Powder Synthesis and Characterization of Al0.5CoCrFeNi High-Entropy Alloy for Additive Manufacturing Prepared by the Plasma Rotating Electrode Process.

The Al0.5CoCrFeNi high-entropy alloy powder was produced by using a plasma rotating electrode process. The morphology, microstructure, and physical properties of the powder were characterized. The powder exhibited a smooth surface and a narrow particle size distribution with a single peak. The relationships between particle size and secondary dendrite arm space as well as cooling rate were evaluated as follows: λ = 0.0105d + 0.062 and vc = 4.34 × 10-5d-2 + 2.62 × 10-2d-3/2, respectively. The Al0.5CoCrFeNi powder mainly consisted of fcc + bcc phases. As the powder particle size decreased, the microstructure of the powder changed from dendritic to columnar or equiaxed, along with a decrease in the fcc content and an increase in the bcc content. The tap density (4.76 g cm-3), flowability (15.01 s × 50 g-1), oxygen content (<300 ppm), and sphericity (>94%) of the powder indicated suitability for additive manufacturing.

Excessive consumption of mucin by over-colonized Akkermansia muciniphila promotes intestinal barrier damage during malignant intestinal environment.

Gut microbiota disorders damage the intestinal barrier, which causes intestinal disease. Thus, we screened the microbiota with significant changes using an in situ malignant colorectal cancer (CRC) model. Among the colonies with increased abundance, Akkermansia muciniphila (A. muciniphila) is known for its characteristic of breaking down mucin, which is an essential component of the intestinal barrier. The role of A. muciniphila remains controversial. To investigate the effect of excess A. muciniphila on the intestinal barrier, we established an over-colonized A. muciniphila mouse model by administering a live bacterial suspension after disrupting the original gut microbiome with antibiotics. The results showed that over-colonization of A. muciniphila decreased intestinal mucin content. The mRNA and protein expression levels of tight junction proteins also decreased significantly in the over-colonized A. muciniphila mouse model. Our findings reveal that excess colonization by A. muciniphila breaks the dynamic balance between mucin secretion and degradation, reduces the thickness of the intestinal mucus layer, and damages the intestinal barrier, which would eventually aggravate the development of colitis and CRC. These results will raise awareness about the safety of A. muciniphila serving as a probiotic.

Effect of Solution Treatment Time on Microstructure Evolution and Properties of Mg-3Y-4Nd-2Al Alloy.

In order to explore the microstructure evolution of an Mg-RE alloy refined by Al during solution treatment, an Mg-3Y-4Nd-2Al alloy was treated at 545 °C for different time periods. Phase evolution of the alloy was investigated. After solution treatment, the Mg-RE eutectic phase in the Mg-3Y-4Nd-2Al alloy dissolves, the granular Al2RE phase does not change, the acicular Al11RE3 phase breaks into the short rod-like Al2RE phase, and the lamellar Al2RE phase precipitates in the grains. With the extension of solution time, the precipitated phase of the lamellar Al2RE increased at first and then decreased, and its orientation relationship with the matrix is <112>Al2RE//<21¯1¯0>Mg and {111}Al2RE//{0002}Mg. The undissolved granular Al2RE phase can improve the thermal stability of the alloy grain by pinning the grain boundary, and the grain size did not change after solution treatment. Solution treatment significantly improved the plasticity of the alloy. After 48 h of solution treatment, the elongation increased to 17.5% from 8.5% in the as-cast state.

Mechanism of Shrinkage in Compacted Graphite Iron and Prediction of Shrinkage Tendency.

Shrinkage greatly influences the mechanical and fatigue properties of compacted graphite iron and it is necessary in order to study the causes of shrinkage in compacted graphite iron and to predict it effectively. In this paper, a kind of cylindrical necking test sample was designed to evaluate the shrinkage in compacted graphite iron, and a method to calculate the size of shrinkage was proposed. By observing the microstructure around the shrinkage zone, it is concluded that concentrated shrinkage mainly appears in the solidification region where the dendritic gap is closed, and the isolated shrinkage mainly occurs in the final solidification region, and the supersaturated carbon elements are gathered on the surface of the shrinkage. The cause of shrinkage in compacted graphite iron is caused by its solidification method, where the austenite dendrites and the eutectic clusters are generated close to the melt zone during the solidification process, leading to the inability to feed the shrinkage. Based on the thermodynamic analysis, the equations between the volume change of each phase, solid phase rate, and time during solidification of compacted graphite iron were established to theoretically explain the formation mechanism of the shrinkage. Taking nine parameters such as the chemical elements and characteristic values of thermal analysis as the input nods, a four-layer BP neural network model for predicting the size of shrinkage in compacted graphite iron was constructed, and the R-squared of the model reached 97%, which indicates it could be used to predict the shrinkage tendency.

