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Tau in Alzheimer's disease (AD) is assessed via cerebrospinal fluid (CSF) and Positron emission tomography (PET). Novel methods to detect phosphorylated tau (pTau) in blood have been recently developed. We aim to investigate agreement of tau status as determined by [We assessed cognitively unimpaired young, cognitively unimpaired, mild cognitive impairment and AD individuals with [The threshold for positivity was 15.085 pg/mL for plasma pTau181 and 17.652 pg/mL for plasma pTau231. Most individuals had concordant statuses, however, 18% of plasma181/PET, 26% of plasma231/PET and 25% of the pTau231/pTau181 were discordant. Positivity to at least one biomarker was often accompanied by diagnosis of cognitive impairment, Aβ positivity, APOEε4 carriership, higher levels of [Plasma pTau181, pTau231 and [Moreover, this study was supported by Weston Brain Institute, Canadian Institute of Health Research and Fonds de Recherche du Québec.

Global warming threatens reef-building corals with large-scale bleaching events; therefore, it is important to discover potential adaptive capabilities for increasing their temperature resistance before it is too late. This study presents two coral species (Platygyra verweyi and Isopora palifera) surviving on a reef having regular hot water influxes via a nearby nuclear power plant that exhibited completely different bleaching susceptibilities to thermal stress, even though both species shared several so-called “winner” characteristics (e.g., containing Durusdinium trenchii, thick tissue, etc.). During acute heating treatment, algal density did not decline in P. verweyi corals within three days of being directly transferred from 25 to 31 °C; however, the same treatment caused I. palifera to lose

Many chemical and physical equilibrium conditions can be determined from minimizing the Gibbs free energies of the system. Efficient analytical representations of the entropy and Gibbs free energy of carbonyl sulfide remain elusive in the communality of science and engineering. Here, we report two analytical representations of the entropy and Gibbs free energy for carbonyl sulfide, and the prediction procedures only involve six molecular constants of the carbonyl sulfide molecule. In the temperature range from 300 to 6000 K, the average relative deviations of the predicted molar entropy and reduced Gibbs free energy values of carbonyl sulfide from the National Institute of Standards and Technology database are arrived at 0.150 and 0.189%, respectively.

Finger mark identification, which is one of the biological recognition methods, has a history of more than 100 years. In this study, polyvinyl alcohol (PVA)/ninhydrin blend nanomembranes were prepa...

Purpose In recent years, the ongoing development and rapid popularization of mobile devices, not only has brought new forms of lifestyle but also has boomed a wide array of service contents, allowing users to engage in entertainment, study and other daily activities, in addition to business transactions. To explore the factors that affect users' continued use of mobile app software, this paper aims to take into account the utilitarian value and privacy, as well as security factors and intends to propose an integrated research model based on the information systems success (ISS) model. Design/methodology/approach The data for this study were collected via an online survey questionnaire. A total of 190 valid responses were used to examine the hypotheses in the research model. The casual model was assessed using partial least squares techniques. Findings The results indicated that the three quality factors (information quality, system quality and service quality) in the ISS model significantly affected satisfaction and utilitarian value. Private and security have significant negative association with utilitarian value. The results also showed that private and security did not significantly affect satisfaction. The findings also provide some directions for further research. Practical implications The results show that user's continued use of mobile app software depends upon the perceived utilitarian value and satisfaction. The quality characteristics are the three critical factors that would affect the perceived utilitarian value and satisfaction. Compared to information quality and service quality, system quality has a higher degree of positive impact, which indicates that users are more concerned about the immediate download ability and ease-of-use provided by the system. Furthermore, the research also finds that privacy and security concerns have a negative influence on the utilitarian value, showing that in the context of task-oriented IS, the perceived risk of privacy and security during the process of using mobile app software services, will negatively affect users’ perception of utilitarian value. The insights provided by this study can help mobile app developers optimize design and marketing strategies. Originality/value This study provides a better understanding of how the factors in the theories influence the continuance usage intention of life style mobile applications.

In Cergy-Pontoise, the artist Dani Karavan is commissioned to conceive the three-kilometer linear path named Axe Majeur (Main Axis), connecting the city center and the vast riverside. Instead of a work of art to contemplate, Karavan builds 12 stations in succession and in the form of instruments with which people are equipped to measure and to process the existent environmental data and to find their own interpretation of the site. By making factual information measurable and translatable into cultural connotations, Karavan’s work implies a mesological point of view from which osmosis between the sculpture and the site invalidates the opposite physical/phenomenal. The paper studies this method based on the notion mediance proposed by the geographer Augustin Berque and on a field survey. Two principles constitute the method: First, Karavan invents a sculptural metrology functioning in the way of the perceptive calibration system. Secondly, the Axe Majeur shows a “total environment” which means not only 12 parts as a single unit but also the inseparable relationship of Karavan’s environment (art) with the whole geographical environment. Each part annotates the signs left behind after Earth’s motion (e.g. topography, geothermal energy) and after cultural activities (e.g. orchard, view of Paris) and turns these signs into the basis on which imagination could be formed and new meaning could arise. By articulating historical and spatial dimension with an environmental symbology, the Axe Majeur constitutes an innovative urban planning method which moves away from an international-vernacular (modernism) or historical-ahistorical (postmodernism) debate. Article received: April 2, 2019; Article accepted: May 25, 2019; Published online: September 15, 2019; Original scholarly paper How to cite this article: Wang, Yi-Ting. "otal Environment (Sculpture) as a Symbology: The Mesological Study of the Axe Majeur in Cergy-Pontoise." AM Journal of Art and Media Studies 19 (2019): 45-58. doi: 10.25038/am.v0i19.318

