosuppressant-sparing benefit.

UDP glucose pyrophosphorylase (UDPGP) family genes have been reported to play essential roles in cell death or individual survival. However, a systematic analysis on UDPGP gene family has not been performed yet. In this study, a total of 454 UDPGP proteins from 76 different species were analyzed. The analyses of the phylogenetic tree and orthogroups divided UDPGPs into three clades, including UDP-N-acetylglucosamine pyrophosphorylase (UAP), UDP-glucose pyrophosphorylase (UGP, containing UGP-A and UGP-B), and UDP-sugar pyrophosphorylase (USP). The evolutionary history of the UDPGPs indicated that the members of UAP, USP, and UGP-B were relatively conserved while varied in UGP-A. Homologous sequences of UGP-B and USP were found only in plants. The expression profile of UDPGP genes in Oryza sativa was mainly motivated under jasmonic acid (JA), abscisic acid (ABA), cadmium, and cold treatments, indicating that UDPGPs may play an important role in plant development and environment endurance. The key amino acids regulating the activity of UDPGPs were analyzed, and almost all of them were located in the NB-loop, SB-loop, or conserved motifs. Analysis of the natural variants of UDPGPs in rice revealed that only a few missense mutants existed in coding sequences (CDSs), and most of the resulting variations were located in the non-motif sites, indicating the conserved structure and function of UDPGPs in the evolution. Furthermore, alternative splicing may play a key role in regulating the activity of UDPGPs. The spatial structure prediction, enzymatic analysis, and transgenic verification of UAP isoforms illustrated that the loss of N- and C-terminal sequences did not affect the overall 3D structures, but the N- and C-terminal sequences are important for UAP genes to maintain their enzymatic activity. These results revealed a conserved UDPGP gene family and provided valuable information for further deep functional investigation of the UDPGP gene family in plants.

With ever-popular ferrocene (Fc) terminated self-assembled monolayers (SAMs) on gold as model highly oriented molecular interfaces, we explored how the long-range electron transfer (ET) of ferrocene (Fc) groups (as guests) is regulated upon “encapsulation” with cucurbit[7]uril (CB[7]) hosts, whose inner cavity provides both a structurally defined and spatially confined nonpolar microenvironment. It was discovered that the CB[7] inclusion results in thermodynamically inhibited oxidation of Fc to Fc+ and retarded ET kinetics between Fc+/Fc and the electrode at a defined distance. By fitting with the Marcus–Hush–Chidsey model, we have shown that both the reorganization energy and electronic coupling coefficient for the Fc+/Fc ET decrease considerably upon inclusion with the CB[7] hosts at these highly oriented molecular interfaces. These results not only augment the potential of supramolecular host–guest inclusion as an effective and convenient means to regulate long-range ET at organized molecular interface...

Purpose. We aimed to evaluate the distribution and determinants of peripapillary retinal nerve fiber layer (pRNFL) thickness and its associations with general sleep quality in Chinese school students. Methods. 1063 grade 7 students aged 13 to 14 years with pRNFL thickness data from a school-based study on grade 7 students in Southwestern China participated in the study. The pRNFL thickness was measured on the optical coherence tomography images of a circular scan centered on the optic disc. Refractive error was measured after cycloplegia using an autorefractor and biometric parameters including axial length (AL) were measured by an IOLMaster. Participants’ sleep quality was measured by the Children’s Sleep Habits Questionnaire (CSHQ). Results. The mean pRNFL thickness was 106.8 ± 10.7 μm among the 1063 participants. There was an increasing trend of spherical equivalent and a decreasing trend of AL with RNFL thickness. In multivariate analysis, each diopter of spherical equivalent increase was associated with 0.64 μm increase in pRNFL thickness. Girls had an increased mean pRNFL thickness compared with boys with a mean difference of 1.65 μm. Per 10 μm increase in pRNFL thickness was significantly associated with a 0.5 reduction in CSHQ score (better sleep quality). Conclusions. More myopic refractive error was the major ocular determinant of decreased pRNFL thickness. In addition, students with thinner pRNFL tended to have a worse sleep quality.

