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ABSTRACTThis study implemented a series of social work groups with physician lectures for new mothers in Shanghai, China, and evaluated the practice effects. Outcome data of the intervention (N = 84) and comparison (N = 38) groups were collected using the Maternal Social Support Scale before, immediately after, and three months after the intervention. Repeated measures analysis of variance was used to compare the service effects in different periods. The intervention group showed a significant increase in total social support in three dimensions (informational, emotional, and instrumental) immediately after the intervention. Informational and total social support increased significantly over time with no group effects.

In this study, crack-free composite coatings with ratios of 40%, 50%, and 60% WC10%-Ni60AA cermet/Inconel 718 were successfully prepared using laser directed energy deposition. WC10%-Ni60AA cermet, as a reinforced particle, consists of 10% tungsten carbide (WC) particles and 90% nickel-based alloy. The bottom layers of the composite coatings were metallurgically well-bonded with substrates. The microstructures of the middle and top layers exhibited a novel eutectic precipitate skeleton structure (Cr23C6 phase), accompanied by an embedded nano-precipitate (MC (M: Nb, Mo) phase). The proportion of the eutectic precipitate skeleton structure increased with an increase in cermet content; in particular, the 60% cermet/Inconel 718 coating exhibited the largest proportion of the skeleton structure, with an area density of 86.15%. An increase in the cermet content improved the grain refinement in the composite coating. Fine equiaxed crystals were obtained in the 60% cermet/Inconel 718 coating, in which the proportion of high-angle grain boundaries (>15°) was 85.7% and the average grain size was 35.77 μm. Furthermore, the hardness and wear resistance of the composite coatings improved as the cermet content increased. The average hardness of the 60% cermet/Inconel 718 coating was 503 HV0.1 and wear loss was 107.9 mg, thereby exhibiting the best wear resistance owing to the synergistic effects of precipitation strengthening, grain refinement strengthening, and dispersion strengthening (unmelted and retained WC particle). Adhesive and abrasive wear were dominant wear mechanisms in the 40% cermet/Inconel 718 coating, whereas oxidative wear and abrasive wear were dominant in the 50% and 60% cermet/Inconel 718 coatings.

An interfacial solar steam generation evaporator for seawater desalination has attracted extensive interest in recent years. Nevertheless, challenges still remain in relatively low evaporation rate, unsatisfactory energy conversion efficiency, and salt accumulation. Herein, we have demonstrated a biomimetic bilayer composite aerogel consisting of bottom hydrophilic and vertically aligned EVOH channels and an upper hydrophobic conical Fe3O4array. Thanks to the design merits, the 3D Fe3O4/V-EVOH evaporator exhibits a high evaporation rate of ∼2.446 kg m–2h–1and an impressive solar energy conversion efficiency of ∼165.5% under 1 sun illumination, which is superior to those of state-of-the-art evaporators reported so far. Moreover, the asymmetrical wettability not only allows the evaporator to self-float on the water but also facilitates the salt ion diffusion in the channels; thus, the evaporator shows no salt crystals on its surface and only a 6% decrease in evaporation performance even after the salt concentration increases from 0 to 10.0 wt %.

In recent years, live-cell-based drug delivery systems have gained considerable attention. However, shear stress, which accompanies blood flow, may cause cell death and weaken the delivery performance. In this study, we found that reducing cholesterol in macrophage plasma membranes enhanced their tumor targeting ability by more than 2-fold. Our study demonstrates that the reduced cholesterol level deactivated the mammalian target of rapamycin (mTOR) and consequently promoted the nuclear translocation of transcription factor EB (TFEB), which in turn enhanced the expression of superoxide dismutase (SOD) to reduce reactive oxygen species (ROS) induced by shear stress. A proof-of-concept system using low cholesterol macrophages attached to MXene (e.g., l-RX) was fabricated. In a melanoma mouse model, l-RX and laser irradiation treatments eliminated tumors with no recurrences observed in mice. Therefore, cholesterol reduction is a simple and effective way to enhance the targeting performance of macrophage-based drug delivery systems.

Skin aging is a systematic and complex process, mainly including intrinsic aging caused by time change and extrinsic aging caused by environmental factors. Photoaging caused by ultraviolet (UV) irradiation is the principle extrinsic factor of skin aging, which can directly or indirectly cause damage to DNA and other biomolecules, generate reactive oxygen species (ROS), and induce a decrease in collagen synthesis and other adverse effect. Herein, to address the causative factors and multiple side effects of skin photoaging, we constructed multifunctional peptide-melanin hybrid nanodots (PMHDs) to achieve multifaceted synergistic anti-skin aging by using melanin-like nanodots (MDs) and functional peptides as active motifs. Among them, the peptide has the activity of promoting collagen synthesis, while the MDs have the function of absorbing UV light and scavenging free radicals. Additionally, the MDs also act as a carrier to increase the cellular uptake of the peptide. The anti-photoaging effects of the PMHDs were systematically verified in a multidimensional manner at the biochemical, cellular and small animal levels, respectively.