G protein‐coupled estrogen receptor‐1 (GPER), a member of the G protein‐coupled receptor (GPCR) superfamily, mediates estrogen‐induced proliferation of normal and malignant breast epithelial cells. However, its role in breast cancer stem cells (BCSCs) remains unclear. Here we showed greater expression of GPER in BCSCs than non‐BCSCs of three patient‐derived xenografts of ER−/PR+ breast cancers. GPER silencing reduced stemness features of BCSCs as reflected by reduced mammosphere forming capacity in vitro, and tumor growth in vivo with decreased BCSC populations. Comparative phosphoproteomics revealed greater GPER‐mediated PKA/BAD signaling in BCSCs. Activation of GPER by its ligands, including tamoxifen (TMX), induced phosphorylation of PKA and BAD‐Ser118 to sustain BCSC characteristics. Transfection with a dominant‐negative mutant BAD (Ser118Ala) led to reduced cell survival. Taken together, GPER and its downstream signaling play a key role in maintaining the stemness of BCSCs, suggesting that GPER is a potential therapeutic target for eradicating BCSCs., What's new? G protein‐coupled estrogen receptor‐1 (GPER) mediates estrogen‐induced proliferation of normal and malignant breast epithelial cells. However, the role of GPER in breast cancer stem cells (BCSC) biology remains unclear. Here, using patient‐derived xenografts of ER–/PR+ breast cancer, the authors found higher expression of GPER in BCSCs than non‐BCSCs. Moreover, the results indicated that stemness features were sustained via GPER‐mediated PKA/BAD phosphorylation. Stimulation by the GPER ligand tamoxifen enhanced BCSC cell viability and population and BAD phosphorylation. The findings revealed a vital role of GPER‐mediated signaling pathways in BCSC survival, suggesting GPER as a potential therapeutic target for eradicating BCSCs.

Aberrant phospho-signaling is a hallmark of cancer. We investigated kinase-substrate regulation of 33,239 phosphorylation sites (phosphosites) in 77 breast tumors and 24 breast cancer xenografts. Our search discovered 2134 quantitatively correlated kinase-phosphosite pairs, enriching for and extending experimental or binding-motif predictions. Among the 91 kinases with auto-phosphorylation, elevated EGFR, ERBB2, PRKG1, and WNK1 phosphosignaling were enriched in basal, HER2-E, Luminal A, and Luminal B breast cancers, respectively, revealing subtype-specific regulation. CDKs, MAPKs, and ataxia-telangiectasia proteins were dominant, master regulators of substrate-phosphorylation, whose activities are not captured by genomic evidence. We unveiled phospho-signaling and druggable targets from 113 kinase-substrate pairs and cascades downstream of kinases, including AKT1, BRAF and EGFR. We further identified kinase-substrate-pairs associated with clinical or immune signatures and experimentally validated activated phosphosites of ERBB2, EIF4EBP1, and EGFR. Overall, kinase-substrate regulation revealed by the largest unbiased global phosphorylation data to date connects driver events to their signaling effects.

The bamboo grasshopper, Ceracris kiangsu Tsai, is a pest of bamboos and widely distributed in China from high temperature plains to low temperature plateaus. In this study, high-throughput sequencing was used to analyze the transcriptome of C. kiangsu. Approximately 129,314,084 reads were generated using an Illumina sequencing. De novo assembly yielded 39,013 unigenes with an average length of 987 bp. Based on sequence similarity searches with known proteins, a total of 19,769 (50.67%) unigenes were identified. Of these annotated unigenes, 2114 and 11,412 unigenes were assigned to clusters of orthologous groups and gene ontology, respectively. Furthermore, 2128 simple sequence repeats (SSRs) were identified in the unigenes Differences were observed in gene expression after hypothermic stress, with the most up-regulated genes including heat shock protein genes (Hsps) and genes involved in ATP-binding. The down-regulation of genes involved in the catalytic activity of metabolic mechanisms was also observed. The obtained transcriptome information revealed the ability of C. kiangsu to build cold-tolerance after exposed to a mild low temperature and the transcriptional responses elicited by hypothermic stress.