Hypertension is a cardiovascular disease that severely impairs human health; however, its specific etiology and pathogenesis are complex. The present study investigated the effects of the calcium sensing receptor (CaSR) on vascular tone in spontaneously hypertensive rats (SHRs), and clarified the role and mechanism of CaSR in regulating this property with respect to the phospholipase C (PLC)‑inositol 1,4,5‑triphosphate (IP3)/adenylate cyclase‑V(AC‑V)/cyclic adenosine monophosphate (cAMP)/renin‑angiotensin system (RAS) pathway in these animals. CaSR protein expression in the mesenteric artery (MA) of rats and CaSR protein expression in SHRs were significantly reduced. Based on wire myography studies, vasoconstriction was significantly augmented and vasodilatation was attenuated in SHRs, and this effect was endothelium‑independent. The CaSR calcimimetic NPSR568 and inhibitor NPS2143 reduced vasoconstriction and enhanced vasodilation in SHRs. Furthermore, pretreatment with PLC‑IP3/AC‑V/cAMP/RAS pathway blockers significantly reduced the vasoconstriction response and enhanced the vasodilator response in SHRs and Wistar‑Kyoto rats (WKY), and these effects were partially dependent on the endothelium. Additionally, pretreatment with CaSR inhibitors were determined to cooperate with the PLC‑IP3/AC‑V/cAMP/RAS pathway inhibitors to significantly reduce vasoconstriction and enhance vasodilation in SHRs and WKY. Our results demonstrated that CaSR is functionally expressed in the MA of SHRs, and that CaSR expression is decreased in SHRs. Additionally, vasoconstriction was enhanced while vasodilatation was attenuated in SHRs; these processes were determined to be endothelium‑independent. CaSR is involved in the regulation of blood pressure and vascular tension in SHRs and WKYs. In association with mechanistic differences, this effect was proposed to be partially endothelium‑dependent and mediated by the PLC‑IP3/AC‑V/cAMP/RAS pathway.

Aim To determine the effect of pirfenidone on the activated human Muller cells by platelet-derived growth factor-BB (PDGF-BB). Methods The primary human Muller cells were separated from retinal tissues and established the pathogenic model by stimulated with PDGF-BB. The Muller cells behaviour of normal group and the model group was measured by MTT assay, Trypan blue assay, cell migration assay, and collagen contraction assay. The expression of transforming growth factor (TGF)-β1, -β2, and pigment epithelium-derived factor (PEDF) was estimated with real-time polymerase chain reaction (PCR), Western blot and immunofluorescence analyses. Results A pathogenic/proliferative model of Muller cells was established by stimulating normal cultured Muller cells with 10 ng/mL PDGF-BB for 48h. After treated with 0.2 and 0.3 mg/mL pirfenidone, the proliferation, migration and collagen contraction was statistically significantly depressed in the model group compared with the normal groups. The expression levels of TGF-β1 and TGF-β2 were significantly down-regulated, while the PEDF expression was significantly up-regulated after treated with 0.2 and 0.3 mg/mL pirfenidone in the model group. Conclusion Pirfenidone effectively suppress the proliferation, migration and collagen contraction of the human Muller cells stimulated with PDGF-BB through down-regulation of TGF-β1/TGF-β2 and up-regulation of PEDF.