Microstructure and Mechanical Properties of EK30 Alloy Synergistically Reinforced by Ag Alloying and Hot Extrusion for Aerospace Applications.

Enhancing the mechanical properties of magnesium alloys to meet the urgent need for their lightweight applications in the aerospace field has always been a great challenge. Herein, the effect of Ag on the microstructure and tensile properties of the Mg-2.5Nd-1.0Sm-0.4Zn-0.1Ca-0.5Zr (EK30) alloy prepared by integrated extrusion and equal-channel angular pressing is studied. The microstructure of as-extruded alloys consists of α-Mg grains and the ß phase. The addition of Ag increases the ß-phase content. The ß phase can promote dynamic recrystallization by inducing a particle-stimulated nucleation mechanism and inhibiting grain growth, which leads to grain refinement and texture weakening. At 250 °C, the ultimate tensile strength of the EK30-2.0Ag alloy (225.9 MPa) increased by 13.8% compared to the Ag-free alloy (198.4 MPa). When the tensile temperature increased from 25 °C to 250 °C, the ultimate tensile strength of the EK30-2.0Ag alloy decreased by 14.3%, from 263.7 MPa to 225.9 MPa. Notably, the addition of Ag slightly reduced the elongation of the alloy at 250 °C; the elongations of the EK30-2.0Ag alloy and the EK30 alloy are 41.5% and 37.0%, respectively. The elongation of the EK30-2.0Ag alloy increased from 22.7% at 25 °C to 52.7% at 275 °C. All alloy tensile fractures exhibited typical plastic fracture characteristics. This study provides an effective way to enhance the high-temperature mechanical properties of magnesium alloys by Ag alloying and a special severe plastic deformation method.

Corrigendum: Lycium barbarum Glycopeptide prevents the development and progression of acute colitis by regulating the composition and diversity of the gut microbiota in mice.

[This corrects the article DOI: 10.3389/fcimb.2022.921075.].

Hawthorn fruit acid consumption attenuates hyperlipidemia-associated oxidative damage in rats.

Context: Hyperlipidemia is a highly prevalent risk factor for atherosclerosis and stroke. The currently available medications used to treat Hyperlipidemia cannot improve its oxidative stress damage. Consumption of hawthorn can regulate blood sugar and blood lipids, and its rich fruit acid is a natural antioxidant that can improve oxidative stress damage. Objective: The present research aimed to investigate the protective effect of hawthorn fruit acid (HFA) on hyperlipidemia and to determine its potential molecular mechanism. Materials and methods: Sprague-Dawley rats were fed a high-fat diet (HFD) to induce hyperlipidemia and treated orally with hawthorn fruit acids (HFA). Serum and liver levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), superoxide dismutase (SOD), hydrogen peroxide (CAT), and malondialdehyde (MDA) were measured. Human hepatocellular carcinoma cell lines (HepG2) cells were treated with 0.1 mM oleic acid and HFA (0.125, 0.25 mg/mL), and intracellular TC, TG, HDL-C, SOD, CAT and MDA were measured. Changes in LDLR, HMGCR, Nrf2, HO-1, NQO1 protein and gene expression were analyzed by Western blot and qPCR. Results: This study found that HFA treatment effectively reduced the level of triglyceride, cholesterol, and glucose, and attenuated hepatic steatosis in rats. Additionally, oxidative stress damage of rats was effectively reduced by treatment with HFA. Western blot and qPCR analysis indicated that HFA treatment inhibited fat accumulation in HepG2 cells by upregulating LDLR and downregulating HMGCR gene expression. HFA inhibits oleic acid (OA)-induced oxidative damage to HepG2 by activating the Nrf2/HO-1 signaling pathway. Conclusion: HFA administration can provide health benefits by counteracting the effects of hyperlipidemia caused by an HFD in the body, and the underlying mechanism of this event is closely related to the activation of the Nrf2/HO-1 signaling pathway.