Chlorophyllide (chlide) is a natural catabolic product of chlorophyll (Chl), produced through the activity of chlorophyllase (chlase). The growth inhibitory and antioxidant effects of chlide from different plant leaf extracts have not been reported. The aim of this study is to demonstrate that chlide in crude extracts from leaves has the potential to exert cytotoxic effects on cancer cell lines. The potential inhibitory and antioxidant effects of chlide in crude extracts from 10 plant leaves on breast cancer cells (MCF7 and MDA-MB-231), hepatocellular carcinoma cells (Hep G2), colorectal adenocarcinoma cells (Caco2), and glioblastoma cells (U-118 MG) were studied using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and DPPH (1,1-diphenyl-2-picrylhydrazyl) assays. The results of the MTT assay showed that chlide in crude extracts from sweet potato were the most effective against all cancer cell lines tested. U-118 MG cells were the most sensitive, while Caco2 cells were the most resistant to the tested crude extracts. The cytotoxic effects of chlide and Chl in crude extracts from sweet potato and of commercial chlorophyllin (Cu-chlin), in descending order, were as follows: chlide > Chl > Cu-chlin. Notably, the IC50 of sweet potato in U-118 MG cells was 45.65 μg/mL while those of Chl and Cu-chlin exceeded 200 μg/mL. In the DPPH assay, low concentrations (100 μg/mL) of chlide and Cu-chlin from crude extracts of sweet potato presented very similar radical scavenging activity to vitamin B2. The concentration of chlide was negatively correlated with DPPH activity. The current study was the first to demonstrate that chlide in crude extracts from leaves have potential cytotoxicity in cancer cell lines. Synergism between chlide and other compounds from leaf crude extracts may contribute to its cytotoxicity.

VEGF stimulates the formation of new blood vessels by inducing endothelial cell (EC) proliferation and migration. Brefeldin A (BFA)-inhibited guanine nucleotide-exchange protein (BIG)1 and 2 accelerate the replacement of bound GDP with GTP to activate ADP-ribosylation factor (Arf)1, which regulates vesicular transport between the Golgi and plasma membrane. Although it has been reported that treating cells with BFA interferes with Arf1 activation to inhibit VEGF secretion, the role of BIG1 and BIG2 in VEGF trafficking and expression, EC migration and proliferation, and vascular development remains unknown. Here, we found that inactivation of Arf1 reduced VEGF secretion but did not affect the levels of VEGF protein. Interestingly, however, BIG1 and BIG2 knockdown significantly decreased the levels of VEGF mRNA and protein in glioblastoma U251 cells and HUVECs. Furthermore, depletion of BIG1 and BIG2 inhibited HUVEC angiogenesis by diminishing cell migration. Angioblast migration and intersegmental vessel sprouting were also impaired when the BIG2 homolog, Arf guanine nucleotide exchange factor (arfgef)2, was knocked down in zebrafish with endothelial expression of green fluorescent protein (GFP). Depletion of arfgef2 by clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) also caused defects in vascular development of zebrafish embryos. Taken together, these data reveal that BIG1 and BIG2 participate in endothelial cell angiogenesis.-Lu, F.-I., Wang, Y.-T., Wang, Y.-S., Wu, C.-Y., Li, C.-C. Involvement of BIG1 and BIG2 in regulating VEGF expression and angiogenesis.

Markers of cancer stemness predispose patients to tumor aggressiveness, drug and immunotherapy resistance, relapse, and metastasis. DDX17 is a cofactor of the Drosha–DGCR8 complex in miRNA biogenesis and transcriptional coactivator and has been associated with cancer stem-like properties. However, the precise mechanism by which DDX17 controls cancer stem-like features remains elusive. Here, we show that the E3 ligase HectH9 mediated K63-polyubiquitination of DDX17 under hypoxia to control stem-like properties and tumor-initiating capabilities. Polyubiquitinated DDX17 disassociated from the Drosha–DGCR8 complex, leading to decreased biogenesis of anti-stemness miRNAs. Increased association of polyubiquitinated DDX17 with p300-YAP resulted in histone 3 lysine 56 (H3K56) acetylation proximal to stemness-related genes and their subsequent transcriptional activation. High expression of HectH9 and six stemness-related genes (BMI1, SOX2, OCT4, NANOG, NOTCH1, and NOTCH2) predicted poor survival in patients with head and neck squamous cell carcinoma and lung adenocarcinoma. Our findings demonstrate that concerted regulation of miRNA biogenesis and histone modifications through posttranslational modification of DDX17 underlies many cancer stem-like features. Inhibition of DDX17 ubiquitination may serve as a new therapeutic venue for cancer treatment. Significance: Hypoxia-induced polyubiquitination of DDX17 controls its dissociation from the pri-miRNA–Drosha–DCGR8 complex to reduce anti-stemness miRNA biogenesis and association with YAP and p300 to enhance transcription of stemness-related genes.

The discrimination of various sulfur -containing species helps us to deeply understand how sulfur affects cellular signaling and other physiological events. Herein, we present a three-dimensional sensor array based on simultaneous variation of the optical properties (fluorescence, light scattering, and UV–vis absorption) of gold–silver alloy nanocluster (AuAgNCs)–gold nanoparticle (AuNPs) composite for the rapid identification of 13 sulfur-containing species and sulfur-oxidizing bacteria. The sensor array is fabricated based on the strong coordination interactions between sulfur-containing compounds and AuAgNCs on the surface of AuNPs. The sulfur species of interest exhibit different affinities toward AuAgNCs and generate unique optical properties. These response patterns could divide the analytes into three categories including organic sulfide, inorganic sulfide, and thiols. Thirteen types of sulfur species including cystine, methionine, GSSG, S2–, SO32–, S2O32–, S2O72–, S2O82–, S4O62–, GSH, N-acetyl-l-c...

