Wenyi Wang

Plasmonic metasurfaces have recently attracted much attention due to their ability to abruptly change the phase of light, allowing subwavelength optical elements for polarization and wavefront control. However, most previously demonstrated metasurface designs suffer from low coupling efficiency and are based on metallic resonators, leading to ohmic loss. Here, we present an alternative approach to plasmonic metasurfaces by replacing the metallic resonators with high-refractive-index silicon cut-wires in combination with a silver ground plane. We experimentally demonstrate that this meta-reflectarray can be used to realize linear polarization conversion with more than 98% conversion efficiency over a 200 nm bandwidth in the short-wavelength infrared band. We also demonstrate optical vortex beam generation using a meta-reflectarray with an azimuthally varied phase profile. The vortex beam generation is shown to have high efficiency over a wavelength range from 1500 to 1600 nm. The use of dielectric resonators in place of their plasmonic counterparts could pave the way for ultraefficient metasurface-based devices at high frequencies.

We investigated the clinical significance of plasma concentrations of Epstein-Barr virus (EBV) DNA in patients with advanced nasopharyngeal carcinoma.Ninety-nine patients with biopsy-proven stage III or IV nasopharyngeal carcinoma and no evidence of metastasis (M0) received 10 weekly chemotherapy treatments followed by radiotherapy. Plasma samples from the patients were subjected to a real-time quantitative polymerase-chain-reaction assay. EBV genotypes of paired samples from plasma and primary tumor were compared.Plasma EBV DNA was detectable before treatment in 94 of the 99 patients, but not in 40 healthy controls or 20 cured patients. The median concentrations of plasma EBV DNA were 681 copies per milliliter among 25 patients with stage III disease, 1703 copies per milliliter among 74 patients with stage IV disease, and 291,940 copies per milliliter among 19 control patients with distant metastasis (P<0.001). Patients with relapse had a significantly higher plasma EBV DNA concentration before treatment than those who did not have a relapse (median, 3035 vs. 1202 copies per milliliter; P=0.02). The consistent genotyping of EBV DNA between paired samples of plasma and primary tumor suggested that the circulating cell-free EBV DNA may originate from the primary tumor. Unlike the rebound of plasma EBV DNA concentrations in the patients who had a relapse, the plasma EBV DNA concentration was persistently low or undetectable in patients with a complete clinical remission. Overall survival (P<0.001) and relapse-free survival (P=0.02) were significantly lower among patients with pretreatment plasma EBV DNA concentrations of at least 1500 copies per milliliter than among those with concentrations of less than 1500 copies per milliliter. Patients with persistently detectable plasma EBV DNA had significantly worse overall survival (P<0.001) and relapse-free survival (P<0.001) than patients with undetectable EBV DNA one week after the completion of radiotherapy.Quantification of plasma EBV DNA is useful for monitoring patients with nasopharyngeal carcinoma and predicting the outcome of treatment.

Nasopharyngeal carcinoma (NPC) is a radiosensitive and chemosensitive tumor. This randomized phase III trial compared concurrent chemoradiotherapy (CCRT) versus radiotherapy (RT) alone in patients with advanced NPC.From December 1993 to April 1999, 284 patients with 1992 American Joint Committee on Cancer stage III to IV (M0) NPC were randomly allocated into two arms. Similar dosage and fractionation of RT was administered in both arms. The investigational arm received two cycles of concurrent chemotherapy with cisplatin 20 mg/m(2)/d plus fluorouracil 400 mg/m(2)/d by 96-hour continuous infusion during the weeks 1 and 5 of RT. Survival analysis was estimated by the Kaplan-Meier method and compared by the log-rank test.Baseline patient characteristics were comparable in both arms. After a median follow-up of 65 months, 26.2% (37 of 141) and 46.2% (66 of 143) of patients developed tumor relapse in the CCRT and RT-alone groups, respectively. The 5-year overall survival rates were 72.3% for the CCRT arm and 54.2% for the RT-only arm (P =.0022). The 5-year progression-free survival rates were 71.6% for the CCRT group compared with 53.0% for the RT-only group (P =.0012). Although significantly more toxicity was noted in the CCRT arm, including leukopenia and emesis, compliance with the combined treatment was good. The second cycle of concurrent chemotherapy was refused by nine patients and was delayed for > or = 1 week for another nine patients. There were no treatment-related deaths in either arm.We conclude that CCRT is superior to RT alone for patients with advanced NPC in endemic areas.

Circularly polarized light is utilized in various optical techniques and devices. However, using conventional optical systems to generate, analyse and detect circularly polarized light involves multiple optical elements, making it challenging to realize miniature and integrated devices. While a number of ultracompact optical elements for manipulating circularly polarized light have recently been demonstrated, the development of an efficient and highly selective circularly polarized light photodetector remains challenging. Here we report on an ultracompact circularly polarized light detector that combines large engineered chirality, realized using chiral plasmonic metamaterials, with hot electron injection. We demonstrate the detector's ability to distinguish between left and right hand circularly polarized light without the use of additional optical elements. Implementation of this photodetector could lead to enhanced security in fibre and free-space communication, as well as emission, imaging and sensing applications for circularly polarized light using a highly integrated photonic platform.

Strong nonlinear light-matter interaction is highly sought-after for a variety of applications including lasing and all-optical light modulation. Recently, resonant plasmonic structures have been considered promising candidates for enhancing nonlinear optical processes due to their ability to greatly enhance the optical near-field; however, their small mode volumes prevent the inherently large nonlinear susceptibility of the metal from being efficiently exploited. Here, we present an alternative approach that utilizes a Fano-resonant silicon metasurface. The metasurface results in strong near-field enhancement within the volume of the silicon resonator while minimizing two photon absorption. We measure a third harmonic generation enhancement factor of 1.5 × 10(5) with respect to an unpatterned silicon film and an absolute conversion efficiency of 1.2 × 10(-6) with a peak pump intensity of 3.2 GW cm(-2). The enhanced nonlinearity, combined with a sharp linear transmittance spectrum, results in transmission modulation with a modulation depth of 36%. The modulation mechanism is studied by pump-probe experiments.

Summary Staphylococcus epidermidis strains are diverse in their pathogenicity; some are invasive and cause serious nosocomial infections, whereas others are non‐pathogenic commensal organisms. To analyse the implications of different virulence factors in Staphylococcus epidermidis infections, the complete genome of Staphylococcus epidermidis strain ATCC 12228, a non‐biofilm forming, non‐infection associated strain used for detection of residual antibiotics in food products, was sequenced. This strain showed low virulence by mouse and rat experimental infections. The genome consists of a single 2499 279 bp chromosome and six plasmids. The chromosomal G + C content is 32.1% and 2419 protein coding sequences (CDS) are predicted, among which 230 are putative novel genes. Compared to the virulence factors in Staphylococcus aureus, aside from δ‐haemolysin and β‐haemolysin, other toxin genes were not found. In contrast, the majority of adhesin genes are intact in ATCC 12228. Most strikingly, the ica operon coding for the enzymes synthesizing interbacterial cellular polysaccharide is missing in ATCC 12228 and rearrangements of adjacent genes are shown. No mec genes, IS256, IS257, were found in ATCC 12228. It is suggested that the absence of the ica operon is a genetic marker in commensal Staphylococcus epidermidis strains which are less likely to become invasive.

During gastrointestinal digestion or food processing of proteins, small peptides can be released and may act as regulatory compounds with hormone-like activities. Numerous biologically active peptides (bioactive peptides) have been identified. Most bioactive peptides are derived from milk and dairy products, with the most common being angiotensin converting enzyme inhibitory peptides. Soybean protein and soybean derived peptides also play an important role in soybean physiological activities, particularly those related to the prevention of chronic diseases. However, the bioactive potential of soybean derived bioactive peptides is yet to be fully appreciated. After a general introduction of approaches and advances in bioactive peptides from food sources, this review focuses on bioactive peptides derived from soybean proteins and their physiological properties. Technological approaches to generate bioactive peptides, their isolation, purification, characterization, and quantification, and further application in food and drug design are also presented. Safety concerns, such as potential toxicity, allergenicity, and sensory aspect of these peptides are likewise discussed.

Intra-tumor heterogeneity (ITH) is a mechanism of therapeutic resistance and therefore an important clinical challenge. However, the extent, origin, and drivers of ITH across cancer types are poorly understood. To address this, we extensively characterize ITH across whole-genome sequences of 2,658 cancer samples spanning 38 cancer types. Nearly all informative samples (95.1%) contain evidence of distinct subclonal expansions with frequent branching relationships between subclones. We observe positive selection of subclonal driver mutations across most cancer types and identify cancer type-specific subclonal patterns of driver gene mutations, fusions, structural variants, and copy number alterations as well as dynamic changes in mutational processes between subclonal expansions. Our results underline the importance of ITH and its drivers in tumor evolution and provide a pan-cancer resource of comprehensively annotated subclonal events from whole-genome sequencing data.

Significance Status epilepticus is a frequent neurological emergency. These unabated seizures reduce quality of life, promote the development of epilepsy, and can cause death. Activation of microglia, the brain’s resident immune cells, is an invariable feature of seizure activity. However, the involvement of blood-borne immune cells in the brain’s inflammatory reaction after seizures remains unresolved. Here we identify a blood cell not normally encountered in the healthy brain, called a monocyte, which invades brain tissue after seizures and contributes to inflammation. Blocking brain entry of the blood monocytes was beneficial, reducing neuronal damage and accelerating weight regain. Treatment strategies aimed at inhibiting peripheral immune cells from entering the brain after seizures could be beneficial.

Cell transplantation using bone marrow stromal cells (BMSCs) to alleviate neurological deficits has recently become the focus of research in regenerative medicine. Evidence suggests that secretion of various growth-promoting substances likely plays an important role in functional recovery against neurological diseases. In an attempt to identify a possible mechanism underlying the regenerative potential of BMSCs, this study investigated the production and possible contribution of neurotrophic factors by transected sciatic nerve defect in a rat model with a 15 mm gap. Cultured BMSCs became morphologically homogeneous with fibroblast-like shape after ex vivo expansion. We provided several pieces of evidence for the beneficial effects of implanted fibroblast-like BMSCs on sciatic nerve regeneration. When compared to silicone tube control animals, this treatment led to (i) improved walking behavior as measured by footprint analysis, (ii) reduced loss of gastrocnemius muscle weight and EMG magnitude, and (iii) greater number of regenerating axons within the tube. Cultured fibroblast-like BMSCs constitutively expressed trophic factors and supporting substances, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF), collagen, fibronectin, and laminin. The progression of the regenerative process after BMSC implantation was accompanied by elevated expression of neurotrophic factors at both early and later phases. These results taken together, in addition to documented Schwann cell-like differentiation, provide evidence indicating the strong association of neurotrophic factor production and the regenerative potential of implanted BMSCs.

Abstract Neoplastic lesions typically express specific carbohydrate antigens on glycolipids, mucins, and other glycoproteins. Such antigens are often under epigenetic control and are subject to reversion and loss upon therapeutic selective pressure. We report here that two of the most common tumor-associated carbohydrate antigens, Tn and sialyl Tn (STn), result from somatic mutations in the gene Cosmc that encodes a molecular chaperone required for formation of the active T-synthase. Diverse neoplastic lesions, including colon cancer and melanoma-derived cells lines, expressed both Tn and STn antigen due to loss-of-function mutations in Cosmc. In addition, two human cervical cancer specimens that showed expression of the Tn/STn antigens were also found to have mutations in Cosmc and loss of heterozygosity for the cross-linked Cosmc locus. This is the first example of somatic mutations in multiple types of cancers that cause global alterations in cell surface carbohydrate antigen expression. [Cancer Res 2008;68(6):1636–46]

Recently, there has been much interest in the extraction of hot electrons generated from surface plasmon decay, as this process can be used to achieve additional bandwidth for both photodetectors and photovoltaics. Hot electrons are typically injected into semiconductors over a Schottky barrier between the metal and semiconductor, enabling generation of photocurrent with below bandgap photon illumination. As a two-dimensional semiconductor single and few layer molybdenum disulfide (MoS2) has been demonstrated to exhibit internal photogain and therefore becomes an attractive hot electron acceptor. Here, we investigate hot electron-based photodetection in a device consisting of bilayer MoS2 integrated with a plasmonic antenna array. We demonstrate sub-bandgap photocurrent originating from the injection of hot electrons into MoS2 as well as photoamplification that yields a photogain of 10(5). The large photogain results in a photoresponsivity of 5.2 A/W at 1070 nm, which is far above similar silicon-based hot electron photodetectors in which no photoamplification is present. This technique is expected to have potential use in future ultracompact near-infrared photodetection and optical memory devices.