Lycium barbarum Glycopeptide prevents the development and progression of acute colitis by regulating the composition and diversity of the gut microbiota in mice.

In most cases, recurrent chronic colitis is caused by the recurrence of acute colitis after incomplete recovery and re-exposure to irritating factors, and the gut microbiome, which is the largest micro-ecosystem in the human body, plays a crucial role in the development of colitis. Plant polysaccharides have always been reported to have the ability for anti-inflammation, and they are closely related to the gut microbiome. Lycium barbarum Glycopeptide (LbGP), the most potent component obtained by further isolation and purification from Lycium barbarum fruit, has been shown to inhibit inflammation in animal models. However, its therapeutic efficacy in colitis and its mechanism in gut microbiota regulation have not been fully studied. In our study, the dextran sulfate sodium (DSS)-induced mouse model was used to dynamically evaluate the effect of LbGP in the treatment of acute colitis and the mechanism from the perspective of the gut microbiome through the 16S rDNA sequence. The results showed that LbGP treatment significantly alleviated acute colitis and improved the gut microbiome compared with that in the model group. Harmful bacteria, such as Lachnoclostridium spp. and Parabacteroides_distasonis, were inhibited and probiotics, such as Bacteroides_acidifaciens, Lactobacillus spp., Turicibacter spp., and Alistipes spp., were increased by LbGP treatment. Further, a Random Forest analysis with 10-fold cross-validation identified a family named Muribaculaceae representing colitis development and recovery upon LbGP treatment. In conclusion, our study demonstrated the capability of LbGP to prevent the development of acute colitis by regulating the composition and diversity of the gut microbiota and highlighted the dynamic process of gut microbiota with the colitis progression. Further, it provides evidence to develop LbGP as a functional food supplement and future drug acting on intestinal disease.

Mucus-permeable polymyxin B-hyaluronic acid/ poly (lactic-co-glycolic acid) nanoparticle platform for the nebulized treatment of lung infections.

The aim of this study was to improve the bioavailability of polymyxin B (PMB) in pulmonary nebulized drug delivery. To this end, we developed a nano-delivery system that penetrates the mucus barrier of the lung. Hydrophilic hyaluronic acid (HA) was combined with a water-in-oil system containing a poly (lactic acid)-glycolic acid copolymer of PMB to prepare HA@PLGA-PMB nanoparticles (NPs) with good surface properties. HA@PLGA-PMB NPs with suitable electrical properties, particle size, and good hydrophilicity prevented strong interactions between the NPs and mucus, thereby allowing more drugs to enter deeper into the lung. Compared to the free drug PMB, NPs had more than 2-fold higher mucus penetration efficiency in vitro and better delivery to infected alveolar cells during in vivo nebulization. NPs had better biocompatibility, which further reduced the drug toxicity. More importantly, NPs showed better antimicrobial therapeutic efficacy in the treatment of lung infections in mice. These findings may provide support for the clinical application of nebulized pulmonary antibiotics.

Red Blood Cell Membrane-Coated Ultrasmall NaGdF4 Nanoprobes for High-Resolution 3D Magnetic Resonance Angiography.