Mechanoelectronic DNA nanoswitches refer to designed oligonucleotide constructs that are composed of conduction-interrupted duplex stems functionally coupled to ligand recognition motifs; they have been shown to undergo remarkable conduction switching upon binding molecular ligands/analytes. Herein we report a divergent pair of such mechanoelectronic DNA switches, the "signal-on" 3'AA-1 switch and the "signal-off" NB-1 switch, both activated by and responded to mercury ions (Hg2+) at nM levels. We first investigated their charge transport efficiency at a biochemical level, by studying how distinct base sequence at the switches' central three-way junction and at the recognition motif (capable of forming T-Hg2+-T metallo-base pairs) influences their overall conductivity. Gel electrophoresis assays revealed that the presence of two unpaired adenines (AA) at the junction led to "signal-on" behavior with increasing Hg2+ concentration; divergently, absence of these adenines led to a "signal-off" behavior. Upon immobilization on gold electrodes, both DNA switches, with enhanced and inhibited conductivity, respectively, showed excellent sensitivity as well as selectivity toward Hg2+ and can be regenerated for multicycle applications. The high performance of these devices, as both nanoswitches and biosensors with robust and reproducible properties, highlights their potential as an outstanding new class of DNA mechanoelectronic components with built-in biosensing capabilities.

The ability of soils and sediments to promote in-situ activation of persulfate and persulfate combined with hydrogen peroxide was investigated for treatment of 1,4-dioxane (dioxane). Experiments were conducted with both batch-reactor and column systems to examine reaction rates and activation mechanisms. Four soils and aquifer sediments were used. ICP-MS and XRD analyses were used to characterize geochemical properties of the solutions and sediments, while EPR spectroscopy was used to characterize radical formation. For the batch experiments, degradation of dioxane was significantly greater in the presence of each of the four subsurface geomedia compared to the controls with no geomedia. This indicates that all four geomedia induced oxidant activation, thereby enhancing dioxane degradation. Dioxane degradation was significantly enhanced by the addition of peroxide to the persulfate solution. It is hypothesized that iron associated with the geomedia is primarily responsible for activation, and that the degree of degradation enhancement relates in part to dissolved-phase iron content. EPR results indicate that manganese oxides and soil organic matter may also have contributed to some degree to persulfate activation, and that manganese oxides enhanced activation of peroxide under the study conditions. Approximately 10% of dioxane was degraded in the miscible-displacement experiments, consistent with the short residence time compared to dioxane's half-life. The pseudo first-order rate coefficients obtained from the batch and column experiments were similar. The results of this study indicate that subsurface geomedia can induce activation of persulfate and peroxide to enhance in-situ chemical oxidation applications.

We demonstrate herein that hemin–graphene hybrid nanosheets (H–GNs) can differentiate hemin-binding DNA aptamers (i.e., guanine-rich DNA sequences that form G-quadruplex structures upon binding hemin) and nonspecific single-stranded oligonucleotides colorimetrically. By exploiting the tendency of the H–GNS to aggregate under high ionic strength and their inherent catalytic activities, excess H–GNS were removed and the amount of H–GNs remaining in the supernatant was quantified. Subsequently, the binding affinity of hemin-binding DNA aptamers to the H–GNS was determined upon titration with the DNA. With the conformity of the experimental data to the Langmuir adsorption isotherm, hemin is hypothesized to be sandwiched between the G-quadruplex DNA and graphene forming a ternary complex as a result of the specific binding of the aptamer with the H–GNS. The binding affinity of the aptamer is not as strong as that of hemin/G-quadruplex in solution, which is attributed to electronic effects imparted by the graphene surface. The catalytic activity of the resulting complex, however, was confirmed to be higher than that of H–GNs alone.

In this work, coil–rod–coil organogold(I) complexes have been successfully assembled into phosphorescent supramolecular polymers via the cooperative nucleation–elongation mechanism. Deeper insights into the supramolecular polymerization behaviors are achieved via solvent-dependent UV-Vis and CD spectroscopic measurements. As compared to the structurally similar organoplatinum(II)-based systems, organogold(I) complexes display a stronger supramolecular polymerization tendency and higher resistance to solvent polarity change for the resulting assemblies. The phenomena are primarily ascribed to the low steric hindrance of the inner alkynyl-gold(I)–isocyanide rod unit.

