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Since 2019, the novel coronavirus (SARS-CoV-2) has caused significant morbidity and millions of deaths worldwide. The Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2 and its variants, has further highlighted the urgent need for the development of effective therapeutic agents. Currently, the highly conserved and broad-spectrum nature of main proteases (M pro ) renders them of great importance in the field of inhibitor study. In this study, we categorize inhibitors targeting M pro into three major groups: mimetic, nonmimetic, and natural inhibitors. We then present the research progress of these inhibitors in detail, including their mechanism of action, antiviral activity, pharmacokinetic properties, animal experiments, and clinical studies. This review aims to provide valuable insights and potential avenues for the development of more effective antiviral drugs against SARS-CoV-2., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Persistent organic pollutants (POPs) in the environment have the characteristics of persistence, bioaccumulation, teratogenicity, carcinogenicity, and mutagenicity. Long-term exposure of low-content POPs will also have a certain impact on marine ecosystems and human beings. The contents of three typical persistent organic pollutants[polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides (OCPs), and polycyclic biphenyls (PCBs)] of surface sediments were analyzed using gas chromatography and mass spectrometry (GC-MS) to assess the pollution characteristics of persistent organic pollutants in Boao coastal waters. The distribution and source of persistent organic pollutants were analyzed in this study, and the ecological risk was assessed using three different methods:the effect interval low/median method (ERL/ERM), mean effect interval median quotient method (M-ERM-Q), and mean potential impact concentration quotient method (M-PEC-Q). The results indicated that the contents (measured by dry weight) of ΣPAHs, ΣOCPs, and ΣPCBs in the study area were 4.5-367.50, 3.99-175.30, and ND-2.89 ng·g -1 , respectively, which were at a low level, and the overall distribution showed a trend of gradually increasing toward the sea. The results of POPs source analysis showed that the PAHs in the study area were mainly from the combustion of wood and coal. Among OCPs, the HCH was mainly from lindane, the historical land-based input had been completely degraded, and the DDT was mainly the traditional DDTs pesticides, with additional continuous DDT input. The PCBs were primarily pentachlorobiphenyls, which might have come from the release of paint on the bottom of the hull in the early stage of shipping and the peeling off of paint from old ships. The ecological risk assessment results showed that there was little difference among the assessment results of the three methods, which showed that only phenanthrene monomer of PAHs in the study area had a slight negative impact, and the DDT and the γ- HCH among PAHs would cause great ecological risk, whereas PCBs and other pollutants would not cause ecological risk. On the whole, the possibility of comprehensive ecological risk caused by the three pollutants was very small.

Histone lysine crotonylation (Kcr) is a novel hydrophobic histone acylation modification, and we recently report its crucial roles in neural differentiation. However, it is still unclear how histone Kcr involve in early neural commitment. Here, we systematically investigate the H3K9cr landscapes during neuroectodermal differentiation of pluripotent P19 embryonal carcinoma cells (ECCs). We reveal that the genome-wide changes in H3K9cr favor neural fate specification, and identify potential co-factors binding H3K9cr. We also uncover that H3K9cr collaborates with H3K9ac to regulate gene expression changes. Our results provide novel insights into the epigenetic mechanisms underlying neural commitment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Resonance frequencies of a mechanical system are the most important parameters that determine the dynamic characteristics of the system. When the frequencies of the harmonic forces under the influence of the system coincide with the resonance (natural) frequencies of the system, a resonance situation occurs and the mechanical system vibrates with high amplitudes. This can cause serious damage to the system by causing effects such as break, fatigue, impact, noise on the bearings, connections and elements in the system. It is possible to eliminate some resonance frequencies of mechanical systems in an examined frequency range using pole-zero cancellation methods by shifting a resonance frequency of the system to an anti-resonance frequency or an anti-resonance frequency to a resonance frequency. Thus, a solution can be obtained for some vibration problems. In this study, a new method using the Sherman-Morrison formula is presented to eliminate some of the resonance frequencies for some FRFs (Frequency Response Functions) of mechanical systems with pole-zero cancellation. In order to eliminate a selected resonance frequency of the system in any FRF determined using the presented method, a mass (kg) and a grounded spring (N/m) modification are made and the required modification values for this are calculated by solving the obtained non-linear equation set numerically. With the proposed method, it is aimed to contribute to the literature by presenting an alternative approach for the solution of vibration problems by cancelling some selected resonance frequencies. The main highlight of the method is there is no need of a matrix inversion for calculating the required modification values. This provides a very fast solution. In addition, the proposed method uses directly the FRFs of the active coordinates (response, excitation and modification) only, which makes the method very useful for practical engineering applications. [ABSTRACT FROM AUTHOR]

