Synthesis of harmine-nitric oxide donor derivatives as potential antitumor agents.

To further improve the anti-tumor activity of Harmine (HM), we took the hybridization approach and synthesized harmine derivatives-furoxan hybrids containing nitric oxide (NO) releasing parts by connecting NO donors with anti-tumor active fragments to harmine. Then, the synthesized compounds were evaluated for their in vitro cytotoxicity against five human cancer cell lines. Among them, compound 10 was found to have the strongest antiproliferative activity against HepG2 (IC50 = 1.79 µM). In addition, compound 10 produced high levels of NO in vitro, verifying that the release of NO was closely correlated to the antiproliferative activity. In addition, Compound 10 also showed good plasma stability. Finally, we also preliminarily investigated the acute toxicity of compound 10 in mice and assessed the absorption of compound 10 by Caco-2 cell permeability assay. In brief, the remarkable biological characteristics of the new harmine derivatives-furoxan hybrids may make them promising candidates for human cancer intervention.

Modeling the Impacts of Manure on Phosphorus Loss in Surface Runoff and Subsurface Drainage.

Simulation of phosphorus (P) transfer from manured agricultural lands to water bodies via surface runoff and subsurface drainage is potentially of great help in evaluating the risks and effects of eutrophication under a range of best management practice scenarios. However, it remains a challenge since few models are capable of providing a reasonably accurate prediction of P losses under manure treatment. The Environmental Policy Integrated Climate (EPIC) model was applied to simulate the impacts on dissolved reactive P (DRP) losses through surface runoff and subsurface drainage from a solid cattle manure-amended corn ( L.)-soybean [ (L.) Merr.] rotation on a clay loam soil (Vertisol) located in the Lake Erie region. Simulations of DRP loss in surface runoff and tile drainage were satisfactory; however, EPIC did not consider DRP loss directly from manure, weakening its accuracy in the prediction of DRP loss in surface runoff. Having previously drawn on EPIC-predicted surface runoff to initiate SurPhos (Surface Phosphorus and Runoff Model) predictions of DRP losses strictly in surface runoff, no comparison had been made of differences in manure application impacts on EPIC- or SurPhos-predicted DRP losses-accordingly, this was assessed. The SurPhos improved the estimation of DRP loss in surface runoff (Nash-Sutcliffe coefficient, 0.53), especially when large rain events occurred immediately after or within 6 wk of manure application. Generally, EPIC can capture the impacts of manure application on DRP loss in surface runoff and subsurface drainage; however, coupling of the EPIC and SurPhos models increased the accuracy of simulation of runoff DRP losses.

Association between microRNA polymorphisms and chronic pancreatitis.

BACKGROUD: MicroRNAs play important roles in the development and progression of many human diseases. mir-146a could significantly suppress the induction of proinflammatory cytokines IL-1ß, IL-6, TNF-α, NF-κB and chemokine MCP-1, which might play important roles in chronic pancreatitis. This study was conducted to evaluate the association between mir-146a rs2910164, a functional polymorphism in the pre-mir-146a, and chronic pancreatitis risk. METHODS: The rs2910164 genotypes were determined in 165 patients with chronic pancreatitis and 200 healthy controls who were frequency matched for age and gender. One single nucleotide polymorphism (rs2910164) was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RLFP). RESULTS: The frequency of individuals who carried [G] allele was significantly higher in cases (62.7%) than in controls (53.7%, p = 0.015), which resulted in a statistically significant pathogenic effect associated with this variant allele (OR: 1.448, CI: 1.076-1.950; p = 0.015). The GC and GG genotypes showed strong and significant increased risk for complication of chronic pancreatitis (OR = 3.668, 95%CI = 1.233-10.916, p = 0.019; OR = 5.667, 95%CI = 1.852-17.336, p = 0.002). The individuals carrying G allele confer a lower expression level of mature mir-146a. CONCLUSION: These findings suggest that the mir-146a rs2910164 may contribute to genetic susceptibility to chronic pancreatitis, and that mir-146a might be involved in chronic pancreatitis development.

Multifunctional Biomimetic Composite Coating with Antireflection, Self-Cleaning and Mechanical Stability.