Two new lignans (1–2), along with five known compounds (3-7) with different structures were isolated from leaves and twigs of Cleistanthus concinnus Croizat. The new lignans were elucidated as (7′R,8′S)-3,3′,5′-trimethoxy-4,4′-dihydroxy-7-en-7′,9- epoxy-8,8′-lignan (1) and (7′R,8′S)-3,3′-dimethoxy-4,4′-dihydroxy-7-en-7′,9-epoxy-8, 8′-lignan (2) by comprehensive spectroscopic analysis including 1D and 2D NMR as well as HREIMS and comparing their NMR data with known compounds in the literature. Among these isolated compounds, compound 1, 2, 3, and 6 were tested for anti- inflammatory effects by inhibiting NO production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Compound 1, 2, and 6 exhibit NO inhibitory activity.

We report a new efficient analytical representation of the molar enthalpy for gaseous substances. The predicted molar enthalpy values are in good agreement with the experimental data in a wide temperature range for the gases Cl2, Br2, and gaseous BBr. The present enthalpy prediction model does not need of a great number of experimental spectroscopy data, and requires only three molecular constants, for which the experimental values can be easily obtained in the literature.

Connected and Autonomous Vehicles (CAVs) have been researched extensively for solving traffic issues and for realising the concept of an intelligent transport system. A well-developed positioning system is critical for CAVs to achieve these aims. The system should provide high accuracy, mobility, continuity, flexibility and scalability. However, high-performance equipment is too expensive for the commercial use of CAVs; therefore, the use of a low-cost Global Navigation Satellite System (GNSS) receiver to achieve real-time, high-accuracy and ubiquitous positioning performance will be a future trend. This research used RTKLIB software to develop a low-cost GNSS receiver positioning system and assessed the developed positioning system according to the requirements of CAV applications. Kinematic tests were conducted to evaluate the positioning performance of the low-cost receiver in a CAV driving environment based on the accuracy requirements of CAVs. The results showed that the low-cost receiver satisfied the “Where in Lane” accuracy level (0·5 m) and achieved a similar positioning performance in rural, interurban, urban and motorway areas.

Fundamental understanding of microRNA (miRNA) regulated cellular processes requires smart tools capable of imaging the expression and distribution of miRNAs in living cells. However, the low-expression of miRNA and a complex intracellular environment bring great challenges for intracellular miRNA imaging. We found that boron doped g-C3N4 nanosheets (BCNNS) are capable of binding copper nanocluster (CuNC)-labeled hairpin DNA and quench the fluorescence of CuNCs. A turn-on fluorescent sensor for the detection of miR-582-3p in living cells is thus developed based on the affinity change of BCNNS and DNA probes upon their recognition to the target. Ratiometric fluorescence measurement is achieved by taking advantage of the inherent fluorescence emission of BCNNS as the cell interior label. By combining the hybridization chain reaction (HCR) amplification and inherent sensitivity of a turn-on fluorescence sensing strategy, this approach gives rise to a limit of detection (LOD) of 49 fmol L-1 for miR-582-3p, within a linear range of 0.2-1 pmol L-1. The LOD is further improved to 12 fmol L-1 with a correlation to ICP-MS by measuring the 63Cu isotope. With the merits of high sensitivity and selectivity of the HCR and the anti-interfering capability of the ratiometric fluorescent probe, the single cell miR-582-3p expression levels are successfully detected, which indicated that this assay provides a sensitive and enzyme-free approach for miRNA imaging in living cells.

Functional implication of stromal heterogeneity in the prostate remains incompletely understood. Using lineage tracing and light-sheet imaging, we show that some fibroblast cells at the mouse proximal prostatic ducts and prostatic urethra highly express Lgr5. Genetic ablation of these anatomically restricted stromal cells, but not nonselective ablation of prostatic stromal cells, rapidly induces prostate epithelial turnover and dedifferentiation that are reversed following spontaneous restoration of the Lgr5

Background Mitochondrial electron transport chain abnormalities have been reported in postmortem pathological specimens of Alzheimer’s disease (AD). However, it remains unclear how amyloid and tau are associated with mitochondrial dysfunction in vivo. The purpose of this study is to assess the local relationships between mitochondrial dysfunction and AD pathophysiology in mild AD using the novel mitochondrial complex I PET imaging agent [18F]BCPP-EF. Methods Thirty-two amyloid and tau positive mild stage AD dementia patients (mean age ± SD: 71.1 ± 8.3 years) underwent a series of PET measurements with [18F]BCPP-EF mitochondrial function, [11C]PBB3 for tau deposition, and [11C] PiB for amyloid deposition. Age-matched normal control subjects were also recruited. Inter and intrasubject comparisons of levels of mitochondrial complex I activity, amyloid and tau deposition were performed. Results The [18F]BCPP-EF uptake was significantly lower in the medial temporal area, highlighting the importance of the mitochondrial involvement in AD pathology. [11C]PBB3 uptake was greater in the temporo-parietal regions in AD. Region of interest analysis in the Braak stage I-II region showed significant negative correlation between [18F]BCPP-EF SUVR and [11C]PBB3 BPND (R = 0.2679, p = 0.04), but not [11C] PiB SUVR. Conclusions Our results indicated that mitochondrial complex I is closely associated with tau load evaluated by [11C]PBB3, which might suffer in the presence of its off-target binding. The absence of association between mitochondrial complex I dysfunction with amyloid load suggests that mitochondrial dysfunction in the trans-entorhinal and entorhinal region is a reflection of neuronal injury occurring in the brain of mild AD.