Enhanced angiography based on magnetic resonance imaging (MRI) has emerged as a noninvasive, robust, and high-resolution imaging technique for the clinical evaluation of vascular diseases. However, the effects of clinical Gd-chelating contrast agents are unsatisfactory for MRI contrast enhancement owing to their short blood half-life caused by rapid vascular extravasation, especially in microvessels. To address these issues, nanoprobes based on red blood cell membrane-coated ultrasmall NaGdF4 nanoparticles that exhibit much higher longitudinal molar relaxivity (r1) than the clinically used contrast agent gadolinium diethylenetriaminepentaacetic acid have been developed. Furthermore, the appropriate hydrodynamic diameter and stealth nature aid the nanoprobes to reside longer within the blood vessels without extravasation, thereby increasing the contrast between the blood vessels and surrounding tissues. Through probe-enhanced three-dimensional (3D) dynamic contrast-enhanced MR angiography, the main arteries and veins of the mouse were readily discernible, and even tiny vessels with sub-millimeter diameters could be clearly depicted. With this level of outstanding MR angiography performance, the embolization and recanalization processes of the carotid artery can be serially monitored with high imaging resolution using only a single injection. Additionally, the results of clearance studies and the toxicity tests further highlight the safety features of the nanoprobe. To summarize, the nanoprobes used in this study exhibit less extravascular leakage and a longer blood half-life, thus successfully overcoming the defects of the conventional low-molecular-weight Gd-based contrast agents and demonstrating their potential usefulness in enhanced MR angiography.

Nanotherapeutics Overcoming the Blood-Brain Barrier for Glioblastoma Treatment.

Glioblastoma (GBM) is the most common malignant primary brain tumor with a poor prognosis. The current standard treatment regimen represented by temozolomide/radiotherapy has an average survival time of 14.6 months, while the 5-year survival rate is still less than 5%. New therapeutics are still highly needed to improve the therapeutic outcome of GBM treatment. The blood-brain barrier (BBB) is the main barrier that prevents therapeutic drugs from reaching the brain. Nanotechnologies that enable drug delivery across the BBB hold great promise for the treatment of GBM. This review summarizes various drug delivery systems used to treat glioma and focuses on their approaches for overcoming the BBB to enhance the accumulation of small molecules, protein and gene drugs, etc. in the brain.

Effect of Al Content on Microstructure Evolution and Mechanical Properties of As-Cast Mg-11Gd-2Y-1Zn Alloy.

In the present paper, the Mg-11Gd-2Y-1Zn alloys with different Al addition were fabricated by the gravity permanent mold method. The effect of Al content on microstructure evolution and mechanical properties of as-cast Mg-11Gd-2Y-1Zn alloy was studied by metallographic microscope, scanning electron microscope, XRD and tensile testing. The experimental results showed that the microstructure of as-cast Mg-11Gd-2Y-1Zn alloy consisted of α-Mg phase and island-shaped Mg3 (RE, Zn) phase. When Al element was added, Al2RE phase and lamellar Mg12REZn (LPSO) phase were formed in the Mg-11Gd-2Y-1Zn alloy. With increasing Al content, LPSO phase and Mg3 (RE, Zn) phase gradually decreased, while Al2RE phase gradually increased. There were only α-Mg and Al2RE phases in the Mg-11Gd-2Y-1Zn-5Al alloy. With the increase of Al content, the grain size decreased firstly and then increased. When the Al content was 1 wt.%, the grain size of the alloy was the minimum value (28.9 µm). The ultimate tensile strength and elongation increased firstly and then decreased with increasing Al addition. And the fracture mode changed from intergranular fracture to transgranular fracture with increasing addition. When Al addition was 1 wt.%, the maximum ultimate tensile strength reached 225.6 MPa, and the elongation was 7.8%. When the content of Al element was 3 wt.%, the maximum elongation reached 10.2% and the ultimate tensile strength was 207.7 MPa.

Enhanced Grain Refinement and Precipitation of the IEECAPed Mg-Sm-Zn-Zr Alloy by Nd Addition.

Achieving magnesium-rare earth alloys with excellent mechanical properties remains a challenging goal in the aerospace industry. The integrated extrusion and equal channel angular pressing were employed to refine grain and improve the mechanical properties of Mg-xNd-2.0Sm-0.4Zn-0.4Zr alloys. The effect of Nd element on microstructure and mechanical properties of the extruded and subsequently aged alloys were carried out by varying the amount of the Nd element from 0 wt.% to 2.5 wt.%. The optical microscopy results indicated that the grain size was remarkably refined by the addition of Nd element. The grain size decreased from 29.7 µm to 10.9 µm with increasing of the Nd element from 0 wt.% to 2.5 wt.%. The transmission electron microscopy results showed that the nano-scaled basal lamellar precipitates, prismatic lamellar precipitates and granular precipitates were formed in α-Mg matrix. The amount of the precipitates increased significantly by the addition of Nd. Moreover, the strength of the alloys significantly improved with Nd. Superior strength and considerable plasticity were obtained as the content of Nd element reached 2.0 wt.%, while the tensile strength of the Mg-2.0Nd-Sm-Zn-Zr alloy (315 ± 5 MPa) increased by 35.8% with respect to the Nd-free alloy (232 ± 3 MPa).

