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Magnesium (Mg) matrix composites (Mg-MMCs) with high strength and ductility properties are crucial for the development of lightweight automobiles. In this study, a novel method is proposed for fabricating Mg-MMCs by incorporating nanocopper (Cu) decorated titanium (Ti) particles (Cu@Ti) to reinforce AZ91 alloys. The in-situ generation of the AlCuMg phase at the interface between the Ti particles and the Mg matrix enhances interface integration and promotes the formation of massive twins. The 5.0 wt% Cu@Ti/AZ91 composite exhibits notable mechanical properties, with a yield strength of 238 MPa, ultimate tensile strength of 368 MPa, elongation of 12%, and modulus of elasticity of 46 GPa. These values represent increases of 8.9%, 5.3%, 50.0%, and 2.0%, respectively, compared to those of AZ91 alloys. The strengthening mechanism is mainly attributed to grain refinement strengthening, thermal expansion coefficient mismatch strengthening, Orowan strengthening, and load transfer strengthening. The plasticity improvement benefits from the optimization of the interface structure, grain refinement and twin formation.

In this study, nano Ti/AZ31 composites were successfully prepared by powder metallurgy method, and the strength and plasticity of the composites were improved in both directions. The SEM shows that the Ti particles were evenly distributed at the grain boundary in the sintered composite, and the Ti particles pin the grain boundary to make the grain of the composite significantly refined. EBSD shows that the addition of nano Ti particles significantly reduces the texture strength of the composite and increases the starting probability of the slip system. TEM shows that nano Ti and AZ31 matrix formed stable Al3Ti and MgO phases at the interface, and shows a strong coherent relationship. The nanoindentation test shows that the Ti/AZ31 interface of the composite was stable, the interface bonding energy and interface fracture toughness were gradiently distributed, and the bonding energy and fracture toughness of the interface bonding area were better than those of the matrix. Tensile test shows that the 1.5 wt%Ti/AZ31 composite obtained the best comprehensive mechanical properties with yield strength, ultimate tensile strength and elongation of 143 MPa, 243 MPa and 11.5%, respectively, obviously higher than those of AZ31 alloys. The increased strength was mainly due to the grain refinement and strengthening at grain boundaries. The improved ductility was the result of weakened texture, increase of slip system start-up probability and strong interfacial bonding between Ti particles and AZ31 matrix.

Carnitine palmitoyltransferase 1A (CPT1A), which resides on the mitochondrial outer membrane, serves as the rate-limiting enzyme of fatty acid β-oxidation. Identifying the compounds targeting CPT1A warrants a promising candidate for modulating lipid metabolism. In this study, we developed a CPT1A-overexpressed mitochondrial membrane chromatography (MMC) to screen the compounds with affinity for CPT1A. Cells overexpressing CPT1A were cultured, and subsequently, their mitochondrial membrane was isolated and immobilized on amino-silica gel cross-linked by glutaraldehyde. After packing the mitochondrial membrane column, retention components of MMC were performed with LC/MS, whose analytic peaks provided structural information on compounds that might interact with mitochondrial membrane proteins. With the newly developed MMC–LC/MS approach, several Chinese traditional medicine extracts, such as Scutellariae Radixand Polygoni Cuspidati Rhizoma et Radix(PCRR), were analyzed. Five noteworthy compounds, baicalin, baicalein, wogonoside, wogonin, and resveratrol, were identified as enhancers of CPT1A enzyme activity, with resveratrol being a new agonist for CPT1A. The study suggests that MMC serves as a reliable screening system for efficiently identifying modulators targeting CPT1A from complex extracts.

Adding Ti particles to magnesium alloy simultaneously enhances its strength and ductility. However, how these particles influence on Mg alloy’s corrosion performance is seldom reported. The corrosion behavior of AZ31-Ti composites containing titanium nanoparticles (1.5 and 5 wt%) and micron particles (10 wt%) prepared by powder metallurgical in 3.5 wt% NaCl solution was investigated. The results indicate that Ti particles serve as the primary location for the cathodic hydrogen reduction reaction, resulting in intense galvanic corrosion between the Ti and Mg matrix. Ti nanoparticles distributed at the interface of the original AZ31 powder were in a discontinuous mesh structure, thus failing to act as a barrier against corrosion. The corrosion products with the existence of numerous cracks gradually peel off during the corrosion process and cannot protect the matrix. The average corrosion rate Pwof AZ31, AZ31-1.5%Ti, AZ31-5%Ti, and AZ31-10%Ti after 7 days of immersion is 27.55, 105.65, 283.67, and 99.35 mm/y, respectively. Therefore, AZ31-Ti composites can be considered as potential candidates for degradable fracturing tools. Otherwise, it is recommended to improve their corrosion resistance through surface treatment.