With the accelerated operation of subway networks, the increasing number of subway transfer stations results in inefficient passenger travel. The target of this paper is to solve the research question of how to reduce transfer waiting time (TWTT) for heterogeneous passengers. The key problem is to determine the optimal concerted train timetable considering the transfer walking time (TWKT) of the passengers. On the basis of field survey data, the regression method was used to establish a TWKT prediction model for general passengers (G) and vulnerable passengers (V), including the elderly, passengers traveling with children, and those carrying large luggage. Afterward, a two-objective integer programming model was formulated to minimize the subway operating costs and TWTT for each group, in which V is given the priority weight to ensure social equity. The headway, loading capacity, and TWKT of heterogeneous passengers were set as optimization model constraints. A genetic algorithm (GA) was designed to find the optimal solution. A case study in which the Beijing Jianguomen Station was selected as the key transfer station was conducted to verify the performance of the proposed model. Key results show that the total TWTT for V and G can be reduced by 18.6% and 27.2%, respectively, with one train saved. Results of the parameter sensitivity analysis reveal the interconnection between the operating cost, heterogeneous passenger proportion, and transfer time. The proposed model can be used for improving transfer efficiency for passengers while considering the enterprise operating costs.

Byline: Jian. Ding, Qiu. Li, ShanShan. He, Jie. Xie, XiaoFei. Liang, Ting. Wu, Dan. Li Background: Developing the natural medicine that allow for the specific targeting cytotoxicity is a very [...]

When disasters, such as earthquakes and collapses, occur, rescuers must go deep into dangerous regions and rush to transport the wounded. Long-term rescue operations in dangerous environments challenge the rescuers’ physical strength and threaten their lives. We propose a human-body reconstruction method for autonomous rescue operations with a wounded rescue robot. This method constructs a human-body model that can support a robot’s autonomous rescue operations given limited scans of the injured. Most casualties lie on the ground in supine positions, so this scanning limit is typical. We propose a scanning viewpoint planning method using deep reinforcement learning and change the viewpoint with the help of a six-degree-of-freedom (DOF) robotic arm to obtain a complete scan of the visible surface. For successful autonomous casualty rescue, a robot must have access to a watertight human-body mesh with precise surfaces and associated semantics. To this end, we develop a neural network that predicts a completely clothed body mesh from visible point clouds. The results of experiments show that our method can reconstruct a watertight body mesh with accurate surfaces and human semantics to satisfy the needs of autonomous robotic casualty rescue operations under scanning limitations.

Balancing the tradeoff between economy, energy, environment, water resources and carbon emissions has become the major challenge for sustainable development. In this study, a fuzzy multi-objective method is developed by integrating multi-objective programming, fuzzy linear programming and multiple scenarios. The developed approach can tackle multiple uncertainties and complexities existing in economy–energy–environment system, random carbon dioxide emission and water consumption control policies mix. Results disclose that (1) policy orientation and carbon emission control policy can achieve both carbon and water resource control goals, and water resource control policies are relatively unnecessary; (2) the tertiary sector will become the leading industry, accounting for more than three quarters of the total output value, the construction industry will also overgrow, and the proportion of the manufacturing industry will drop significantly; (3) coal still dominates in the energy production and total quantity consumed, and petroleum consumption will fall, coal accounts for about 75 percent of total energy consumption and electricity for about 15 percent; (4) according to different sources, carbon dioxide emissions are mainly from coal and electricity utilization. Coal’s contribution gradually rose to 65 percent, while electricity dropped from 35 percent to 30 percent. For each industry, the mining industry, the electricity industry and the tertiary sector are the primary sources. (5) the sulfur dioxide control policy and carbon dioxide control policy has a strong correlation, and nitrogen oxide control policies have a specific correlation with them. The water resource control policy and particulate matter control policy are relatively independent.

Additive manufacturing enables the development of high-performance materials by in-situ alloying of multiple components. In this study, Inconel 718-based composite, reinforced with tungsten carbide (WC), was synthesized on a 316L stainless steel substrate using laser directed energy deposition (DED). The microstructural evolution, distribution density of WC particles, and strengthening mechanisms of the DED-processed metal matrix composite (MMC) with different WC particle sizes and ratios are systematically investigated. It illustrated that increasing laser power enables the microstructure transforming from equiaxed to dendritic, which is attributed to the different cooling rates and temperature gradients. In addition, the morphology of the 60% WC ratio of the particle composite shows macrocracks. The incorporation of different sized WC affects retained WC distribution density and tailors a gradient layer around the edge of the WC particle. The in-situ WC-W2C phases precipitated in the deposited layer and the evenly distributed high level of ex-situ retained WC particles induce solid solution strengthening and dispersion strengthening, respectively. As a result, the optimal size of the 90 μm WC/Inconel 718 shows the highest wear resistance. The underlying strengthening mechanisms are elucidated. Consequently, the wear mechanism of Inconel 718-based composite reveals the typical abrasive wear characteristics in the presence of WC particles.

