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Building sufficient recycled water infrastructure is an effective way to solve problems related to water shortages and environmental degradation, and is of great strategic significance for saving resources, protecting the ecological environment, and promoting sustainable social and economic development. Although recycled water is environmentally friendly, the public is still skeptical about its use, which has led to the failure of a large number of recycled water infrastructure investments; therefore, increasing the public’s willingness to re-use is critical for the construction of recycled water infrastructure. To identify the influence mechanism of user comments on public re-use behaviors, we conducted an eye-tracking experiment in China. The results demonstrated that (1) perceived usefulness, perceived quality, and perceived risk have significant impacts on the public’s willingness to buy; (2) user reviews can enhance the public’s perceived usefulness of recycled products and increase their willingness to buy; and (3) in the process of consumption, the public tends to pay attention to negative reviews, where user reviews alter the perceived risks and perceived prices of recycled products, thereby affecting the willingness to buy of consumers. This study provides a scientific reference for the construction of recycled water infrastructure and the further promotion of recycled water.

BackgroundPartial epithelial-mesenchymal transition (p-EMT) is a distinct clinicopathological feature prevalent in oral cavity tumors of The Cancer Genome Atlas. Located at the invasion front, p-EMT cells require additional support from the tumor stroma for collective cell migration, including track clearing, extracellular matrix remodeling and immune evasion. The pathological roles of otherwise nonmalignant cancer-associated fibroblasts (CAFs) in cancer progression are emerging.MethodsGene set enrichment analysis was used to reveal differentially enriched genes and molecular pathways in OC3 and TW2.6 xenograft tissues, representing mesenchymal and p-EMT tumors, respectively. R packages of genomic data science were executed for statistical evaluations and data visualization. Immunohistochemistry and Alcian blue staining were conducted to validate the bioinformatic results. Univariate and multivariate Cox proportional hazards models were performed to identify covariates significantly associated with overall survival in clinical datasets. Kaplan–Meier curves of estimated overall survival were compared for statistical difference using the log-rank test.ResultsCompared to mesenchymal OC3 cells, tumor stroma derived from p-EMT TW2.6 cells was significantly enriched in microvessel density, tumor-excluded macrophages, inflammatory CAFs, and extracellular hyaluronan deposition. By translating these results to clinical transcriptomic datasets of oral cancer specimens, including the Puram single-cell RNA-seq cohort comprising ~6000 cells, we identified the expression of stromal TGFBI and HYAL1 as independent poor and protective biomarkers, respectively, for 40 Taiwanese oral cancer tissues that were all derived from betel quid users. In The Cancer Genome Atlas, TGFBI was a poor marker not only for head and neck cancer but also for additional six cancer types and HYAL1 was a good indicator for four tumor cohorts, suggesting common stromal effects existing in different cancer types.ConclusionsAs the tumor stroma coevolves with cancer progression, the cellular origins of molecular markers identified from conventional whole tissue mRNA-based analyses should be cautiously interpreted. By incorporating disease-matched xenograft tissue and single-cell RNA-seq results, we suggested that TGFBI and HYAL1, primarily expressed by stromal CAFs and endothelial cells, respectively, could serve as robust prognostic biomarkers for oral cancer control.

The atmospheric partial pressure of CO2 (pCO2) has been increasing dramatically since the beginning of the industrial revolution and about 30% of the CO2 produced by anthropogenic activities was absorbed by the ocean. This led to a perturbation of the seawater carbonate chemistry resulting in a decrease of the average surface ocean pH by 0.1 and termed ocean acidification (OA). Projections suggest that pCO2 may reach 900 μatm by the end of the twenty-first century lowering the average pH of the surface ocean by 0.4 units. The negative impacts of OA on many species of marine invertebrates such as mollusks, echinoderms, and crustaceans are well documented. However, less attention has been paid to the impacts of low pH on fitness and immune system in crustaceans. Here, we exposed Pacific white shrimps to 3 different pHs (nominal pH 8.0, 7.9, and 7.6) over a 100-days experiment. We found that, even though there were no significant effects on fitness parameters (survival, growth and allometries between length and weight), some immune markers were modified under low pH. A significant decrease in total hemocyte count and phenoloxidase activity was observed in shrimps exposed to pH 7.6 as compared to pH 8.0; and phagocytosis rate significantly decreased with decreasing pH. A significant increase in superoxide production was also observed at pH 7.6 as compared to pH 8.0. All these results suggest that a 100-days exposure to pH 7.6 did not have a direct effect on fitness but lead to a modulation of the immune response.