Background: Performance evaluation is an important means to promote the hospital's medical ability and management ability. Therefore, the aim of this study was to explore the effect of DRG payment mode on the performance of inpatient services in large tertiary hospitals. Methods: Based on the relevant report data of DRG pilot hospital and control hospital from 2015 to 2020, CN-DRG was used as grouping method, and case mix index (CMI), DRG group number, cost consumption index, time consumption index, low-risk group mortality and other indicators were used to analyze the impact of DRG on hospital inpatient service performance from the aspects of medical service ability, medical service efficiency, medical safety. Results: The average annual growth rate of DRG group was 4.07%, the average annual growth rate of CMI was 0.95%, the time consumption index and cost consumption index were lower than 1, and the mortality rate of low-risk group decreased by 27.56%. Conclusions: DRG medical insurance payment can improve the performance of inpatient service in the process of hospital management.

Alzheimer’s disease biomarkers are primarily evaluated through MRI, PET and CSF methods in order to diagnose and monitor disease. Recently, advances in the assessment of blood-based biomarkers have shown promise for simple, inexpensive, accessible and minimally invasive tools with diagnostic and prognostic value for Alzheimer’s disease. Most recently, plasma phosphorylated tau181 has shown excellent performance. The relationship between plasma phosphorylated tau181 and cerebral metabolic dysfunction assessed by [18F]fluorodeoxyglucose PET in Alzheimer’s disease is still unknown. This study was performed on 892 older individuals (297 cognitively unimpaired; 595 cognitively impaired) from the Alzheimer’s Disease Neuroimaging Initiative cohort. Plasma phosphorylated tau181 was assessed using single molecular array technology and metabolic dysfunction was indexed by [18F]fluorodeoxyglucose PET. Cross-sectional associations between plasma and CSF phosphorylated tau181 and [18F]fluorodeoxyglucose were assessed using voxelwise linear regression models, with individuals stratified by diagnostic group and by β-amyloid status. Associations between baseline plasma phosphorylated tau181 and longitudinal (24 months) rate of brain metabolic decline were also assessed in 389 individuals with available data using correlations and voxelwise regression models. Plasma phosphorylated tau181 was elevated in β-amyloid positive and cognitively impaired individuals as well as in apolipoprotein E ε4 carriers and was significantly associated with age, worse cognitive performance and CSF phosphorylated tau181. Cross-sectional analyses showed strong associations between plasma phosphorylated tau181 and [18F]fluorodeoxyglucose PET in cognitively impaired and β-amyloid positive individuals. Voxelwise longitudinal analyses showed that baseline plasma phosphorylated tau181 concentrations were significantly associated with annual rates of metabolic decline in cognitively impaired individuals, bilaterally in the medial and lateral temporal lobes. The associations between plasma phosphorylated tau181 and reduced brain metabolism, primarily in cognitively impaired and in β-amyloid positive individuals, supports the use of plasma phosphorylated tau181 as a simple, low-cost, minimally invasive and accessible tool to both assess current and predict future metabolic dysfunction associated with Alzheimer’s disease, comparatively to PET, MRI and CSF methods., Graphical Abstract Graphical Abstract, Lussier et al. report that plasma phosphorylated tau181 is associated cross-sectionally with CSF phosphorylated tau181 and [18F]fluorodeoxyglucose PET in 823 individuals from the Alzheimer’s Disease Neuroimaging Initiative cohort. The authors also report a significant association between baseline plasma p-tau181 and longitudinal change in brain glucose metabolism indexed by [18F]fluorodeoxyglucose PET.

To investigate the effects of different surface treatments and adhesive self-etch functional monomers on the immediate repair bond strength and integrity of the repaired resin composite interface.Ninety-eight resin composite blocks made of a nanohybrid resin composite were randomly divided into seven groups, each with 14 blocks, including positive control group: non-conditioned surface, Group A1: Gluma Comfort Bond, Group A2: Gluma Comfort Bond and sandblasting, Group B1: Tokuyama Bond Force IITM adhesive system, Group B2: Tokuyama Bond Force IITM adhesive system and sandblasting, Group C: polishing, and Group D: sandblasting. Resin composite identical to the substrate was applied and the repaired specimens were subjected to shear bond strength (SBS) testing. Representative samples from all groups received scanning electron microscopy and surface profilometry to determine their mode of failure. The data were processed with SPSS 20.0 software package.SBS of Group D was significantly higher than that of positive control group (P0.05). SBS of Group A1, A2, B1 and B2 was significantly higher than that of Group C and D (P0.05). Comparison of SBS among Group B1, D and A1 showed no significant difference(P0.05). SBS between Group B2 and positive control group had no significant difference(P0.05). Except specimens with sandblasting and the use of TBF II system, SBS of positive control group was significantly higher than that of Group A1 and C(P0.05). The polished specimens had significantly more adhesive failures than those with sandblasted surfaces (P0.05). Specimens treated with polishing and Gluma Comfort Bond showed significantly more adhesive failures than those treated with polishing and TBF II system (P0.05). The sandblasted surfaces conditioned with TBF II showed significantly more cohesive failures than those treated with polishing and TBF II (P0.05). The sandblasted specimens provided significantly more irregular and rougher surface finish than the polishing technique (P0.05).Sandblasting of the composite substrate and the use of TBF II adhesive system shows the highest repair bond strength, higher adhesive interfacial failures and fewer cohesive failures; however, it is noteworthy that the composite substrate types yield statistically higher food residue rate, which results in poor oral hygiene maintenance. Therefore, the application of this repair protocol should match up with correct oral health behaviors.