Computing metasurfaces are two-dimensional artificial nanostructures capable of performing mathematical operations on the input electromagnetic field, including its amplitude, phase, polarization, and frequency distributions. Rapid progress in the development of computing metasurfaces provide exceptional abilities for all-optical image processing, including the edge-enhanced imaging, which opens a broad range of novel and superior applications for real-time pattern recognition. In this paper, we review recent progress in the emerging field of computing metasurfaces for all-optical image processing, focusing on innovative and promising applications in optical analog operations, image processing, microscopy imaging, and quantum imaging.

The development of wireless monitoring is currently restricted by the short lifetime of batteries, requiring frequent replacement. Utilization of abundant mechanical energy from the surrounding environment has attracted increasing attention in real-time monitoring. Herein, a coil-levitated hybrid generator was developed for the efficient harvesting of mechanical energy from mechanical motion. The novel coil-levitated structure adapted to the metal and magnetic environment. The output currents were systematically analyzed at different operation modes based on the unique combination of triboelectrification, electromagnetic induction, and piezoelectric effect. Under the excitation of vibration frequency and amplitude of 8 Hz and 5 mm respectively, the as-constructed triboelectric nanogenerator delivered a peak power density of 11.40 W/m3at 10 MΩ. Meanwhile, the middle electromagnetic part and bottom piezoelectric generator provided peak power densities of 6.97 and 79.93 W/m2at 10000 Ω, respectively. More importantly, the battery charging experiment was verified, in which a 30 mA h Li-ion battery can be charged from 2.57 to 3.27 V in about 90 min. In sum, a self-powered temperature and vibration monitoring system was successfully developed based on hybrid generator, promising for realizing wireless monitoring of mechanical equipment without any external power supply.

The linear robot path is tangential and curvature discontinuity, which will lead to vibration and unnecessary hesitation during execution. Local corner transition method and local spline interpolation method are used in state-of-art industrial robot controller to reduce vibration, while local corner transition method cannot interpolate target points and local spline interpolation method cannot constrain chord errors. This research proposes a robot path local interpolation method that eliminates deficiencies of each method. The smoothing method satisfies all of the following requirements: G1continuity, target point interpolation and chord tolerance confined, shape-preserving (free of self-intersection), and unified parameterization. The generated smooth path consists of linear path and circular arc path with G1continuity. A geometric iterative method cooperating with local corner transition method is used to generate local interpolation path. Simulations and actual experiments verify the generated smooth path is G1continuous, tolerance constrained, shape-preserving, and have high computational efficiency.

Enhancing the monodispersity and surface properties of nanoporous zeolitic imidazolate frameworks (ZIFs) are crucial for maximizing their performance in advanced nanocomposites for separations. Herein, we developed an in situ method to synthesize monodispersed ZIF-8 nanocrystals with unique dopamine (DA) surface decoration layer (ZIF-8-DA) in an aqueous solution at room temperature. Interestingly, the in situ formation of the monodispersed ZIF-8-DA nanocrystals experiences a triple-stage crystallization process, resulting in a rhombic dodecahedron architecture, which is greatly different from the synthesis of conventional ZIF-8. The crystallinity and abundant microporosity of ZIF-8-DA nanocrystals is well maintained even with the DA surface decoration. Owing to the advanced surface compatibility and pore properties of ZIF-8-DA, ZIF-8-DA/Matrimid mixed-matrix membranes exhibit both higher gas permeability and selectivity than the pristine Matrimid polyimide membrane, which breaks out the traditional “trade-off” phenomena between permeability and selectivity.

ObjectiveTo explore the impact of the dietary patterns of truck drivers on their driving behaviours and the mediation effect of fatigue between these factors.MethodsA sample of 389 male truck drivers from a transport company in Suzhou, China completed the Food Frequency Questionnaire (FFQ), the Multidimensional Fatigue Inventory (MFI), the Positive Driver Behaviours Scale (PDBS) and the Driver Behaviour Questionnaire (DBQ). The associations among dietary patterns, fatigue and driving behaviour were examined using pathway analysis.ResultsFour dietary patterns were identified based on principal component analysis: animal-derived foods, staple foods, snacks and vegetables. The pathway analysis showed that the vegetable-rich pattern had a direct positive impact on positive driving behaviour (β=0.211, p<0.001); the animal-derived pattern had a direct positive impact on errors (β=0.094, p<0.05) and ordinary violations (β=0.071, p<0.05); the snacks pattern had a direct negative impact on positive driving behaviour (β=−0.191, p<0.001); fatigue mediated the effect of dietary patterns on driving behaviours (p<0.001); and the staple foods had an indirect effect on driving behaviours.ConclusionsOverall, the driving behaviours of truck drivers are correlated with their dietary patterns. Drivers who preferred vegetables and staple foods had more positive driving behaviour, while the animal-derived food and snack patterns were related to dangerous driving behaviour. The experience of fatigue could explained the underlying mechanism between these factors.