Light is a major environmental cue affecting various physiological and metabolic processes in plants. Although plant photoreceptors are well characterized, the mechanisms by which light regulates downstream responses are less clear. In Arabidopsis thaliana, the accumulation of photoprotective anthocyanin pigments is light dependent, and the R2R3 MYB transcription factor MYB75/PAP1 regulates anthocyanin accumulation. Here, we report that MYB75 interacts with and is phosphorylated by MAP KINASE4 (MPK4). Their interaction is dependent on MPK4 kinase activity and is required for full function of MYB75. MPK4 can be activated in response to light and is involved in the light-induced accumulation of anthocyanins. We show that MPK4 phosphorylation of MYB75 increases its stability and is essential for light-induced anthocyanin accumulation. Our findings reveal an important role for a MAPK pathway in light signal transduction.

Carbon nanotubes (CNTs) were functionalized by a simple non-covalent modification with sodium lignosulfonate (SLS), and the hybrid polyethersulfone (PES) ultrafiltration membranes were prepared by phase inversion method with different ratios of functionalized carbon nanotubes (f-CNTs). SEM analysis indicated that obvious finger-like pores appeared in f-CNT/PES hybrid membranes. The f-CNTs were uniformly dispersed on the membrane surface, causing super hydrophilicity and high water flux of the f-CNT/PES hybrid membranes. Filtration and protein adsorption tests indicated that the antifouling performances were dramatically increased, the amount of protein pollutants adsorbed by the hybrid membranes was significantly lower than the nascent membranes, and most of the water flux can be recovered after three cycles of the BSA solution fouling process. The antibacterial tests confirmed that no prepared membranes showed excellent antibacterial properties to Escherichia coli (E. coli). However, the hybrid membrane showed good antibacterial properties treated with a low-voltage electric field (direct current (DC), about 1.5 V cm−1), and the antibacterial rate (AR) closed to 100% after testing for 3 h.

Abstract Background Age-related sarcopenia is a serious global health issue in elderly individuals and for the community as it induces disability and significant economic burden. The purpose of the study is to understand the factors associated with sarcopenia and the role of growth hormone (GH) and insulin-like growth factor (IGF-1) in the occurrence of sarcopenia. Methods Elderly patients ( n = 3276) were included in this cross-sectional study. Survey and measurement of body composition (bioelectrical impedance), grip strength, and step speed were performed according to the Asian Working Group on Sarcopenia (AWGS) diagnostic criteria. Hematological and hormonal indicators were compared between patients with and without sarcopenia in order to identify the associated factors. Results There were significant differences in the demographic parameters between the sarcopenia and non-sarcopenia groups (all P &lt; 0.05). There were significant differences between the two groups regarding the blood levels of GH, IGF-1, testosterone (T), and mechanical growth factor (MGF) (all P &lt; 0.001). Correlation analyses showed that the appendicular skeletal muscle mass (ASMI) was positively associated with gender and BMI, and with GH, T, IGF-1, MGF, BUN, Cr, and Hb levels, but negatively associated with HDL-C (all P &lt; 0.05). Logistic multivariable regression analysis showed that IGF-1, MGF, BMI, and gender were independently associated with appendicular skeletal muscle mass (ASMI) (all P &lt; 0.05). Conclusions GH and IGF-1 are associated with sarcopenia in the elderly. IGF-1 and MGF are independently associated with the reduction of skeletal muscle mass, along with BMI and gender.

Fault detection is a critical step for machine condition monitoring and maintenance. With advances in machine learning technologies, automated faulty condition identification can be achieved by training an artificial intelligent (AI) model if sufficient data is available. In most practical applications, it is unlikely that enough data from faulty cases are available for supervised training of AI models for anomaly detection. This work is based on training data that are exclusively constituted of healthy signals (i.e., semi-supervised) and aims to develop an automated algorithm capable of identifying any abnormal mechanical behaviour captured by vibration measurements. A deep learning method with long short-term memory (LSTM) architectures combined with a one-class support vector machine (SVM) is used to separate abnormal data from normal vibration signals collected during an endurance test of a reduction gearbox and helicopter test flight data measured by multiple sensors situated at different locations of the aircraft. For the gearbox dataset, a detailed understanding of the physical mechanisms by which different types of faults (gear wear and bearing faults) affect the vibration signal led to the design of two anomaly detection architectures: i) an LSTM regression + one-class SVM for detecting new deterministic components introduced by gear faults; and ii) a two-step LSTM regression + one-class SVM for detecting new random components caused by bearing failures. For the helicopter dataset, which does not contain consecutive time-series, we show that the LSTM regression is not advantageous, and a better performance can be achieved by a simpler one-class SVM outlier detection based on statistical features. This work contributes to the field of machine condition monitoring by introducing a novel two-step LSTM configuration for removing deterministic components associated with dominant gear signals in the first step and removing the ‘residual deterministic’ components associated with varying gear signals in the second step.

The appearance of the composite membrane provides a new research direction for reducing membrane fouling. In this study, polyaniline (PANI) and Ti3C2Tx (MXene) were combined by the electrostatic assembly method where PANI was used to adjust the distance between MXene layers and construct the conductive network. The conducting mixed ultrafiltration membranes were prepared by the non-solvent induced phase separation method, in which MXene and PANI were mixed into a polyethersulfone (PES) matrix. The permeation flux of pure water of the MXene-PANI/PES membrane was increased by 200.9%, the retention rate of bovine serum albumin (BSA) was kept above 99%, and the retention rate of Congo Red and Methyl blue dyes was 99.1% and 98.4%, respectively, this goes well beyond the PES membrane. In addition, through a series of conductivity tests, it has been proved that the conductive properties of composite membranes were greatly improved, and the conductivity of the MXene-PANI/PES composite membrane can reach 0.5 S m−1. After applying a negative voltage to the membrane, the negative charge around the surface of the membrane repels the negatively charged contaminant under the action of an electrostatic repulsion force, thereby the enrichment of pollutants on the membrane surface can be effectively reduced, and the FRR reached 93.7%. On the basis of ensuring membrane conductivity, we improved the permeability, selective separation, and anti-fouling ability of the membrane. This research shows great potential for the efficient development of an anti-fouling conductive separation membrane based on MXene.

Tailings are one of the largest quantities of hazardous waste in the world, and their treatment is difficult and expensive. In this work, a new, low-cost technique coupling microbially induced carbonate precipitation (MICP) and inorganic additives was proposed, optimized, and applied. The results showed that CaO was the best additive among the six tested, with an optimum dosage of 5%. A 90-day experiment indicated that the MICP-CaO coupled technique was highly effective for all the concerned heavy metals (Cu, Ni, Pb, and Cr) in the Cu-Ni tailings. During the stabilization period (20-90 days), the passivation rates were stable at 78.8 ± 2.9% (Cu), 78.1 ± 1.0% (Ni), 89.2 ± 1.0% (Pb), and 97.8 ± 0.5% (Cr), 2%-866% higher than the single technique of either MICP or CaO. Multiple analyses demonstrated that the synergistic effect of MICP and CaO produced a large amount of calcite (1.5% of the tailings). This calcite cemented the tailings particles, sequestrated heavy metal ions into the lattices, and played a key role in heavy metal passivation. Moreover, CaO and MICP improved the strength and compactness of solidified body, respectively. This work demonstrates the feasibility of the MICP-CaO coupled technique in tailings solidification, which can be applied in practical projects.

The resonance demodulation technique has been extensively used for rolling bearing diagnostics. This paper presents a scheme of using the resonance demodulation technique for early detection of gear tooth cracks. The objective is to supplement the current techniques of gearbox fault diagnosis based on the synchronous signal averaging technique. The proposed scheme focuses on the fact that gear tooth crack will produce vibration impacts that would excite the structural resonances when the cracked tooth is engaged. Using this scheme, the regular gear meshing harmonics are first removed from the synchronous signal average to generate the residual signal. The residual signal is then band-pass filtered around a structural resonance within the range of gear meshing harmonics. The bandpassed residual signal is demodulated to extract the features related to the crack-induced sudden change in a complete revolution of the gear of interest. A number of statistical measures can then be used on the demodulated signal as an indicator on the existence and status of the crack. In this paper, an analytic signal model is also proposed to describe the gear meshing signal and its processing, the resonance demodulation technique is presented based on the signal model. The method is validated using numerically simulated data, test data from a gear rig, and helicopter in-flight vibration data. The results show that the resonance demodulation technique is an effective tool for the early detection of gear tooth cracks.

Abstract This paper presents a model-based technique for the detection and diagnosis of gear faults. Based on the signal averaging technique, the proposed technique first establishes an autoregressive (AR) model on the vibration signal of the gear of interest in its healthy-state. The model is then used as a linear prediction error filter to process the future-state signal from the same gear. The health condition of the gear is diagnosed by characterizing the error signal between the filtered and unfiltered signals. The technique is validated using both numerical simulation and experimental data. The results show that the AR model technique is an effective tool in the detection and diagnosis of gear faults and it may lead to an effective solution for in-flight diagnosis of helicopter transmissions.

Cosmc is a molecular chaperone thought to be required for expression of active T-synthase, the only enzyme that galactosylates the Tn antigen (GalNAcalpha1-Ser/Thr-R) to form core 1 Galbeta1-3GalNAcalpha1-Ser/Thr (T antigen) during mucin type O-glycan biosynthesis. Here we show that ablation of the X-linked Cosmc gene in mice causes embryonic lethality and Tn antigen expression. Loss of Cosmc is associated with loss of T-synthase but not other enzymes required for glycoprotein biosynthesis, demonstrating that Cosmc is specific in vivo for the T-synthase. We generated genetically mosaic mice with a targeted Cosmc deletion and survivors exhibited abnormalities correlated with Tn antigen expression that are related to several human diseases.

Functionalization of multi-wall carbon nanotubes (MWCNTs) was achieved by grafting carboxyl groups and amino groups. Fourier transform infrared spectroscopy was used to detect the changes produced by functional groups on the surface of the MWCNTs. Three different MWCNTs were incorporated into epoxy resin and the friction and wear behavior of MWCNT/epoxy composites was investigated using a M-2000 wear testing machine at different sliding speeds under different applied loads. Scanning electron microscopy was used to observe the worn surfaces of the samples. The results indicated that the functional groups had been grafted on the surface of MWCNTs. Compared with neat epoxy, the composites with MWCNTs showed a lower friction coefficient and wear rate, and the wear rate decreased with the increase of MWCNT loading. Combining epoxy resin with MWCNTs is an efficient method to improve the wear resistance and decrease the coefficient of friction.

Tunable metasurfaces open new doors for achieving dynamic wavefront manipulation in an ultracompact footprint. Dielectric metasurfaces are particularly attractive for this application due to their low-loss modes. However, their volumetric modes make them difficult to dynamically tune compared to plasmonic variants with strong field confinement. We overcome this challenge by combining dielectric resonators with an epsilon-near-zero (ENZ) mode in a thin film. By tuning the coupling between modes in the resonators and the ENZ thin film, active control over the transmittance amplitude is achieved. Operating at the wavelength of the Huygens mode, we demonstrate transmittance modulation with an on-state transmittance of 70% and a modulation depth of 31%. In addition, we create a tunable diffraction grating and demonstrate its potential use in beam steering applications. This approach provides a new avenue for high-speed and low-power modulation of dielectric metasurfaces.

Abstract The treatment of atopic dermatitis (AD) has long been viewed as a problematic issue by the medical profession. Although a wide variety of complementary therapies have been introduced, they fail to combine the skin moisturizing and drug supply for AD patients. This study reports the development of a thermo-sensitive Poloxamer 407/Carboxymethyl cellulose sodium (P407/CMCs) composite hydrogel formulation with twin functions of moisture and drug supply for AD treatment. It was found that the presence of CMCs can appreciably improve the physical properties of P407 hydrogel, which makes it more suitable for tailored drug loading. The fabricated P407/CMCs composite hydrogel was also characterized in terms of surface morphology by field emission scanning electron microscopy (FE-SEM), rheological properties by a rheometer, release profile in vitro by dialysis method and cytotoxicity test. More importantly, the findings from transdermal drug delivery behavior revealed that P407/CMCs showed desirable percutaneous performance. Additionally, analysis of cytotoxicity test suggested that P407/CMCs composite hydrogel is a high-security therapy for clinical trials and thus exhibits a promising way to treat AD with skin moisturizing and medication.

The use of two-dimensional (2D) materials in optoelectronics has attracted much attention due to their fascinating optical and electrical properties. However, the low optical absorption of 2D materials arising from their atomic thickness limits the maximum attainable external quantum efficiency. For example, in the visible and near-infrared regimes monolayer MoS2 and graphene absorb only ∼10% and 2.3% of incoming light, respectively. Here, we experimentally demonstrate the use of Fano-resonant photonic crystals to significantly boost absorption in atomically thin materials. Using graphene as a test bed, we demonstrate that absorption in the monolayer thick material can be enhanced to 77% within the telecommunications band, the highest value reported to date. We also show that the absorption in the Fano-resonant structure is non-local, with light propagating up to 16 μm within the structure. This property is particularly beneficial in harvesting light from large areas in field-effect-transistor based graphene photodetectors in which separation of photo-generated carriers only occurs ∼0.2 μm adjacent to the graphene/electrode interface.

