[Composition changes reveal relationship between color and enzymatic reaction of Magnoliae Officinalis Cortex during "sweating" process].

In this study, we employed Q Exactive to determine the main differential metabolites of Magnoliae Officinalis Cortex du-ring the "sweating" process. Further, we quantified the color parameters and determined the activities of polyphenol oxidase(PPO), peroxidase(POD), and tyrosinase of Magnoliae Officinalis Cortex during the "sweating" process. Gray correlation analysis was performed for the color, chemical composition, and enzyme activity to reveal the effect of enzymatic reaction on the color of Magnoliae Officinalis Cortex during the "sweating" process. Magnoliae Officinalis Cortex sweating in different manners showed similar metabolite changes. The primary metabolites that changed significantly included amino acids, nucleotides, and sugars, and the secondary metabolites with significant changes were phenols and phenylpropanoids. Despite the different sweating methods, eleven compounds were commonly up-regulated, including L-glutamic acid, acetylarginine, hypoxanthine, and xanthine; six compounds were commonly down-re-gulated, including L-arginine, L-aspartic acid, and phenylalanine. The brightness value(L~*), red-green value(a~*), and yellow-blue value(b~*) of Magnoliae Officinalis Cortex kept decreasing during the "sweating" process. The changes in the activities of PPO and POD during sweating were consistent with those in the color parameter values. The gray correlation analysis demonstrated that the main differential metabolites such as amino acids and phenols were closely related to the color parameters L~*, a~* and b~*; POD was correlated with amino acids and phenols; PPO had strong correlation with phenols. The results indicated that the color change of Magnoliae Officinalis Cortex during "sweating" was closely related to the reactions of enzymes dominated by PPO and POD. The study analyzed the correlations among the main differential metabolites, color parameters, and enzyme activities of Magnoliae Officinalis Cortex in the "sweating" process. It reveals the common law of material changes and ascertains the relationship between color changes and enzymatic reactions of Magnoliae Officinalis Cortex during "sweating". Therefore, this study provides a reference for studying the "sweating" mechanism of Magnoliae Officinalis Cortex and is of great significance to guarantee the quality of Magnoliae Officinalis Cortex.

Creating rat hepatocyte organoid as an in vitro model for drug testing.

BACKGROUND: Liver organoids have recently been applied as models for liver disease and drug screening, especially when combined with liver-on-a-chip technologies. Compared to hepatocyte-like cells, primary hepatocytes have high functionality but cannot maintain their function when cultured in vitro. Mesenchymal stem cells (MSCs) enhance hepatocyte function and maintain hepatocyte metabolism when co-cultured with hepatocytes. MSCs can help induced pluripotent stem cells to generate an organoid structure via the MSC-based traction force triggered by extracellular matrix (ECM) proteins. In this study, primary hepatocytes were co-cultured with MSCs on a liver-derived ECM to generate liver organoids within a short duration. AIM: To create hepatocyte organoids by co-culturing primary hepatocytes with MSCs on a porcine liver extracellular matrix (PLECM) gel. METHODS: Perfusion and enzymatic hydrolysis were used to form the PLECM gel. Rat hepatocytes and human MSCs were mixed and plated on pre-solidified PLECM gel in a 48-well plate for 48 h to generate organoids. Generated organoids were evaluated through hematoxylin and eosin, periodic acid-Schiff, immuno-histological, and immunofluorescence staining, and quantitative PCR for alb, CYP450 gene markers, and urea cycle genes. Culture medium was collected to detect albumin (ALB) and urea production on days 2, 4, 6, 8, 14, and 20. RESULTS: The whole porcine liver was perfused and enzymatically hydrolyzed to form a PLECM gel. The structural components and basement membrane composition of the ECM, such as collagen type I, collagen type IV, fibronectin, and laminin, were demonstrated to be retained. Through interaction of human MSCs with the liver-derived ECM, primary hepatocytes and human MSCs assembled together into a 3D construction and generated primary hepatocyte organoids for 48 h. The mRNAs of the gene alb, the CYP450 gene markers cyp1a1, cyp1a2, and cyp3a2 as well as urea cycle genes arg-1, asl, ass-1, cps-1, nags were highly expressed in hepatocyte organoids. Long-term survival of the primary hepatocyte organoids, as well as stable functionality, was demonstrated via ALB and urea production in vitro. CONCLUSION: Our new method of creating primary hepatocyte organoids by co-culturing hepatocytes with MSCs on liver-derived ECM hydrogels could be used to develop models for liver disease and for drug screening.

Extremely brilliant GeV γ-rays from a two-stage laser-plasma accelerator.

Recent developments in laser-wakefield accelerators have led to compact ultrashort X/γ-ray sources that can deliver peak brilliance comparable with conventional synchrotron sources. Such sources normally have low efficiencies and are limited to 107-8 photons/shot in the keV to MeV range. We present a novel scheme to efficiently produce collimated ultrabright γ-ray beams with photon energies tunable up to GeV by focusing a multi-petawatt laser pulse into a two-stage wakefield accelerator. This high-intensity laser enables efficient generation of a multi-GeV electron beam with a high density and tens-nC charge in the first stage. Subsequently, both the laser and electron beams enter into a higher-density plasma region in the second stage. Numerical simulations demonstrate that more than 1012 γ-ray photons/shot are produced with energy conversion efficiency above 10% for photons above 1 MeV, and the peak brilliance is above 1026 photons s-1 mm-2 mrad-2 per 0.1% bandwidth at 1 MeV. This offers new opportunities for both fundamental and applied research.