Antireflective and self-cleaning coatings have attracted increasing attention in the last few years due to their promising and wider applications such as stealth, display devices, sensing, and other fields. However, existing antireflective and self-cleaning functional material are facing problems such as difficult performance optimization, poor mechanical stability, and poor environmental adaptability. Limitations in design strategies have severely restricted coatings' further development and application. Fabrication of high-performance antireflection and self-cleaning coatings with satisfactory mechanical stability remain a key challenge. Inspired by the self-cleaning performance of nano-/micro-composite structure on natural lotus leaves, SiO2/PDMS/matte polyurethane biomimetic composite coating (BCC) was prepared by nano-polymerization spraying technology. The BCC reduced the average reflectivity of the aluminum alloy substrate surface from 60% to 10%, and the water contact angle (CA) was 156.32 ± 0.58°, illustrating the antireflective and self-cleaning performance of the surface was significantly improved. At the same time, the coating was able to withstand 44 abrasion tests, 230 tape stripping tests, and 210 scraping tests. After the test, the coating still showed satisfactory antireflective and self-cleaning properties, indicating its remarkable mechanical stability. In addition, the coating also displayed excellent acid resistance, which has important value in aerospace, optoelectronics, industrial anti-corrosion, etc.

High performance plant-derived thermoplastic polyester elastomer foams achieved by manipulating charging order of mixed blowing agents.

Plant-derived thermoplastic polyester elastomer (TPEE) is an environment friendly polymer known for its exceptional tear strength and mechanical properties, whose monomers are generated from crops. To prepare high-performance TPEE foams is still challenging due to the intrinsic shrinkage behavior. Herein, two microcellular foaming routes with different charging orders of mixed blowing agents, namely "CO2 firstly charging process (CO2-F-process)" and "N2 firstly charging process (N2-F-process)", were developed to elucidate the effects of mixed blowing agents on foaming behavior. Compared with the case in N2-F-process, more carbon dioxide and less nitrogen were adsorbed in CO2-F-process. Thus, TPEE foams prepared by N2-F-process show less shrinkage and higher creep recovery ratio than those prepared by CO2-F-process. Thanks to better structural stability and smaller shrinkage, TPEE foams prepared by N2-F-process exhibited enhanced strength and resilience. For the foams with similar density, compression strength can be increased by 52 %, and energy loss coefficient can be reduced to 50 %, by using N2-F-process. Thus, not only biomass TPEE foams with enhanced mechanical performance shows promising prospects in those areas that needs lightweight, insulation and high resilience, but also novel microcellular foaming technique with mixed blowing agents opens a new way for developing high-performance polymeric foams.

Preparation and In Vitro Characterization of Microneedles Containing Inclusion Complexes Loaded with Progesterone.

OBJECTIVE: In order to improve patient compliance and the ease of use during progesterone application, and to increase the clinical application of progesterone, progesterone was made into a microneedle. METHODS: Progesterone complexes were prepared using a single-factor and central composite design. In the preparation of the microneedles, the tip loading rate was used as an evaluation index. The selection of tip materials among the biocompatible materials of gelatin (GEL), hyaluronic acid (HA), and polyvinylpyrrolidone (PVP), and the use of polyvinyl alcohol (PVA) and hydroxypropyl cellulose (HPC) as backing layers, respectively, were carried out and the resulting microneedles were evaluated accordingly. RESULTS: The progesterone inclusion complexes prepared at a molar ratio of 1:2.16 progesterone and hydroxypropyl-ß-cyclodextrin (HP-ß-CD), a temperature of 50 °C, and reaction time of 4 h had high encapsulation and drug-loading capacities of 93.49% and 9.55%, respectively. Gelatine was finally chosen as the material for the preparation of the micro-needle tip based on the drug loading rate of the tip. Two types of microneedles were prepared: one with 7.5% GEL as the tip and 50% PVA as the backing layer, and one with 15% GEL as the tip and 5% HPC as the backing layer. The microneedles of both prescriptions exhibited good mechanical strength and penetrated the skin of rats. The needle tip loading rates were 49.13% for the 7.5% GEL-50% PVA microneedles and 29.31% for the 15% GEL-5% HPC microneedles. In addition, in vitro release and transdermal experiments were performed using both types of microneedles. CONCLUSION: The microneedles prepared in this study enhanced the in vitro transdermal amount of progesterone drug by releasing the drug from the microneedle tip into the subepidermis.

Luteolin inhibits triple-negative breast cancer by inducing apoptosis and autophagy through SGK1-FOXO3a-BNIP3 signaling.