• Al3Ti particles were in-situ synthesized for Ti particles reinforced AZ31 alloys by mechanical milling. • The orientation relationship between Al3Ti particles and Mg matrix was (10 1 ¯ 0)Mg // (001)Al3Ti; [ 1 ¯ 2 1 ¯ 3]Mg // [100]Al3Ti. • Al-HCP and TiAl-MT configurations show higher interfacial stability with the lower interface energy. • The mechanical failure is inclined to initiate in the interior of Mg bulk rather than the interface. The interfaces between in-situ Al 3 Ti particles and magnesium (Mg) matrix are crucial role in high-performance titanium (Ti) reinforced AZ31 alloy. Herein, the interfaces between Al 3 Ti particles and the Mg matrix are fabricated and investigated using advanced characterization tools and first-principles calculations. The orientation relationship (OR) and atomic interface structure between the Al 3 Ti particles and matrix are characterized using a high-resolution transmission electron microscope. The OR is determined to be (10 1 ¯ 0) Mg //(001) Al3Ti ; [ 1 ¯ 2 1 ¯ 3] Mg //[100] Al3Ti. Based on the characterized OR, the interface properties (including atomic structure, work of adhesion, interface energy, and fracture mechanism) are investigated using first-principles calculations. The relaxed interface structure indicates that the TiAl-terminated bridge site configurations (MT1) and hollow site configurations (HCP1) are unstable and would convert into other bridge site configurations (MT). Furthermore, the work of adhesion and interface energy suggests that Al-terminated hollow site configurations (HCP) and bridge site configurations (MT) are more stable than other configurations. In addition, the calculations of work of fracture show that fracture of the interfaces with Al-MT1, Al-HCP, and TiAl-MT configurations may initiate from bulk Mg interior. The findings may help to understand and tailor the deformation mechanisms and mechanical properties of Ti-reinforced Mg alloys. [ABSTRACT FROM AUTHOR]

Membrane protein immobilization is particularly significant in in vitro drug screening and determining drug–receptor interactions. However, there are still some problems in the immobilization of membrane proteins with controllable direction and high conformational stability, activity, and specificity. Cell membrane chromatography (CMC) retains the complete biological structure of membrane proteins. However, conventional CMC has the limitation of poor stability, which results in its limited life span and low reproducibility. To overcome this limitation, we propose a method for the specific covalent immobilization of membrane proteins in cell membranes. We used the SNAP-tag as an immobilization tag fused to the epidermal growth factor receptor (EGFR), and Cys145 located at the active site of the SNAP-tag reacted with the benzyl group of O6-benzylguanine (BG). The SNAP-tagged EGFR was expressed in HEK293 cells. We captured the SNAP-tagged EGFR from the cell membrane suspension onto a BG-derivative-modified silica gel. Our immobilization strategy improved the life span and specificity of CMC and minimized loss of activity and nonspecific attachment of proteins. Next, a SNAP-tagged EGFR/CMC online HPLC-IT-TOF-MS system was established to screen EGFR antagonists from Epimedii folium. Icariin, magnoflorine, epimedin B, and epimedin C were retained in this model, and pharmacological assays revealed that magnoflorine could inhibit cancer cell growth by targeting the EGFR. This EGFR immobilization method may open up possibilities for the immobilization of other membrane proteins and has the potential to serve as a useful platform for screening receptor-binding leads from natural medicinal herbs.

Mitochondrial Membrane Chromatography (MMC) is a bioaffinity chromatography technique developed to study the interaction between target proteins embedded in the mitochondrial membrane and their ligand compounds. However, the MMC stationary phases (MMSP) prepared by chemical immobilization are prone to nonspecific binding in candidate agent screening inevitably. To address these challenges, Twin Strep-Tag/Strep Tactin was employed to establish a specific affinity system in the present study. We prepared a carnitine palmitoyltransferase 1A (CPT1A) MMSP by specifically linking Strep-tactin-modified silica gel with the Twin Strep-Tag on the CPT1A-oriented mitochondrial membrane. This Twin Strep-Tag/Strep Tactin modified CPT1A/MMC method exhibited remarkably better retention behavior, longer stationary phase lifespan, and higher screening specificity compared with previous MMC systems with glutaraldehyde immobilization. We adopted the CPT1A-specific MMC system in screening CPT1A ligands from traditional Chinese medicines, and successfully identified novel candidate ligands: ononin, isoliquiritigenin, and aloe-emodin, from Glycyrrhiza uralensisFisch and Senna tora(L.) Roxb extracts. Biological assessments illustrated that the compounds screened promote CPT1A enzyme activity without affecting CPT1A protein expression, as well as effectively reduce the lipid droplets and triglyceride levels in the high fat induction HepG2 cells. The results suggest that we have developed an MMC system, which is promising for studying the bioaffinity of mitochondrial membrane proteins to candidate compounds. This system provides a platform for a key step in mitochondrial medicine discovery, especially for bioactive molecule screening from complex herbal extracts.