To effectively isolate low-frequency vibrations, we present a rigid–flexible coupling quasi-zero-stiffness (QZS) vibration isolator with high-static-low-dynamic stiffness (HSLDS) characteristics. Specifically, the QZS isolator is realized by the development of a compliant constant-force mechanism, formed by parallelly combining a diamond-shape mechanism and a nonlinear bi-stable beam in parallel. To evaluate performance of the QZS isolator, we derived an analytical force–displacement model and dynamic model based on pseudo-rigid body method and Lagrange's equations. Then, finite element analysis was performed in Workbench to verify theoretical analysis and identify the optimal design parameters. Furthermore, the dynamic responses of the QZS isolator are established with the harmonic balance method. Finally, the relationships among displacement transmissibility and factors including damping, BSB, payload mass, and material property are discussed. The results have shown that our QZS isolator design can effectively isolate vibrations in low frequency. [ABSTRACT FROM AUTHOR]

This study aims to potential the potential utilization of nonlinear energy sinks (NESs) for controlling longitudinal vibrations in a double-rod system. The research introduces a longitudinal vibration prediction model for a double-rod system equipped with NESs. The generalized Hamilton principle is employed to derive governing equations of the double-rod system. The longitudinal vibration responses of the double-rod system are numerically solved through the application of Galerkin truncation method. The longitudinal vibration responses of the double-rod system are impacted by NESs, as they yield accurate numerical results. The installation of both NES 1 and NES 2 concurrently is recommended for mitigating the vibration of the double-rod system. Under reasonable single-frequency excitations, modifying the parameters of NESs can significantly alter both the vibration state and magnitudes of vibration in the double-rod system. Furthermore, the synchronous optimization of parameters in NES 1 and NES 2 is crucial for effectively controlling vibrations in the double-rod system. Sensitive parameter areas of NESs provide the possibility of controlling the vibration of the double-rod system by utilizing NESs. [ABSTRACT FROM AUTHOR]

This paper aims to obtain an analytical solution for free vibration and stability analysis of shallow curved sandwich panels made of a porous metal-foam core and nanocomposites reinforced sheets resting on a Winkler-Pasternak elastic foundation. In this regard, two nanocomposites, carbon nanotubes (CNTs) and graphene nanoplatelets (GNPs) are considered for reinforcing the face-sheets. The governing equations are developed by considering the transversal shear strains based on the first-order shear deformation theory (FSDT). The obtained system of differential equations representing the dynamic equilibrium and compatibility of the proposed curved sandwich panels are solved analytically, using the principal of Galerkin method. In order to examine the results of developed formulation, some benchmark examples are adopted from the existing literature and the obtained results corresponding to the considered examples are compared with those are presented in the references. Using the achieved numerical results in the framework of a comprehensive parametric study, the effects of various material and geometrical factors and also various boundary conditions on the natural frequencies and buckling loads of the proposed sandwich panels are assessed. By performing the extensive parametric study it was observed that several results corresponding to the free vibration and stability of the proposed sandwich panels can be achieved by the present method without spending much time for computations. On the contrary, in order to achieve the similar results using the numerical methods, a time-consuming process is required which can justify the novelty of the present work. [ABSTRACT FROM AUTHOR]