Background: Triple-negative breast cancer (TNBC) is one of the most prominent neoplasm disorders and lacks efficacious treatments yet. Luteolin (3',4',5,7-tetrahydroxyflavone), a natural flavonoid commonly presented in plants, has been reported to delay the progression of TNBC. However, the precise mechanism is still elusive. We aimed to elucidate the inhibition and molecular regulation mechanism of luteolin on TNBC. Methods: The effects of luteolin on the biological functions of TNBC cells were first evaluated using the corresponding assays for cell counting kit-8 assay, flow cytometry, wound-healing assay, and transwell migration assay, respectively. The mechanism of luteolin on TNBC cells was then analyzed by RNA sequencing and verified by RT-qPCR, Western blot, transmission electron microscopy, etc. Finally, in vivo mouse tumor models were constructed to further confirm the effects of luteolin on TNBC. Results: Luteolin dramatically suppressed cell proliferation, invasion, and migration while favoring cell apoptosis in a dose- and time-dependent manner. In TNBC cells treated with luteolin, SGK1 and AKT3 were significantly downregulated while their downstream gene BNIP3 was upregulated. According to the results of 3D modeling, the direct binding of luteolin to SGK1 was superior to that of AKT3. The inhibition of SGK1 promoted FOXO3a translocation into the nucleus and led to the transcription of BNIP3 both in vitro and in vivo, eventually facilitating the interaction between BNIP3 and apoptosis and autophagy protein. Furthermore, the upregulation of SGK1, induced by luteolin, attenuated the apoptosis and autophagy of the TNBC. Conclusion: Luteolin inhibits TNBC by inducing apoptosis and autophagy through SGK1-FOXO3a-BNIP3 signaling.

A coupled Computational Fluid Dynamics and Wells-Riley model to predict COVID-19 infection probability for passengers on long-distance trains.

Coupled Wells-Riley (WR) and Computational Fluid Dynamics (CFD) modelling (WR-CFD) facilitates a detailed analysis of COVID-19 infection probability (IP). This approach overcomes issues associated with the WR 'well-mixed' assumption. The WR-CFD model, which makes uses of a scalar approach to simulate quanta dispersal, is applied to Chinese long-distance trains (G-train). Predicted IPs, at multiple locations, are validated using statistically derived (SD) IPs from reported infections on G-trains. This is the first known attempt to validate a coupled WR-CFD approach using reported COVID-19 infections derived from the rail environment. There is reasonable agreement between trends in predicted and SD IPs, with the maximum SD IP being 10.3% while maximum predicted IP was 14.8%. Additionally, predicted locations of highest and lowest IP, agree with those identified in the statistical analysis. Furthermore, the study demonstrates that the distribution of infectious aerosols is non-uniform and dependent on the nature of the ventilation. This suggests that modelling techniques neglecting these differences are inappropriate for assessing mitigation measures such as physical distancing. A range of mitigation strategies were analysed; the most effective being the majority (90%) of passengers correctly wearing high efficiency masks (e.g. N95). Compared to the base case (40% of passengers wearing low efficiency masks) there was a 95% reduction in average IP. Surprisingly, HEPA filtration was only effective for passengers distant from an index patient, having almost no effect for those in close proximity. Finally, as the approach is based on CFD it can be applied to a range of other indoor environments.

Inflight transmission of COVID-19 based on experimental aerosol dispersion data.

BACKGROUND: An issue of concern to the travelling public is the possibility of in-flight transmission of coronavirus disease 2019 (COVID-19) during long- and short-haul flights. The aviation industry maintains that the probability of contracting the illness is small based on reported cases, modelling and data from aerosol dispersion experiments conducted on-board aircraft. METHODS: Using experimentally derived aerosol dispersion data for a B777-200 aircraft and a modified version of the Wells-Riley equation we estimate inflight infection probability for a range of scenarios involving quanta generation rate and face mask efficiency. Quanta generation rates were selected based on COVID-19 events reported in the literature while mask efficiency was determined from the aerosol dispersion experiments. RESULTS: The MID-AFT cabin exhibits the highest infection probability. The calculated maximum individual infection probability (without masks) for a 2-hour flight in this section varies from 4.5% for the 'Mild Scenario' to 60.2% for the 'Severe Scenario' although the corresponding average infection probability varies from 0.1% to 2.5%. For a 12-hour flight, the corresponding maximum individual infection probability varies from 24.1% to 99.6% and the average infection probability varies from 0.8% to 10.8%. If all passengers wear face masks throughout the 12-hour flight, the average infection probability can be reduced by ~73%/32% for high/low efficiency masks. If face masks are worn by all passengers except during a one-hour meal service, the average infection probability is increased by 59%/8% compared to the situation where the mask is not removed. CONCLUSIONS: This analysis has demonstrated that while there is a significant reduction in aerosol concentration due to the nature of the cabin ventilation and filtration system, this does not necessarily mean that there is a low probability or risk of in-flight infection. However, mask wearing, particularly high-efficiency ones, significantly reduces this risk.