Wearable pressure sensors with high sensitivity, broad dynamic response range, and low detection limit are highly desirable to enable the applications in electronic skins and soft robotics. In this work, we report a high-performance wearable pressure sensor based on microstructured polydimethylsiloxane (PDMS)/Ag and rough polyimide/Au interdigital electrodes. By tailoring the touchpoints, the resulting pressure sensors show ultrahigh sensitivity (259.32 kPa–1 in the range of 0–2.5 kPa), broad dynamic response range (0–54 kPa), fast response (∼200 μs), and low detection limit (0.36 Pa). Furthermore, the effect of different sensor structural configurations, PDMS geometrical feature, and Ag thickness on the performance of the pressure sensors are systematically investigated. Thanks to these merits, the fabricated pressure sensor is capable of real-time monitoring pulse wave and can act as artificial skin for robot hand to detect weak pressure changes, leading to the great application promise in the fields of biomedical, real-time health monitoring, and intelligent robot. Ministry of Education (MOE) Nanyang Technological University Accepted version This work was supported in part by the Shenzhen Basic Research Grant: JCYJ20150925163313898, JCYJ20170413153246713, the National Nature Science Foundation of China: 11804354, 61574157, 61774164. This work was supported in part by the Singapore Ministry of Education Academic Research Fund Tier 2 (MOE2015-T2-1- 066 and MOE2015-T2-2-010), Singapore Ministry of Education Academic Research Fund Tier 1 (RG85/16), and Nanyang Technological University (start-up grant M4081515: L.W.).

Cooperative supramolecular polymerization of π-conjugated compounds into one-dimensional nanostructures has received tremendous attentions in recent years. It is commonly achieved by incorporating amide linkages into the monomeric structures, which provide hydrogen bonds for intermolecular non-covalent complexation. Herein, the effect of amide linkages is elaborately studied, by comparing supramolecular polymerization behaviors of two structurally similar monomers with the same platinum(II) acetylide cores. As compared to the N-phenyl benzamide linkages, N-[(1S)-1-phenylethyl] benzamide linkages give rise to effective chirality transfer behaviors due to the closer distances between the chiral units and the platinum(II) acetylide core. They also provide stronger intermolecular hydrogen bonding strength, which consequently brings higher thermo-stability and enhanced gelation capability for the resulting supramolecular polymers. Supramolecular polymerization is further strengthened by varying the monomers from monotopic to ditopic structures. Hence, with the judicious modulation of structural parameters, the current study opens up new avenues for the rational design of supramolecular polymeric systems.

Anthocyanins are antioxidant and anti-inflammatory ingredients in various fruit beverages, for which their conservation and quantitation are important for the food industry. In this paper, we report a simple, portable device for accurate on-site determination of total monomeric anthocyanins in fruit beverages employing a Wi-Fi scanner coupled with a flexible microchip and a free mobile app. The detection principle is based on the pH-induced colorimetric reactions of anthocyanins performed in a specially designed microchip and validated with standard spectrophotometric measurements. The microchip with multiple testing vials was prepared with the benchtop molding method with a common PDMS elastomer and a transparency film, the photo of the scanned microchip is wirelessly sent to a smartphone and the RGB values of individual reaction vials in the microchip are analyzed with a free mobile app to determine the corresponding concentrations. It was demonstrated that the quantitation performance of this POCT device is comparable with conventional spectrophotometry in the determination of total anthocyanins in both standard solutions and fruit beverages.

Chitosan is the only cationic polysaccharide found in nature. It has broad application prospects in biomaterials, but its application is limited due to its poor solubility in water. A novel chitosan derivative was synthesized by amidation of chitosan with 18&beta, glycyrrhetinic acid and sialic acid. The chitosan derivatives were characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, and measurement of the zeta potential. We also investigated the solubility, cytotoxicity, and blood compatibility of chitosan derivatives. 18&beta, glycyrrhetinic acid and sialic acid could be grafted onto chitosan molecular chains. The thermal stability of the synthesized chitosan derivatives was decreased and the surface was positively charged in water and phosphate-buffered saline. After chitosan had been modified by 18 &beta, glycyrrhetinic acid and sialic acid, the solubility of chitosan was improved greatly in water and phosphate-buffered saline, and percent hemolysis was &lt, 5%. Novel amphiphilic chitosan derivatives could be suitable polymers for biomedical purposes.

