There are numerous prescription drugs and non-prescription drugs that cause drug-induced liver injury (DILI), which is the main cause of liver disease in humans around the globe. Its mechanism becomes clearer as the disease is studied further. For an instance, when acetaminophen (APAP) is taken in excess, it produces N-acetyl-p-benzoquinone imine (NAPQI) that binds to biomacromolecules in the liver causing liver injury. Treatment of DILI with traditional Chinese medicine (TCM) has shown to be effective. For example, activation of the Nrf2 signaling pathway as well as regulation of glutathione (GSH) synthesis, coupling, and excretion are the mechanisms by which ginsenoside Rg1 (Rg1) treats APAP-induced acute liver injury. Nevertheless, reducing the toxicity of TCM in treating DILI is still a problem to be overcome at present and in the future. Accumulated evidences show that hydrogel-based nanocomposite may be an excellent carrier for TCM. Therefore, we reviewed TCM with potential anti-DILI, focusing on the signaling pathway of these drugs' anti-DILI effect, as well as the possibility and prospect of treating DILI by TCM based on hydrogel materials in the future. In conclusion, this review provides new insights to further explore TCM in the treatment of DILI. 

Progress in the treatment of drug-induced liver injury with natural products.

The intracellular fate and transport mechanism of shape, size and rigidity varied nanocarriers for understanding their oral delivery efficiency.

The difficulty in exerting beneficial effects of fine grains, high number density nano-precipitates as well as weakened texture simultaneously is currently the bottleneck limiting the development of high performance (high strength, high plasticity, and isotropic) age-hardenable Mg-RE alloys. The key difficulty is that the generation of excessive dynamic precipitates is always accompanied by the formation of fully dynamic recrystallized ultrafine grains during thermal deformation, causing a significant depletion of solutes within the entire matrix and finally seriously weakening the subsequent aging nano-precipitation. In this work, the process of extreme short-time (2 min) heat treatment (ESHT) followed by peak aging treatment is applied to an ultrafine-grained weak-textured Mg-RE-Ag as-extruded alloy with numerous dynamic precipitates. The precipitation hardening response is dramatically increased (ΔHV = 37.2 HV) and the yield strength is increased by nearly 50 MPa. This is attributed to the fact that concentration of main solutes in matrix is greatly increased within only 2 min of heat treatment promoting the precipitation of nano-precipitates (prismatic β′ and basal γ′′) in the absence of excessive grain growth. The large difference between the initial and equilibrium solute concentrations, the extremely short distance required for solute diffusion within sub-microscale grains, and the effective pinning of grain boundaries by excess dynamic precipitates are responsible for the unusual microevolution during the ESHT. In addition, the formation of precipitation-free zones (PFZs) is attributed to 'uphill' diffusion during aging, and novel γ′′-PFZs and β′-PRZs are found. The ESHT followed by peak aging treatment provides a new way to simultaneously exert the beneficial effects of fine grains and high number density nano-precipitates. 

Regulating microstructure and improving precipitation hardening response of fine-grained Mg-RE-Ag hot-extruded alloy by extreme short-time heat treatment

Thrombotic diseases have a high rate of mortality and disability, and pose a serious threat to global public health. Currently, most thrombolytic drugs especially protein drugs have a short blood-circulation time, resulting in low thrombolytic efficiency. Therefore, a platelet membrane (Pm) cloaked nanotube (NT-RGD/Pm) biomimetic delivery system with enhanced thrombolytic efficiency is designed. Nanotubes (NT) with an excellent clot-penetration properties are used to load a protein thrombolytic drug urokinase (Uk). Platelet-targeting arginine glycine-aspartic peptide (RGD) is grafted onto the surface of the nanotubes (NT-RGD) prior to cloaking. Multiple particle tracking (MPT) technique and confocal laser scanning microscope (CLSM) analysis are applied and the results show that the nanotubes possess a strong penetration and diffusion capacity in thrombus clots. After the Pm cloaking on NT-RGD/Uk, it shows a thrombus microenvironmental responsive release property and the half-life of Uk is six times longer than that of free Uk. Most importantly, NT-RGD-Uk/Pm exhibits a 60% thrombolytic efficiency in the FeCl3 -induced thrombosis mouse model, and it is able to significantly reduce the bleeding side effects of Uk. This Pm-cloaked nanotube system is an effective and promising platform for the controlled and targeted delivery of drugs for the thrombus treatment.

Platelet Membrane Cloaked Nanotubes to Accelerate Thrombolysis by Thrombus Clot-Targeting and Penetration.