In this article, the entire removal process was based on a cycle absorption system in which a primary-absorber was used to scrub SO2by urea, then residual NO and SO2could be oxidized by the vaporized H2O2/catalysts in the catalytic system, and finally, the soluble gaseous pollutants and the remaining gaseous oxidants were absorbed by ammonium sulfite that was produced from the primary-absorber. The complex catalysts formed by iron recovery from the bauxite residue (red mud) were restructured with adenosine triphosphate (ATP) to generate mesopores with surface-active sites (FeOH) for efficient H2O2catalysis. Further, 95.2% SO2and 88.6% NO were removed from flue gas under the operation conditions where SO2concentration was 2000 ppm, NO concentration was 500 ppm, O2concentration was 7%, CO2concentration was 10%, catalytic temperature was 140 °C, H2O2feeding rate was 1.5 mL/h, and the total gas flow rate was 1.5 L/min. The results suggested that the catalytic performance is closely related to the structure of support ATP, which was elucidated by a series of experiments in different Fe loadings and BET characterization. From electron spin resonance (ESR) results, H2O2generally decompose not only into the •OH free radical by iron oxide but also into •HOO and related reactive oxygen species. According to the results of X-ray photoelectron spectroscopy (XPS) and temperature-programmed reduction (TPR), the content of FeOH and lattice oxygen in the modified ATP catalyst played an important role in the adsorption of H2O2on the protonated surface of the low-acid catalyst. Furthermore, the rational catalytic mechanism of catalyst/H2O2at low and high temperatures (corresponding to 140 and 200 °C) was proposed by transient response experiments.

Unlike the conventional spin Hall effect of light (SHEL) originating from the light-matter interaction, the spin-dependent splitting in the geometric SHEL is purely a geometric effect and independent from the properties of matter. Here it is shown that the geometric SHEL is not only of fundamental theoretical interest in understanding the spin-orbit interaction of light, but also sheds light on important technological applications. This Letter describes the theoretical foundation and experimental realization of optical differential operation and one-dimensional edge detection based on the geometric SHEL.

Fluorescence correlation spectroscopy (FCS) encodes the information on the equilibrium constant (K), the relative fluorescence brightness of fluorophore (Q), and the forward and backward reaction rate constants (k+and k–) on a physical or chemical relaxation. However, it has been a long-standing problem to completely resolve the FCS data to get the thermodynamic and kinetic information. Recently, we have solved the problem for fluorescence autocorrelation spectroscopy (FACS). Here, we extend the method to fluorescence cross-correlation spectroscopy (FCCS), which appears when FCS is coupled with fluorescence resonance energy transfer (FRET). Among 12 total second-order and third-order pre-exponential factors in a relaxation process probed by the FRET-FCS technique, 3 are independent. We presented and discussed 3 sets of explicit solutions to use these pre-exponential factors to calculate Kand Q. Together with the relaxation time, the acquired Kwill allow people to obtain k+and k–, so that the goal of deciphering the FRET-FCS data will be fully reached. The theory is verified by extensive computer simulations and tested experimentally on a system of oligonucleotide hybridization.

To improve airflow injection capacity of the main nozzle and decrease backflow phenomenon, a new main nozzle structure with two throats is designed. Negative pressure value and negative pressure zone length are first proposed evaluating the strength of backflow phenomenon. Commercial computational fluid dynamic (CFD) code “Fluent” is performed to simulate the flow field inside and outside the main nozzle. Exit velocity increases about 10 m/s in new main nozzle. Airflow core length of the new main nozzle is 35% higher than that of commonly used main nozzle. Smaller negative pressure value and shorter negative pressure zone length mean a weaker backflow phenomenon in the new main nozzle. Bigger air drag force indicates stronger weft insertion ability in the new main nozzle.

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We propose a simple, efficient, and fast tunable method to generate arbitrary vector vortex beams on the hybrid-order Poincaré sphere in an electrically driven way. The scheme incorporates the tunability and switching capabilities of liquid crystals into dielectric metasurfaces to form an efficient vector vortex beam generator. By applying certain voltages on the liquid crystal phase retarder, the generator converts a linearly polarized Gaussian beam into any desirable vector vortex beams. We demonstrate that the evolution route of the corresponding vector vortex states is just a closed circuit on the hybrid-order Poincaré sphere when the phase retardation varies from 0 to 2π. Several special cases are selected to demonstrate our scheme, and the experimental results coincide well with the theoretical predictions.