The education community has gradually recognized the value of augmented reality (AR) technology and its positive impacts on student learning performance. Still, few studies have proposed specific solutions and results to confirm this phenomenon for first graders in English vocabulary learning. Hence, this research explores the effects of AR apps on first graders’ English learning motivation and performance in addition to analyzing the moderating effects of learning styles. For this purpose, the class was divided into the experimental group that used an AR app in learning and a control group that used traditional learning methods. A series of stochastics analyses were carried out. Based on the results, this study finds that incorporating AR apps into English vocabulary learning can significantly improve first graders’ motivation and English vocabulary learning performance. The study’s findings will be beneficial to educational practitioners and researchers in developing instructional theories, strategies, and materials and improving elementary students’ learning motivation and performance.

According to pigeon racing rules in Taiwan, the pigeon raiser must decide which juveniles will be chosen as soon as possible. Differentiating the sex of young pigeons based on appearances, and other traditional methods, can be time-consuming and require several pieces of equipment. Recombinase polymerase amplification (RPA) combined with a lateral-flow dipstick (LFD) could further simplify the presentation of amplification results. A designed reverse primer and probe were labeled with biotin and FAM (fluorescein), respectively, to serve as ligands in the LFD. With the addition of a designed forward primer, the RPA-LFD can be used to perform sex identification of pigeon DNA. The optimal conditions were determined to require at least 6.3 pg of the DNA template, a temperature of 37 °C, and a reaction time of at least 20 min. Under these conditions, the test band area on the strip appeared as a dark color if the sample contained female template DNA, whereas the male DNA samples did not produce any test signal in any of the conditions. The results of random samples using RPA-LFD under the optimal conditions agreed with the results of the same samples determined by PCR-agarose gel electrophoresis. The approach in this study represents a rapid and accurate method for pigeon sexing.

Plaque-type psoriasis is a common skin disorder. Tirbanibulin (KX01) is a new Src kinase inhibitor with potent antiproliferative activity against keratinocytes and has been approved for treatment of actinic keratosis. This Phase I study investigates the safety and activity of KX01 ointment in patients with plaque-type psoriasis. We recruited 28 patients from two medical centers in Taiwan. This study was performed in four stages. Double-blind treatments were randomized in stages I (KX01 0.01% + placebo, two rounds of two-week treatment) and II (KX01 0.1% + placebo, four weeks) and open-labelled in stages III (KX01 1%, five days) and IV (KX01 1%, five days weekly for four weeks). The safety, tolerability, KX01 concentration, target area score, physician global assessment, and disease relapse were determined. Most treatment-emergent adverse events were mild-to-moderate application site reactions. Three (50.0%) subjects from the stage IV group showed ≥50% reduction in the target area score (TAS50), while two subjects (33.3%) showed a clinically meaningful improvement in the physician global assessment score. KX01 0.01%, 0.1%, and 1% were safe and well-tolerated. KX01 1% at four weeks showed a promising activity for the treatment of plaque-type psoriasis.

(1) Background: Excessive use of chemical fertilizers accelerates soil acidification and increases greenhouse gas emissions. In this context, the farmland application of organic fertilizers not only reuses agricultural waste but also improves soil quality. (2) Methods: Two organic fertilizers made from chicken manure—G508 and G509—were field applied, implementing once or twice (denoted by X1 and X2, respectively) the recommended amount of nitrogen for three crops. In addition, an incubation experiment was conducted to assess the mineralization of the organic fertilizers. (3) Results: G508 did not undergo a composting process and, thus, had a higher content of nitrogen compared to G509. Therefore, although the soil properties improved under G509, the total mineral nitrogen released was lower than G508. Compared to chemical fertilizer treatment, the application of G508 and G509 increased the soil’s pH value, concentrations of organic matter, available phosphorus, and exchangeable concentrations of potassium, calcium, and magnesium. In addition, the crop yield under G508X2 treatment was even higher than that under chemical fertilizer treatment. (4) Conclusions: Although G508 and G509 were both processed using chicken manure, they exhibited different nutrient-release behaviors during mineralization and also had different influences on the soil properties and growth of the three crops.