The present study investigated the stability and efficacy of a biosurfactant produced by Klebsiella sp. KOD36 under extreme conditions and its potential for enhancing the solubilization and degradation of phenanthrene in various environmental matrices. Klebsiella sp. KOD36 produced a mono-rhamnolipids biosurfactant with a low critical micelle concentration (CMC) value. The biosurfactant was stable under extreme conditions (60 °C, pH 10 and 10% salinity) and could lower surface tension by 30% and maintained an emulsification index of > 40%. The emulsion index was also higher (17–43%) in the presence of petroleum hydrocarbons compared to synthetic surfactant Triton X-100. Investigation on phenanthrene degradation in three different environmental matrices (aqueous, soil-slurry and soil) confirmed that the biosurfactant enhanced the solubilization and biodegradation of phenanthrene in all matrices. The high functional stability and performance of the biosurfactant under extreme conditions on phenanthrene degradation show the great potential of the biosurfactant for remediation applications under harsh environmental conditions.

In this work, an enzyme-free fluorescence resonance energy transfer (FRET) strategy was established for rapid and specific detection of the DNA sequence from Vibrio parahaemolyticus (VP) using hybridization chain reaction (HCR) amplification and triplex DNA. The triplex forming oligonucleotide (TFO) was labelled with carboxyfluorescein (FAM) as fluorescence donor, and hairpin sequence H1 was labelled by tetramethylrhodamine (TAMRA) as fluorescence receptor. In the present target VP DNA, the hairpin structure of molecular beacon (MB) was opened, the free end was released and hybridized with H1-TAMRA, and the HCR reaction was triggered by the alternate supplementation of H1-TAMRA and H2 to produce the notch double helix analogue. After the addition of TFO-FAM, a triplex structure was formed between HCR products (H1-TAMRA/H2) and TFO-FAM. A close contact between the donor and the receptor resulted in FRET. Under the optimal conditions, the fluorescence quenching value was inversely proportional to the concentration of target VP DNA in the range of 0.1–50 nmol L−1, and the detection limit was 35 pmol L−1.

Acute lung injury (ALI), which could be induced by multiple factors such as lipopolysaccharide (LPS), refer to clinical symptoms of acute respiratory failure, commonly with high morbidity and mortality. Reportedly, active ingredients from green tea have anti-inflammatory and anticancer properties, including epigallocatechin-3-gallate (EGCG). In the present study, protein kinase C alpha (PRKCA) is involved in EGCG protection against LPS-induced inflammation and ALI. EGCG treatment attenuated LPS-stimulated ALI in mice as manifested as improved lung injury scores, decreased total cell amounts, neutrophil amounts and macrophage amounts, inhibited the activity of MPO, decreased wet-to-dry weight ratio of lung tissues, and inhibited release of inflammatory cytokines TNF-α, IL-1β, and IL-6. PRKCA mRNA and protein expression showed to be dramatically decreased by LPS treatment while reversed by EGCG treatment. Within LPS-stimulated ALI mice, PRKCA silencing further aggravated, while PRKCA overexpression attenuated LPS-stimulated inflammation and ALI through MAPK signaling pathway. PRKCA silencing attenuated EGCG protection. Within LPS-induced RAW 264.7 macrophages, EGCG could induce PRKCA expression. Single EGCG treatment or Lv-PRKCA infection attenuated LPS-induced increases in inflammatory factors; PRKCA silencing could reverse the suppressive effects of EGCG upon LPS-stimulated inflammatory factor release. In conclusion, EGCG pretreatment inhibits LPS-induced ALI in mice. The protective mechanism might be associated with the inhibitory effects of PRKCA on proinflammatory cytokine release via macrophages and MAPK signaling pathway.