Hepatitis B, one of the most common contagious viral hepatitis with high infection rate, is challenging to treat. Although the treatment for hepatitis B has been improved over the years, many therapeutic drugs still have either severe adverse effects or insufficient effectiveness via systemic administration. In this study, we confirmed that glycyrrhetinic acid can enhance the accumulation of entecavir in HepaRG cell and liver. Then we constructed a novel albumin nanoparticle co-loading entecavir and glycyrrhetinic acid (ETV-GA-AN) to improve liver accumulation of entecavir and investigated its ability to deliver both drugs to liver. In vitrocellular uptake study and in vivotissue distribution experiment showed that these negatively charged ETV-GA-AN (112 ± 2 nm in diameter) can increase the accumulation of entecavir in hepatic HepaRG cells and improve entecavir distribution in liver. We also revealed the mechanism that glycyrrhetinic acid enhances intracellular accumulation of entecavir by inhibiting the activity of specific efflux transporters. Our delivery system is the first liver-targeted albumin nanoparticle that utilizes the site-specific co-delivery strategy to delivery entecavir and glycyrrhetinic acid. As it combines high efficiency and low toxicity, it possess great potential for treating hepatitis B.

Many web applications suffer from various web attacks due to the lack of awareness concerning security. Therefore, it is necessary to improve the reliability of web applications by accurately detecting malicious URLs. In previous studies, keyword matching has always been used to detect malicious URLs, but this method is not adaptive. In this paper, statistical analyses based on gradient learning and feature extraction using a sigmoidal threshold level are combined to propose a new detection approach based on machine learning techniques. Moreover, the naïve Bayes, decision tree and SVM classifiers are used to validate the accuracy and efficiency of this method. Finally, the experimental results demonstrate that this method has a good detection performance, with an accuracy rate above 98.7%. In practical use, this system has been deployed online and is being used in large-scale detection, analysing approximately 2 TB of data every day.

Membrane technology has been considered a promising strategy for carbon capture to mitigate the effects of increasing atmospheric CO2levels because CO2-philic membranes have demonstrated significant application potential, especially, for CO2/light gas separation. In this regard, poly(ethylene oxide) (PEO), which is a representative CO2-philic material, has attracted extensive research attention owing to its specific dipole–quadrupole interaction with CO2. Herein, we report a facile one-step synthesis protocol via the in situpolymerization of highly flexible polyethylene glycol to overcome the limitations of PEO, including high crystallinity and poor mechanical strength. The robust structure derived from intricate entanglements between short PEO chains and the polymer matrix enables an extremely high loading of linear polyethylene glycol (up to 90 wt%). Consequently, the separation performance easily surpasses the upper-bound limit. Moreover, the high structural stability allows for the concurrent increase of CO2permeability and CO2/light gas selectivity at high feed pressure (up to 20 bar (1 bar = 105Pa)). This study provides a promising strategy to simultaneously improve the toughness and gas separation properties of all-polymeric membranes, demonstrating significant potential for industrial carbon capture and gas purification.

Lysozyme, as widely used bacteriostatic enzyme, the rapid and low-cost isolation of lysozyme with high purity was the basis and premise of its application. In this work, a facile approach of spray coating was proposed to engineer composite membranes consisted of sulfonated polystyrene microspheres and poly(ethylene vinyl alcohol) nanofibers. The sulfonic acid groups offer strong interaction between the ligand and lysozyme, endowing high lysozyme adsorption capacity. And simultaneously, the porous channels of nanofibrous membranes guarantee high water flux. The FTIR and XPS results indicate the incorporation of sulfonated polystyrene spheres. The EVOH/SPS composite membranes exhibit both high water permeability and lysozyme adsorption capacity. Importantly, the constructed chromatography columns possess high performance of water flux with 9172 L h−1 m−2, and excellent adsorption capacity at static and dynamic state, revealing enormous potential for application.

Background Direct-acting antivirals (DAAs) have greatly improved the treatment of HCV infection. To improve response and prevent resistance, combination regimens have been the focus of clinical development. Regimens are often first assessed in vitro, with most combination studies to date using subgenomic replicon systems, which do not replicate the complete HCV life cycle and preclude study of entry and assembly inhibitors. Infectious full-length HCV systems have been developed and are being used to test drug efficacy.Methods Using cell-based HCV Con1b replicon and an infectious full-length HCV (HCVcc-Luc) infection system, we systematically tested the synergy, additivity or antagonism of combinations of protease, NS5A and nucleotide NS5B inhibitor classes as well as the combination of these DAAs with host-targeting agent cyclosporin A or non-antibody entry inhibitor (S)-chlorcyclizine. Two computational software packages, MacSynergyII and CalcuSyn, were used for data analysis.Results Combinations between different classes showed good consistency across the two viral assay systems and two software platforms. Combinations between NS5A and nucleotide NS5B inhibitors were synergistic, while combinations of protease inhibitors with the other two classes were additive to slightly antagonistic. As expected, combinations of antivirals of the same class were additive. Combination studies between these DAA classes and cyclosporin A or (S)-chlorcyclizine demonstrated additive to synergistic effects and highly synergistic effects, respectively. Combinations of these drugs did not show any added or unexpected cytotoxicity.Conclusions Our results show that in vitrocombination studies of anti-HCV DAAs in the HCVcc system may provide useful guidance for drug combination designs in clinical studies. We also demonstrate that these DAAs in combination with host-targeting agents or entry inhibitors may improve HCV treatment response.