The role of serum uric acid (SUA) in the role of advanced fibrosis is not fully explored. The study assesses the risk of advanced fibrosis according to SUA in an Asian population with a total of 3612 subjects enrolled in one health management center between 2006 and 2008. The fibrosis-4 score was used for the prediction of the high risk of advanced fibrosis. SUA scores higher than 7.6 mg/dL in men and 6.6 mg/dL in women were defined as hyperuricemia. A proportional odds model was used to assess cumulative risks of advanced fibrosis. The prevalence of high risk of advanced fibrosis was 2.5% in the hyperuricemia group and 0.6% in the normal SUA group (p < 0.001). After adjustment for confounding factors, the odds ratios (OR) for more severe advanced fibrosis were 1.37 (95% confidence interval [CI]: 1.07–1.78) in the hyperuricemia group. Hyperuricemia only increased the risk of advanced fibrosis in the non-T2DM group (OR, 1.29; 95% CI, 1.04 to 1.74) instead of T2DM group (OR, 1.85; 95% CI, 0.97 to 3.53). SUA is a risk factor for a higher risk of advanced fibrosis, with the disease likely progressing from a steatotic to a fibrotic picture. The focus should be more emphasized in non-T2DM groups.

Melanoma is a high-risk skin cancer because it tends to metastasize early and ultimately leads to death. In this study, we introduced a noninvasive multifunctional optical coherence tomography (MFOCT) for the early detection of premetastatic pathogenesis in cutaneous melanoma by label-free imaging of microstructures (i.e., providing the thickness and the scattering information) and microcirculation (i.e., providing depth-resolved angiography and lymphangiography). Using MFOCT-based approaches, we presented an in vivo longitudinal observation of the tumor microenvironment in Braf V600E/V600E;Pten−/− mice with inducible melanoma monitored for 42 days. Quantitative analysis of MFOCT images identified an increased number of lymphatic and vascular vessels during tumor progression and faster lymphangiogenesis (beginning on day 21) than angiogenesis (beginning on day 28) in the melanoma microenvironment. We further observed lymphatic vessel enlargement from the first week of melanoma development, implying tumor cells interacting with the vessels and increased likelihood of metastasis. MFOCT identified cutaneous melanoma‒associated angiogenesis and lymphangiogenesis before the possible visual perception of the tumor (≥42 days) and before metastasis could be diagnosed using micropositron emission tomography (35 days). Thus, the proposed quantitative analysis using MFOCT has the potential for early detection of cutaneous melanoma progression or prediction of metastatic melanoma in a mouse model. However, retrospective and extensive experiments still need to be performed in the future to confirm the value of MFOCT in clinical application.

Abstract Objective This study aimed to investigate the function and mechanism of neddylation of HDAC1 underlying drug resistance of AML cells. Methods Evaluation experiments of effects of HDAC1 on drug resistance of AML cells were performed with AML cell transfected with constructs overexpressing HDAC1 or multi-drug resistance AML cells transfected with siRNA for HDAC1 through observing cell viability, percentage of apoptotic cell, doxorubicin-releasing index and multidrug resistance associated protein 1 (MRP1) expression. Neddylation or ubiquitination of HDAC1 was determined by immunoprecipitation or Ni2+ pull down assay followed by western blot. The role of HDAC1 was in vivo confirmed by xenograft in mice. Results HDAC1 was significantly upregulated in refractory AML patients, and in drug-resistant AML cells (HL-60/ADM and K562/A02). Intracellular HDAC1 expression promoted doxorubicin resistance of HL-60, K562, and primary bone marrow cells (BMCs) of remission AML patients as shown by increasing cell viability and doxorubicin-releasing index, inhibiting cell apoptosis. Moreover, HDAC1 protein level in AML cells was regulated by the Nedd8-mediated neddylation and ubiquitination, which further promoted HDAC1 degradation. In vivo, HDAC1 overexpression significantly increased doxorubicin resistance; while HDACs inhibitor Panobinostat markedly improved the inhibitory effect of doxorubicin on tumor growth. Furthermore, HDAC1 silencing by Panobinostat and/or lentivirus mediated RNA interference against HDAC1 effectively reduced doxorubicin resistance, resulting in the inhibition of tumor growth in AML bearing mice. Conclusion Our findings suggested that HDAC1 contributed to the multidrug resistance of AML and its function turnover was regulated, at least in part, by post-translational modifications, including neddylation and ubiquitination.