The paper presents a semi-analytical method, named the Double Legendre Polynomial Method (DLPM), which is extended for modeling the axisymmetric free vibration of a functionally graded piezoelectric (FGP) hollow cylinder resonator. The FGP resonator is composed of two-phase graded piezoelectric materials, Lead zirconate titanate (PZT4) and aluminum nitrid (AlN), on the top and bottom surfaces, respectively, where the material properties gradually change along the thickness direction. The integration of FGP materials with piezoelectric materials is an innovative aspect in material science, and this paper explores their dynamic behavior, providing insights into their mechanical and electrical properties and contributes to expand our understanding of the axisymmetric free vibration of FGP hollow cylinder resonators as a crucial factor for optimizing their performance across a wide range of applications, including sensors, actuators, energy harvesting, and structural health monitoring systems. The DLPM is applied to solve the wave governing differential equations of motion, offering a new tool for studying the dynamic behavior of FGP hollow cylinders under axisymmetric vibration. The study investigates the effects of the diameter-thickness ratio on the effective electromechanical coupling coefficient and the resonant and anti-resonant frequencies of the FGP hollow cylinder. The results show that as the diameter-thickness ratio increases, the frequency-diameter product appears to become more stable. This observation is a valuable insight for optimizing the design of these resonators. Furthermore, the study presents the electrical input admittance, the natural frequencies as well as the mechanical displacement and electric potential profiles of the resonator. All the provided results are based on the calculation of the resonant frequencies. The validity of the presented results was verified by the comparison with the existing ones reported in the literature. [ABSTRACT FROM AUTHOR]

Various quasi-zero stiffness (QZS) systems with high-static and low-dynamic stiffness (HSLDS) have been applied extensively to attenuate low-frequency vibrations. However, in the majority of cases, the negative stiffness unit exhibits nonlinear stiffness behaviors, and the method of realizing QZS is limited to compensate the nonlinear negative stiffness through linear springs. Hence, a novel linkage anti-vibration structure (LAVS) via linear positive and negative stiffness compensation mechanism is proposed and studied for exploring its advantages in low-frequency vibration isolation. The LAVS is composed of a symmetric polygonal structure (SPS) and a vertical spring. The static stiffness behavior is first investigated, revealing the inherent positive and negative stiffness compensation mechanism of linear springs to the SPS. By tuning structural parameters, the linear spring can completely compensate the linear negative stiffness of the SPS to achieve enhanced QZS over a larger stroke. Numerical simulations are carried out to verify the theoretical result and demonstrate the effectiveness of the presented stiffness compensation mechanism. Based on the Lagrange principle, a dynamic equation is established and then solved via the multiple scales method to obtain the displacement transmissibility. The effects of key parameters such as the rod lengths, equilibrium points and damping factors on the amplitude–frequency characteristics and vibration transmissibility are analyzed. Compared with a SMD and a typical X-shaped QZS isolation systems, the presented LAVS exhibits an enhanced QZS zone with a larger load capacity and can realize superb vibration isolation performance with guaranteed stable equilibrium. The proposed linear positive and negative stiffness compensation mechanism presents new insights for passive vibration isolation design in many engineering applications. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Clinical Hepatology / Linchuang Gandanbing Zazhi is the property of Journal of Clinical Hepatology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: The design of a new meta-structure with quasi-zero stiffness (QZS) characteristics based on human body structure not only expands the diversity of quasi-zero stiffness structures but also demonstrates excellent performance in the field of low-frequency vibration damping. Methods: Firstly, a quasi-zero stiffness unit structure combining a horizontal cosine beam and vertical cosine beam is designed based on the human body structure, and multiple unit structures are combined into one meta-structure; secondly, according to the material-structural properties of the unit, a functional relationship is established for the positive stiffness structure using the segmental function method, which is combined with the functional relationship of the negative stiffness structure to obtain the theoretical model of the unit structure and then derives the mechanics of the whole meta-structure behavior of the whole meta-structure. Then, the unit structure model and the meta-structure model are designed and simulated, the static properties of the meta-structure are investigated, and photosensitive resin is chosen as the material in the simulation process. Finally, the transmittance comparison between the meta-structure and the linear vibration isolation structure with different damping coefficients is analyzed by theory, and the vibration isolation performance of the meta-structure is simulated. Results: The static simulation analysis of the meta-structure verifies the theoretical solution of the meta-structure very well. According to the theoretical formulation, different parameters can be input to obtain the quasi-zero stiffness properties of the structure. The quasi-zero stiffness properties of the structure are independent of the inherent material properties. Due to the nonlinear nature of the quasi-zero stiffness unit structure, it not only has a lower peak transmittance, but also a lower resonant frequency and a wider isolation range compared with the linear vibration isolator. Conclusions: The designed quasi-zero stiffness meta-structure is suitable for low-frequency vibration isolation of precision instruments, which can be realized by different materials, and more complex meta-structures can be designed on this basis in the future, which has great potential for application in engineering practice. [ABSTRACT FROM AUTHOR]