Modeling of phosphorus loss from field to watershed: A review.

Phosphorus (P) losses from nonpoint sources into surface water resources through surface runoff and tile drainage play a significant role in eutrophication. Accordingly, the number of studies involving the modeling of agricultural P losses, the uncertainties of such models, and the best management practices (BMPs) supported by the modeling of hypothetical P loss reduction scenarios has increased significantly around the world. Many improvements have been made to these models: separate manure P pools, variable source areas allowing the determination of critical source areas of P loss, analyses of modeling uncertainties, and understanding of legacy P. However, several elements are still missing or have yet to be sufficiently addressed: the incorporation of preferential flow into models, the modification of P sorption-desorption processes considering recent research data (e.g., pedotransfer functions for labile, active, or stable P, along with P sorption coefficients), BMP parameterization, and scale-up issues, as well as stakeholder-scientist and experimentalist-modeler interactions. The accuracy of P loss modeling can be improved by (a) incorporating dynamic P sorption-desorption processes and new P subroutines for direct P loss from manure, fertilizer, and dung, (b) modeling preferential flow, connectivity between field and adjacent water bodies, and P in-stream processes, (c) including an assessment of model uncertainty, (d) integrating field and watershed models for BMP calibration and scaling field results up to larger areas, and (e) building a holistic interaction between stakeholders, experimentalists, and modelers.

LncRNA SLCO4A1-AS1 promotes colorectal cancer cell proliferation by enhancing autophagy via miR-508-3p/PARD3 axis.

Aberrant expressions of various long non-coding RNAs (lncRNAs) have been involved in the progression and pathogenesis of various carcinomas. However, the expression and biological function of SLCO4A1-AS1 in colorectal cancer (CRC) remain poorly understood. Gain- and loss-of-function assays were applied to determine the roles of SLCO4A1-AS1 in autophagy and CRC progression. qRT-PCR and in situ hybridization (ISH) results showed that SLCO4A1-AS1 was positively associated with PARD3 expression in CRC tissues. In vitro and in vivo studies revealed that SLCO4A1-AS1 knockdown repressed cytoprotective autophagy as assayed by transmission electron microscopy (TEM), and inhibited cell proliferation by directly targeting partition-defective 3 (PARD3). Mechanistically, SLCO4A1-AS1 acted as a sponge of miR-508-3p, leading to upregulation of PARD3 and promotion of CRC cell proliferation. The current study demonstrates that the SLCO4A1-AS1/miR-508-3p/PARD3/autophagy pathway play a critical role in CRC cell proliferation, and might provide novel targets for developing therapeutic strategies for CRC.

Modeling phosphorus losses from soils amended with cattle manures and chemical fertilizers.

While applied manure/fertilizer is an important source of P loss in surface runoff, few models simulate the direct transfer of phosphorus (P) from soil-surface-applied manure/fertilizer to surface runoff. The SurPhos model was tested with 2008-2010 growing season daily surface runoff data from clay loam experimental plots subject to different manure/fertilizer applications. Model performance was evaluated on the basis of the coefficient of determination (R2), Nash-Sutcliffe efficiency (NSE), percent bias (PBIAS), and the ratio of the root mean square error to the standard deviation of observed values (RSR). The model offered an acceptable performance in simulating soil labile P dynamics (R2 = 0.75, NSE = 0.55, PBIAS = 10.43%, and RSR = 0.67) and dissolved reactive P (DRP) loss in surface runoff (R2 ≥ 0.74 and NSE ≥ 0.69) for both solid and liquid cattle manure, as well as inorganic fertilizer. Simulated direct P loss in surface runoff from solid and liquid cattle manure accounted for 39% and 40% of total growing season DRP losses in surface runoff. To compensate for the unavailability of daily surface runoff observations under snow melt condition, the whole four years' (2008-2011) daily surface runoff predicted by EPIC (Environmental Policy Integrated Climate) was used as SurPhos input. The accuracy of simulated DRP loss in surface runoff under the different manure/fertilizer treatments was acceptable (R2 ≥ 0.55 and NSE ≥ 0.50). For the solid cattle manure treatment, of all annual DRP losses, 19% were derived directly from the manure. Beyond offering a reliable prediction of manure/fertilizer P loss in surface runoff, SurPhos quantified different sources of DRP loss and dynamic labile P in soil, allowing a better critical assessment of different P management measures' effectiveness in mitigating DRP losses.