Abstract Modern nanotechnology research has generated numerous experimental data for various nanomaterials. However, the few nanomaterial databases available are not suitable for modeling studies due to the way they are curated. Here, we report the construction of a large nanomaterial database containing annotated nanostructures suited for modeling research. The database, which is publicly available through http://www.pubvinas.com/ , contains 705 unique nanomaterials covering 11 material types. Each nanomaterial has up to six physicochemical properties and/or bioactivities, resulting in more than ten endpoints in the database. All the nanostructures are annotated and transformed into protein data bank files, which are downloadable by researchers worldwide. Furthermore, the nanostructure annotation procedure generates 2142 nanodescriptors for all nanomaterials for machine learning purposes, which are also available through the portal. This database provides a public resource for data-driven nanoinformatics modeling research aimed at rational nanomaterial design and other areas of modern computational nanotechnology.

Transcriptome deconvolution in cancer and other heterogeneous tissues remains challenging. Available methods lack the ability to estimate both component-specific proportions and expression profiles for individual samples. We present DeMixT, a new tool to deconvolve high-dimensional data from mixtures of more than two components. DeMixT implements an iterated conditional mode algorithm and a novel gene-set-based component merging approach to improve accuracy. In a series of experimental validation studies and application to TCGA data, DeMixT showed high accuracy. Improved deconvolution is an important step toward linking tumor transcriptomic data with clinical outcomes. An R package, scripts, and data are available: https://github.com/wwylab/DeMixTallmaterials.

We designed novel nanodescriptors that can characterize the nanostructure diversity and also be quickly calculated in batches, to profile nanoparticles.

This paper reviews the AIM 2020 challenge on efficient single image super-resolution with focus on the proposed solutions and results. The challenge task was to super-resolve an input image with a magnification factor $$\times $$ 4 based on a set of prior examples of low and corresponding high resolution images. The goal is to devise a network that reduces one or several aspects such as runtime, parameter count, FLOPs, activations, and memory consumption while at least maintaining PSNR of MSRResNet. The track had 150 registered participants, and 25 teams submitted the final results. They gauge the state-of-the-art in efficient single image super-resolution.

Beyond nutrition effect, quercetin is applied as a complement or an alternative for promoting human health and treating diseases. However, its complicated neuroprotective mechanisms have not yet been fully elucidated. This study provides evidence of an alternative target for quercetin, and sheds light on the mechanisms of its neuroprotection against cerebral ischemia/reperfusion (I/R) injury in Sprague–Dawley rats. Oral pretreatment using quercetin has alleviated cerebral I/R-induced neurological deficits, brain infarction, blood–brain barrier disruption, oxidative stress, TNF-α and IL-1β mRNA expression, along with apoptotic caspase 3 activity. The neuroprotective, anti-oxidative, anti-inflammatory, and anti-apoptotic effects of quercetin were replicated in rat hippocampal slice cultures and neuron/glia cultures which suffered from oxygen–glucose deprivation and reoxygenation (OGDR). Biochemical studies revealed a reduction of extracellular signal-regulated kinase (ERK) and Akt phosphorylation, along with an increase in protein tyrosine and serine/threonine phosphatase activity in cerebral I/R rat cortical tissues and OGDR hippocampal slice and neuron/glia cultures. Quercetin alleviated the changes in ERK/Akt phosphorylation and protein phosphatase activities. Inhibition of ERK or Akt alone was enough to cause apoptotic cell death and cytotoxicity in hippocampal slice cultures and neuron/glia cultures, while activators of ERK or Akt alleviated OGDR-induced cytotoxicity. Taken together, our results demonstrate that quercetin alleviated the increment of protein tyrosine and serine/threonine phosphatase activity, along with the reduction of ERK and Akt phosphorylation, which may play pivotal roles in the expansion of brain injury after cerebral I/R.

Nanofiber membranes (NFMs) prepared with electrostatic spinning have attracted more and more attention in wastewater treatment owing to its unique advantages of high porosity and large specific surface area. However, the low removal rate of small molecular weight dyes and membrane fouling are the main obstacles for its large-scale application. Therefore, new polyacrylonitrile (PAN)-ZnO NFM was prepared simply and efficiently combined with electrostatic spinning technology and magnetron sputtering. Under the action of electrocatalysis, PAN-ZnO NFM exhibited not only high removal rate (>95%) for Congo red (CR), rhodamine B (RhB), sunset yellow (YS), methyl orange (MO) and methylene blue (MB), but also excellent water flux (1016 L m−2 h−1 Bar−1). Moreover, the electrocatalytic stability investigation of PAN-ZnO NFM showed that the membrane still maintained an excellent dye removal rate (>90%) after 10 h of continuous electrocatalytic filtration. Apart from, PAN-ZnO NFM also displayed excellent mechanical properties (252 MPa of Young's modulus) and antifouling ability. The permeate flux recovery rate of more than 90% after electrocatalytic cleaning for 5 min. Due to its excellent properties in dye removal rate, water flux, electrocatalytic stability, and antifouling, PAN-ZnO NFM exhibited an excellent application prospect in textile wastewater treatment.

$f(Q)$ gravity is the extension of symmetric teleparallel general relativity (STGR), in which both curvature and torsion vanish and gravity is attributed to nonmetricity. This work performs theoretical analyses of static and spherically symmetric solutions with an anisotropic fluid for general $f(Q)$ gravity. We find that the off-diagonal component of the field equation due to a coincident gauge leads to stringent restrictions on the functional form of $f(Q)$ gravity. In addition, although the exact Schwarzschild solution only exists in STGR, we obtain Schwarzschild-like solutions in nontrivial $f(Q)$ gravity and study its asymptotic behavior and deviation from the exact one.

Renewable and low-cost biochar's intrinsic porous structure limitations make its porous structure mediation highly significant for performance enhancement. We employ graphene oxide (GO) as an additive at a low dosage for the deed-leaf-derived biochar's microporous structure mediation to promote the wastewater treatment ability toward a typical antibiotic pollutant - tetracycline hydrochloride (TCH). While KOH-based activation enables biochars with a microporous structure and improved graphitization, GO transforms part of micropores of such activated biochar into mesopores (i.e. forming hierarchical porosity), driven by the thermal pyrolysis of oxygen groups enriched on GO. The GO additive-induced process overcomes the loss of surface resulted from conventional pore widening, promoting mass transport as well as improving the accessibility to pore interiors and compatibility for large-size contaminant molecules. The increase of the sp2-to-sp3 carbon ratio from 0.59 to 0.79 with GO incorporation facilitates π-π stacking interactions with aromatic pollutants (including TCH and organic dyes), which are more critical than the electrostatic attraction and hydrogen bonding interactions. Apart from superior adsorption capacities of 193.43 and 336.70 mg/g obtained at 303 and 313 K, respectively, the graphene-modified hierarchically porous biochar is recyclable, reusable, resistant to interfering metal cations, and universal for binding a range of organic pollutants bearing different charge states, demonstrating equilibrium adsorption capacities of 186.58, 190.38, 268.43, and 254.88 mg/g for TCH, methylene blue, Rhodamine B, and methyl orange, raised by 26.8%, 41.6%, 32.1%, and 105.3%, respectively, compared to the counterpart without GO-enabled micropore widening. The greater adaptability to different-size pollutants presents higher practical application viability.

Commercial buildings are great demand response resources in the energy and regulation markets. Many commercial building heating, ventilation and air conditioning (HVAC) systems are composed of a chiller producing chilled water, and multiple Air-Handling Units (AHUs) distributing cooled air to thermal zones. Demand response of such systems has the potential to closely track energy and regulation market signals. However, existing control methods are mostly focused on fan control, neglecting the impact of the air loop fan control on the power consumption of water loop pumps and chillers. This paper presents a complete modeling of a commercial building HVAC system consisting of chiller, water pump and multiple AHUs, and develops a two-level control to follow five-minute energy market signals and four-second frequency regulation signals. The first-level coarse control provides commands for both water and air loop variables, the second-level fine control adjusts the fan commands while maintaining the water loop inputs within the five-minute control period. As a result, the water-loop power serves as a basis to track energy market signals and the air-loop fan control can be adjusted flexibly for frequency regulation. A high-fidelity model in Dymola is built to validate the model and control. The validation is conducted through co-simulation between Matlab and Dymola model via the Building Controls Virtual Test Bed (BCVTB). The simulation results show significant tracking improvement with the proposed two-level control framework.

Protein has been identified as one of the major membrane foulants in wastewater treatment and reclamation applications. The specific molecular configuration of bovine serum albumin (BSA) impedes electron transfer at the interface, resulting in poor electrochemical signal, and is often used as a blocker for electrochemical biosensors. To improve the precision and speed of fouling detection, the study proposes integrating the electrical properties with the organic fouling process of the membrane to provide the BSA fouling electrical response signal. The unique electrical properties of carboxylate multi-walled carbon nanotubes (O-MWCNTs) were introduced into polyvinylidene fluoride (PVDF) ultrafiltration membranes using a pre-coating method. The conductive coated layer of O-MWCNT facilitates real-time observation of membrane fouling and enables timely cleaning of the membrane to improve fouling resistance. To improve the loading and binding strength of the O-MWCNTs, phenylenediamine (MXAD) was utilized as a cross-linking agent, which improved the composite membrane's overall performance and decreased the membrane's resistance from 1.33 × 106 Ω–37.91 Ω. The electrical signal received from the four-probe resistivity meter showed a response to the fouling level. The combined comparison of the normalized flux and electrical signal trends resulted in a more visual, rapid, sensitive, and accurate indication of membrane BSA fouling, which paves the way for the detection of electrical BSA fouling and subsequent cleaning and reuse of the separation membranes.

Considerable evidence indicates that vitamin D may reduce the risk of several cancers, including breast cancer. This study examined associations of breast cancer with sun exposure, the principal source of vitamin D, and vitamin D receptor gene (VDR) polymorphisms (FokI, TaqI, BglI) in a population-based case-control study of Hispanic, African-American, and non-Hispanic White women aged 35–79 years from the San Francisco Bay Area of California (1995–2003). In-person interviews were obtained for 1,788 newly diagnosed cases and 2,129 controls. Skin pigmentation measurements were taken on the upper underarm (a sun-protected site that measures constitutive pigmentation) and on the forehead (a sun-exposed site) using reflectometry. Biospecimens were collected for a subset of the study population (814 cases, 910 controls). A high sun exposure index based on reflectometry was associated with reduced risk of advanced breast cancer among women with light constitutive skin pigmentation (odds ratio = 0.53, 95% confidence interval: 0.31, 0.91). The association did not vary with VDR genotype. No associations were found for women with medium or dark pigmentation. Localized breast cancer was not associated with sun exposure or VDR genotype. This study supports the hypothesis that sunlight exposure reduces risk of advanced breast cancer among women with light skin pigmentation.

Nasopharyngeal carcinoma (NPC) has been proved to be an Epstein-Barr virus (EBV)-associated cancer. By use of nested polymerase chain reactions (PCRs), we examined whether the presence of EBV DNA in the peripheral-blood cells (PBC) can serve as a prognostic indicator for NPC.Peripheral blood from 124 patients with NPC who had no evidence of distant metastasis and 114 healthy volunteers with serologically positive findings for EBV infection was collected prospectively. Plasma and erythrocytes were separated. DNA was extracted from PBCs and analyzed by a nested PCR using primers specific to Epstein-Barr virus nuclear antigen 1 (EBNA-1). All patients were treated by radiotherapy with or without chemotherapy. Clinical parameters and status of EBNA-1 in PBCs were used for survival analysis using the Kaplan-Meier method and the Cox proportional hazards model.Positive rates of EBNA-1 DNA in PBCs of NPC patients and healthy volunteers are 71% and 14%, respectively (P =.001). No significant difference was observed with regard to the clinical characteristics of patients who were EBNA-1-positive (n = 88) and those who were EBNA-1-negative (n = 36). After a median follow-up period of 38 months (range, 24 to 56 months), 29 of 88 EBNA-1-positive patients and only one of 36 EBNA-1-negative patients developed distant metastases (P =.00015). Kaplan-Meier estimates of overall survival (P =.0010), metastasis-free survival (P =.0004), and progression-free survival (P =.0004) were significantly lower for the patients in the EBNA-1-positive group than for those in the EBNA-1-negative group. Multivariate Cox analysis confirmed the same results.The presence of EBNA-1 DNA in PBCs is a novel, important risk factor for patients with NPC that indicates a significantly higher risk of developing distant metastasis as well as a lower survival rate.

Kinetic and column adsorption of phosphate from aqueous solution using modified wheat residue (MWS) as an adsorbent were studied in a batch reactor. The respective characteristic rate constants and activation energy were presented after linear and non-linear fitting. In addition, the effects of influent concentration of phosphate and flow rates on the column adsorption were also investigated. The results showed that the adsorption process could reach equilibrium in 10-15 min, and the pseudo-second-order equation generated the best agreement with experimental data for adsorption systems. The activation energy was 3.39 kJ mol(-1) indicating that the synthesis process was a physical adsorption. In the column tests, the increase of influent concentration and flow rate both decreased the breakthrough time, and the MWS-packed column exhibited excellent phosphate removal from aqueous solution. These results provide strong evidence of the potential of MWS for the technological applications of phosphate removal from aqueous solutions.