Purpose: For fixed or hinged single cables, the vibration equation is well developed. However, the form of boundary constraints between fixed and hinged is used extensively for the single cable in practical engineering, such as the restraint of struts between multi-span cables. As the struts with different lengths and stiffness are placed in the single cable, the mode shape of the multi-span cables is affected significantly. Moreover, with the decrease in the aspect ratio of single-span cable, the effect of the cable bending stiffness cannot be overlooked. The above effects in single and multi-span cables are studied in the proposed model. Methods: The vibration equation of the multi-span cable is developed in two steps. To establish the vibration equation of the single cable with general elastic constraint, the constraints at the ends of the strut are simplified as the compression springs that can bear the pressure. The bending springs that can consider the bending stiffness are also set at both ends simultaneously, then the vibration equation of the single cable with a general elastic constraint can be derived. For a multi-span cable structure, the strut is simplified into the elastic constraints of a single-span cable. By combining the aforementioned vibration equations of single-span cables which have general constraints, the vibration equation of multi-span cables can be established. Results: The vibration frequency equations of m span multi-span cable with constraint stiffness are established, and the objective function optimization algorithm is validated. Conclusion: The analytical solution of the multi-span cable vibration equation in this paper is then validated by the comparison with the multi-span cable vibration model established by the finite element method. The comparison demonstrated that the proposed method is valid and practical. [ABSTRACT FROM AUTHOR]

Purpose: To suppress the low-frequency vibration of dynamic systems such as underwater vehicles, this research proposes a novel geometrically nonlinear vibration isolator using hybrid nonlinear inertial and negative stiffness element. Methods: A spring and an inerter are integrated together into a 4-rod linkage structure to form geometric nonlinearity. The performance of isolator under force or base-motion excitation is analysed. The performance of the proposed isolator in a flexible base structure simulating vibration isolation in ships is also considered. The transmissibilities and vibrational energy transfer are used to evaluate the effectiveness of isolation. Results: The results demonstrate better performance in low-frequency vibration isolation comparing to conventional linear isolator. The combined use of spring and inerter in the linkage mechanism can create a frequency band of ultra-low transmissibility and energy flow at low frequencies. Conclusion: Structural parameters of the proposed hybrid nonlinear element can be designed to alter the dynamic characteristic of the nonlinear isolator to attenuate low-frequency vibration transmission. The proposed nonlinear isolator demonstrates a strong potential for application in naval architecture. [ABSTRACT FROM AUTHOR]

In this paper, the absolute nodal coordinate formulation is used to establish the dynamic model of a flexible two-link mechanism with a nonlinear energy sink (NES). And the Moore–Penrose generalized inverse of constraint equations is utilized to eliminate the constraint violation existing in the dynamic model. The developed model without NES is verified with that established in ADAMS via comparisons of displacement responses at the endpoint. Then, the effects of torsional stiffness, length ratio between link 1 and link 2, and excitation frequency on the structural dynamic characteristics of the flexible two-link mechanism are studied. Next, the mass and stiffness of NES are optimized by the genetic algorithm for maximizing vibration attenuation. Finally, the results of numerical examples show that the proposed method can optimize the vibration suppression effect of NES under given conditions, which proves the effectiveness of this approach. [ABSTRACT FROM AUTHOR]