Background: Epidemiological studies suggest that the risk of neurodevelopmental disorders such as autism spectrum disorder (ASD) and schizophrenia is increased by prenatal exposure to viral or bacterial infection during pregnancy. It is still unclear how activation of the maternal immune response interacts with underlying genetic factors to influence observed ASD phenotypes. Methods: The current study investigated how maternal immune activation (MIA) in mice impacts gene expression in the frontal cortex in adulthood, and how these molecular changes relate to deficits in cognitive flexibility and social behavior, and increases in repetitive behavior that are prevalent in ASD. Poly(I:C) (20 mg/kg) was administered to dams on E12.5 and offspring were tested for social approach behavior, repetitive grooming, and probabilistic reversal learning in adulthood (n = 8 vehicle; n = 9 Poly(I:C)). We employed next-generation high-throughput mRNA sequencing (RNA-seq) to comprehensively investigate the transcriptome profile in frontal cortex of adult offspring of Poly(I:C)-exposed dams. Results: Exposure to poly(I:C) during gestation impaired probabilistic reversal learning and decreased social approach in MIA offspring compared to controls. We found long-term effects of MIA on expression of 24 genes, including genes involved in glutamatergic neurotransmission, mTOR signaling and potassium ion channel activity. Correlations between gene expression and specific behavioral measures provided insight into genes that may be responsible for ASD-like behavioral alterations. Conclusions: These findings suggest that MIA can lead to impairments in cognitive flexibility in mice similar to those exhibited in ASD individuals, and that these impairments are associated with altered gene expression in frontal cortex.

Butyrate is widely accepted as a proliferation inhibitor in colon cancer but less thoroughly characterized in the colonic epithelium of objects with type 2 diabetes mellitus. The present study investigated the regulatory effect of butyrate on proliferation, the related molecule high-mobility group box 1 (HMGB1) and the receptor for advanced glycation end products (RAGE) in the colon of db/db type 2 diabetic model mice and non-cancerous NCM460 colon cells. Proliferation and the expression of HMGB1 and RAGE were increased and could be partially reversed by butyrate treatment in the colon of db/db mice, which were consistent in NCM460 cells under a high glucose state. In NCM460 cells, under the normal glucose state, proliferation increased by overexpression of HMGB1. Under a high glucose state, increased expression of HMGB1 was accompanied with a release from cell nuclei into the cytoplasm and extracellular matrix. Down-regulation of HMGB1 could lower the expression of RAGE and attenuate the abnormally increased proliferation. And overexpression of HMGB1 reversed the suppressing effect of butyrate on abnormally increased proliferation. Conclusively, butyrate suppressed the abnormally increased proliferation in colonic epithelial cells under diabetic state by targeting HMGB1. Keywords: Diabetes, Butyrate, Proliferation, HMGB1, Colonic epithelial cells

A series of AM60-1Ce-xCa (x=0, 0.5, 1.5, 2.5) magnesium alloys were prepared by gravity casting method and analyzed by means of XRD, DSC and SEM. The effects of Ca on normal temperature mechanical properties and high temperature creep behavior of alloys were characterized by tensile and constant creep test. Microstructure analysis indicated that Ca was preferentially combined with Al in the alloy to form the high melting point Al2Ca phase at the grain boundary. The addition of Ca can refine the crystal grains and reduces the content of β-Mg17Al12 phase. With the increase of Ca content in the alloy, Al2Ca phases at the grain boundary gradually changed to the network of lamellar structure, and replaced the β-Mg17Al12 phase as the main strengthening phase gradually. The creep resistance of the alloy continuously increases because the high-temperature stable phase Al2Ca firmly nailed at grain boundaries impedes the sliding of grain boundaries. However, when the addition of Ca was more than 1.5%, mechanical properties of the alloy started to decrease, which was probably due to the large amount of irregularly shaped Al2Ca phases at the grain boundary. Experimental results show that the optimal addition amount of Ca is 1.5wt.%.

The unknown two-dimensional obstacles, including different shapes, numbers, locations, and in the vicinity of the planning path for an outdoor quadrotor, are on-line detected by a 360-degree Li-Dar Sweep Scanse. Based on the comparison among detected triangles containing extreme points of each obstacle, the central orientation of the triangle with the maximum detected distance and the angle larger than the specific threshold is assigned to fly a specific distance for obstacle avoidance. Nevertheless, the quadrotor probably encounters a dead end and is then navigated to a specific altitude for the continuous procedure of obstacle detection. By on-line detection at different waypoints for the same obstacle, an obstacle mapping is also established by all the obstacle detections. Since the sensing signals of an outdoor quadrotor are easily affected by stochastic noise and the quadrotor is operated in “x” configuration, an extended Kalman filter based fuzzy tracking incremental control (EKF-FTIC) is employed to simultaneously execute the path tracking, obstacle avoidance, and target approach. Finally, the experiments with 5 unknown obstacles in the neighborhood of a planning path connecting start point with end point validate the effectiveness and feasibility of the proposed method.