Ultrafiltration membrane fouling by extracellular organic matters (EOM) of Microcystis aeruginosa in stationary phase: influences of interfacial characteristics of foulants and fouling mechanisms.

This paper focused on the membrane fouling caused by extracellular organic matters (EOM) which was extracted from lab-cultured Microcystis aeruginosa in stationary phase. The characteristics of EOM such as molecular weight distribution, hydrophobicity and fluorescence were measured. It was found that high molecular weight (MW) and hydrophilic organics accounted for the major parts of algal EOM which was comprised of protein-like, polysaccharide-like and humic-like substances. Ultrafiltration (UF) experiments were carried out in a stirring cell and hydrophobic polyethersulfone (PES) membranes which carried negative charge were used. Prefiltration, calcium addition and XAD fractionation were employed to change the interfacial characteristics of EOM. Then the effects of these interfacial characteristics on flux decline, reversibility and mass balance of organics were compared. Algal EOM proved to cause serious membrane fouling during UF. The fraction of algal EOM between 0.45 µm and 100 kDa contributed a significant portion of the fouling. Hydrophobic organics in EOM tended to adhere to membrane surface causing irreversible fouling, while the cake layer formed by hydrophilic organics caused greater resistance to water flow due to hydrophilic interaction such as hydrogen bond and led to faster flux decline during UF. The results also indicated that the algal EOM was negatively charged and the electrostatic repulsion could prevent organics from adhering to membrane surface. In term of fouling mechanisms, cake layer formation, hydrophobic adhesion and pore plugging were the main mechanisms for membrane fouling caused by algal EOM.

Characterization of dissolved extracellular organic matter (dEOM) and bound extracellular organic matter (bEOM) of Microcystis aeruginosa and their impacts on UF membrane fouling.

Extracellular organic matter (EOM) of cyanobacteria was classified into the dissolved EOM (dEOM) which was released into culture solution and the bound EOM (bEOM) which surrounded the cells. The dEOM and bEOM extracted from Microcystis aeruginosa in stationary phase were used to study their characteristic differences and then their impacts on ultrafiltration (UF) membrane fouling. Component analyses showed that dEOM was comprised of proteins, polysaccharides and humic-like substances, while that bEOM contained only proteins and polysaccharides. Additionally, polysaccharides dominated in dEOM with a polysaccharide/DOC ratio of 1.11 mg mg(-1), while proteins were the primary components of bEOM with a protein/DOC ratio of 1.08 mg mg(-1). Results of size fractionation and XAD resin fractionation revealed that bEOM was mainly distributed in the high-MW and hydrophobic fractions, while that dEOM was more hydrophilic. Result of UF experiments indicated that dEOM which had a higher organic content and stronger hydrophilicity caused more severe flux decline and reversible fouling, and that bEOM led to slower flux decline but more irreversible fouling due to less electrostatic repulsive and more hydrophobic adhesion. The impacts of these two kinds of EOM on the UF fouling caused by cyanobacterial cells were also investigated. It was found that both flux decline and irreversible membrane fouling caused by the cells were aggravated when cells were together with EOM, especially for bEOM which might increase the surface hydrophobicity of the cells.

Hybrid process of BAC and sMBR for treating polluted raw water.

The hybrid process of biological activated carbon (BAC) and submerged membrane bioreactor (sMBR) was evaluated for the drinking water treatment from polluted raw water, with the respective hydraulic retention time of 0.5 h. The results confirmed the synergetic effects between the BAC and the subsequent sMBR. A moderate amount of ammonium (54.5%) was decreased in the BAC; while the total removal efficiency was increased to 89.8% after the further treatment by the sMBR. In the hybrid process, adsorption of granular activated carbon (in BAC), two stages of biodegradation (in BAC and sMBR), and separation by the membrane (in sMBR) jointly contributed to the removal of organic matter. As a result, the hybrid process managed to eliminate influent DOC, UV(254), COD(Mn), TOC, BDOC and AOC by 26.3%, 29.9%, 22.8%, 27.8%, 57.2% and 49.3%, respectively. Due to the pre-treatment effect of BAC, the membrane fouling in the downstream sMBR was substantially mitigated.