Influence of Solution Treatment Time on Precipitation Behavior and Mechanical Properties of Mg-2.0Nd-2.0Sm-0.4Zn-0.4Zr Alloy.

The effect of solution treatment time on the microstructure and mechanical properties of aged the Mg-2.0Nd-2.0Sm-0.4Zn-0.4Zr (wt.%) alloy were investigated to give full play to the performance of the alloy. As the solution treatment time increased from 2 h to 12 h at 788 K, the grain size of the solution-treated alloy significantly increased, and the network-like ß-Mg12(Nd, Sm, Zn) phase gradually dissolved into the α-Mg matrix. It should be noted that no obvious residual ß phase can be observed when the solution treatment time was more than 8 h. After the solution-treated alloy was further aged at 473 K for 18 h, a large number of nanoscale precipitates were observed in the α-Mg matrix. The solution treatment time was 2 h, the α-Mg matrix mainly consisted of spherical-shaped and basal plate-shaped precipitates. Upon the increase of solution treatment time to 8 h, the key strengthening phases transformed from spherical-shaped precipitates and basal plate-shaped precipitates to prismatic plate-shaped ß' precipitates. The orientation relationship between ß' precipitates and α-Mg matrix was (1¯10)ß' // (11¯00)α and [112]ß' // the [224¯3]α. Further increasing of solution treatment time from 8 h to 12 h, the key strengthening phases mainly were still ß' precipitates. The solution treatment of aged alloy was carried out at 788 K for 8 h, which achieved optimal ultimate tensile strength (UTS) of 261 ± 4.1 MPa, yield strength (YS) of 154 ± 1.5 MPa, and elongation of 5.8 ± 0.1%, respectively.

Enhanced Bioavailability of Dihydrotanshinone I-Bovine Serum Albumin Nanoparticles for Stroke Therapy.

Dihydrotanshinone I (DHT) is a natural component in Salvia miltiorrhiza and has been widely researched for its multiple bioactivities. However, poor solubility and biocompatibility of DHT limit its desirable application for clinical purposes. Herein, DHT was encapsulated with bovine serum albumin (BSA) to enhance bioavailability. Compared to free DHT, DHT-BSA NPs (nanoparticles) showed an improved solubility in normal saline and increased protection against hydrogen peroxide-induced oxidative damage in PC12 cells. In addition, DHT-BSA NPs administered by intravenous injection displayed a significant efficacy in the middle cerebral artery occlusion/reperfusion models, without any impact on the cerebral blood flow. In summary, DHT-BSA NPs show an enhanced bioavailability compared with free DHT and a successful penetration into the central nervous system for stroke therapy, demonstrating their application potential in cardio-cerebrovascular diseases.

Notoginsenoside R1 Improves Cerebral Ischemia/Reperfusion Injury by Promoting Neurogenesis via the BDNF/Akt/CREB Pathway.

Notoginsenoside R1 (R1), a major component isolated from P. notoginseng, is a phytoestrogen that exerts many neuroprotective effects in a rat model of ischemic stroke. However, its long-term effects on neurogenesis and neurological restoration after ischemic stroke have not been investigated. The aim of this study was to evaluate the effects of R1 on neurogenesis and long-term functional recovery after ischemic stroke. We used male Sprague-Dawley rats subjected to middle cerebral artery occlusion/reperfusion (MCAO/R). R1 was administered by intraperitoneal (i.p.) injection immediately postischemia. We showed that R1 significantly decreased infarct volume and neuronal loss, restored neurological function, and stimulated neurogenesis and oligodendrogenesis in rats subjected to MCAO/R. More importantly, R1 promoted neuronal proliferation in PC12 cells in vitro. The proneurogenic effects of R1 were associated with the activation of Akt/cAMP responsive element-binding protein, as shown by the R1-induced increase in brain-derived neurotrophic factor (BDNF) expression, and with the activation of neurological function, which was partially eliminated by selective inhibitors of BDNF and PI3K. We demonstrated that R1 is a promising compound that exerts neuroprotective and proneurogenic effects, possibly via the activation of BDNF/Akt/CREB signaling. These findings offer insight into exploring new mechanisms in long-term functional recovery after R1 treatment of ischemic stroke.