Mas-related G protein-coupled receptor X2 (MrgprX2) plays a crucial role in anaphylactoid reactions and allergic diseases. Some antagonists with reasonable potency and selectivity have been reported. Cell membrane chromatography (CMC) is effective for discovering ligands. Protein-tag-based CMC models (e.g., SNAP tags and HALO tags) have enhanced performance but also increased nonspecific adsorption of small molecules. The Avi tag, a short peptide sequence, binds biotin specifically via BirA catalysis. Our study showed that 2-iminobiotin (IB) can be a BirA substrate, enabling the development of a new cell membrane stationary phase (CMSP) based on the chemical properties (modifying carboxyl silica gel and specifically labeling the Avi tag) of IB. First, we constructed the MrgprX2-Avi-tag HEK293T cell line. Next, we synthesized IB-modified silica gel (SiO2–IB) stepwise. Finally, we immobilized Avi-tagged MrgprX2 cell membranes on SiO2–IB under BirA catalysis. We characterized the developed CMSP and used it to establish a MrgprX2-Avi-tag/CMC-HPLC/MS two-dimensional screening platform, successfully screening vitexicarpin fromViticis Fructusextract via a 2D/CMC platform. In vitroand in vivoexperiments confirmed that vitexicarpin targets the MrgprX2 receptor, demonstrating antiallergic effects. Our IB-Avi tag-based CMC approach effectively decreased nonspecific adsorption of the screening materials. The Avi-tag-based 2D/CMC platform is suitable for screening potential drug candidates.

A simple aqueous coordination self-assembly route has been demonstrated for the synthesis of copper containing ordered mesoporous polymers with mimosa tannin as the precursor and triblock copolymer Pluronic F127 (EO106PO70EO106) as the template. The introduction of naturally occurring mimosa tannin in lieu of the toxic and costly synthetic precursors makes the aqueous coordination self-assembly strategy a greener and scalable approach for the soft-templating synthesis of ordered mesoporous polymers. Well-dispersed metallic copper nanoparticles were generated in situ without additional chemical reduction process. The synthesized copper containing catalysts with uniform mesopores (8–9 nm), high surface area (532 m2/g), and large pore volume (0.65 cm3/g) exhibit high catalytic activity for the aerobic oxidation of both activated benzyl alcohol and nonactivated aliphatic and alicyclic alcohols. Under the optimized conditions, the conversions of benzyl alcohol, n-butanol, n-hexanol, n-octanol, cyclohexanol, and cyclooctanol with high selectivity to the corresponding aldehydes and ketones reached 86%, 64%, 56%, 56%, 84%, and 82%, respectively.

It is a great challenge to simultaneously improve the strength and ductility of magnesium matrix composites (MMCs). In this work, AZ91 alloys reinforced with 1 wt%, 2 wt%, and 3 wt% Ti particles were produced using stir casting combined with ball milling process. The microstructure of the extruded composite sheets was analyzed by X-ray diffraction (XRD), scanning electron microscope (SEM), electron backscatter diffraction (EBSD). Transmission electron microscopy (TEM) was utilized to observe the structure of the Ti/Mg interface. The mechanical properties of the composite sheets were also investigated. The results show that the adding Ti particles, the texture strength was decreased, and the growth of recrystallization grains was also restrained. Due to the interfacial reaction between Ti and Al, the formation of β-phase (Mg17Al12) was inhibited. The tensile test demonstrated that the Ti particles could significantly improve the mechanical properties of the AZ91 alloy sheets. Compared to AZ91 sheet, 2Ti/AZ91 composite sheet along extrusion direction (ED) showed the best comprehensive mechanical properties. The improvement in mechanical properties was mainly attributed to grain refinement, texture weakening, mismatched coefficient of thermal expansion (CTE), and work hardening.

A highly sensitive high performance liquid chromatography-electrochemical detection (HPLC-ECD) method being used to detect released serotonin in real time from rat basophilic leukemia 2H3 (RBL-2H3) cells which can be stimulated by potential allergens was established to evaluate the sensitization of potential allergens. Chromatographic separation was carried out on a Chromolith R Speed ROD RP-18e column (50 mm × 4.6 mm I.D., 2 μm). The linearity of serotonin in samples was good, with correlation coefficients greater than 0.9986 within the corresponding concentration range. The relative standard deviation (RSD) percentages were in the range of 0.72%–2.96% for inter-day precision and in the range of 2.02%–3.48% for intra-day precision. The relative errors (REs) were within ±3.21%. The recovery of serotonin was in the range of 100.98%–101.56%, and the RSDs of recovery were less than 2.28%. The method allows for simple sample preparation, short analysis time, and high sensitivity, specificity, and reliability. This method was successfully used to detect serotonin released by RBL-2H3 cells stimulated by different concentrations of schisandrin A and harpagoside. The results demonstrate that schisandrin A and harpagoside can trigger RBL-2H3 cells to release serotonin in a dose-dependent manner. The study contributes to the further use of evaluation of potential allergens.

Agrimony is a traditional Chinese medicine and a herb of Agrimonia pilosa Ledebbelonging to the Rosaceaefamily. Many pharmacological effects of agrimony have been demonstrated in previous studies. Few studies have screened the active compounds in this complex product for chronic prostatitis. In this study, a two dimensional online method was established. A Sprague-Dawley (SD) rat prostate CMC-online-HPLC/MS method was used to screen, analyze, and identify active compounds acting on α1adrenergic receptor from agrimony. Viathis online method agrimonolide was screened, analyzed, and identified as the active compound acting on α1adrenergic receptor. Thus, agrimonolide is a potential α1adrenergic receptor antagonist and requires further study.