The synthesis of helically coiled nanotubes and nanowires through the use of In and Sn catalysts, respectively, in a floating-catalyst-based CVD process, is demonstrated. The figure is a scanning electron microscopy image of helically coiled carbon nanowires prepared from a thermal decomposition of xylene and acetylene in the presence of Fe–Sn catalyst particles. The bright spot at the tip of each nanowire represents the catalyst particle.

Nasopharyngeal carcinoma (NPC) has been proven as an Epstein-Barr virus (EBV)-associated cancer. Serum anti-EBV antibodies and plasma EBV DNA have been investigated as surrogate markers for NPC. A comparison of the prognostic impacts of both assays has never been reported.Paired serum and plasma samples from 114 previously untreated NPC patients were collected and subjected to an immunofluorescence assay for immunoglobulin (Ig)A and IgG antibodies against the viral capsid antigen (VCA) and a real-time quantitative polymerase chain reaction assay for EBV DNA measurement. The effects of both assays on patient prognosis were thoroughly investigated.Relapsed patients had significantly higher pretreatment EBV DNA concentration than patients without relapse (p = 0.0006). No associations of VCA-IgA (p = 0.9669) or VCA-IgG (p = 0.6125) were observed between patients with and without relapse. The 4-year overall survival (60.3% vs. 93.1%, p < 0.0001) and relapse-free survival rates (54.4% vs. 77.9%, p = 0.0009) were significantly lower in patients with higher pretreatment EBV DNA load than in those with lower EBV DNA load. Patients with persistently detectable EBV DNA after treatment had significantly worse 4-year overall (30.8% vs. 84.6%, p < 0.0001) and relapse-free survival rates (15.4% vs. 74.0%, p < 0.0001) than those with undetectable EBV DNA. The VCA-IgA and VCA-IgG titer could not predict survivals (all p > 0.1). Cox multivariate analyses also showed the same results.Plasma EBV DNA is superior to serum EBV VCA antibodies in prognostic predictions for NPC.

Soybean is a complex matrix containing several potentially bioactive components. The objective was to develop a statistical model to predict the in vitro anticancer potential of soybean varieties based on the correlation between protein composition and bioactive components after simulated gastrointestinal enzyme digestion with their effect on leukemia mouse cells. The IC 50 values of the hydrolysates of soy genotypes (NB1-NB7) on L1210 leukemia cells ranged from 3.5 to 6.2 mg/mL. Depending on genotype, each gram of soy hydrolysates contained 2.7-6.6 micromol of total daidzein, 3.0-4.7 micromol of total genistein, 0.5-1.3 micromol of glycitein, 2.1-2.8 micromol of total saponins, 0.1-0.2 micromol of lunasin, and 0.1-0.6 micromol of Bowman-Birk inhibitor (BBI). The IC 50 values calculated from a partial least-squares (PLS) analysis model correlated well with experimental data ( R (2) = 0.99). Isoflavones and beta-conglycinin positively contributed to the cytotoxicity of soy on L1210 leukemia cells. Lunasin and BBI were potent L1210 cell inhibitors (IC 50 = 13.9 and 22.5 microM, respectively), but made modest contributions to the activity of defatted soy flour hydrolysates due to their relatively low concentrations. In conclusion, the data demonstrated that beta-conglycinins are among the major protein components that inhibit leukemia cell growth in vitro. Furthermore, it was feasible to differentiate soybean varieties on the basis of the biological effect of their components using a statistical model and a cell-based assay.

In this letter, we propose a novel dual-frequency miniaturized periodic element for creating a dual-band frequency selective surface (FSS) having closely spaced bands of operation. Using this element and its complementary structure, the dual-bandstop and dual-bandpass FSSs can be simultaneously created without extra effort. The mechanism responsible for the two element resonances and the new way to make these resonances closer is revealed. Based on this revelation, the newly proposed element can be simply and quickly designed to be compact in size and to have two resonances closely spaced. Furthermore, the dual-band FSS created using this element demonstrates excellent resonance stability with respect to different polarizations and incidence angles. Both the bandstop and bandpass FSS prototypes are fabricated and examined. Their measured and full-wave simulated results validate the performance. The created element size is about 8% of the free-space wavelength at the first resonant frequency, and the ratio of the second resonant frequency to the first one is only 1.4.

Mice deficient in the LDL receptor (Ldlr(-/-) mice) have been widely used as a model to mimic human atherosclerosis. However, the time-course of atherosclerotic lesion development and distribution of lesions at specific time-points are yet to be established. The current study sought to determine the progression and distribution of lesions in Ldlr(-/-) mice.Ldlr-deficient mice fed regular chow or a high-fat (HF) diet for 0.5 to 12 months were analyzed for atherosclerotic lesions with en face and cross-sectional imaging. Mice displayed significant individual differences in lesion development when fed a chow diet, whereas those on a HF diet developed lesions in a time-dependent and site-selective manner. Specifically, mice subjected to the HF diet showed slight atherosclerotic lesions distributed exclusively in the aortic roots or innominate artery before 3 months. Lesions extended to the thoracic aorta at 6 months and abdominal aorta at 9 months. Cross-sectional analysis revealed the presence of advanced lesions in the aortic sinus after 3 months in the group on the HF diet and in the innominate artery at 6 to 9 months. The HF diet additionally resulted in increased total cholesterol, LDL, glucose, and HBA1c levels, along with the complication of obesity.Ldlr-deficient mice on the HF diet tend to develop site-selective and size-specific atherosclerotic lesions over time. The current study should provide information on diet induction or drug intervention times and facilitate estimation of the appropriate locations of atherosclerotic lesions in Ldlr(-/-) mice.

Over the past two decades, live kidney donation by older individuals (≥55 years) has become more common. Given the strong associations of older age with cardiovascular disease (CVD), nephrectomy could make older donors vulnerable to death and cardiovascular events. We performed a cohort study among older live kidney donors who were matched to healthy older individuals in the Health and Retirement Study. The primary outcome was mortality ascertained through national death registries. Secondary outcomes ascertained among pairs with Medicare coverage included death or CVD ascertained through Medicare claims data. During the period from 1996 to 2006, there were 5717 older donors in the United States. We matched 3368 donors 1:1 to older healthy nondonors. Among donors and matched pairs, the mean age was 59 years; 41% were male and 7% were black race. In median follow-up of 7.8 years, mortality was not different between donors and matched pairs (p = 0.21). Among donors with Medicare, the combined outcome of death/CVD (p = 0.70) was also not different between donors and nondonors. In summary, carefully selected older kidney donors do not face a higher risk of death or CVD. These findings should be provided to older individuals considering live kidney donation.

Experimental Blood-Brain Barrier (BBB) permeability models for drug molecules are expensive and time-consuming. As alternative methods, several traditional Quantitative Structure-Activity Relationship (QSAR) models have been developed previously. In this study, we aimed to improve the predictivity of traditional QSAR BBB permeability models by employing relevant public bio-assay data in the modeling process.We compiled a BBB permeability database consisting of 439 unique compounds from various resources. The database was split into a modeling set of 341 compounds and a validation set of 98 compounds. Consensus QSAR modeling workflow was employed on the modeling set to develop various QSAR models. A five-fold cross-validation approach was used to validate the developed models, and the resulting models were used to predict the external validation set compounds. Furthermore, we used previously published membrane transporter models to generate relevant transporter profiles for target compounds. The transporter profiles were used as additional biological descriptors to develop hybrid QSAR BBB models.The consensus QSAR models have R(2) = 0.638 for five-fold cross-validation and R(2) = 0.504 for external validation. The consensus model developed by pooling chemical and transporter descriptors showed better predictivity (R(2) = 0.646 for five-fold cross-validation and R(2) = 0.526 for external validation). Moreover, several external bio-assays that correlate with BBB permeability were identified using our automatic profiling tool.The BBB permeability models developed in this study can be useful for early evaluation of new compounds (e.g., new drug candidates). The combination of chemical and biological descriptors shows a promising direction to improve the current traditional QSAR models.

Purpose To assess subspecialty practice characteristics of the U.S. radiologist workforce. Materials and Methods This study used the Medicare Physician and Other Supplier Public Use File and did not constitute human subject research. The authors identified 33 090 radiologists who billed for professional services between 2012 and 2014 and used a validated classification system to map services to seven subspecialties and quantify subspecialty-focused effort on the basis of work relative value units (RVUs). Radiologists with more than half of their billed work RVUs in a single subspecialty were designated subspecialists; the remainder were classified as generalists. Matching radiologists with various characteristics extracted from other publicly available data sets, associations were explored through use of analysis of variance and multivariable logistic regression. Results More than half (55.3%) of U.S. radiologists practice predominantly as generalists but dedicate on average 36.0% effort to one subspecialty. Among radiologists practicing as majority subspecialists, neuroradiologists (10.1% of all radiologists) and breast imagers (8.4%) are most common. Subspecialization is more common (P < .001) among radiologists who are female, are earlier in their career, work in larger practices, have academic affiliations, and practice in the Northeast. By subspecialty, female representation varies from 8.6% (interventional radiology) to 63.1% (breast imaging); cardiothoracic imagers were more commonly early career radiologists, and nuclear medicine physicians were later career radiologists. Subspecialization is considerably more common in larger (≥100 members) practices (63.1%). An academic affiliation is the strongest independent predictor of subspecialization (odds ratio, 3.56; 95% confidence interval: 3.30, 3.84). Conclusion Despite an increased focus on radiology subspecialization, most U.S. radiologists are majority general radiologists on the basis of their work RVUs. Subspecialization is by far more prevalent in larger and academic practices. © RSNA, 2017 Online supplemental material is available for this article.

Low-cost, high-throughput in vitro bioassays have potential as alternatives to animal models for toxicity testing. However, incorporating in vitro bioassays into chemical toxicity evaluations such as read-across requires significant data curation and analysis based on knowledge of relevant toxicity mechanisms, lowering the enthusiasm of using the massive amount of unstructured public data.We aimed to develop a computational method to automatically extract useful bioassay data from a public repository (i.e., PubChem) and assess its ability to predict animal toxicity using a novel bioprofile-based read-across approach.A training database containing 7,385 compounds with diverse rat acute oral toxicity data was searched against PubChem to establish in vitro bioprofiles. Using a novel subspace clustering algorithm, bioassay groups that may inform on relevant toxicity mechanisms underlying acute oral toxicity were identified. These bioassays groups were used to predict animal acute oral toxicity using read-across through a cross-validation process. Finally, an external test set of over 600 new compounds was used to validate the resulting model predictivity.Several bioassay clusters showed high predictivity for acute oral toxicity (positive prediction rates range from 62-100%) through cross-validation. After incorporating individual clusters into an ensemble model, chemical toxicants in the external test set were evaluated for putative acute toxicity (positive prediction rate equal to 76%). Additionally, chemical fragment -in vitro-in vivo relationships were identified to illustrate new animal toxicity mechanisms.The in vitro bioassay data-driven profiling strategy developed in this study meets the urgent needs of computational toxicology in the current big data era and can be extended to develop predictive models for other complex toxicity end points. https://doi.org/10.1289/EHP3614.

Hepatotoxicity accounts for a substantial number of drugs being withdrawn from the market. Using traditional animal models to detect hepatotoxicity is expensive and time-consuming. Alternative in vitro methods, in particular cell-based high-throughput screening (HTS) studies, have provided the research community with a large amount of data from toxicity assays. Among the various assays used to screen potential toxicants is the antioxidant response element beta lactamase reporter gene assay (ARE-bla), which identifies chemicals that have the potential to induce oxidative stress and was used to test > 10,000 compounds from the Tox21 program.The ARE-bla computational model and HTS data from a big data source (PubChem) were used to profile environmental and pharmaceutical compounds with hepatotoxicity data.Quantitative structure-activity relationship (QSAR) models were developed based on ARE-bla data. The models predicted the potential oxidative stress response for known liver toxicants when no ARE-bla data were available. Liver toxicants were used as probe compounds to search PubChem Bioassay and generate a response profile, which contained thousands of bioassays (> 10 million data points). By ranking the in vitro-in vivo correlations (IVIVCs), the most relevant bioassay(s) related to hepatotoxicity were identified.The liver toxicants profile contained the ARE-bla and relevant PubChem assays. Potential toxicophores for well-known toxicants were created by identifying chemical features that existed only in compounds with high IVIVCs.Profiling chemical IVIVCs created an opportunity to fully explore the source-to-outcome continuum of modern experimental toxicology using cheminformatics approaches and big data sources.Kim MT, Huang R, Sedykh A, Wang W, Xia M, Zhu H. 2016. Mechanism profiling of hepatotoxicity caused by oxidative stress using antioxidant response element reporter gene assay models and big data. Environ Health Perspect 124:634-641; http://dx.doi.org/10.1289/ehp.1509763.