In the present study, the dynamic behavior of rotating carbon fiber reinforced polymer (CFRP) composite tapered plates reinforced with graphene nanoparticles has been investigated using a finite element (FE) formulation. The mechanical properties of CFRP laminates containing 0–0.5 wt% graphene nanoparticles were assessed using ASTM standard tests. The experimental dynamic analysis was conducted on CFRP and graphene reinforced CFRP composites under cantilever end conditions. The first‐order shear deformation theory (FSDT)‐based FE model was developed using MATLAB software to obtain the natural frequencies of the graphene reinforced CFRP plates. The validity of the FE results is compared with literature, and it shows excellent agreement for composite structures. Furthermore, parametric analysis is performed to explore the influence of wt% of graphene, rotating speed, setting angle, and ply thickness on the dynamic responses of graphene reinforced CFRP tapered plates. Highlights: Effects of graphene reinforcement in CFRP composites are investigated.The mechanical characteristics were evaluated using ASTM standards.FSDT is employed to model the rotating tapered graphene‐CFRP plates.Vibration behavior of graphene‐CFRP composites is studied experimentally.Effects of various factors on the vibrations of the CFRP plates are studied. [ABSTRACT FROM AUTHOR]

Purpose: This article demonstrates the possibility of energy harvesting by mistuned pendulums with torsional coupling. Two pendulums of different lengths with coils and magnets at the pivots are used as electromagnetic harvesters. The ambient energy source to the system is considered in the form of harmonic base excitations. Torsional coupling is achieved by connecting the pendulums with a torsional spring. The non-linearity of the underlying dynamics arises due to mechanical coupling and forcing amplitude. Numerical results are presented to analyze the performance of the pendulum energy harvester under different torsional coupling values. Method: The mathematical model of the electro-mechanical system with torsionally coupled pendulums under harmonic excitation is developed. The mistuning is introduced by two pendulums with different lengths l1 and l2. The coupling between them is achieved by a torsional spring of stiffness kc. These pendulums are connected to the shafts of the electromagnetic generators with a magnet attached to the pendulum as a rotor and coil as stator. Current i is generated due to electromagnetic induction whenever pendulum oscillates. The numerical and harmonic balance method analysis were carried out. Runge-Kutta integration was used for numerical analysis. The analysis was carried out to determine the effect of coupling, length and resistive coefficient. The bifurcation diagram and Poincare plots were used for dynamic analysis and cross recurrence plots for analysis of relations between pendulum harvesters. Results: The effect of coupling on harvester performance was carried out, the variation of maximum power and frequency band with coupling can be categorized into 3 zones. The ranges for Zone-I, II and III of maximum power are [0-0.059], [0.06-0.11] and above 0.11 respectively. In Zone-I total power and the total band are dominating over pendulum-1 and pendulum-2. In Zone-II, the performance of pendulum-2 is comparable with the total performance. In contrast, the performance of pendulum-1 is low. Saturation of maximum power and bandwidth can be observed in zone-III. Uncoupled pendulum-1 and 2 exhibits a periodic oscillation. A low amplitude quasi-periodic response of pendulum-1 and high amplitude quasiperiodic response of pendulum-2 can be observed for coupling of β = 0.04. Both pendulums exhibit high amplitude chaotic response at β = 0.07. The introduction of coupling induced nonlinearity in both pendulums. the amplitude and velocity also increased due to the quasi-periodicity and chaos induced in pendulums due to the coupling and better energy harvesting capabilities can be expected. The harmonic balance analysis indicates that there is a possibility of obtaining a high amplitude current at lower frequencies provided proper initial conditions are chosen. Conclusion: A twin electromagnetic pendulum energy harvester with torsional coupling is analyzed in order to optimize the efficient energy harvesting and study the energy harvester dynamics. The paper categorized the three distinct zones based on the coupling ratio β and length ratio α2. One can select parameters from these zones based on need. Zones-II and III are the most promising zones. If one wants to harvest broader energy Zone-II is preferable with harvesting only from the energy harvester with a low resonant frequency which in turn saves material cost. To harvest peak power one can, select Zone-III and harvest from both energy harvesters. The performance in the respective zones can be further enhanced by using optimal initial conditions to obtain high energy orbits at lower frequencies. The probability of obtaining high energy orbits decreases with an increase in the coupling ratio. The effect synchronization with coupling on energy harvesting plays an important role form magnitude and bandwidth point of view. The analytical results obtained by the Harmonic Balance Method are in good agreement with numerical results. [ABSTRACT FROM AUTHOR]