Background Acute myeloid leukemia (AML) patients with FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) have a high relapse rate and poor prognosis. This study aims to explore the underlying mechanism of combining Gilteritinib with ATO at low concentration in the treatment of FLT3-ITD positive leukemias. Methods We used both in vitro and in vivo studies to investigate the effects of combination of Gilteritinib with ATO at low concentration on FLT3-ITD positive leukemias, together with the underlying molecular mechanisms of these processes. Results Combination of Gilteritinib with ATO showed synergistic effects on inhibiting proliferation, increasing apoptosis and attenuating invasive ability in FLT3-ITD-mutated cells and reducing tumor growth in nude mice. Results of western blot indicated that Gilteritinib increased a 160KD form of FLT3 protein on the surface of cell membrane. Detection of endoplasmic reticulum stress marker protein revealed that IRE1a and its downstream signal phosphorylated JNK were suppressed in Gilteritinib-treated FLT3-ITD positive cells. The downregulation of IRE1a induced by Gilteritinib was reversed with addition of ATO. Knockdown of IRE1a diminished the combinatorial effects of Gilteritinib plus ATO treatment and combination of tunicamycin (an endoplasmic reticulum pathway activator) with Gilteritinib achieved the similar effect as treatment with Gilteritinib plus ATO. Conclusions Thus, ATO at low concentration potentiates Gilteritinib-induced apoptosis in FLT3-ITD positive leukemic cells via IRE1a-JNK signal pathway, targeting IRE1a to cooperate with Gilteritinib may serve as a new theoretical basis on FLT3-ITD mutant AML treatment.

To enable the optimal, biocompatible and non-destructive application of the highly useful copper (Cu+)-mediated alkyne-azide ‘click’ cycloaddition in water, we have isolated and characterized a 79-nucleotide DNA enzyme or DNAzyme, ‘CLICK-17’, that harnesses as low as sub-micromolar Cu+; or, surprisingly, Cu2+ (without added reductants such as ascorbate) to catalyze conjugation between a variety of alkyne and azide substrates, including small molecules, proteins and nucleic acids. CLICK-17’s Cu+ catalysis is orders of magnitude faster than that of either Cu+ alone or of Cu+ complexed to PERMUT-17, a sequence-permuted DNA isomer of CLICK-17. With the less toxic Cu2+, CLICK-17 attains rates comparable to Cu+, under conditions where both Cu2+ alone and Cu2+ complexed with a classic accelerating ligand, THPTA, are wholly inactive. Cyclic voltammetry shows that CLICK-17, unlike PERMUT-17, powerfully perturbs the Cu(II)/Cu(I) redox potential. CLICK-17 thus provides a unique, DNA-derived ligand environment for catalytic copper within its active site. As a bona fide Cu2+-driven enzyme, with potential for being evolved to accept only designated substrates, CLICK-17 and future variants promise the fast, safe, and substrate-specific catalysis of ‘click’ bioconjugations, potentially on the surfaces of living cells.

As the performance of hairpin DNA (hpDNA)-based biosensors is highly dependent on the yield of stem-loop (hairpin) conformations, we report herein a versatile fluorometric in situ hybridization protocol for examining hpDNA self-assembled monolayers (SAMs) on popularly used biochip substrates. Specifically, the ratio of fluorescence (FL) intensities of hpDNA SAMs (in an array format) before and after hybridization was adopted as the key parameter for performing such a determination. Upon confirming the existence of mixed and tunable DNA conformations in binary deposition solutions and efficient hybridization of the hairpin strands with the target DNA via gel electrophoresis assays, we tested the fluorometric protocol for determining the coverages of hpDNA in hpDNA/ssDNA SAMs prepared on gold; its accuracy was validated by Exonuclease I (Exo I)-assisted electrochemical quantitation. To further confirm its versatility, this FL protocol was adopted for quantifying hairpin conformations formed on glass and polycarbonate (PC) substrates. The molar ratios of surface-tethered hairpin conformations on the three different substrates were all found to be proportional to but less than those in the binary deposition solutions, and were dependent on the substrate morphology. The findings reported herein are beneficial for the construction of highly efficient DNA hairpin-based sensing surfaces, which essentially facilitates the creation of hpDNA-based biosensors with optimal detection performance.