Bacterial wilt caused by Ralstonia solanacearum is a complex and destructive disease that affects over 200 plant species. To investigate the interaction of R. solanacearum and its tomato (Solanum lycopersicum) plant host, a comparative proteomic analysis was conducted in tomato stems inoculated with highly and mildly aggressive R. solanacearum isolates (RsH and RsM, respectively). The results indicated a significant alteration of the methionine cycle (MTC) and downregulation of γ-aminobutyric acid (GABA) biosynthesis. Furthermore, transcriptome profiling of two key tissues (stem and root) at three stages (0, 3 and 5 days post-inoculation) with RsH in resistant and susceptible tomato plants is presented. Transcript profiles of MTC and GABA pathways were analyzed. Subsequently, the MTC-associated genes SAMS2, SAHH1 and MS1 and the GABA biosynthesis-related genes GAD2 and SSADH1 were knocked-down by virus-induced gene silencing and the plants' defense responses upon infection with R. solanacearum RsM and RsH were analyzed. These results showed that silencing of SAHH1, MS1 and GAD2 in tomato leads to decreased resistance against R. solanacearum. In summary, the infection assays, proteomic and transcriptomic data described in this study indicate that both MTC and GABA biosynthesis play an important role in pathogenic interaction between R. solanacearum and tomato plants.

Sulfur dioxide (SO2) is being recognized as a possible endogenous gasotransmitter with importance on par with that of NO, CO, and H2S. Herein we describe a series of SO2 prodrugs that are activated for SO2 release via a bioorthogonal click reaction. The release rate can be tuned by adjusting the substituents on the prodrug.

Tool condition monitoring has been considered as one of the key enabling technologies for manufacturing optimization. Due to the high cost and limited system openness, the relevant developed systems have not been widely adopted by industries, especially Small and Medium-sized Enterprises. In this research, a cost-effective, wireless communication enabled, multi-sensor based tool condition monitoring system has been developed. Various sensor data, such as vibration, cutting force and power data, as well as actual machining parameters, have been collected to support efficient tool condition monitoring and life estimation. The effectiveness of the developed system has been validated via machining cases. The system can be extended to wide manufacturing applications.

Hybrid ultrafiltration membranes of poly(vinylidene fluoride) (PVDF) and poly(ethylene glycol)-multi-walled carbon nanotubes (PMWCNTs) have been prepared via phase inversion method. Compared with pristine PVDF membranes, PMWCNT/PVDF hybrid membranes showed a significant higher water flux (384 L m−2 h−1), more stable rejection rate of bovine serum albumin (BSA) and better antifouling properties because of better hydrophilicity. Besides, the antifouling properties of PMWCNT/PVDF hybrid membranes can be further reduced applying a weak electric field (direct current, about 2 V cm−1). More important, PMWCNTs/PVDF membrane exhibited the lowest hemolysis ratio of 0.4% ever reported, which has improved the hemocompatibility and safety of blood. Moreover, after the introduction of weak electric field, the adhesion of red blood cells is minimized. This study shows that the novel PMWCNT/PVDF hybrid membranes have excellent antifouling ability and hemocompatibility which opens up a new field for the application of PVDF membranes.

The flash-tank-cycle vapor injection technique has been developed for heat pump operation under cold climate, however, lack of effective control strategy has limited its practical acceptance. This paper presents a novel control strategy for a two-stage air source heat pump water heater with flank-tank-cycle vapor injection. The intermediate pressure setpoint for the injection loop is regulated by the upper electronic expansion valve. Then, a real-time optimization or optimal control framework adjusts the intermediate pressure setpoint to minimize the total power consumption, with the compressor capacity used to satisfy the load demand via an inner-loop controller. In particular, the extremum seeking controller is applied as a model-free real-time optimization strategy for such purpose. To evaluate the proposed control strategy, a Modelica based dynamic simulation model is developed for such system. Simulations under fixed, staircase and realistic ambient temperature profiles validate the effectiveness of the proposed control strategy. Besides real-time optimization of system efficiency, a major merit of this strategy is to retain the use of saturated vapor for the injection line, instead of levitating the superheat. The inherent efficiency of the flash tank cycle is thus maintained without additional devices, and the liquid level can be maintained in a proper range.

Palygorskite (Pal) is a highly hydrophilic clay mineral with tubular structure and high aspect ratio, which facilitates the attachment of nanoparticles to their surface. It has become a promising new membrane preparation additive due to its lotus root like tubular structure, low price and environmental friendliness. Silver nanoparticles (AgNPs) have excellent antibacterial ability, and their incorporation into the membrane can significantly improve the bacteriostasis of the membrane. Herein, Pal was coated by polydopamine (PDA), which acted as both the adhesive and reducing agent for AgNPs. The incorporation of the Pal/Ag nanocomposite resulted in a thin polyamide (PA) layer with rough surface morphology, which facilitated the improvement of membrane permeability. Furthermore, the Pal's parallel tubes with a 0.37 × 0.63 nm2 cross-sectional area provided nanochannels allowing fast pass through of water molecules. The as-prepared TFN-7.5Pal/Ag membrane exhibited a permeate flux of 39.9 LMH at 16 bar, which was 1.6 times as high as that of the TFC membrane, accompanied with an acceptable NaCl rejection of 98.3%. Besides, antibacterial tests demonstrated that the TFN membrane presented excellent antibacterial performance against Escherichia coli (98.0%).

This review describes an adult rat model of status epilepticus (SE) induced by diisopropyl fluorophosphate (DFP), and the beneficial outcomes of transient inhibition of the prostaglandin-E2 receptor EP2 with a small molecule antagonist, delayed by 2–4 h after SE onset. Administration of six doses of the selective EP2 antagonist TG6-10-1 over a 2–3 day period accelerates functional recovery, attenuates hippocampal neurodegeneration, neuroinflammation, gliosis and blood-brain barrier leakage, and prevents long-term cognitive deficits without blocking SE itself or altering acute seizure characteristics. This work has provided important information regarding organophosphate-induced seizure related pathologies in adults and revealed the effectiveness of delayed EP2 inhibition to combat these pathologies.

A structurally controlled polyethersulfone (PES) membrane, as the substrate of the thin film composite nanofiltration (NF) membranes, was designed and fabricated with aligned carbon nanotubes (ACNTs) by a direct current electric field. The morphology and properties of the NF membranes were simultaneously affected by the PES substrate with especial macrovoids and ACNTs, increasing the permeability from 6.4 to 29.7 L/m2 h bar. It was confirmed by FT-IR and XPS that the poly(piperazine amide) selective layer of the modified NF membrane has an increased content of –COOH for enhanced hydrophilicity. The zeta potential proves that the surface of the NF membrane modified by electric field has weaker negative charge than that of unmodified membrane in the range of pH = 5–9. Under the combined action of the Donnan effect and size exclusion, the rejection of MgCl2 increased while maintaining the dianion rejection above 95%. Particularly, the NF membrane modified with ACNTs exhibited better chlorine resistance and antifouling ability, thus improving the stability and perdurability of membranes. Our work utilizes the characteristics of ACNTs to explore its potential in NF membranes.

The microstructure of photocatalysts plays a key role in enhancing their photocatalytic performance. Herein, resorcinol/formaldehyde (RF) polymer resin was prepared using the extended Stöber process and used for hard templates. Hollow TiO2 spheres (HTS) were synthesized via hydrolysis of a versatile kinetics-controlled coating and carbonization method. The physicochemical properties of as-prepared catalysts were characterized. The pure RF template had a uniform diameter of ~450 nm. By adjusting the ammonia dosage from 0.1 to 0.35 mL, monodisperse [email protected]2 spheres were obtained with a porous TiO2 shell of ~25–160 nm in thickness. The concentration of ammonia had a significant effect on the micromorphology, and hence, the photocatalytic properties of the HTS. The Brunauer-Emmett-Teller surface area and pore volume were ~30 m2/g and 0.082 cm3/g, respectively. The intrinsically high conductivity of the HTS microspheres and their high surface area resulting from this robust hollow structure was beneficial for photocatalytic performance toward phenol decomposition.

Occupant activities in buildings are connected by different transportation measures. For smart communities, it is possible to synergize the energy management of smart buildings with the vehicle operation/travel information available from transportation infrastructure, e.g. the intelligent transportation systems (ITS). Such information enables the prediction of upcoming building occupancy and upcoming charging load of electric vehicles (EVs). This paper presents a predictive energy management strategy for smart community, which features water-based district cooling for a cluster of buildings driven by a multi-chiller central plant, and each building hosts a number of EV charging stations. A scenario-based stochastic model predictive control (SCMPC) framework, in which the upcoming building occupancy and charging load, ambient temperature, humidity and solar irradiance are assumed to be stochastically predictable. The SCMPC targets demand response operation at community level, involving both time-of-use and demand charges, and the combined power consumption by the central plant and EV charging observing to the transformer limit as a coupled constraint. To evaluate the propagation of the above uncertain factors through the receding-horizon SCMPC process, moving-horizon probabilistic models are established for EV arrival information. By developing a functional mockup interface (FMI) based co-simulation platform developed with Modelica and Python, the proposed method is validated via simulation study, and the performance indices are evaluated.

Cr(VI) reduction to Cr(III) has been demonstrated to be an effective method for Cr(VI) detoxification. Herein, we fabricated polyaniline (PANI) nanorod forests-modified Carbon fiber felt (CFF) as CFF-PANI cathode in a Flow-through electrode system (FES) with the counter CFF anode for enhancing Cr(VI) reduction. The CFF-PANI was synthetized via in-situ polymerization under different aniline concentration to investigate the effect of PANI nano-structures on Cr(VI) reduction. It was revealed that BET and electrochemical surface area of PANI nanorods significantly affected the Cr(VI) reduction, and CFF-PANI cathode with the largest BET and electrochemical surface area exhibited ∼ 45% higher Cr(VI) removal and ∼ 35% lower specific energy consumption than the CFF cathode. A decrease-then-stable Cr(VI) removal was observed within 120 min operation time, which was attributed to the electro-adsorption of Cr(VI) species on CFF anode. In-situ sampling experiments revealed that the electrochemical oxidation on CFF anode inhibited the Cr(VI) electro-adsorption, and at applied voltage above 0.7 V, the Cr(VI) reduction on cathode was the main mechanism for Cr(VI) removal. The operation of FES at 0.8 V had the lowest specific energy consumption (48.5 Wh/mol) and maintained ∼ 95% energy efficiency for Cr(VI) reduction with minor competitive reduction of H2O or O2 species. The results suggested that CFF-PANI can be a promising cathode for Cr(VI) reduction from aqueous solutions.

Presented herein is an investigation for the nonlinear vibration and stability analysis of rotating functionally graded (FG) piezoelectric nanobeams based on the nonlocal strain gradient theory. The present model can be regarded as a simplified version for the rotating nanowire of biomechanical nanogenerators. The Hamilton principle is used to derive nonlinear equations of motion and their related boundary conditions, which are then discretized to form a set of algebraic equations. Accordingly, the nonlinear vibration frequencies and buckling loads of the nanobeams can be determined by an iterative method. A parametric study of rotational velocity, nonlocal parameter, material length parameter, power-law index, and electrostatic voltage on the dynamic stability behavior of such nanobeams is also presented. In the cantilever case, increasing the nonlocal parameter and material length parameter can result in a stiffness-hardening effect that is unaffected by rotational velocity and the material length parameter to nonlocal parameter ratio. Yet, this has not been reported previously. More importantly, incorporating the effect of geometric nonlinearity on the dynamic responses and stability results of the nanobeams is indispensable. In particular, new observations for the coupling effect of vibration amplitude and power-law index on the electric potential effect are useful for the design of rotating microelectromechanical devices.

In order to solve the contradiction between permeability flux and selectivity in nanofiltration membrane desalination technology, a novel interfacial polymerization layer structure was designed. In this structure, the hydrophilic modified carbon nanotubes (CNT) untangled and protruded the PA layer under the electric field, resulting in the generation of microporous water channels between CNT and polyamide molecules. Thanks to this unique membrane surface structure, the permeability of the nanofiltration membrane was significantly enhanced, reaching 24.4 L·m−2·h−1·bar−1, in which the rejection of MgCl2 and Na2SO4 were also maintained at 96.1 % and 97.3 %, respectively. At the same time, the surface of the nanofiltration membrane remained intact in the chlorine resistance test, and the total fouling rate caused by lysozyme (LYZ) protein solution was only 2.89 %, demonstrating excellent chlorine resistance and pollution resistance. The design of changing surface structure through electric field-assisted nanomaterials provides a new innovative strategy for the development of separation membrane.