Abstract Background To examine the influence of HOXD10 on the metabolism and growth of colon carcinoma cells by suppressing the RHOC/AKT/MAPK pathway. Methods Thirty-seven paired colon cancer and its adjacent samples from The Cancer Genome Atlas (TCGA) were analyzed. Chip Analysis Methylation Pipeline (ChAMP) analysis was employed for differential methylated points (DMPs) and the differential methylation regions (DMRs) screening. The HOXD10 mRNA expression and DNA methylation levels were detected by RT-PCR. The Cell proliferation, migration, invasion and apoptosis were respectively measured by MTT assay, transwell assay, wound healing assay and flow cytometry assay in carcinoma cell lines after treated with 5-aza-2′-deoxycytidine (5-Aza-dC) or transfected with HOXD10-expressing plasmid. The expression of HOXD10 and RHOC was revealed by immunohistochemistry in disparate differentiation colon carcinoma tissues, and the dephosphorylation of AKT and MAPK pathways were detected by RT-PCR and western blot. Results The bioinformatics analysis demonstrated that HOXD10 was hypermethylated and low-expressed in colorectal cancer tissues. The detection of RT-PCR indicated the similar results in colorectal cancer cell lines and tissues. The induction of demethylation was recovered by treatment with 5-Aza-dC and the HOXD10 in colorectal cancer cell lines was re-expressed by transfection with a HOXD10 expression vector. The demethylation or overexpression of HOXD10 suppressed proliferation, migration, invasion and promoted apoptosis in colorectal cancer cells. HXOD10 suppressed the tumor growth and detected an opposite trend of protein RHOC. AKT and MAPK pathways were notably inactivated after the dephosphorylation due to the overexpression of HOXD10. Conclusions HOXD10 was suppressed in colon adenocarcinoma cells, which down-regulated RHOC/AKT/MAPK pathway to enhance colon cancer cells apoptosis and constrain the proliferation, migration and invasion.

Macrophages are mainly active cells of the immune system and play a role in the defense of pathogens. However, the overactivation of macrophages by fatal pathogens can result in toxic responses. 2-hydroxyethyl methacrylate (HEMA), which is a hydrophilic monomer, is used in dental adhesive reagents and composite resins as well as biocompatible hydrogels. The mechanisms underlying the genotoxicity engendered by HEMA-induced apoptosis that leads to cytotoxicity remain unclear. Accordingly, this study was conducted to clarify such mechanisms. The results showed that HEMA induced cell toxicity in RAW264.7 macrophages depending on the concentration. A higher HEMA concentration was associated with a higher level of apoptosis and genotoxicity. Moreover, HEMA induced a concentration-dependent increase in mitochondrial dysfunction and the intrinsic caspase pathway, including the activation of caspase-3 and caspase-9. HEMA was also found to upregulate intracellular reactive oxygen species generation and to decrease the activity of antioxidant enzymes, including superoxide dismutase and catalase. Taken together, the mitochondrial-dependent intrinsic caspase pathway and intracellular reactive oxygen species accumulation were found to mediate HEMA-induced genotoxicity and apoptosis, leading to cytotoxicity in RAW264.7 macrophages.

Background: Ethyl carbamate (EC), a byproduct that naturally forms in fermented foods, can cause tumors and cell death and is classified as a probable human carcinogen (Group 2A). EC is naturally formed through the alcoholysis reaction between ethanol and carbamyl compounds. The major precursors and dominantly emerging stages of EC differ with disparate food types, including soy sauce. This work aimed to clarify the formation of EC and its influence factors throughout the soy sauce production process with or without high-pressure process (HPP) treatment. Methods: Tetragenococcus halophilus, Pediococcus acidilactici, Zygosaccharomyces rouxii, and Candida versatilis were added to soy sauce. The levels of citrulline and EC were measured, and a 16S and ITS assay investigated the microbiota. Results: L-citrulline production was found in each group after fermentation for one month. In addition, L-citrulline levels were generated the most in group D (500 MPa treated raw soy sauce with 12% saltwater and mixed fermentation bacteria, including T. halophilus,P. acidilactici,Z. rouxii, and C. versatilis) and group E (soy sauce fermentation with 12% saltwater without HPP treatment) compared to group F (soy sauce fermentation with 18% saltwater without HPP treatment). Conclusions: These results indicated that salt concentration and mixed fermentation bacteria (T. halophilus,P. acidilactici,Z. rouxii,C. versatilis) might not be major factors for L-citrulline production.