PURPOSE: High myopia is associated with blinding ocular morbidities. Identifying novel biomarkers may provide clues on pathogenic pathways that are currently unknown. We aimed to identify serum metabolic biomarkers and investigate the metabolic alterations in relation to high myopia. METHODS: Forty adults with high myopia and 40 with low myopia aged 60 years or older from the Weitang Geriatric Diseases study were included in the case-control study. Refractive error was determined by autorefraction followed by subjective refraction. We performed the metabolomic analysis of serum samples from patients with high myopia and age- and sex- matched controls with low myopia, using a nontargeted gas chromatography coupled to time-of-flight mass spectrometer. The area under the receiver operating characteristic curve (AUC) was computed to assess the discrimination capacities of each metabolite marker. Databases including KEGG and MetaboAnalyst were utilized to search for the potential pathways of metabolites. RESULTS: Serum metabolomic profiles could well distinguish high myopia from low myopia. Twenty metabolic biomarkers were identified as potential serum biomarkers for high myopia, yielding AUC values of 0.59–0.71. Metabolic pathways in relation to high myopia, mainly characterized by increased energy metabolism, increased oxidative stress, abnormal amino acid metabolism, and altered biotin metabolism, provide a foundation to support myopia progression. CONCLUSIONS: This study identified valuable metabolic biomarkers and pathways that may facilitate an improved understanding of the disease pathogenesis. The finding holds translational value in the development of new therapeutic measures for high myopia-related complications.

Background: Vascular injury and inflammation during percutaneous coronary intervention (PCI) are associated with increased risk of post-PCI adverse outcomes. Colchicine decreases neutrophil recruitment to sites of vascular injury. The anti-inflammatory effects of acute colchicine administration before PCI on subsequent myocardial injury are unknown. Methods: In a prospective, single-site trial, subjects referred for possible PCI (n=714) were randomized to acute preprocedural oral administration of colchicine 1.8 mg or placebo. Results: Among the 400 subjects who underwent PCI, the primary outcome of PCI-related myocardial injury did not differ between colchicine (n=206) and placebo (n=194) groups (57.3% versus 64.2%, P =0.19). The composite outcome of death, nonfatal myocardial infarction, and target vessel revascularization at 30 days (11.7% versus 12.9%, P =0.82), and the outcome of PCI-related myocardial infarction defined by the Society for Cardiovascular Angiography and Interventions (2.9% versus 4.7%, P =0.49) did not differ between colchicine and placebo groups. Among 280 PCI subjects in a nested inflammatory biomarker substudy, the primary biomarker end point, change in interleukin-6 concentrations did not differ between groups 1-hour post-PCI but increased less 24 hours post-PCI in the colchicine (n=141) versus placebo group (n=139; 76% [−6 to 898] versus 338% [27 to 1264], P =0.02). High-sensitivity C-reactive protein concentration also increased less after 24 hours in the colchicine versus placebo groups (11% [−14 to 80] versus 66% [1 to 172], P =0.001). Conclusions: Acute preprocedural administration of colchicine attenuated the increase in interleukin-6 and high-sensitivity C-reactive protein concentrations after PCI when compared with placebo but did not lower the risk of PCI-related myocardial injury. Registration: URL: https://www.clinicaltrials.gov ; Unique Identifiers: NCT02594111, NCT01709981.