The ability to predict hazards of mechanical systems accurately can significantly enhance the predictive maintenance task. However, predicting hazards of systems accurately is non-trivial, especially when historical failure data are sparse or zero. The proposed proportional covariate model (PCM) overcomes this difficulty. This paper describes the concepts of PCM briefly and focuses on the estimation of the hazards of mechanical systems using accelerated life tests and condition monitoring data. This new approach to hazard estimation can reduce the number of accelerated life tests significantly. The hazard estimation can further be refined and updated with on-line condition monitoring data on a continual basis.

Proteinaceous microspheres filled with nitroxides dissolved in an organic liquid have been synthesized for the first time using high intensity ultrasound; these were used to measure oxygen concentrations in living biological systems. The microspheres have an average size of 2.5 microns, and the proteinaceous shell is permeable to oxygen. Encapsulation of the nitroxides into the microsphere greatly increased the sensitivity of the electron paramagnetic resonance signal line width to oxygen because of the higher solubility of oxygen in organic solvents. The encapsulation also protected the nitroxide from bioreduction. No decrease in intensity of the electron paramagnetic resonance signal was observed during 70 min after intravenous injection of the microspheres into a mouse. Measurement of the changes in oxygen concentration in vivo by means of restriction of blood flow, anesthesia, and change of oxygen content in the respired gas were made using these microspheres.

The authors investigated the clinical implication of plasma Epstein-Barr virus (EBV) DNA assay and (18) F-fluoro-2-deoxy-D-glucose ((18) F-FDG) positron emission tomography (PET) in the detection of recurrent nasopharyngeal carcinoma (NPC).Two hundred forty-five patients with NPC who had previously received treatment and were in a state of remission were monitored prospectively using a plasma EBV DNA assay every 3 to 6 months. (18) F-FDG PET studies were obtained when abnormal EBV DNA or clinically suggestive signs of recurrence were noted.Thirty-six of 245 patients (14.7%) patients had abnormal EBV DNA tests and underwent PET scans. In the remaining 209 patients, 3658 blood tests were negative. PET scans also were obtained in 5 patients who had undetectable EBV DNA levels but signs that were clinically suggestive of disease recurrence. Subsequent analyses focused on 41 patients who had PET studies. In lesion-based analyses, the sensitivity, specificity, and accuracy of PET by visual interpretation were 81.8%, 77.1%, and 79.2%, respectively, for all 125 lesions. In patient-based analyses, the accuracy of PET by visual interpretation was 51.2%. All 36 patients who had detectable plasma levels of EBV DNA had demonstrable NPC recurrences, whereas no recurrences were noted in 5 patients who had undetectable EBV DNA levels but signs that clinically mimicked a recurrence. Compared with annual PET, the annual cost of blood tests every 3 to 6 months per patient saved approximately 77% ∼ 88% in expenses.The plasma EBV DNA assay correctly predicted all NPC recurrences, and PET had high capacity to localize potential lesion sites. The authors concluded that applying the strategy of EBV DNA screening followed by PET scanning may guide appropriate further treatment planning in a cost-effective manner.

Lipoprotein-associated phospholipase A2 (lp-PLA2) has been detected in human and rabbit atherosclerotic lesions, where it co-localizes with its substrate, oxidized LDL (oxLDL). Here, we investigated whether oxLDL may exert a regulatory effect on lp-PLA2 expression.Using human monocytic THP-1 cells as a model system, we found that oxLDL up-regulated the expression of lp-PLA2 while another substrate of the enzyme, platelet activating factor, had no such effect. The up-regulatory effect of oxLDL could be conferred by its oxidized phospholipids (oxPCs, the exact substrates of lp-PLA2), but not their hydrolyzed products, lysophosphatidylcholines (lysoPCs). OxLDL induced the activation of p38 mitogen-activating protein kinase (MAPK) through phosphatidylinositol 3-kinase (PI3K). Inhibition of either PI3K or p38 MAPK completely blocked oxLDL-induced lp-PLA2 expression. In addition, inhibition of lp-PLA2 activity in the conditioned medium significantly decreased lipid accumulation in macrophages as detected by oil red staining.The present study shows that oxLDL, and more specifically its unhydrolyzed oxidized phospholipids, can up-regulate lp-PLA2 expression in monocytes through the PI3K and p38 MAPK pathway. In turn, lp-PLA2 promotes lipoprotein uptake in macrophages. Our results uncover a new link between oxLDL and lp-PLA2, and may provide insight into this interaction in the context of atherosclerosis.

For two-dimensional (2-D) directions-of-arrival (DOA) estimation problem, both the mutual coupling and the failure in pairing can cause severe performance degradation. In this paper, a new elevation and azimuth direction finding algorithm is developed to overcome the above-mentioned two difficulties in the L-shaped array configuration. The key points of this paper are: (i) constructing several correlation matrices to blindly compensate the effect of unknown mutual coupling using the outputs of properly chosen sensors and (ii) deriving a rank-reduction propagator method to estimate elevation and azimuth angles so as to avoid pairing parameters. Simulation results are presented to validate the performance of the proposed method.

Inhibition of apoptosis may attenuate the irreversible injury associated with reperfusion. In the current study, we focused on the cytoprotective effects and the underlying mechanism of sodium tanshinone IIA silate (STS) against damage induced by oxygen-glucose deprivation/recovery (OGD/R). in H9c2 cardiomyocytes and the underlying mechanisms.We used a model of cardiac ischaemia/reperfusion, OGD/R in H9c2 cardiomyocytes, to assess the cardioprotective effects of STS. Apoptosis of cells was measured with Hoechst 33342-based fluorescence microscopy, and annexin V-FITC-based flow cytometry. Caspase-3 and caspase-8 activities and mitochondrial membrane potential were also measured using commercial kits. TNF-α in the cell culture supernatant fractions were measured with sandwich elisa, and protein levels assayed using Western blot.STS inhibited OGD/R-induced apoptosis by suppressing JNK-mediated activation of NF-κB, TNF-α expression, activation of caspase-3 and caspase-8 and the Bax/Bcl-2 ratio. Additionally, positive feedback between NF-κB and TNF-α and amplification of TNF-α were inhibited, suggesting that STS plays a protective role against apoptosis in cardiomyocytes, even upon activation of pro-inflammatory cytokines. Interestingly, the cytoprotective effects of STS on OGD/R-induced apoptosis and promotion of cell survival were attenuated after inhibition of PI3K.The inhibitory effects of STS on TNF-α and positive feedback signalling of the NF-κB/TNF-α pathways may play important roles in myocardial protection against ischaemia/reperfusion. These protective effects of STS are mediated by suppressing JNK activity through activation of the PI3K-Akt pathway.

Summary Cancer develops through a process of somatic evolution. Here, we use whole-genome sequencing of 2,778 tumour samples from 2,658 donors to reconstruct the life history, evolution of mutational processes, and driver mutation sequences of 39 cancer types. The early phases of oncogenesis are driven by point mutations in a small set of driver genes, often including biallelic inactivation of tumour suppressors. Early oncogenesis is also characterised by specific copy number gains, such as trisomy 7 in glioblastoma or isochromosome 17q in medulloblastoma. By contrast, increased genomic instability, a nearly four-fold diversification of driver genes, and an acceleration of point mutation processes are features of later stages. Copy-number alterations often occur in mitotic crises leading to simultaneous gains of multiple chromosomal segments. Timing analysis suggests that driver mutations often precede diagnosis by many years, and in some cases decades, providing a window of opportunity for early cancer detection.

Many studies of nanomaterials make non-systematic alterations of nanoparticle physicochemical properties. Given the immense size of the property space for nanomaterials, such approaches are not very useful in elucidating fundamental relationships between inherent physicochemical properties of these materials and their interactions with, and effects on, biological systems. Data driven artificial intelligence methods such as machine learning algorithms have proven highly effective in generating models with good predictivity and some degree of interpretability. They can provide a viable method of reducing or eliminating animal testing. However, careful experimental design with the modelling of the results in mind is a proven and efficient way of exploring large materials spaces. This approach, coupled with high speed automated experimental synthesis and characterization technologies now appearing, is the fastest route to developing models that regulatory bodies may find useful. We advocate greatly increased focus on systematic modification of physicochemical properties of nanoparticles combined with comprehensive biological evaluation and computational analysis. This is essential to obtain better mechanistic understanding of nano-bio interactions, and to derive quantitatively predictive and robust models for the properties of nanomaterials that have useful domains of applicability.

Numerous chemical data sets have become available for quantitative structure-activity relationship (QSAR) modeling studies. However, the quality of different data sources may be different based on the nature of experimental protocols. Therefore, potential experimental errors in the modeling sets may lead to the development of poor QSAR models and further affect the predictions of new compounds. In this study, we explored the relationship between the ratio of questionable data in the modeling sets, which was obtained by simulating experimental errors, and the QSAR modeling performance. To this end, we used eight data sets (four continuous endpoints and four categorical endpoints) that have been extensively curated both in-house and by our collaborators to create over 1800 various QSAR models. Each data set was duplicated to create several new modeling sets with different ratios of simulated experimental errors (i.e., randomizing the activities of part of the compounds) in the modeling process. A fivefold cross-validation process was used to evaluate the modeling performance, which deteriorates when the ratio of experimental errors increases. All of the resulting models were also used to predict external sets of new compounds, which were excluded at the beginning of the modeling process. The modeling results showed that the compounds with relatively large prediction errors in cross-validation processes are likely to be those with simulated experimental errors. However, after removing a certain number of compounds with large prediction errors in the cross-validation process, the external predictions of new compounds did not show improvement. Our conclusion is that the QSAR predictions, especially consensus predictions, can identify compounds with potential experimental errors. But removing those compounds by the cross-validation procedure is not a reasonable means to improve model predictivity due to overfitting.

MWCNTs were successfully functionalized with PEG. PEG-<italic>g</italic>-MWCNTs/PSf membranes showed higher hydrophilicity and good antifouling capability. The nano-hybrid membranes exhibited excellent mechanical properties.

A significant protruding graphene edge effect on the carbocatalytic activity of a graphene film for efficient conversion of 4-nitrophenol to 4-aminophenol.

Engineering of A-site deficiency in perovskites can be critical for designing new materials with required functional properties. In this article, A-site deficient Sr2-xFe1.4Ni0.1Mo0.5O6-δ (x = 0-0.1, Sr2-xFNM) perovskites have been synthesized and characterized as anode materials for solid oxide fuel cells. X-ray photoelectron spectroscopy data indicate that Sr deficiency changes valence states of B-site cations. The introduction of A-site deficiency has shown to improve the chemical stability of the as-prepared materials under reducing conditions. With increasing of Sr deficiency, the conductivity in 5% H2/Ar increases markedly, reaching a peak value of 26.6 S cm−1 at x = 0.05. While further increasing of x reduces the conductivity by affecting the mobility of electronic charge carriers. The La0.9Sr0.1Ga0.8Mg0.2O3 electrolyte-supported cell with La0.6Sr0.4Fe0.8Co0.2O3 cathode and Sr1.95Fe1.4Ni0.1Mo0.5O6-δ anode demonstrates a maximum power density of 606 mW cm−2 at 800 °C operating in H2. Such designed A-site deficiency perovskite has the potential to be applied as SOFC anode materials.

Classification consistency and accuracy are viewed as important indicators for evaluating the reliability and validity of classification results in cognitive diagnostic assessment (CDA). Pattern‐level classification consistency and accuracy indices were introduced by Cui, Gierl, and Chang. However, the indices at the attribute level have not yet been constructed. This study puts forward a simple approach to estimating the indices at both the attribute and the pattern level through one single test administration. Detailed elaboration is made on how the upper and lower bounds for the attribute‐level accuracy can be derived from the variance of error of the attribute mastery probability estimate. In addition, based on Cui's pattern‐level indices, an alternative approach to estimating the attribute‐level indices is also proposed. Comparative analysis of simulation results indicate that the new indices are very desirable for evaluating test‐retest consistency and correct classification rate.

SO2 is widely recognized as an air pollutant and is a known cause of acid rain. At sufficiently high level, it also causes respiratory diseases. A much lesser known side of SO2 is its endogenous nature and possible physiological roles. There is mounting evidence that SO2 is produced during normal cellular metabolism and may possibly function as a signaling molecule in normal physiology. The latter aspect is still at the stage of being carefully examined as to the validity of classifying SO2 as a gasotransmitter with endogenous signaling roles. One difficulty in studying the biological and pharmacological roles of SO2 is the lack of adequate tools for its controllable and precise delivery. Traditional methods of using SO2 gas or mixed sulfite salts do not meet research need for several reasons. Therefore, there has been increasing attention on the need of developing SO2 donors or prodrugs that can be used as tools for the elucidation of SO2's physiological roles, pharmacological effects, and possible mechanism(s) of action. In this review, we aim to review basic sulfur chemistry in the context of sulfur signaling and various chemical strategies used for designing SO2 donors. We will also discuss potential pharmacological applications of SO2 donors, lay out desirable features for such donors and possibly prodrugs, analyze existing problems, and give our thoughts on research needs.