Efficient generation of relativistic near-single-cycle mid-infrared pulses in plasmas.

Ultrashort intense optical pulses in the mid-infrared (mid-IR) region are very important for broad applications ranging from super-resolution spectroscopy to attosecond X-ray pulse generation and particle acceleration. However, currently, it is still difficult to produce few-cycle mid-IR pulses of relativistic intensities using standard optical techniques. Here, we propose and numerically demonstrate a novel scheme to produce these mid-IR pulses based on laser-driven plasma optical modulation. In this scheme, a plasma wake is first excited by an intense drive laser pulse in an underdense plasma, and a signal laser pulse initially at the same wavelength (1 micron) as that of the drive laser is subsequently injected into the plasma wake. The signal pulse is converted to a relativistic multi-millijoule near-single-cycle mid-IR pulse with a central wavelength of ~5 microns via frequency-downshifting, where the energy conversion efficiency is as high as approximately 30% when the drive and signal laser pulses are both at a few tens of millijoules at the beginning. Our scheme can be realized with terawatt-class kHz laser systems, which may bring new opportunities in high-field physics and ultrafast science.

Exploration of the structure-activity relationship and druggability of novel oxazolidinone-based compounds as Gram-negative antibacterial agents.

To gain further knowledge of the structure-activity relationship and druggability of novel oxazolidinone-based UDP-3-O-acyl-N-acetylglucosamine deacetylase (LpxC) inhibitors as Gram-negative antibacterial agents, compounds containing the hydrophobic tails with different lengths and terminal substitutions were synthesized and their antibacterial activities against standard and clinically isolated Gram-negative strains were evaluated. We summarized their structure-activity relationships and found that oxazolidinone-based compounds exhibited a narrower antibacterial spectrum compared with threonine-based compounds. Furthermore, we parallelly compared the metabolic stabilities of the compounds with the classic threonine scaffold and the novel oxazolidinone scaffold in liver microsomes. The results indicated that the druggability of the oxazolidinone scaffold may be inferior to the classic threonine scaffold in the design of LpxC inhibitors.

Ultra-bright γ-ray emission and dense positron production from two laser-driven colliding foils.

Matter can be transferred into energy and the opposite transformation is also possible by use of high-power lasers. A laser pulse in plasma can convert its energy into γ-rays and then e - e + pairs via the multi-photon Breit-Wheeler process. Production of dense positrons at GeV energies is very challenging since extremely high laser intensity ~1024 Wcm-2 is required. Here we propose an all-optical scheme for ultra-bright γ-ray emission and dense positron production with lasers at intensity of 1022-23 Wcm-2. By irradiating two colliding elliptically-polarized lasers onto two diamondlike carbon foils, electrons in the focal region of one foil are rapidly accelerated by the laser radiation pressure and interact with the other intense laser pulse which penetrates through the second foil due to relativistically induced foil transparency. This symmetric configuration enables efficient Compton back-scattering and results in ultra-bright γ-photon emission with brightness of ~1025 photons/s/mm2/mrad2/0.1%BW at 15 MeV and intensity of 5 × 1023 Wcm-2. Our first three-dimensional simulation with quantum-electrodynamics incorporated shows that a GeV positron beam with density of 2.5 × 1022 cm-3 and flux of 1.6 × 1010/shot is achieved. Collective effects of the pair plasma may be also triggered, offering a window on investigating laboratory astrophysics at PW laser facilities.

Dense GeV electron-positron pairs generated by lasers in near-critical-density plasmas.

Pair production can be triggered by high-intensity lasers via the Breit-Wheeler process. However, the straightforward laser-laser colliding for copious numbers of pair creation requires light intensities several orders of magnitude higher than possible with the ongoing laser facilities. Despite the numerous proposed approaches, creating high-energy-density pair plasmas in laboratories is still challenging. Here we present an all-optical scheme for overdense pair production by two counter-propagating lasers irradiating near-critical-density plasmas at only ∼1022 W cm-2. In this scheme, bright γ-rays are generated by radiation-trapped electrons oscillating in the laser fields. The dense γ-photons then collide with the focused counter-propagating lasers to initiate the multi-photon Breit-Wheeler process. Particle-in-cell simulations indicate that one may generate a high-yield (1.05 × 1011) overdense (4 × 1022 cm-3) GeV positron beam using 10 PW scale lasers. Such a bright pair source has many practical applications and could be basis for future compact high-luminosity electron-positron colliders.

All-optical bright γ-ray and dense positron source by laser driven plasmas-filled cone.

An all-optical scheme for bright γ-rays and dense e-e+ pair source is proposed by irradiating a 1022 W/cm2 laser onto a near-critical-density plasmas filled Al cone. Two-dimensional (2D) QED particle-in-cell (PIC) simulations show that, a dense electron bunch is confined in the laser field due to the radiation reaction and the trapped electrons oscillate transversely, emitting bright γ-rays forward in two ways: (1) nonlinear Compton scattering due to oscillation of electrons in the laser field, and (2) Compton backwardscattering resulting from the bunch colliding with the reflected laser by the cone tip. Finally, the multi-photon Breit-Wheeler process is initiated, producing abundant e-e+ pairs with a density of ∼ 1027m-3. The scheme is further demonstrated by full 3D PIC simulations, which indicates a positron number up to 2 × 109. This compact γ-rays and e-e+ pair source may have many potential applications, such as the laboratory study of astrophysics and nuclear physics.