The synergistic anticancer effect of gemcitabine (GEM) and resveratrol (RSVL) has been noted in certain cancer types. However, whether the same phenomenon would occur in lung cancer is unclear. Here, we uncovered the molecular mechanism by which RSVL enhances the anticancer effect of GEM against lung cancer cells both in vitro and in vivo. We established human lung adenocarcinoma HCC827 xenografts in nude mice and treated them with GEM and RSVL to detect their synergistic effect in vivo. Tumor tissue sections from nude mice were subjected to hematoxylin and eosin staining for blood vessel morphological observation, and immunohistochemistry was conducted to detect CD31-positive staining blood vessels. We also established the HCC827-human umbilical vein endothelial cell (HUVEC) co-culture model to observe the tubule network formation. Human angiogenesis antibody array was used to screen the angiogenesis-related proteins in RSVL-treated HCC827. RSVL suppressed the expression of endoglin (ENG) and increased tumor microvessel growth and blood perfusion into tumor. Co-treatment of RSVL and GEM led to more tumor growth suppression than treatment of GEM alone. Mechanistically, using the HCC827-HUVEC co-culture model, we showed that RSVL-suppressed ENG expression was accompanied with augmented levels of phosphorylated extracellular signal-regulated kinase (ERK) 1/2 and increased tubule network formation, which may explain why RSVL promoted tumor microvessel growth in vivo. RSVL promoted tumor microvessel growth via ENG and ERK and enhanced the anticancer efficacy of GEM. Our results suggest that intake of RSVL may be beneficial during lung cancer chemotherapy.

Iodine-free quasi-solid-state electrolytes were developed for dye-sensitized solar cells (DSSCs) by removing I2 from the conventional I−/I3− redox electrolyte and gelling the electrolyte with metal oxide nanoparticles. The inorganic nanoparticles played a dual role of gelling agent and charge transport enhancer. The removal of I2 improved the long-term stability of DSSCs, but reduced the ionic diffusivity of electrolyte and thus the solar-to-electricity efficiency of DSSCs. By introducing a suitable nanoparticle gelator into the electrolyte, the ionic diffusivity and the interfacial charge transfer could be enhanced due to the formation of 3-D networks that facilitate Grotthuss-type ion exchange. Three different metal oxide nanoparticles (SiO2, TiO2, and ZnO) were evaluated, and the best performance was obtained by TiO2 nanoparticles. The I2-free quasi-solid-state DSSCs gelled by 15% TiO2 achieved an efficiency of 8.00% vs. a 6.94% efficiency attained by the I2-free liquid-state reference cells. The I2-free quasi-solid-state DSSCs gelled by 15% TiO2 also exhibited good long-term at-rest stability with an estimated life span of five to six years under ambient condition based on an accelerated stability test performed at 65°C with 65% relative humidity.

Effects of rhamnolipids on the removal of 2,4,2,4-tetrabrominated biphenyl ether (BDE-47) by Phanerochaete chrysosporium (P. chrysosporium) had been investigated, as well as the influence of carbon source (i.e. glucose). The results showed that the removal efficiency was over 90% in all treatments in 7 d. Rhamnolipids at low concentrations (0.05 and 0.1 CMC (critical micelle concentration)) could promote the removal of BDE-47, however, the inhibition effects occurred at high concentrations (0.5 and 1.0 CMC). The further study indicated that rhamnolipids at low concentrations not only promote the growth of mycelium, but also had obvious promotion on ligninolytic enzymes activity (i.e. manganese peroxidase (MnP), lignin peroxidase (LiP) and laccase (Lac)), especially for MnP and Lac. However, the opposite effect was generated at high rhamnolipids concentrations. Meanwhile, glucose played an active role for BDE-47 removal. For better understanding the degradation mechanism, the degradation product analysis and molecular docking had been introduced to this study. The degradation product analysis indicated that OH-PBDEs were the major degradation products and hydroxylation should be the important degradation pathway. The docking results showed that the ideal binding conformation occurred between ligninolytic enzymes and BDE-47, and hydrophobic interactions were the main interaction. Moreover, hydrogen bonds and hydrophobic interactions both existed in ligninolytic enzymes and rhamnolipids interaction. That might be the reason that rhamnolipids affected enzymes activity. These results indicated that P. chrysosporium might be a type of ideal microorganisms in the removal of BDE-47 pollution, and rhamnolipids could be a type of additives for better removal efficiency.