Piecewise linear (G01-based) tool paths generated by CAM systems lack G1and G2continuity. The discontinuity causes vibration and unnecessary hesitation during machining. To ensure efficient high-speed machining, a method to improve the continuity of the tool paths is required, such as B-spline fitting that approximates G01 paths with B-spline curves. Conventional B-spline fitting approaches cannot be directly used for tool path B-spline fitting, because they have shortages such as numerical instability, lack of chord error constraint, and lack of assurance of a usable result. Progressive and Iterative Approximation for Least Squares (LSPIA) is an efficient method for data fitting that solves the numerical instability problem. However, it does not consider chord errors and needs more work to ensure ironclad results for commercial applications. In this paper, we use LSPIA method incorporating Energy term (ELSPIA) to avoid the numerical instability, and lower chord errors by using stretching energy term. We implement several algorithm improvements, including (1) an improved technique for initial control point determination over Dominant Point Method, (2) an algorithm that updates foot point parameters as needed, (3) analysis of the degrees of freedom of control points to insert new control points only when needed, (4) chord error refinement using a similar ELSPIA method with the above enhancements. The proposed approach can generate a shape-preserving B-spline curve. Experiments with data analysis and machining tests are presented for verification of quality and efficiency. Comparisons with other known solutions are included to evaluate the worthiness of the proposed solution.

ABSTRACTTherapy for hepatitis C virus (HCV) infection has advanced with the recent approval of direct-acting antivirals in combination with peginterferon and ribavirin. New antivirals with novel targets are still needed to further improve the treatment of hepatitis C. Previously reported screening methods for HCV inhibitors either are limited to a virus-specific function or apply a screening method at a single dose, which usually leads to high false-positive or -negative rates. We developed a quantitative high-throughput screening (qHTS) assay platform with a cell-based HCV infection system. This highly sensitive assay can be miniaturized to a 1,536-well format for screening of large chemical libraries. All candidates are screened over a 7-concentration dose range to give EC50s (compound concentrations at 50% efficacy) and dose-response curves. Using this assay format, we screened a library of pharmacologically active compounds (LOPAC). Based on the profile of dose-dependent curves of HCV inhibition and cytotoxicity, 22 compounds with adequate curves and EC50s of <10 μM were selected for validation. In two additional independent assays, 17 of them demonstrated specific inhibition of HCV infection. Ten potential candidates with efficacies of >70% and CC50s (compound concentrations at 50% cytotoxicity) of <30 μM from these validated hits were characterized for their target stages in the HCV replication cycle. In this screen, we identified both known and novel hits with diverse structural and functional features targeting various stages of the HCV replication cycle. The pilot screen demonstrates that this assay system is highly robust and effective in identifying novel HCV inhibitors and that it can be readily applied to large-scale screening of small-molecule libraries.

Semisynthetic 8,8-dialkyldihydroberberines (8,8-DDBs) were found to possess mid- to low-nanomolar potency against Plasmodium falciparumblood-stage parasites, Leishmania donovaniintracellular amastigotes, and Trypanosoma brucei bruceibloodstream forms. For example, 8,8-diethyldihydroberberine chloride (5b) exhibited in vitro IC50values of 77, 100, and 5.3 nM against these three parasites, respectively. In turn, two 8,8-dialkylcanadines, obtained by reduction of the corresponding 8,8-DDBs, were much less potent against these parasites in vitro. While the natural product berberine is a weak DNA binder, the 8,8-DDBs displayed no affinity for DNA, as assessed by changes in the melting temperature of poly(dA·dT) DNA. Selected 8,8-DDBs showed efficacy in mouse models of visceral leishmaniasis and African trypanosomiasis, with 8,8-dimethyldihydroberberine chloride (5a) reducing liver parasitemia by 46% in L. donovani-infected BALB/c mice when given at an intraperitoneal dose of 10 mg/kg/day for five days. The 8,8-DDBs may thus serve as leads for discovering new antimalarial, antileishmanial, and antitrypanosomal drug candidates.

ABSTRACTDihydroquinoline derivative OSU-40 (1-benzyl-1,2-dihydro-2,2,4-trimethylquinolin-6-yl acetate) is selectively potent against Trypanosma brucei rhodesiense in vitro(50% inhibitory concentration [IC50], 14 nM; selectivity index, 1,700) and has been proposed to cause the formation of reactive oxygen species (ROS) in African trypanosomes (J. Fotie et al., J. Med. Chem. 53:966–982, 2010). In the present study, we sought to provide further support for the hypothesis that OSU-40 kills trypanosomes through oxidative stress. Inducible RNA interference (RNAi) was applied to downregulate key enzymes in parasite antioxidant defense, including T. bruceitrypanothione synthetase (TbTryS) and superoxide dismutase B (TbSODB). Both TbTryS RNAi-induced and TbSODB RNAi-induced cells showed impaired growth and increased sensitivity toward OSU-40 by 2.4-fold and 3.4-fold, respectively. Decreased expression of key parasite antioxidant enzymes was thus associated with increased sensitivity to OSU-40, consistent with the hypothesis that OSU-40 acts through oxidative stress. Finally, the dose-dependent formation of free radicals was observed after incubation of T. bruceiwith OSU-40 utilizing electron spin resonance (ESR) spectroscopy. These data support the notion that the mode of antitrypanosomal action for this class of compounds is to induce oxidative stress.