Multi-frame image super-resolution focuses on reconstructing a high-resolution image from a set of low-resolution images with high similarity. Combining image prior knowledge with fidelity model, the Bayesian-based methods have been considered as an effective technique in super-resolution. The minimization function derived from maximum a posteriori probability (MAP) is composed of a fidelity term and a regularization term. In this paper, based on the MAP estimation, we propose a novel initialization method for super-resolution imaging. For the fidelity term in our proposed method, the half-quadratic estimation is used to choose error norm adaptively instead of using fixed L <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> norms. Besides, a spatial weight matrix is used as a confidence map to scale the estimation result. For the regularization term, we propose a novel regularization method based on adaptive bilateral total variation (ABTV). Both the fidelity term and the ABTV regularization guarantee the robustness of our framework. The fidelity term is mainly responsible for dealing with misregistration, blur, and other kinds of large errors, while the ABTV regularization aims at edge preservation and noise removal. The proposed scheme is tested on both synthetic data and real data. The experimental results illustrate the superiority of our proposed method in terms of edge preservation and noise removal over the state-of-the-art algorithms.

Acute myocardial infarction is one of the most threaten disease in the world. In previous studies, exosome derived miR-126 has been verified that exert an pro-angiogenic function through exosomal transfer. However, the function of miR-126 in ischemic reperfusion injury remains unknown. The aim of the study was to investigate the function and mechanism of miR-126 in ischemic reperfusion injury. H2O2 and CoCl2-treated neonatal rat ventricular cardiomyocytes were used to analyze the function of miR-126 in vitro. Tunel, JC-1, ROS, LDH and cell survival rates were detected to evaluate the function of miR-126. Rat acute myocardial infarction was performed to elucidate the function of miR-126 in vivo. We found that miR-126 could reduce the apoptosis and improved cell survival of H2O2-treated and CoCl2-treated neonatal rat ventricular cardiomyocytes. MiR-126 also attenuates the ROS elevation and mitochondrial membrane potential through JC-1 detection. miR-126 also improved the cardiac function in vivo. Luciferase activity revealed that miR-126 could bind to ERRFI1, suggesting miR-126 functioned through regulating ERRFI1. We verified the function and mechanism of miR-126 and provide evidence that miR-126 may play important role in ischemic reperfusion injury, and understanding the precise role of miR-126 will undoubtedly shed new light on the clinical treatment.

Smart drugs, such as antibody-drug conjugates, for targeted therapy rely on the ability to deliver a warhead to the desired location and to achieve activation at the same site. Thus, designing a smart drug often requires proper linker chemistry for tethering the warhead with a vehicle in such a way that either allows the active drug to retain its potency while being tethered or ensures release and thus activation at the desired location. Recent years have seen much progress in the design of new linker activation strategies. Herein, we review the recent development of chemical strategies used to link the warhead with a delivery vehicle for preferential cleavage at the desired sites.

This review provides insights into the mechanism underlying the pathogenesis of myopia and potential targets for clinical intervention. Although the etiology of myopia involves both environmental and genetic factors, recent evidence has suggested that the prevalence and severity of myopia appears to be affected more by environmental factors. Current pharmacotherapeutics are aimed at inhibiting environmentally induced changes in visual input and subsequent changes in signaling pathways during myopia pathogenesis and progression. Recent studies on animal models of myopia have revealed specific molecules potentially involved in the regulation of eye development. Among them, the dopamine receptor plays a critical role in controlling myopia. Subsequent studies have reported pharmacotherapeutic treatments to control myopia progression. In particular, atropine treatment yielded favorable outcomes and has been extensively used; however, current studies are aimed at optimizing its efficacy and confirming its safety. Furthermore, future studies are required to assess the efficacy of combinatorial use of low-dose atropine and contact lenses or orthokeratology.

To enhance the anti-fouling performance of polysulfone (PSF) membranes, polyaniline (PANI) nanofibers were used as additives in a facile method to prepare PANI/PSF blended membranes (PPMs). The fouling behavior between the membrane and natural organic matters (NOM) pollutant was further analyzed by implementing extended Derjaguin–Landau–Verwey–Overbeek (XDLVO) theory. Overall, the performance of the PPMs was improved in comparison with that of the pristine PSF membrane. The pure water flux of the PPM increased to 2.4 times that of pristine PSF, reaching up to 169 L·m−2 h−1 bar−1. The tensile strength of the hybrid membranes also increased after the incorporation of PANI nanofibers. In particular, in anti-fouling measurement, the PPMs exhibited enhanced anti-fouling properties for filtration serum albumin (BSA), humic acid (HA) and sodium alginate (SA) solutions. The anti-fouling mechanism was analyzed by the interfacial interaction energy, which were obtained by applying the XDLVO theory. Results confirmed that there are reduced attractive interaction energies between the PPMs and NOM pollutants molecules in comparison to the interaction between the pristine PSF and NOM pollutants molecules.

It has been promising to utilize the vapor injection method to enhance the performance of the transcritical CO2 heat pump under the working condition of low ambient temperature and high water inlet temperature. The complicated optimization process of both the discharge pressure and the medium pressure has prevented the system from further application. We introduce the multi-variable extreme seeking control strategy to realize the real-time power consumption minimization of the sub-cooler vapor injection trans-critical CO2 system. The multi-variable ESC controller takes the power consumption as the feedback, the discharge pressure and the medium pressure setpoint as the manipulated inputs. The control strategy is evaluated on a dynamic simulation model for the proposed system using Dymola and ThermalSystems from TLK-Thermo, GmbH. The simulation is conducted under the working conditions of the fixed design condition, the staircase of water inlet temperature and the realistic ambient temperature profile. Simulation results show that ESC can optimize the discharge pressure and intermediate pressure for high system efficiency with good steady-state and transient performance.

In terrestrial plants a basal innate immune system, pattern-triggered immunity (PTI), has evolved to limit infection by diverse microbes. The remodeling of actin cytoskeletal arrays is now recognized as a key hallmark event during the rapid host cellular responses to pathogen attack. Several actin binding proteins have been demonstrated to fine tune the dynamics of actin filaments during this process. However, the upstream signals that stimulate actin remodeling during PTI signaling remain poorly characterized. Two second messengers, reactive oxygen species (ROS) and phosphatidic acid (PA), are elevated following pathogen perception or microbe-associated molecular pattern (MAMP) treatment, and the timing of signaling fluxes roughly correlates with actin cytoskeletal rearrangements. Here, we combined genetic analysis, chemical complementation experiments, and quantitative live-cell imaging experiments to test the role of these second messengers in actin remodeling and to order the signaling events during plant immunity. We demonstrated that PHOSPHOLIPASE Dβ (PLDβ) isoforms are necessary to elicit actin accumulation in response to flg22-associated PTI. Further, bacterial growth experiments and MAMP-induced apoplastic ROS production measurements revealed that PLDβ-generated PA acts upstream of ROS signaling to trigger actin remodeling through inhibition of CAPPING PROTEIN (CP) activity. Collectively, our results provide compelling evidence that PLDβ/PA functions upstream of RBOHD-mediated ROS production to elicit actin rearrangements during the innate immune response in Arabidopsis.

Whole-organ mapping was used to study molecular changes in the evolution of bladder cancer from field effects. We identified more than 100 dysregulated pathways, involving immunity, differentiation, and transformation, as initiators of carcinogenesis. Dysregulation of interleukins signified the involvement of inflammation in the incipient phases of the process. An aberrant methylation/expression of multiple HOX genes signified dysregulation of the differentiation program. We identified three types of mutations based on their geographic distribution. The most common were mutations restricted to individual mucosal samples that targeted uroprogenitor cells. Two types of mutations were associated with clonal expansion and involved large areas of mucosa. The α mutations occurred at low frequencies while the β mutations increased in frequency with disease progression. Modeling revealed that bladder carcinogenesis spans 10–15 years and can be divided into dormant and progressive phases. The progressive phase lasted 1-2 years and was driven by β mutations.

Global health and economy are deeply influenced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its newly emerging variants. Nanobodies with nanometer-scale size are promising for the detection and treatment of SARS-CoV-2 and its variants because they are superior to conventional antibodies in terms of cryptic epitope accessibility, tissue penetration, cost, formatting adaptability, and especially protein stability, which enables their aerosolized specific delivery to lung tissues. This review summarizes the progress in the prevention, detection, and treatment of SARS-CoV-2 using nanobodies, as well as strategies to combat the evolving SARS-CoV-2 variants. Generally, highly efficient generation of potent broad-spectrum nanobodies targeting conserved epitopes or further construction of multivalent formats targeting non-overlapping epitopes can promote neutralizing activity against SARS-CoV-2 variants and suppress immune escape.

Abstract: An increased production of reactive oxygen species is thought to be critical to the pathogenesis of Parkinson's disease. At autopsy, patients with either presymptomatic or symptomatic Parkinson's disease have a decreased level of glutathione in the substantia nigra pars compacta. This change represents the earliest index of oxidative stress in Parkinson's disease discovered to this point. This study compares the sensitivity of dopaminergic and nondopaminergic neurons in dissociated mesencephalic cultures to the depletion of glutathione. We have found that dopaminergic neurons are more resistant to the toxicity of glutathione depletion than nondopaminergic neurons. The possibility that dopaminergic neurons have a higher baseline glutathione level than nondopaminergic neurons is suggested by measurements of levels of cellular glutathione in a parallel system of immortalized embryonic dopaminergic and nondopaminergic cell lines. We also examined the role of glutathione in 1‐methyl‐4‐phenylpyridinium toxicity. Decreasing the glutathione level of dopaminergic neurons potentiates their susceptibility to 1‐methyl‐4‐phenylpyridinium toxicity, although 1‐methyl‐4‐phenylpyridinium does not deplete glutathione from primary mesencephalic cultures. Our data suggest that although a decreased glutathione content is not likely to be the sole cause of dopaminergic neuronal loss in Parkinson's disease, decreased glutathione content may act in conjunction with other factors such as 1‐methyl‐4‐phenylpyridinium to cause the selective death of dopaminergic neurons.

Abstract Lunasin is a novel chemopreventive peptide featuring a cell adhesion motif composed of arginine–glycine–aspartate (RGD) which has been associated to cytotoxicity to established cell lines. The objectives of this study were to determine the effect of lunasin on the viability of L1210 leukemia cells and to understand the underlying mechanisms involved. Pure lunasin and lunasin enriched soy flour (LES) caused cytotoxicity to L1210 leukemia cells with IC 50 of 14 and 16 μM (lunasin equivalent), respectively. Simulated gastrointestinal digestion showed that 25% of the original amount of lunasin survived 3 h of pepsin digestion and 3% of lunasin remained after sequential pepsin–pancreatin digestion for a total of 6 h. Cell cycle analysis showed that lunasin caused a dose‐dependent G2 cell cycle arrest and apoptosis. Treatment of L1210 leukemia cells with 1 mg/mL of LES for 18 h led to an increase in the amount of apoptotic cells from 2 to 40%. Compared to untreated cells, treatment with 1 mg/mL LES showed a 6‐fold increase on the expressions of caspases‐8 and ‐9, and and a 12‐fold increase on the expression of caspase‐3. These results showed for the first time that lunasin, a naturally occurring peptide containing an RGD motif, caused apoptosis to L1210 leukemia cells through caspase‐3 activation.

Giant reed (GR) was modified into giant reed quaternary amino anion exchanger (GR-QE) for the removal of phosphate by reacting with epichlorohydrin, ethylenediamine (EDA) and triethylamine in the presence of N,N-dimethylformamide (DMF). Factors like GR dosage, temperatures and volumes of organic liquid chemicals were used in single-factor experiments and orthogonal experiments for determining optimal conditions, with phosphate removal efficiency and zeta potentials as indicators. The results indicated that the optimal conditions obtained in the orthogonal experiments were consistent with those in the single-factor experiments. The GR utilization on a large-scale was realized, and the dosage of EDA was considered as the key influential factor in the preparation of GR-QE. Under these conditions, the nitrogen content in GR-QE was about 7.78%, while it was 0.9% in GR. The phosphate removal was about 82.1%, zeta potential was 23.2 mV.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is thought to play modulatory roles in the development of atherosclerosis. Here we evaluated the effects of a specific lp-PLA2 inhibitor on atherosclerosis in ApoE-deficient mice and its associated mechanisms.ApoE-deficient mice fed an atherogenic high-fat diet for 17 weeks were divided into two groups. One group was administered the specific lp-PLA2 inhibitor, darapladib (50 mg/kg/day; p.o.) daily for 6 weeks, while the control group was administered saline. We observed no differences in body weight and serum lipids levels between the two groups at the end of the dietary period. Notably, serum lp-PLA2 activity as well as hs-CRP (C-reactive protein) and IL-6 (Interleukin-6) levels were significantly reduced in the darapladib group, compared with the vehicle group, while the serum PAF (platelet-activating factor) levels were similar between the two groups. Furthermore, the plaque area through the arch to the abdominal aorta was reduced in the darapladib group. Another finding of interest was that the macrophage content was decreased while collagen content was increased in atherosclerotic lesions at the aortic sinus in the darapladib group, compared with the vehicle group. Finally, quantitative RT-PCR performed to determine the expression patterns of specific inflammatory genes at atherosclerotic aortas revealed lower expression of MCP-1, VCAM-1 and TNF-α in the darapladib group.Inhibition of lp-PLA2 by darapladib leads to attenuation of in vivo inflammation and decreased plaque formation in ApoE-deficient mice, supporting an anti-atherogenic role during the progression of atherosclerosis.