Quasi-zero stiffness (QZS) isolators have attracted extensive attention due to their high-static–low-dynamic stiffness. The effectiveness of the traditional QZS (T-QZS) isolators to attenuate low-frequency vibration has been extensively studied. The T-QZS isolator, however, cannot usually provide satisfactory vibration mitigation performance under ultra-low frequency excitation. To tackle this challenge, we propose a semi-active QZS isolator featuring magnetorheological elastomer (SAQZS-MRE isolator). The prominent merit of the proposed design is that the applied MRE material can provide varying stiffness and damping to the proposed SAQZS-MRE isolator, making the isolator suitable for vibration isolation under wide-band low-frequency range. The dynamic viscoelasticity properties of the MRE are experimentally characterized, to formulate the dynamic modeling of the SAQZS-MRE isolator. The open-loop vibration isolation characteristics of the SAQZS-MRE isolator are assessed using the harmonic balance method (HBM). Subsequently, two semi-active control strategies including skyhook and fast convergence switch (FCS) are effectively utilized in the proposed SAQZS-MRE isolator to evaluate their closed-loop performance. The results demonstrate that the SAQZS-MRE isolator with FCS control can eliminate the resonance peak and reduce the initial isolation frequency. In the higher frequency range, it can also improve the vibration isolation performance compared with the SAQZS-MRE isolator with passive control. [ABSTRACT FROM AUTHOR]

Carbon fiber-reinforced polymer (CFRP) composite is extensively exploited in numerous industrial and non-industrial applications because of its extraordinary mechanical characteristics. Most of the time, the CFRP composite structures are exposed to extreme and heavy machining process and get damaged. In the component assembly of the structures, one of the conventional damages that still occurs on the CFRP laminates are holes that are created on the specimen by drilling tools. Therefore, the mechanical properties of open-hole CFRP laminates are important issue that should be addressed by engineers. For this purpose, the tensile, flexural and compressive strengths of an open-hole CFRP laminate are experimentally and numerically determined in this research. A finite element method is developed to validate the precision of the experimental data. [ABSTRACT FROM AUTHOR]

In this research, the displacement components of a cylindrical shell, subjected to full or partial circumferentially varying edge loads and asymmetric external pressure, are determined analytically based on the first-order shear deformation theory. The kinematic of the problem is defined by nonlinear von Karman theory, and the constitutive equations obey Hooke's law. The governing equations, which are a system of nonlinear nonhomogeneous partial differential equations, are derived by applying the virtual work principle, and they are solved analytically by employing the perturbation technique and the Fourier series method. The presented procedure makes it possible to analyze a shell under continuous or discrete partial loads. The results are compared with the Abaqus finite elements package and the available results in the literature. [ABSTRACT FROM AUTHOR]

In this paper, a novel integration of the vibration attenuation and self-powered sensing of three-dimensional functionally graded (3D FG) pipes conveying fluid under the end supports of complex constraints is presented to study the nonlinear dynamics. The integrated facilities contain the piezoelectric energy harvester (PEH) and the nonlinear energy sink (NES), the PEH is linked with the ground configuration, and the NES is described by the combinations of a mass, linear viscous damping, and the nonlinear cubic stiffness. Also, the material properties of the pipes smoothly varying in the axial, radial, and circumferential directions are taken into account, and the nonlinear electromechanical model of distributed parameters for the proposed system is established using Hamilton's principle according to the von Kármán geometric nonlinearity incorporated with the Euler–Bernoulli beam theory. Application of Galerkin truncation to the nonlinear model gains the ordinary differential equations, the steady-state responses of which are predicted by a semi-analytical method, namely the harmonic balance (HB) combined with the alternating frequency/time (AFT) approach, and Floquet theory is utilized to predict stability and bifurcation behavior of periodic solutions. The effectiveness of the proposed analytical solutions is verified by comparing them with those determined by the Runge–Kutta method. A numerical example illustrates that the presented integration plays a significant role in the vibration suppression and self-powered sensing of the 3D FG pipes conveying fluid. [ABSTRACT FROM AUTHOR]