Gas separation (GS) and pervaporation (PV) mainly based on solution-diffusion mechanism, are two important processes for the challenging transport and separation of gaseous and vapor molecules. Various types of contemporary nanomaterials such as covalent organic frameworks (COFs) and metal organic frameworks (MOFs) have demonstrated unique channels with tuneable surface that govern transport and separation of targeted molecules. New opportunities have been revealed through incorporation of emerging nanomaterials into the structure of conventional polymeric membranes and resulted in several advantages notably improved performance and reduced energy consumptions. Due to the broad applications of GS and PV processes in the chemical industry and energy sector, the present manuscript aims to review the principle for gas separation and pervaporation in membrane molecular separation process in terms of solution-diffusion theory. In addition, the current status of membranes containing emerging nanomaterials for GS and PV are discussed comprehensively from different aspects. Furthermore, the current applications of nanomaterials incorporated mixed matrix membranes (MMMs) are described. Finally, the perspectives and future directions of remarkable performance membranes incorporated with diverse emerging nanomaterials are explained so as to facilitate the rapid advancement of energetic-efficient membranes toward practically industrial applications.

The melting–recrystallization characterizations of quenched β-form isotactic polypropylene (β-iPP) lamellar crystals in ultrathin films were investigated via the self-seeding method. We found lath-like shaped α-iPP crystals generated within the region occupied by the initial β-iPP lamellae and calculated their average number density (Nα). Intriguingly, two slopes were derived from the semi-logarithmic plot of Nαversus partial melting temperature (Ts), which reflects that Nαis determined by βα-recrystallization and αα-recrystallization as Tsis below and above 157 °C, respectively. Furthermore, our experimental observations clearly demonstrate that two phase selection pathways, that is, ββ- and βα-recrystallization, are possible upon melting of the quenched β-iPP lamellae. In particular, we found that ββ-recrystallization emerges as the preferred route for the case of an initial β phase with sufficiently high thermal stability, which is probably thermodynamically controlled rather than kinetically controlled. Otherwise, βα-recrystallization will be the dominant process due to the growth kinetics.

Clean utilization of catalytically cracked diesel is of paramount importance in the industry. The separation of polycyclic aromatic hydrocarbons (PAHs) from catalytically cracked diesel can significantly reduce the content of aromatics and increase the cetane number to improve the quality of diesel. In this work, for extracting the PAH 1-methylnaphthalene from the model fluid catalytic cracking diesel, the liquid–liquid equilibrium phase behavior for the quaternary systems (n-decane + 1-tetradecene + 1-methylnaphthalene + sulfolane/dimethyl sulfoxide) were explored at 303.15, 323.15, and 343.15 K under 0.1 MPa. The separation performance was characterized by the separation factor and distribution coefficient. The results showed that sulfolane was a suitable extractant compared to DMSO. The reliability of the measured phase equilibrium data was evaluated by the Hand and Othmer–Tobias equations. The UNIQUAC and NRTL models were applied to fit the tie-line data of the investigated mixtures with the AARD and rmsd lower than 0.01. The intermolecular interaction was explored by the σ-profile analysis to compare the separation performance of sulfolane and DMSO.

The self-nucleation behavior of β-form isotactic polypropylene (β-iPP) crystals in ultrathin films has been probed by atomic force microscopy (AFM) and optical microscopy (OM). The hexagonal β-iPP single crystals can be obtained via a self-seeding method at much higher crystallization temperatures (e.g., 156 °C). We found that the average number nucleation density (N) of β-iPP lamellar crystals deceases with increasing self-nucleation temperature (Ts) and heating rate (Vh). Upon heating the polymorphic structures induced by shear flow to a temperature between 143 and 156 °C, since α-iPP grows about 20–2400% faster than β-iPP, the former overtakes and engulfs the growth front of the later when crystallized for a sufficiently long time. However, the morphological observations show that both α-iPP and β-iPP were grown by homoepitaxy on their own crystals, and no trace of the epitaxial overgrowth of α-iPP lamellae on the entire growth front of β-iPP was observed, that is, a high-temperature βα growth transition appears to be absent, which probably indicates that the free energy barrier for secondary αα nucleation and ββ nucleation is much lower than that of βα nucleation in ultrathin films.