Porcine epidemic diarrhea virus (PEDV) has become increasingly problematic around the world, not only for its hazards to livestock but also due to the possibility that it is a zoonotic disease. Although vaccine therapy has made some progress toward PEDV control, additional effective therapeutic strategies against PEDV are needed, such as the development of chemotherapeutic agents. The aim of this work was to identify novel anti-PEDV agents by designing and synthesizing a series of phenanthridine derivatives. Among them, three compounds (compounds 1, 2, and 4) were identified as potent anti-PEDV agents exhibiting suppression of host cell heat shock cognate 70 (Hsc70) expression. Mechanism studies revealed that host Hsc70 is involved in the replication of PEDV, and its expression can be suppressed by destabilization of the mRNA, resulting in inhibition of PEDV replication. Activity against PEDV in vivo in PEDV-infected piglets suggested that phenanthridine derivatives are the first host-acting potential anti-PEDV agents.

Our study details the stepwise evolution of gilteritinib resistance in FLT3-mutated acute myeloid leukemia (AML). Early resistance is mediated by the bone marrow microenvironment, which protects residual leukemia cells. Removing these supportive extrinsic ligands drives evolution of late, intrinsic resistance. Whole exome sequencing, CRISPR/Cas, metabolomics, proteomics, and pharmacologic approaches were used to mechanistically define both early and late resistance. Early resistant cells undergo metabolic reprogramming, grow more slowly, and are dependent upon Aurora kinase B (AURKB). Late resistant cells are characterized byexpansion of pre-existing NRAS mutant subclones and continued metabolic reprogramming. Our model closely mirrors the timing and mutations of AML patients treated with gilteritinib.Pharmacological inhibition of AURKB resensitized both early resistant cell cultures and primary leukemia cells from gilteritinib-treated AML patients. These findings support a combinatorial strategy to target early resistant AML cells with AURKB inhibitors and gilteritinib before the expansion of pre-existing resistance mutations occurs.

The V-Dem Dataset v11.1 covers 202 countries, with a year coverage: 1789-2020 483 V-Dem indicators, 82 indices and 5 high-level indices.

Bioglass-based material has been widely used in the field of biomedical science. In this study, the proper concentration of epigallocatechin-3-gallate (EGCG) for a mesoporous bioglass (MBG) scaffold was determined based on the sponge replication method. The fabrication procedure performed using a foam exchange technique resulted in an interconnected network of pores scaffolds with no cracks. In the minimum bactericidal concentrations of the bacteria assessed, the antibacterial concentration of EGCG against E. coli (200 &mu, g/mL) was higher than that against S. aureus (25 &mu, g/mL). The MBG and EGCG-MBG scaffolds exhibited excellent apatite mineralization and drug release abilities (the highest cumulative drug release from the EGCG-MBG scaffold was 75.37%). Thus, a 200 &mu, g/mL EGCG can prevent cell apoptosis and directly enhance cell proliferation. Hence, a low-dose EGCG-MBG scaffold is another option for bone recruitment material.

Pin1 is a peptidyl-prolyl isomerase that regulates the structure and function of eukaryotic RNA polymerase II (Pol II) through interaction with the C-terminal domain (CTD) of Rpb1, the largest subunit of Pol II. We demonstrated that this function is important for cellular response to oxidative stress in the fission yeast Schizosaccharomyces pombe. In response to oxidative stress, the Atf1 transcription factor targets Sty1, the mitogen-activated protein kinase (MAPK), to specific stress-responsive promoters. Anchored Sty1 recruits Pol II through direct association with Rpb1-CTD and phosphorylates the reiterated heptad sequence at Serine 5. Pin1 binds phosphorylated CTD to promote dissociation of Sty1 from it, and directly recruits Ssu72 phosphatase to facilitate dephosphorylation of CTD for transcription elongation. In the absence of Pin1, the association of Sty1-Atf1 with Rpb1 persists on stress-responsive promoters failed to generate transcripts of the corresponding genes effectively. The identified characteristic features of the fission yeast Pin1 are conserved in humans. We demonstrated that elevated Pin1 level in cancer cells might help to sustain survival under oxidative stress generated from their altered metabolic pathways. Together, these results suggest a conserved function of Pin1 in cellular response to oxidative stress among eukaryotic cells that might have clinical implication.