Nowadays, the grinding process is mostly automatic, yet post-grinding quality inspection is mostly carried out manually. Although the conventional inspection technique may have cumbersome setup and tuning processes, the data-driven model, with its vision-based dataset, provides an opportunity to automate the inspection process. In this study, a convolutional neural network technique with transfer learning is proposed for three kinds of inspections based on 750–1000 surface raw images of the ground workpieces in each task: classifying the grit number of the abrasive belt that grinds the workpiece, estimating the surface roughness of the ground workpiece, and classifying the degree of wear of the abrasive belts. The results show that a deep convolutional neural network can recognize the texture on the abrasive surface images and that the classification model can achieve an accuracy of 0.9 or higher. In addition, the external coaxial white light was the most suitable light source among the three tested light sources: the external coaxial white light, the high-angle ring light, and the external coaxial red light. Finally, the model that classifies the degree of wear of the abrasive belts can also be utilized as the abrasive belt life estimator.

Aortic valve rupture (AVR) due to blunt chest trauma is extremely rare in the pediatric population, and little attention has been paid to such damages. Early diagnosis of AVR may not be easy in patients with multiple competing injuries and poor acoustic windows. We report a case of delayed diagnosis of AVR in a 12-year-old boy after falling from a height of 15 meters, who presented with recurrent hemoptysis and ventilator dependence. This rare case highlights the importance of performing transesophageal echocardiography in trauma patients when the images of transthoracic echocardiography are suboptimal, especially for those presenting with signs and symptoms suggestive of heart failure. The overall prognosis of aortic valve replacement is good.

Despite the ability of combination antiretroviral therapy (cART) to increase the life expectancy of patients infected with human immunodeficiency virus (HIV), viral reservoirs persist during life-long treatment. Notably, two cases of functional cure for HIV have been reported and are known as the “Berlin Patient” and the “London Patient”. Both patients received allogeneic hematopoietic stem cell transplantation from donors with homozygous CCR5 delta32 mutation for an associated hematological malignancy. Therefore, there is growing interest in creating an HIV-resistant immune system through the use of gene-modified autologous hematopoietic stem cells with non-functional CCR5. Moreover, studies in CXCR4-targeted gene therapy for HIV have also shown great promise. Developing a cure for HIV infection remains a high priority. In this review, we discuss the increasing progress of coreceptor-based hematopoietic stem cell gene therapy, cART, milder conditioning regimens, and shock and kill strategies that have important implications for designing potential strategies aiming to achieve a functional cure for the majority of people with HIV.

Activation of the epidermal growth factor receptor (EGFR) is crucial for development, tissue homeostasis, and immunity. Dysregulation of EGFR signaling is associated with numerous diseases. EGFR ubiquitination and endosomal trafficking are key events that regulate the termination of EGFR signaling, but their underlying mechanisms remain obscure. Here, we reveal that ZNRF1, an E3 ubiquitin ligase, controls ligand-induced EGFR signaling via mediating receptor ubiquitination. Deletion of ZNRF1 inhibits endosome-to-lysosome sorting of EGFR, resulting in delayed receptor degradation and prolonged downstream signaling. We further demonstrate that ZNRF1 and Casitas B-lineage lymphoma (CBL), another E3 ubiquitin ligase responsible for EGFR ubiquitination, mediate ubiquitination at distinct lysine residues on EGFR. Furthermore, loss of ZNRF1 results in increased susceptibility to herpes simplex virus 1 (HSV-1) infection due to enhanced EGFR-dependent viral entry. Our findings identify ZNRF1 as a novel regulator of EGFR signaling, which together with CBL controls ligand-induced EGFR ubiquitination and lysosomal trafficking.

Objectives This study examined the associations between the Second-Generation Cessation Payment Scheme (SCPS) and the use of smoking cessation treatments. Furthermore, these associations were compared between light and heavy smokers in Taiwan.Design This study had a cross-sectional design.Setting Data were obtained from the Taiwan Adult Smoking Behaviour Surveillance System 2010–2011 and 2013–2014; data for each year consisted of a nationally representative sample of adults aged 18 years and older.Participants Current smokers who had either quit or made a serious attempt to quit smoking were selected for the analysis.Primary outcome measure The primary outcome measure was the use of a smoking cessation clinic or pharmacy in a twice daily to quit smoking.Results According to multivariate analysis, the SCPS was positively associated with the combined use of a smoking cessation clinic and a pharmacy (OR=3.947; 95% CI: 1.359 to 11.463) when individual-level predictors (gender, age, education level, marital status, monthly household income, daily cigarette consumption, smoking status and self-reported health) were controlled. Heavy smokers showed a significant increase in the sole use of a pharmacy (OR=1.676; 95% CI: 1.094 to 2.569) and combined use of a smoking cessation clinic and pharmacy (OR=8.984; 95% CI: 1.914 to 42.173) after the SCPS was introduced. In addition, when related factors were controlled, the use of smoking cessation services was more frequent among heavy smokers than light smokers, including any treatment (OR=1.594; 95% CI: 1.308 to 1.942), a smoking cessation clinic (OR=1.539; 95% CI: 1.232 to 1.922), a pharmacy (OR=1.632; 95% CI: 1.157 to 2.302) and the combination of a smoking cessation clinic and pharmacy (OR=4.608; 95% CI: 1.331 to 15.949) .Conclusions The SCPS subsidisation policy increased the use of smoking cessation treatments, particularly among heavy smokers.

