A Network Pharmacology Approach to Investigate the Mechanism of Erjing Prescription in Type 2 Diabetes.

Erjing prescription (EJP) was an ancient formula that was recorded in the General Medical Collection of Royal Benevolence of the Song Dynasty. It has been frequently used to treat type 2 diabetes mellitus (T2DM) in the long history of China. The formula consists of Lycium barbarum L. and Polygonatum sibiricum F. Delaroche with a ratio of 1 : 1. This study aimed to identify the potential effects and mechanisms of EJP treatment T2DM. The target proteins and possible pathways of EJP in T2DM treatment were investigated by the approach of network pharmacology and real-time PCR (RT-PCR). 99 diabetes-related proteins were regulated by 56 bioactive constituents in EJP in 26 signal pathways by Cytoscape determination. According to GO analysis, 606 genes entries have been enriched. The PPI network suggested that AKT1, EGF, EGFR, MAPK1, and GSK3ß proteins were core genes. Among the 26 signal pathways, the PI3K-AKT signal pathway was tested by the RT-PCR. The expression level of PI3K p85, AKT1, GSK3ß, and Myc mRNA of this pathway was regulated by EJP. The study based on network pharmacology and RT-PCR analysis revealed that the blood sugar level was regulated by EJP via regulating the PI3K-AKT signal pathway. Plenty of new treatment methods for T2DM using EJP were provided by network pharmacology analysis.

Extremely Dense Gamma-Ray Pulses in Electron Beam-Multifoil Collisions.

Sources of high-energy photons have important applications in almost all areas of research. However, the photon flux and intensity of existing sources is strongly limited for photon energies above a few hundred keV. Here we show that a high-current ultrarelativistic electron beam interacting with multiple submicrometer-thick conducting foils can undergo strong self-focusing accompanied by efficient emission of gamma-ray synchrotron photons. Physically, self-focusing and high-energy photon emission originate from the beam interaction with the near-field transition radiation accompanying the beam-foil collision. This near field radiation is of amplitude comparable with the beam self-field, and can be strong enough that a single emitted photon can carry away a significant fraction of the emitting electron energy. After beam collision with multiple foils, femtosecond collimated electron and photon beams with number density exceeding that of a solid are obtained. The relative simplicity, unique properties, and high efficiency of this gamma-ray source open up new opportunities for both applied and fundamental research including laserless investigations of strong-field QED processes with a single electron beam.

Dermatotoxicology of microneedles (MNs) in man.

Developed within the last few decades, microneedles (MNs) have only recently seen wide-scale use among the general population, especially in the area of cosmetics. With the FDA only starting to regulate microneedling devices and the many new microneedling products that enter the modern global market, it is of utmost importance to establish the safety profile and reasonable expectations of the microneedling practice and its products. In our review of current literature, the authors searched the keyword "microneedle" with the following terms: "safety", "side effect", "toxicology", "adverse effect", "adverse event", "infection", "dermatitis", "granuloma", "scarring", and "hyperpigmentation". Despite wide-scale implementation of MNs, we are likely only beginning to understand the potential of MNs as a medical and consumer product, and we should, therefore, be aware of any potential adverse events associated with the product.

Sebo-pharmacokinetics: a proposed percutaneous sebum egression method.

BACKGROUND/AIMS: The sebaceous gland is widely believed a critical factor in the pathogenesis of acne vulgaris. Although extensive studies document the ability of oral and topical treatments to improve acne, little is known about the quantification and mechanism of drug delivery via the sebaceous gland. A percutaneous egression method presents a way to study how drugs reaching the bloodstream can enter the skin. METHODS: A literature search was performed across databases (PubMed, Embase, and Google Scholar) and the University of California, San Francisco (UCSF) textbook library with relevant search terms. RESULTS: This search failed to reveal data on sebo-pharmacokinetics (PK); however, many articles center on pharmacodynamics (PD) - i.e. functional improvement instigated by oral or topical treatments. Experiments on humans and hamsters - representative sebaceous gland models - demonstrate indirect PD measures of sebaceous gland function. DISCUSSION: Here, we summarize the current available data on drug delivery via the sebaceous gland and suggest a practical method to directly document sebo-PK in man and animal.

Should we instruct patients to rub topical agents into skin? The evidence.