In recent years, α-glucosidase inhibitors (AGIs) have played a significant role in the treatment of type II diabetes (T2D), so it is necessary to develop a reliable and sensitive method to find new AGIs. Herein, we establish a novel method based on fluorescent carbon nitride nanoparticles (CNNPs) for the sensitive detection of the activity of α-glucosidase (α-glu) and the screening of its inhibitors. A CNNP-based fluorescent probe is synthesized from green raw materials, urea and lysine, by a one-pot method. In the presence of α-glu, the substrate 4-nitrophenyl-α-D-glucopyranoside (pNPG) is hydrolyzed to generate 4-nitrophenol (pNP), leading to the fluorescence (FL) quenching of CNNPs due to the inner filter effect (IFE). On the other hand, the activity of α-glu is inhibited after the addition of AGIs, which turns on the FL of CNNPs. In this way, the detection of α-glu activity and the screening of AGIs are achieved. The linear range is 1.25–10.00 U L−1 with a limit of detection as low as 0.17 U L−1 and the IC50 values of two typical inhibitors (gallic acid and acarbose) are 813 μM and 465 μM, respectively. The CNNP probe is further applied for the determination of α-glu activity in human serum samples with satisfactory results.

Background and Purpose: Humans have been fighting vitiligo for centuries but still being inferior due to the lack of efficiency drugs and therapies. While some research has implied the therapeutic potential of Wnt/β-catenin signalling on curing vitiligo but correlation mechanism is not clear and no Wnt-specific anti-vitiligo drug has been reported. Here, We identified how vitiligo could be treated by regulating Wnt and two lead compounds of new anti-vitiligo drugs have been found. Experimental Approach: Wnt agonists were rational synthesized and then be evaluated their effects on vitiligo in B16 cells and C57B/L mouse. Furthermore, Co-IP and Site-directed mutagenesis were employed to indicate the mechanism and the target of the compounds. Key Results: HCJA121 and HCJA404 could significantly promote the synthesis of melanin, restore the pigmented function of skin, and improve the symptoms of vitiligo. Mechanism studies indicated that HCJA121 and HCJA404 target the DAX domain of Axin by binding to LYS781 and LEU784 then potentiate the Axin-LRP6 association and eventually promoted melanogenesis. Conclusions and Implications: These findings imply an alternative regulatory mechanism of melanogenesis and the Axin protein could be a new target for anti-vitiligo agents which reveal a therapeutic strategy for vitiligo. Besides, HCJA121 and HCJA404 may represent potential compounds for vitiligo treatment.

Dysregulation of phosphorylation-mediated signaling drives the initiation and progression of many diseases. A substrate-specific kinase assay capable of quantifying the altered site-specific phosphorylation of its phenotype-dependent substrates provides better specificity to monitor a disease state. We report a sensitive and rapid substrate-specific kinase assay by integrating site-specific peptide reporter and multiple reaction monitoring (MRM)-MS platform for relative and absolute quantification of substrate-specific kinase activity at the sensitivity of nanomolar kinase and nanogram cell lysate. Using non-small cell lung cancer as a proof-of-concept, three substrate peptides selected from constitutive phosphorylation in tumors (HDGF-S165, RALY-S135, and NRD1-S94) were designed to demonstrate the feasibility. The assay showed good accuracy (15% nominal deviation) and reproducibility (15% CV). In PC9 cells, the measured activity for HDGF-S165 was 3.2 ± 0.2 fmol μg

Midgut microbiota can participate in the detoxification and metabolism processes in insects, but there are few reports on the relationship between midgut microbiota and insecticide resistance in mosquitoes. In this study, we performed metagenomic sequencing on a susceptible strain (SS), a field-collected Hainan strain (HN), and a deltamethrin-resistant strain (RR) of Culex pipiens quinquefasciatus to understand the diversity and functions of their midgut microbiota. The results revealed differences in midgut microbiota among the three strains of Cx. pipiens quinquefasciatus. At the phylum level, Proteobacteria was the most prominent, accounting for nearly 70% of their midgut microbes. At the genus level, Aeromonas made up the highest proportion. In addition, Aeromonas, Morganella, Elizabethkingia, Enterobacter, Cedecea, and Thorsellia showed significant differences between strains. At the species level, Bacillus cereus, Enterobacter cloacae complex sp. 4DZ3-17B2, Streptomyces sp. CNQ329, and some species of Pseudomonas and Wolbachia were more abundant in the two resistant strains. Principal component analysis (PCA) showed that the SS strain had significantly different metagenomic functions than the two deltamethrin-resistant strains (HN and RR strain). The HN and RR strains differed from the SS strain in more than 10 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The analysis of species abundance and functional diversity can provide directions for future studies.