Antibiotic resistance is emerging as a "global public health concern". To address the growing epidemic of multidrug-resistant pathogens, the development of novel antimicrobials is urgently needed. In this study, by biomimicking cationic antibacterial peptides, we designed and synthesized a series of new membrane-active nonivamide and capsaicin derivatives as peptidomimetic antimicrobials. Through modulating charge/hydrophobicity balance and rationalizing structure-activity relationships of these peptidomimetics, compound 51 was identified as the lead compound. Compound 51 exhibited potent antibacterial activity against both Gram-positive bacteria (MICs = 0.39-0.78 μg/mL) and Gram-negative bacteria (MICs = 1.56-6.25 μg/mL), with low hemolytic activity and low cytotoxicity. Compound 51 displayed a faster bactericidal action through a membrane-disruptive mechanism and avoided bacterial resistance development. Furthermore, compound 51 significantly reduced the microbial burden in a murine model of keratitis infected by Staphylococcus aureus or Pseudomonas aeruginosa. Hence, this design strategy can provide a promising and effective solution to overcome antibiotic resistance.

Membrane-Active Nonivamide Derivatives as Effective Broad-Spectrum Antimicrobials: Rational Design, Synthesis, and Biological Evaluation.

Intestinal-targeted nanotubes-in-microgels composite carriers for capsaicin delivery and their effect for alleviation of Salmonella induced enteritis.

Co-doping of multiple ions can effectively adjust the biological properties of hydroxyapatite (HA) for various biomedical applications. In this study, we prepared Sr2+ and Cu2+ double-doped hollow HA and characterized them by SEM, EDS, XRD, FTIR, and other methods. We found that Sr2+ and Cu2+ were uniformly distributed in the hollow carbonic acid HA microspheres. As the proportion of metal elements increases, the microspherical appearance and crystallinity properties also change. In addition, we also prepared porous titanium scaffolds through 3D printing technology and constructed composite scaffolds of porous titanium scaffolds, Sr2+ and Cu2+ double-doped HA, and gelatin. In vitro cell experiments and bacterial experiments, the composite scaffolds, especially the 10%Cu-10%Sr- HA/Gel/Ti group scaffolds, have good biocompatibility and integration with bone tissues, promoting the proliferation and differentiation of BMSCs while having excellent antibacterial properties. These composite scaffolds can simultaneously achieve bone defect filling, osteoblast differentiation, and antibacterial functions, owning broad clinical application prospects.

Titanium scaffold loaded with strontium and copper double-doped hydroxyapatite can inhibit bacterial growth and enhance osteogenesis

A cellular automata model was established to simulate grain coarsening processes pinned by second-phase particles. The influences of particle coarsening, precipitation, growth and dissolution, which contain complex changes of size and number density of the particles, on the grain coarsening kinetics were investigated by considering the following two factors: average pinning force per particle and particle number density. The simulation results showed that the average pinning force per particle was related to the particle size, but little influenced by the particle number density. The investigations about the grain boundary/particles interactions showed that the increase of number fraction of particles, which located at the grain boundary junctions, should be the reason for the increase of average pinning force per particle. Then the limiting grain size was researched and compared to the results of some other models. The results showed that the average number of particles to stagnate a grain was related to both the number density and size of particles. At last, the comparisons between the present simulation results and the other simulation and experimental results showed that the present models were efficient in simulating the grain coarsening processes pinned by second-phase particles.

/pdf/influences-of-second-phase-particle-precipitation-coarsening-3ubgxwl9.pdf

Influences of Second Phase Particle Precipitation, Coarsening, Growth or Dissolution on the Pinning Effects during Grain Coarsening Processes

The austenitization of low alloy steels during rapid heating processes was involved in many kinds of advanced heat treatment technologies. Most of the previous research on the austenitization kinetics was focused on the spherical pearlite microstructures, which were different from the lamellar pearlite microstructures. In the present research, to predict the non-isothermal austenitization process of an Fe-C-Cr steel with lamellar pearlite, a novel 3-dimensional (3D) cellular automata model, which considered the influences of the coupling diffusion of Cr and C, and the interfacial diffusion between pearlite lamellae and the pearlite lamellar orientation, was established based on the thermodynamic equilibrium data obtained from the Thermo-Calc software and the simulation results of the DICTRA module. To clarify the influences of the heating rate on the austenitization kinetics and validate the simulation results, the austenitization processes of a Fe-1C-1.41Cr steel for different heating rates were studied with a series of dilatometric experiments. The good agreements between the cellular automata simulation results and the experimental results showed that the newly proposed cellular automata model is reasonable. The experimental results show an obvious change of the transition activity energies from the low to high heating rates. The transition from partitioning local equilibrium (PLE) to non-partitioning local equilibrium (NPLE) mechanisms was proved with DICTRA simulations. Basing on the simulation results, the influences of the pearlite lamellae orientation on the austenitization kinetics and the topological aspects of austenite grains were evaluated. In addition, the topological aspects of the rapidly austenitized grains were also compared to the normal grains.

/pdf/prediction-of-the-non-isothermal-austenitization-kinetics-of-25dkiuik.pdf

Prediction of the Non-Isothermal Austenitization Kinetics of Fe-C-Cr Low Alloy Steels with Lamellar Pearlite Microstructure

Uniform pinning force model for the polycrystalline systems pinned by second-phase particles of different sizes, number densities and shapes

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