Adolescence is a pivotal point in the life course, characterised by transformative physical, cognitive, and emotional growth, an openness to change, and a drive to reshape the social environment. It offers unique opportunities to adopt changes in diet and physical activity that can persist into later life. Yet pre-existing nutritional problems, including micronutrient deficiencies, food insecurity, and poor-quality diets, persist at the same time as adolescents face the rapid emergence of an obesity epidemic. Adolescent growth and nutrition has been largely overlooked in intervention and policy research. Most intervention studies have emphasised micronutrient supplementation, with few taking into account the multiple drivers of adolescent diets. This Series paper highlights that effective interventions and policies will need to cut across sectors; be supported by multifaceted and multilevel policy; and extend across education, health, food systems, social protection, and digital media. Better data standardisation and systems will be essential in coordinating and monitoring these responses. In a context of shifts in planetary ecosystems and commercial drivers, resilient food systems will need to both ensure access to healthy and affordable foods and provide the infrastructure and incentives for continuing physical activity. Intergenerational partnerships with young people will be essential in bringing about transformative change and ensuring that food policies reflect their needs and aspirations.

Triboelectric nanogenerators (TENGs) are effective for harvesting mechanical energy and converting into electricity. Such devices have high output voltage and low current, appearing as high output impedance. Impedance mismatches involving these devices create challenges in power usage, storage, and management. Herein, a dual‐tip‐assisted TENG is developed and its electrical output performance under airtight condition is investigated. The generated charges can rapidly accumulate at the dual tip and produce a high potential difference. Such a potential difference accelerates the induced charges’ transfer speed and quantity. Gas discharge occurs once the potential exceeds some threshold, providing a conduction path for accumulated charges. With the help of such dual‐tip peak power multiplier, TENG's peak‐to‐peak short‐circuit current and open‐circuit voltage are 433% and 145% higher, respectively. The peak power reaches a maximum of 34.8 mW with a 100 kΩ load resistance, whereas that of the original TENG is 1.5 mW with a 100 MΩ load resistance, indicating 22.2 times of peak power increase and an optimal matching impedance decrease by three orders of magnitude. The results indicate that this multiplier is meaningful for the optimization of TENG's output and impedance. A dual‐tip‐assisted triboelectric nanogenerator is demonstrated that uses a peak power multiplier. The gas in the dual‐tip structure ionizes to form a conductive path, which increases the peak power from the triboelectric nanogenerator. The influence of the peak power multiplier's design parameters on the output voltage is investigated to provide guidance for optimization.

Colorectal cancer (CRC) ranks as the second leading cause of cancer-related deaths in the Western world. It has a nearly 50% metastasis rate and only a subset of patients respond to current treatment strategy. UVRAG, a key autophagy effector and a guardian of chromosomal stability, is truncated by a frameshift (FS) mutation in CRC with microsatellite instability (MSI). However, the pathological and clinical significance of this UVRAG truncation remains less understood. Our recent study discovered that this FS mutation yields a much shortened form of the UVRAG protein, which counteracts most of the tumor-suppressor functions of wild-type (WT) UVRAG in autophagy, centrosome stability, and DNA repair in a dominant-negative fashion. Whereas this truncated mutation of UVRAG promotes tumorigenesis, epithelial-to-mesenchymal transition, and metastasis, it appears to sensitize CRC tumors to adjuvant chemotherapy, making it a potential molecular marker to individualize therapeutic approach in CRC.

While the cell imposes multiple barriers to virus entry, enveloped viruses are remarkably still able to gain entry to their cellular hosts by hitchhiking and remodeling the endomembrane system to traffic within, and eventually escape from, endosomal organelles for their genome release. Elucidating viral entry mechanisms and their interaction with the host trafficking network is necessary for antiviral therapy. Here, we focus on the use of host autophagy molecular factors during the entry of prototypic negative-stranded RNA viruses, and highlight recent progress in our understanding of the role of one such factor, UVRAG, in both viral and cellular endocytic membrane trafficking and fusion events.

For decades, a marvelous amount of work has been performed to identify molecules that regulate distinct stages of membrane transport in the ER-Golgi secretory pathway and autophagy, which are implicated in many human diseases. However, an important missing piece in this puzzle is how the cell dynamically coordinates these crisscrossed trafficking pathways in response to different stimuli. Our recent study has identified UVRAG as a mode-switching protein that coordinates Golgi-ER retrograde and autophagic trafficking. UVRAG recognizes phosphatidylinositol-3-phosphate (PtdIns3P) and locates to the ER, where it couples the ER tethering complex containing RINT1 to govern Golgi-ER retrograde transport. Intriguingly, when autophagy is induced, UVRAG undergoes a “partnering shift” from the ER tethering complex to the BECN1 autophagy complex, resulting in concomitant inhibition of Golgi-ER transport and the activation of ATG9 autophagic trafficking. Therefore, Golgi-ER retrograde and autophagy-related membrane trafficking are functionally interdependent and tightly regulated by UVRAG to ensure spatiotemporal fidelity of protein transport and organelle homeostasis, providing distinguished insights into trafficking-related diseases.

Over-the-counter allergy drug chlorcyclizine was identified and characterized as an anti-HCV drug in vitro and in vivo.