Background: At least 15 factors influence the ability of compounds to penetrate the skin. Massage (rubbing) may be another factor that has gone relatively unrecognized. Method: PubMed, Google Scholar, and EMBASE databases were accessed online in March 2018 in search of studies measuring absorption through skin with and without rubbing or massage. Results: While some studies noted no difference in dermal absorption with regards to rubbing, others have demonstrated the opposite. In general, massage technique does indeed sometimes enhance dermal absorption. In addition to increase skin temperature and blood flow, rubbing likely modifies stratum corneum (SC) structure to enhance diffusion rates and increase retained penetrant amount within the skin. Conclusions: Understanding the mechanism of massage and its role in percutaneous penetration may help elucidate skin barrier function, dermal absorption, skin decontamination, and dermatotoxicology. To achieve such goals, an in vitro model that models in vivo behaviors must first be established. Subsequently, experiments with different penetrants, vehicles, massage time, and other variables may be considered.

Stratum corneum substantivity: drug development implications.

There are at least 15 factors that influence the ability of chemicals to penetrate the skin. Substantivity is yet another factor and allows penetrants to remain on and in skin for many days. As many skin pathologies involve stratum corneum and require multiple dosing of topicals, understanding substantivity mechanisms may provide insight for topical dosing strategies. Substantivity is also of importance in the development of other consumer products that necessitate adherence to skin, including sunscreens, insect repellents, and cosmetics. Furthermore, while stratum corneum adherence may delay percutaneous penetration, reducing the risk of systemic toxicity, excessive substantivity may play a role in the toxic accumulation of harmful penetrants. Continued research in this area may offer insight into dermatotoxicology and dermatopharmacology.

The limitations of environmental management systems in Australian agriculture.

The efficacy of government-supported programs to encourage improved management of land and water systems associated with agricultural land in Australia has been mixed. The broad approach of Australian governments is reviewed briefly. Evidence is presented from case assessments of a program to promote adoption of environmental management systems (EMSs) to improve environmental outcomes from agricultural practices. EMSs are systems implemented to manage the environmental impacts and ameliorate environmental risk associated with business activity. Data are presented on reported EMS activity and experience of four selected groups of farmers in Victoria, south-eastern Australia, representing broad-acre cropping, beef and dairy farming. The pro-environmental behaviours of farmers were mediated through voluntary adoption of government and industry sponsored EMSs, often with financial incentives and other support. Findings from the study were that adoption of EMS practices with sufficient public benefits is unlikely to occur at sufficient scale for significant environmental impact. Farmers more readily adopted practices which were financially beneficial than those which had a positive environmental impact. Although the focus on voluntary market-based instrument (MBI) type programs is popular in western countries, enforcing regulation is an important, but usually politically unpopular, component of land use policy. The comparative advantage of EMSs differed for the industries studied, but overall there were insufficient market drivers for widespread EMS adoption in Australia. Environmental outcomes could be more effectively achieved by directly funding land management practices which have highest public net benefits. Having a clear and unambiguous management objective for a particular land management policy is more likely to achieve outcomes than having multiple objectives as occurs in a number of international programs currently.

Social benchmarking to improve river ecosystems.

To complement physical measures or indices of river health a social benchmarking instrument has been developed to measure community dispositions and behaviour regarding river health. This instrument seeks to achieve three outcomes. First, to provide a benchmark of the social condition of communities' attitudes, values, understanding and behaviours in relation to river health; second, to provide information for developing management and educational priorities; and third, to provide an assessment of the long-term effectiveness of community education and engagement activities in achieving changes in attitudes, understanding and behaviours in relation to river health. In this paper the development of the social benchmarking instrument is described and results are presented from the first state-wide benchmark study in Victoria, Australia, in which the social dimensions of river health, community behaviours related to rivers, and community understanding of human impacts on rivers were assessed.

Generating monoenergetic heavy-ion bunches with laser-induced electrostatic shocks.

A method for efficient laser acceleration of heavy ions by electrostatic shock is investigated using particle-in-cell (PIC) simulation and analytical modeling. When a small number of heavy ions are mixed with light ions, the heavy ions can be accelerated to the same velocity as the light ions so that they gain much higher energy because of their large mass. Accordingly, a sandwich target design with a thin compound ion layer between two light-ion layers and a micro-structured target design are proposed for obtaining monoenergetic heavy-ion beams.

Second-harmonic generation of electron-bernstein waves in an inhomogeneous plasma.

In the injection of electron-Bernstein waves (EBW) into a plasma, proposed for plasma heating and current drive in over-dense plasma, conversion of the fundamental to its second harmonic is predicted analytically and observed in computations. The mechanism is traced to the existence of locations where one can have both wave number and frequency matching between the fundamental and its harmonic. Further, at such locations, the second harmonic commonly has minimal group velocity, and this allows the amplitude of the second harmonic to build to values exceeding that of the fundamental at power levels less than anticipated in experiments. The second-harmonic power can then be deposited at half-harmonic resonances of the original wave, often far from the desired location of energy deposition. Estimates for the power at which this is significant are given.