BackgroundTo investigate the association of plasma pTau181, assessed with a new immunoassay, with neurodegeneration of white matter and gray matter cross-sectionally and longitudinally, in aging and Alzheimer’s disease.MethodsObservational data was obtained from the Alzheimer’s Disease Neuroimaging Initiative, in which participants underwent plasma assessment and magnetic resonance imaging. Based on their clinical diagnosis, participants were classified as cognitively unimpaired and cognitively impaired. Linear regressions and linear mixed-effect models were used to test the cross-sectional and longitudinal associations between baseline plasma pTau181 and neurodegeneration using voxel-based morphometry.ResultsWe observed a negative correlation at baseline between plasma pTau181 and gray matter volume in cognitively unimpaired individuals. In cognitively impaired individuals, we observed a negative association between plasma pTau181 and both gray and white matter volume. In longitudinal analyses conducted in the cognitively unimpaired group, plasma pTau181 was negatively correlated with gray matter volume, starting 36 months after baseline assessments. Finally, in cognitively impaired individuals, plasma pTau181 concentrations were negatively correlated with both gray and white matter volume as early as 12 months after baseline, and neurodegeneration increased in an incremental manner until 48 months.ConclusionsHigher levels of plasma pTau181 correlate with neurodegeneration and predict further brain atrophy in aging and Alzheimer’s disease. Plasma pTau181 may be useful in predicting AD-related neurodegeneration, comparable to positron emission tomography or cerebrospinal fluid assessment with high specificity for AD neurodegeneration.

BackgroundAlzheimer’s disease (AD) biomarkers are primarily evaluated through MRI, PET, and CSF methods in order to diagnose and monitor disease. Recently, advances in the assessment of blood-based biomarkers have shown promise for simple, inexpensive, accessible, and minimally invasive tools with diagnostic and prognostic value for AD. Most recently, plasma phosphorylated tau181 (p-tau181) has shown excellent performance. The relationship between plasma p-tau181 and cerebral metabolic dysfunction assessed by [18F]FDG PET in AD is still unknown.MethodsThis study was performed on a total of 892 individuals (297 cognitively unimpaired; 595 cognitively impaired) from the ADNI cohort. Plasma p-tau181 was assessed using single molecular array (Simoa) technology and metabolic dysfunction was indexed by [18F]FDG PET. Cross-sectional associations between plasma and CSF p-tau181 and [18F]FDG were assessed using voxelwise linear regression models, with individuals stratified by diagnostic group and by Aβ status. Associations between baseline plasma p-tau181 and longitudinal rate of brain metabolic decline were also assessed in a subset (n=389) of individuals using correlations and voxelwise regression models.ResultsPlasma p-tau181 was elevated in Aβ+ and cognitively impaired individuals as well as in APOE ε4 carriers, and was significantly associated with age, worse cognitive performance, and CSF p-tau181. Cross-sectional analyses showed strong associations between plasma p-tau181 and [18F]FDG PET in Aβ+ and cognitively impaired individuals. Voxelwise longitudinal analyses showed that baseline plasma p-tau181 concentrations were significantly associated with annual rates of metabolic decline only in cognitively impaired individuals, bilaterally in the medial and lateral temporal lobes.ConclusionsThe associations between plasma p-tau181 and reduced brain metabolism, primarily in cognitively impaired and in Aβ+ individuals, supports the use of plasma p-tau181 as a simple, low-cost, minimally invasive, and accessible tool to both assess current and predict future metabolic dysfunction associated with AD, comparatively to PET, MRI, and CSF methods.

A broad variety of unactivated acyclic and alicyclic substrates cleanly undergo site-selective alkenylation of unactivated C(sp

With the development of the urbanization process, the demand for water resources has increased significantly, but the pollution of water resources has caused serious problems. These changes pose a potential threat to water resource carrying capacity in many regions. However, how to determine the areas of highest risk in water resource carrying capacity is an urgent problem which remains to be solved. Resounding to these circumstances, this study establishes a TODIM-PROMETHEE Ⅱ (An acronym in Portuguese for interactive and multiple attribute decision making- preference ranking organization method for enrichment evaluation Ⅱ) based decision support framework to address this issue for the regions of intensive governance, thereby providing support. In this framework, a novel theoretical concept, namely probabilistic linguistic Z-numbers, is proposed to describe group decision information. The related knowledge of probabilistic linguistic Z-numbers is developed, including a comparison method, distance, and operational rules. Subsequently, a case study involving the evaluation of water resource carrying capacity is conducted to demonstrate the feasibility of the decision support model, followed by sensitivity analysis, comparison analysis, and discussion. The findings demonstrate that the constructed framework demonstrates great performance to address this issue.

Extracellular vesicles (EVs) are released by nearly all cell types as part of normal cell physiology, transporting biological cargo, including nucleic acids and proteins, across the cell membrane. In pathological states such as cancer, EV-derived cargo may mirror the altered state of the cell of origin. Exosomes are the smaller, 50–150 nanometer-sized EVs released from fusion of multivesicular endosomes with the plasma membrane. Exosomes play important roles in cell-cell communication and participate in multiple cancer processes, including invasion and metastasis. Therefore, proteomic analysis of exosomes is a promising approach to discover potential cancer biomarkers, even though it is still at an early stage. Herein, we critically review the advances in exosome isolation methods and their compatibility with mass spectrometry (MS)-based proteomic analysis, as well as studies of exosomes in pathogenesis and progression of prostate and bladder cancer, two common urologic cancers whose incidence rates continue to rise annually. As urological tumors, both urine and blood samples are feasible for noninvasive or minimally invasive analysis. A better understanding of the biological cargo and functions of exosomes via high-throughput proteomics will help provide new insights into complex alterations in cancer and provide potential therapeutic targets and personalized treatment for patients.