Classical Active Ingredients and Extracts of Chinese Herbal Medicines: Pharmacokinetics, Pharmacodynamics, and Molecular Mechanisms for Ischemic Stroke.

Stroke is a leading cause of death and disability worldwide, and approximately 87% of cases are attributed to ischemia. The main factors that cause ischemic stroke include excitotoxicity, energy metabolism disorder, Ca+ overload, oxidative damage, apoptosis, autophagy, and inflammation. However, no effective drug is currently available for the comprehensive treatment of ischemic stroke in clinical applications; thus, there is an urgent need to find and develop comprehensive and effective drugs to treat postischemic stroke. Traditional Chinese medicine (TCM) has unique advantages in treating ischemic stroke, with overall regulatory effects at multiple levels and on multiple targets. Many researchers have studied the effective components of TCMs and have achieved undeniable results. This paper reviews studies on the anticerebral ischemia effects of TCM monomers such as tetramethylpyrazine (TMP), dl-3-n-butylphthalide (NBP), ginsenoside Rg1 (Rg1), tanshinone IIA (TSA), gastrodin (Gas), and baicalin (BA) as well as effective extracts such as Ginkgo biloba extract (EGB). Research on the anticerebral ischemia effects of TCMs has focused mostly on their antioxidative stress, antiapoptotic, anti-inflammatory, proangiogenic, and proneurogenic effects. However, the research on the use of TCM to treat ischemic stroke remains incompletely characterized. Thus, we summarized and considered this topic from the perspective of pharmacokinetics, pharmacological effects, and mechanistic research, and we have provided a reference basis for future research and development on anticerebral ischemia TCM drugs.

Effects of Poly(cyclohexanedimethylene terephthalate) on Microstructures, Crystallization Behavior and Properties of the Poly(ester ether) Elastomers.

To understand the role of molecular structure on the crystallization behavior of copolyester in thermoplastic poly(ether ester) elastomers (TPEEs), series of poly(butylene-co-1,4-cyclohexanedimethylene terephthalate) (P(BT-co-CT))-b-poly(tetramethylene glycol) (PTMG) are synthesized through molten polycondensation process. The effects of poly(cyclohexanedimethylene terephthalate) (PCT) content on the copolymer are investigated by Fourier transform infrared spectroscopy (FT-IR), ¹H and 13C nuclear magnetic resonance (NMR), gel permeation chromatographs (GPC), wide-angle X-ray diffraction (WAXD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), mechanical, and visible light transmittance tests. FT-IR and NMR results confirm the incorporation of PCT onto the copolymer. WAXD and DSC indicate that the crystalline structure of the copolymers changed from α-PBT lattice to trans-PCT lattice when the molar fraction of PCT (MPCT) is above 30%, while both crystallization and melting temperatures reach the minima. An increase in MPCT led to an increase in the number sequence length of PCT, the thermal stability and the visible light transmittance of the copolymer, but to a slight decrease in tensile strength and elastic modulus.

Solid State Reaction Mechanism and Microstructure Evolution of Ni-Al Powders during High Energy Ball Milling Revisited by TEM.

Microstructure evolution during the formation of B2-NiAl by high energy ball milling of equiatomic elemental mixtures was studied by X-ray diffractometer, scanning electron microscopy, and transmission electron microscopy (TEM). The crystallite size, lattice defects and ordering of the B2-NiAl were monitored via TEM as function of milling time. The diffusion reaction, Ni+Al→NiAl3 or/and Ni2Al3, occurred during high energy ball milling, and to a certain extent offered the stored energy for the explosive exothermic reaction, Ni+Al→B2-NiAl. The fine microstructure of newly formed B2-NiAl after 5 h milling involved high density defects, e.g. antiphase boundary, long range ordering domains, vacancies, and dislocations.