Laser-driven coherent betatron oscillation in a laser-wakefield cavity.

The origin of beam disparity in emittance and betatron oscillation orbits, in and out of the polarization plane of the drive laser of laser-plasma accelerators, is explained in terms of betatron oscillations driven by the laser field. As trapped electrons accelerate, they move forward and interact with the laser pulse. For the bubble regime, a simple model is presented to describe this interaction in terms of a harmonic oscillator with a driving force from the laser and a restoring force from the plasma wake field. The resulting beam oscillations in the polarization plane, with period approximately the wavelength of the driving laser, increase emittance in that plane and cause microbunching of the beam. These effects are observed directly in 3D particle-in-cell simulations.

Wave excitation in inhomogeneous dielectric media.

The equation describing the propagation of a mode driven by external currents in an inhomogeneous dielectric is derived from the principle of the conservation of wave energy density and wave momentum density. The wave amplitude in steady state is obtained in terms of a simple spatial integration of the driving current. The contribution from the spatial derivative of the dielectric response is found to be important. The analytical predictions are verified through comparison with deltaf particle-in-cell computations of electron Bernstein wave propagation, thus showing applicability to kinetic systems.

Bubble regime for ion acceleration in a laser-driven plasma.

Proton trapping and acceleration by an electron bubble-channel structure in laser interaction with high-density plasma is investigated by using three-dimensional particle-in-cell simulations. It is shown that protons can be trapped, bunched, and efficiently accelerated for appropriate laser and plasma parameters, and the proton acceleration is enhanced if the plasma consists mainly of heavier ions such as tritium. The observed results are analyzed and discussed in terms of a one-dimensional analytical three-component-plasma wake model.

Longitudinal cooling of non-neutral plasma by energy exchange.

The optimal values of Q and Deltaomega (Deltaomega identical withomega-Omega) for cooling a pure electron plasma with a microwave bath have been calculated. An electron plasma, which has no internal degree of freedom, cannot be cooled below the temperature of a heat bath. However, longitudinal cooling can be achieved by energy transfer from the poorly cooled longitudinal degree of freedom to the well-cooled (by synchrotron radiation) transverse degree of freedom. To do this, a microwave bath is introduced to the electron plasma. A microwave tuned to a frequency below the gyrofrequency forces electrons moving towards the microwave to absorb a microwave photon. The electrons move up one in Landau state and then lose their longitudinal momenta. In this process, the longitudinal temperature of the electron plasma decreases. On the basis that the perpendicular temperature is below the Landau temperature of the plasma, we set up two level transition equations and then derive a Fokker-Planck equation from them. With the aid of a finite element method (FEM) code for the equation, the cooling times for several values of the magnetic field, the microwave cavity (Q), and the relative detuning frequency from the gyrofrequency (Deltaomega) are calculated. Thus optimal values of the microwave cavity and the detuning frequency for longitudinal cooling of a strongly magnetized electron plasma with a microwave bath have been found. By applying these optimal values with an appropriate microwave intensity, the best cooling can be obtained. For an electron plasma magnetized to 10 T, the cooling time to the solid state is approximately two hours.

Finding a nonlinear lattice with improved integrability using Lie transform perturbation theory.

A condition for improved dynamic aperture for nonlinear, alternating gradient transport systems is derived using Lie transform perturbation theory. The Lie transform perturbation method is used here to perform averaging over fast oscillations by canonically transforming to slowly oscillating variables. This is first demonstrated for a linear sinusoidal focusing system. This method is then employed to average the dynamics over a lattice period for a nonlinear focusing system, provided by the use of higher order poles such as sextupoles and octupoles along with alternate gradient quadrupoles. Unlike the traditional approach, the higher order focusing is not treated as a perturbation. The Lie transform method is particularly advantageous for such a system where the form of the Hamiltonian is complex. This is because the method exploits the property of canonical invariance of Poisson brackets so that the change of variables is accomplished by just replacing the old ones with the new. The analysis shows the existence of a condition in which the system is azimuthally symmetric in the transformed, slowly oscillating frame. Such a symmetry in the time averaged frame renders the system nearly integrable in the laboratory frame. This condition leads to reduced chaos and improved confinement when compared to a system that is not close to integrability. Numerical calculations of single-particle trajectories and phase space projections of the dynamic aperture performed for a lattice with quadrupoles and sextupoles confirm that this is indeed the case.