BackgroundProcalcitonin (PCT) has been widely investigated as an infection biomarker. The study aimed to prove that serum PCT, combining with other relevant variables, has an even better sepsis-detecting ability in critically ill patients.MethodsWe conducted a retrospective cohort study in a regional teaching hospital enrolling eligible patients admitted to intensive care units (ICU) between July 1, 2016, and December 31, 2016, and followed them until March 31, 2017. The primary outcome measurement was the occurrence of sepsis. We used multivariate logistic regression analysis to determine the independent factors for sepsis and constructed a novel PCT-based score containing these factors. The area under the receiver operating characteristics curve (AUROC) was applied to evaluate sepsis-detecting abilities. Finally, we validated the score using a validation cohort.ResultsA total of 258 critically ill patients (70.9±16.3 years; 55.4% man) were enrolled in the derivation cohort and further subgrouped into the sepsis group (n = 115) and the non-sepsis group (n = 143). By using the multivariate logistic regression analysis, we disclosed five independent factors for detecting sepsis, namely, "serum PCT level," "albumin level" and "neutrophil-lymphocyte ratio" at ICU admission, along with "diabetes mellitus," and "with vasopressor." We subsequently constructed a PCT-based score containing the five weighted factors. The PCT-based score performed well in detecting sepsis with the cut-points of 8 points (AUROC 0.80; 95% confidence interval (CI) 0.74-0.85; sensitivity 0.70; specificity 0.76), which was better than PCT alone, C-reactive protein and infection probability score. The findings were confirmed using an independent validation cohort (n = 72, 69.2±16.7 years, 62.5% men) (cut-point: 8 points; AUROC, 0.79; 95% CI 0.69-0.90; sensitivity 0.64; specificity 0.87).ConclusionsWe proposed a novel PCT-based score that performs better in detecting sepsis than serum PCT levels alone, C-reactive protein, and infection probability score.

Background: Hepatectomy is one potential treatment for intrahepatic cholangiocarcinoma (IHCC). Recurrent rate is high after curative resection and most recurrences occur within residual liver parenchyma. The aim of this study was to elucidate the impact of different treatment modalities on recurrent diseases in patients with IHCC after primary liver resection. Methods: Between February 1999 and December 2015, we retrospectively identified patients who received curative resection for IHCC. Patients who experienced recurrences were included. Locoregional therapies included re-hepatectomy, radiofrequent ablation, and transhepatic arterial chemoembolization. These patients were categorized into three groups: intrahepatic recurrence without locoregional therapies (group A), intrahepatic recurrence with locoregional therapies (group B) and extrahepatic metastases (group C). Results: Forty-three patients were included and there were 12, 15, and 16 patients in groups A, B, and C, respectively. The median disease-free survival times were 8.3, 9.1, and 8.7 months in groups A, B, and C ( p = 0.099). The median after-recurrence overall survival times (period between recurrence and death/censor) were 6.4, 34.0, and 8.3 months in groups A, B, and C ( p = 0.001). Locoregional therapies showed favorable benefit in multivariant analysis (hazard ratio: 0.274, confidence interval: 0.083–0.908, p = 0.010). Conclusion: Locoregional therapies offered favorable benefits for patients with recurrent intrahepatic cholangiocarcinoma.

Rice planthoppers are common insect pests in Taiwan, and they have caused significant damage in the past. The majority of rice planthoppers have seen a drastic decline in their population since the mid-2000s, a trend that has anecdotally attributed to widespread and better pest control, as well as improved rice cultivation management. By analyzing 40 years of the airborne net trap data of rice planthoppers collected in Southwest Taiwan, it was found that the pests’ yearly population, computed with a logarithmic transformation, resembles a signature climate pattern in the global oceans with a robust multi-decadal variability. An ocean temperature-based index derived from the patterns of multi-decadal variability shows a marked resemblance with the population change of common rice planthoppers, with overlapping peaks during the 1990–2010 period. The climate dynamics associated with the regional weather pattern in the vicinity of Taiwan are discussed. Phase reversal of this multi-decadal climate variability in the future may produce favorable climatic conditions for the rice planthopper population to increase back to its historical levels.