Objective To describe 12-month rates and patterns of coprescription of drugs that potentially create drug-drug interactions (DDIs) through shared metabolic or transport pathways for 9 enzyme-targeted kinase inhibitor oral antineoplastic drugs (OADs). Patients and Methods We used a deidentified pharmacy claims database identifying patients prescribed dasatinib, erlotinib, everolimus, imatinib, lapatinib, nilotinib, pazopanib, sorafenib, or sunitinib between January 1, 2008, and May 31, 2010. Coprescribing was 1 or more overlapping days of supply between the OAD and potential DDI drugs during the 12-month period beginning on the OAD index date. Product labels identified the cytochrome P450 metabolic enzymes used and whether P-glycoprotein was used by the OADs. Drugs that induce and/or inhibit these pathways were identified from the label and online resources. Results Sample sizes ranged from 96 (pazopanib group) to 4617 (imatinib group). Coprescribing rates with drugs that may decrease OAD effectiveness were 359/1546 (23%) (sunitinib group) to 1851/3263 (57%) (erlotinib group). Coprescribing rates with drugs that may increase OAD toxicity were 364/1546 (24%) (sunitinib group) to 71/96 (74%) (pazopanib group). Patients coprescribed DDI drugs had a median of 1 to 4 more medications present on the OAD index date than those not coprescribed a DDI drug. Most groups coprescribed DDI drugs had a median of 180 or more OAD days of supply during follow-up. The proportion of OAD days of supply with overlapping days of DDI drugs ranged from 7% to 85%. Generally, oncologists prescribed the OAD and nononcologists the DDI drug. Conclusion Coprescription of drugs that induce or inhibit metabolic pathways used by enzyme-targeted kinase inhibitor OADs is high. The clinical consequences need further study.

Myofibroblast accumulation is a pathological feature of lung diseases requiring oxygen therapy. One possible source for myofibroblasts is through the epithelial-to-mesenchymal transition (EMT) of alveolar epithelial cells (AEC). To study the effects of oxygen on alveolar EMT, we used RLE-6TN and ex vivo lung slices and found that hyperoxia (85% O 2 , H85) decreased epithelial proteins, presurfactant protein B (pre-SpB), pro-SpC, and lamellar protein by 50% and increased myofibroblast proteins, α-smooth muscle actin (α-SMA), and vimentin by over 200% ( P &lt; 0.05). In AEC freshly isolated from H85-treated rats, mRNA for pre-SpB and pro-SpC was diminished by ∼50% and α-SMA was increased by 100% ( P &lt; 0.05). Additionally, H85 increased H 2 O 2 content, and H 2 O 2 (25–50 μM) activated endogenous transforming growth factor-β1 (TGF-β1), as evident by H2DCFDA immunofluorescence and ELISA ( P &lt; 0.05). Both hyperoxia and H 2 O 2 increased SMAD3 phosphorylation (260% of control, P &lt; 0.05). Treating cultured cells with TGF-β1 inhibitors did not prevent H85-induced H 2 O 2 production but did prevent H85-mediated α-SMA increases and E-cadherin downregulation. Finally, to determine the role of TGF-β1 in hyperoxia-induced EMT in vivo, we evaluated AEC from H85-treated rats and found that vimentin increased ∼10-fold ( P &lt; 0.05) and that this effect was prevented by intraperitoneal TGF-β1 inhibitor SB-431542. Additionally, SB-431542 treatment attenuated changes in alveolar histology caused by hyperoxia. Our studies indicate that hyperoxia promotes alveolar EMT through a mechanism that is dependent on activation of TGF-β1 signaling.

Water deficit causes multiple negative impacts on plants, such as reactive oxygen species (ROS) accumulation, abscisic acid (ABA) induction, stomatal closure, and decreased photosynthesis. Here, we characterized OsC3H47, which belongs to CCCH zinc-finger families, as a drought-stress response gene. It can be strongly induced by NaCl, PEG, ABA, and drought conditions. Overexpression of OsC3H47 significantly enhanced tolerance to drought and salt stresses in rice seedlings, which indicates that OsC3H47 plays important roles in post-stress recovery. However, overexpression of OsC3H47 reduced the ABA sensitivity of rice seedlings. This suggests that OsC3H47 is a newly discovered gene that can control rice drought-stress response, and it may play an important role in ABA feedback and post-transcription processes.

Academic Radiologist Subspecialty Identification Using a Novel Claims-Based Classification SystemAndrew B. Rosenkrantz1, Wenyi Wang2, Danny R. Hughes2,3, Luke A. Ginocchio1, David A. Rosman4 and Richard Duszak, Jr5Audio Available | Share

Esterase-triggered SO₂prodrugs with tunable release rates.

In this paper, the partial substitution of atomic elements from the A site of a perovskite is investigated in order to develop cathode materials for solid oxide fuel cell (SOFC) applications. Herein, Sr2−xCaxFe1.5Mo0.5O6−δ (SCFM), compounds were investigated by characterizing structural properties, chemical compatibility, electrical properties, electrochemical performance and stability. Thermal expansion coefficients were found to decrease when increasing the Ca content. X-ray photoelectron spectroscopy analysis suggests that Ca doping significantly affects the Fe2+/Fe3+ and Mo6+/Mo5+ ratios. For a doping level of x = 0.4, the sample showed the lowest interface polarization (Rp), the highest conductivity and a maximum power density of 1.26 W cm−2 at 800 °C. These results suggest that SCFM cathode materials are excellent candidates for intermediate temperature solid oxide fuel cells applications.

Purpose To explore associations between county-level measures of radiologist supply and subspecialization and county structural and health-related characteristics. Methods Medicare Physician and Other Supplier Public Use Files were used to subspecialty characterize 32,844 radiologists participating in Medicare between 2012 and 2014. Measures of radiologist supply and subspecialization were computed for 3,143 US counties. Additional county characteristics were identified using the 2014 County Health Rankings database. Mann-Whitney tests and Spearman correlations were performed. Results Counties with at least one (versus no) Medicare-participating radiologist had significantly (P < .001) larger populations (197,050 ± 457,056 versus 20,253 ± 23,689), lower rural percentages (39.5% ± 26.5% versus 74.6% ± 25.6%), higher household incomes ($47,608 ± $12,493 versus $42,510 ± $9,893), higher mammography screening rates (62.4% ± 7.0% versus 56.6% ± 15.3%), and lower premature deaths (7,581 ± 2,085 versus 7,784 ± 3,409 years of life lost). Counties’ radiologists per 100,000 population and percent of subspecialized radiologists showed moderate positive correlations with counties’ population (r = +0.505-+0.599) and moderate negative correlations with counties’ rural percentage (r = −0.434 to −0.523). Radiologist supply and degree of subspecialization both showed concurrent positive or negative weak associations with counties’ percent age 65+ (r = −0.256 to −0.271), percent Hispanic (r = +0.209-+0.234), and income (r = +0.230-+0.316). Radiologists per 100,000 population showed weak positive correlation with mammography screening (r = +0.214); percent of radiologists subspecialized showed weak negative correlation with premature death (r = −0.226). Conclusion Geographic disparities in radiologist supply at the community level are compounded by superimposed variation in the degree of subspecialization of those radiologists. The potential impact of such access disparities on county-level health warrants further investigation.

The aim of this study was to assess both existing Medicare provider code assignments and a new claims-based system for subspecialty classification of private practice radiologists.Websites of the 100 largest US radiology private practices were used to identify 1,476 radiologists self-identified with a single subspecialty ([1] abdominal, [2] breast, [3] cardiothoracic, or [4] musculoskeletal imaging; [5] nuclear medicine; [6] interventional radiology; [7] neuroradiology). Concordance of existing Medicare radiology subspecialty provider codes (present only for nuclear medicine and interventional radiology) was first assessed. Next, using a classification approach based on Neiman Imaging Types of Service (NITOS) piloted among academic practices, the percentage of subspecialty work relative value units (wRVUs) from 2012 to 2014 Medicare claims were used to assign each radiologist a unique subspecialty.Existing Medicare provider codes matched only 8.0% of nuclear medicine physicians and 10.7% of interventional radiologists to their self-reported subspecialties. The NITOS-based system mapped a median 51.9% of private practice radiologists' wRVUs to self-identified subspecialties (range, 23.3% [nuclear medicine] to 73.6% [neuroradiology]). The 50% NITOS-based wRVU threshold previously established for academic radiologists correctly assigned subspecialties to 48.8% of private practice radiologists but incorrectly categorized 2.9%. Practice patterns of the remaining 48.3% were sufficiently varied such that no single subspecialty assignment was possible.Existing Medicare provider codes poorly mirror subspecialty radiologists' own practice website-designated subspecialties. Actual payer claims data permit far more granular and accurate subspecialty identification for many radiologists. As new payment models increasingly focus on subspecialty-specific performance measures, claims-based identification methodologies show promise for reproducibly and transparently matching radiologists to practice-relevant metrics.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have obtained excellent therapeutic effects against non-small cell lung cancer (NSCLC) harboring activating EGFR mutations.However, some patients have exhibited primary resistance which becomes a major obstacle in effective treatment of NSCLC.The mechanisms of EGFR-TKIs resistance involved are still poorly understood.Many studies suggest that miRNAs play an important role in regulating drug sensitivity of EGFR-TKIs.The aim of the present study was to examine differentially expressed miRNAs in plasma between EGFR-TKIs sensitive and EGFR-TKIs primary resistance patients.MiRNA microarray of plasma from patients' blood identified 16 differentially expressed miRNAs of which 15 (hsv2-miR-H19, hsa-miR-744-5p, hsa-miR-3196, hsa-miR-3153, hsa-miR-4791, hsa-miR-4803, hsa-miR-4796-3p, hsa-miR-372-5p, hsa-miR-138-2-3p, hsa-miR-16-1-3p, hsa-miR-1469, hsa-miR-585-3p, ebv-miR-BART14-5p, hsa-miR-769-3p, hsa-miR-548aq-5p) were down regulated while only hsa-miR-503-3p was up regulated in primary resistant patients' plasma.Volcano plot and hierarchical clustering were performed to examine the accuracy of the miRNAs.Then validation with quantitative real-time PCR was performed and the result was in accordance with the array data.Functional analysis of these differentially expressed miRNAs with Ingenuity Pathway Analysis (IPA) revealed a common signaling network including MYC, CCND1, IGF1 and RELA.In conclusion, our finding may play important role in understanding the mechanisms underlying the problem and should be further evaluated as potential biomarkers in primary resistance of NSCLC.

Anatase titania coated CNTs (TCNTs) and sodium lignin sulfonate (SLS) were introduced to chitosan membrane to improve the conductivity based on extra proton transfer channels built by TCNTs and sulfonate groups supplied by SLS. Water uptake, mechanical properties, oxidation stability and methanol-rejecting property of composite membranes were characterized. The results show that TCNTs and SLS doped membranes have enhanced conductivity and the sample with 5% TCNTs and 2% SLS doped (CS/TCNT-5/SLS-2) achieved a conductivity of 0.0367 S cm−1 at room temperature and 0.0647 S cm−1 at 60 °C, which is much higher than pure chitosan membrane. Moreover, with TCNTs incorporation, the mechanical properties, oxidation stability and methanol-rejecting property also improved. Overall, selectivity of CS/TCNT-5/SLS-2 sample achieved 28.2 × 104 S s cm−3 which is much higher than 3.8 × 104 S s cm−3 of pure chitosan membrane. Thus, with enhanced properties, chitosan composite membrane could be promising as proton exchange membrane (PEM) in the use of direct methanol fuel cell (DMFC).

Alzheimer's disease (AD) pathology consists of extracellular deposits of amyloid-β peptides (Aβ) and intracellular neurofibrillary tangles. These pathological alterations are accompanied by a neuroinflammatory response consisting of increased expression of inflammatory mediators. An anti-inflammatory strategy designed to prevent or delay the development of AD would benefit from knowing when neuroinflammation appears in the transgenic models during prodromal disease stages relative to Aβ pathology. We investigated the expression patterns of inflammatory mediators in the brain of 5xFAD mice in comparison to development of Aβ deposition. Expression changes in inflammatory mediators and glial markers are more robust in female mice starting at three months of age, in contrast to males in which there is no clear trend through five months. Female and male 5xFAD mice also displayed an age-dependent increase in cortical Aβ deposition congruent with neuroinflammation. Thus, in the 5xFAD mouse model of AD, administration of an anti-inflammatory agent would be most efficacious when administered before three months of age.