Intranasal administration of mucus-penetrating nanoparticles is an emerging trend to increase drug delivery to the brain. In order to overcome rapid nasal mucociliary clearance, low epithelial permeation, and local enzymatic degradation, we investigated the influence of PEGylation on nose-to-brain delivery of polycaprolactone (PCL) nanoparticles (PCL-NPs) encapsulating bexarotene, a potential neuroprotective compound. PEGylation with 1, 3, 5, and 10% PCL-PEG did not affect particle diameter or morphology. Upon incubation with artificial nasal mucus, only 5 and 10% of PCL-PEG coating were able to ensure NP stability and homogeneity in mucus. Rapid mucus-penetrating ability was observed for 98.8% of PCL-PEG5% NPs and for 99.5% of PCL-PEG10% NPs. Conversely, the motion of non-modified PCL-NPs was markedly slower. Fluorescence microscopy showed that the presence of PEG on NP surface did not reduce their uptake by RMPI 2650 cells. Fluorescence tomography images evidenced higher translocation into the brain for PCL-PEG5% NPs. Bexarotene loaded into PCL-PEG5% NPs resulted in area under the curve in the brain (AUCbrain) 3 and 2-fold higher than that for the drug dispersion and for non-PEGylated NPs (p < 0.05), indicating that approximately 4% of the dose was directly delivered to the brain. Combined, these results indicate that PEGylation of PCL-NPs with PCL-PEG5% is able to reduce NP interactions with the mucus, leading to a more efficient drug delivery to the brain following intranasal administration. [ABSTRACT FROM AUTHOR]

Platelets contribute to thrombus formation in a variety of ways. Platelet adhesion, activation, and thrombus growth depend greatly on the type of hemodynamic environment surrounding an inciting event. Microfluidic systems may be used to explore these relationships. In this review, we describe some important considerations required in the design of a microfluidic system and identify some limitations that may require use of a macroscale system. [ABSTRACT FROM PUBLISHER]

As part of its development policy to relieve rural poverty in west China, the Chinese government has introduced measures such as agricultural tax exemptions, agricultural subsidies, and scientific, technological and restructuring improvements to agriculture. Following these actions, farmers' incomes have increased greatly and the economy in poor areas of west China has seen rapid improvements. However, agricultural restructuring, infrastructure construction and ecological restoration projects have reduced the area of land under arable farming, restricting opportunities for increasing total grain yield. Regional food security is therefore threatened and an imbalance between economic development and food security is created. Shaanxi is a representative province in west China where agricultural restructuring has resulted in large areas of arable land being converted into orchards that produce higher economic returns. This study randomly surveyed 1430 farm households in three counties in the apple-producing region of Shaanxi Province (Luochuan, Changwu and Baishui). The standard of living and household income of farmers in the fruit production areas were higher than in grain-producing areas, thus discouraging grain production. Land under agriculture in the counties studied comprised 59% orchards and 39% arable, with 2% under other uses. Per capita, 204.3 kg of grain was produced, 51% of that required for self-sufficiency. Other staple foods produced amounted to only 13.9% of that needed for self-sufficiency. As a result, nearly half of the grain needed by the community was purchased from outside, resulting in very poor regional food security. Clearly, fruit production in this region seriously affects regional food security. Coordination of relationships between rural economic development and regional food security is key for sustainable development of the regional agriculture and economy of west China. [ABSTRACT FROM AUTHOR]

The article presents abstracts on medical topics to be presented at the Second International Symposium on Development of the Enteric Nervous System in London, England from February 22-25, 2009, which include gene regulatory network underlying neural crest formation, development of the mucosal plexus of the human enteric nervous system, and interactions between L1cam and Sox10 during enteric nervous system development.