Public rejection of recycled water hinders the application of recycled water use projects in green communities. An effective information outreach strategy could help to overcome this obstacle. This study used message frames and reference points as control variables to design experimental materials and conduct eye-movement experiments to determine the effect of different information promotion strategies. The results of the study show that: (1) compared with the loss frame, the gain-framed messages are more effective; (2) self-referencing messages are more suitable for recycled water use promotion than other-referencing messages; (3) message frame (gain vs. loss) and reference point (self vs. others) have an interactive effect on the public’s information cognitive behavior; (4) the average duration of fixations for advertising message plays an intermediary role in the path of message frame and reference point jointly influencing the public acceptance. This study provides managerial implications for determining information dissemination strategies for applying recycled water-use projects in green communities.

Sponge cities provide broad hydrological functions to alleviate urban flooding and other water-related problems in China. Conventional impervious paving cannot meet contemporary sustainable city goals. The permeable paving technology offers primary benefits such as increasing stormwater infiltration, drainage, purification, groundwater recharge, and microclimatic amelioration. Few studies have evaluated the embracive range of benefits and the social functions holistically. This study aimed to develop a comprehensive benefit evaluation system to cover a broad range of indicators. Nineteen indicators were selected based on the literature review, field studies, and research experience. Organized in a three-tiered hierarchical structure, they were divided into environmental, economic, and social benefits. A grey intuitionistic fuzzy comprehensive evaluation model was built by combining intuitionistic fuzzy analysis with a grey comprehensive evaluation. The computational tools could determine the differential weights of indicators and benefit scores. Taking an example of a permeable pavement project in Quanzhou City, the comprehensive benefits were assessed and validated using our evaluation model. The results show that (1) the comprehensive benefits of the project met the economic feasibility criteria with advantages over conventional paving; (2) the environmental benefits were prominently expressed; (3) the social benefits were assessed and confirmed. The results verified the feasibility and applicability of the quantitative-qualitative model. The method could permit the integrated and systematic benefit assessment of permeable paving designs. It also provides guidance and reference to evaluate the performance of permeable pavements and their comprehensive range of benefits. The findings could reference choosing and refining designs, optimizing the benefits, and promoting a science-oriented development of permeable paving.

Membrane fouling remains one of the most critical drawbacks in membrane filtration processes. Although the effect of various operating parameters—such as flow velocity, concentration, and foulant size—are well-studied, the impact of particle shape is not well understood. To bridge this gap, this study investigated the effect of polystyrene particle sphericity (sphere, peanut and pear) on external membrane fouling, along with the effect of particle charge (unmodified, carboxylated, and aminated). The results indicate that the non-spherical particles produce higher critical fluxes than the spherical particles (i.e., respectively 24% and 13% higher for peanut and pear), which is caused by the looser packing in the cake due to the varied particle orientations. Although higher crossflow velocities diminished the differences in the critical flux values among the particles of different surface charges, the differences among the particle shapes remained distinct. In dead-end filtration, non-spherical particles also produced lower flux declines. The shear-induced diffusion model predicts all five particle types well. The Derjaguin-Landau-Verwey-Overbeek (DLVO) and extended DLVO (XDLVO) models were used to quantify the interaction energies, and the latter agreed with the relative critical flux trends of all of the PS particles. As for the flux decline trends, both the DLVO and XDLVO results are in good agreement.

The population with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is increasing. However, no medicine is indicated for treating these diseases clinically nowadays. Therefore, there is an urgent need to develop a new drug to overcome NAFLD and NASH. Capillarisin, a 2-phenoxychromone originating from Artemisia capillaris Thunb., is well-known for its liver-protective effects. As a result, a series of 2-phenoxychromones was prepared and evaluated for its protective activity against lipid droplet formation in oleic acid (OA)-treated Huh7 cells by means of high-content screening. In the light of the results, the compounds with trimethoxy groups on the phenyl ring possessed better inhibitory properties against lipid accumulation in Huh7 cells, compared to other functional groups on the same ring. Nonetheless, the compounds with a hydroxy group at the C-5 position of the chromone exhibited apparent cytotoxicity. Finally, the active compound, 5,7-dimethoxy-2-(3,4,5-trimethoxyphenoxy)-chromen-4-one (7e), with an IC50 value of 32.2 ± 2.1 μM against lipid accumulation and no significant cytotoxicity, reduced the accumulation of lipid droplets by up-regulating peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α) to facilitate the catabolism of fat, which shows promise for further optimization to manage NAFLD and NASH.