Orientation-Dependent Mechanical Behaviors of BCC-Fe in Light of the Thermo-Kinetic Synergy of Plastic Deformation.

The orientation-dependent mechanical behaviors of metallic alloys are governed by deformation mechanisms, but the underlying physics remain to be explored. In this work, the mechanical responses along different orientations and behind the mechanisms of BCC-Fe are investigated by performing molecular dynamic simulations. It is found that the mechanical properties of BCC-Fe exhibit apparent anisotropic characteristics. The <100>-oriented BCC-Fe presents a Young's modulus of E = 147.56 GPa, a strength of σy = 10.15 GPa, and a plastic strain of εy = 0.084 at the yield point, whereas the <111> orientation presents E = 244.84 GPa, σy = 27.57 GPa, and εy = 0.21. Based on classical dislocation theory, the reasons for such orientation-dependent mechanical behaviors are analyzed from the perspective of thermo-kinetic synergy upon deformation. It turns out that the anisotropic mechanical responses of BCC-Fe are associated with the magnitude of the thermodynamic driving force (ΔG) and kinetic energy barrier (Q) for dislocation motion, which dominate the corresponding deformation mechanism. Compared with the low ΔG (6.395 GPa) and high Q (11.95 KJ/mol) of the <100>-oriented BCC-Fe dominated by deformation twinning, the <111> orientation governed by dislocation slip presents a high ΔG (17.37 GPa) and low Q (6.45 KJ/mol). Accordingly, the orientation-dependent deformation behaviors of BCC-Fe are derived from the thermo-kinetic synergy for dislocation motion.

Effective immobilization and biosafety assessment of antimony in soil with zeolite-supported nanoscale zero-valent iron.

Antimony (Sb) contamination in certain areas caused by activities such as antimony mining and smelting poses significant risks to human health and ecosystems. In this study, a stable composite material consisting of natural zeolite-supported nanoscale zero-valent iron (Z-ZVI) was successfully prepared. The immobilization effect of Z-ZVI on Sb in contaminated soil was investigated. Experimental results showed that Z-ZVI exhibited superior performance compared to pure nano zero-valent iron (nZVI) in terms of stability, with a lower zeta potential (-25.16 mV) at a pH of 7 and a higher specific surface area (54.54 m2/g). It can be easily applied and dispersed in contaminated soils. Additionally, Z-ZVI demonstrated a more abundant porous structure. After 60 days of treatment with 3% Z-ZVI, the leaching concentration of Sb in the contaminated soil decreased from 1.32 mg/L to 0.31 mg/L (a reduction of 76%), and the concentration of available Sb species decreased from 19.84 mg/kg to 0.71 mg/kg, achieving a fixation efficiency of up to 90%. X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) analysis confirmed the effective immobilization of Sb in the soil through reduction of antimonate to antimonite, precipitation, and adsorption processes facilitated by Z-ZVI. Moreover, the addition of Z-ZVI effectively reduced the bioavailability of Sb in the contaminated soil, thereby mitigating its toxicity to earthworms. In conclusion, Z-ZVI can be utilized as a promising material for the safe remediation and antimony and other heavy metal-contaminated soils.

African American patients with Multiple Sclerosis (MS) have higher proportions of CD19+ and CD20+ B-cell lineage cells in their cerebrospinal fluid than White MS patients.

OBJECTIVES: To compare proportions of B-cell lineage CD19+ and CD20+ cells in CSF of African-American (AA) and White (W) patients with MS. BACKGROUND: AA MS patients are more likely to have oligoclonal bands in CSF, higher IgG index in CSF, and higher circulating plasmablasts in blood than W MS patients. It is unknown whether the proportion of B-cells in CSF differs between AA and W patients in MS. METHODS: Demographics, disease-related information, treatment history were retrospectively collected on patients with MS who self-identified as AA or W and underwent flow cytometry of CSF during diagnostic work-up. Proportion of B-lymphocytes, T-lymphocytes, NK cells, monocytes, and plasma cells were analyzed with flow cytometry. RESULTS: 20 AA and 56 W MS patients fulfilled our inclusion criteria. The groups had similar demographics, CSF cell counts, protein and glucose CSF concentrations, and oligoclonal band number. IgG index was higher in AA compared to W (1.08 vs. 0.85, p = 0.031). AA had higher proportions of CD19+ (5.46 % AA vs. 2.26 % W, p = 0.006) and CD20+ (4.64 % AA vs. 1.91 % W, p = 0.004) cells but did not significantly differ in proportion of CD4+, CD8+, CD38+ bright B-cells, NK cells and monocytes. CONCLUSIONS: B-cells are overrepresented in the CSF of African American patients with MS relative to Whites.

[Pathogenesis of glucocorticoid-induced osteoporosis based on label-free mass proteomics].

OBJECTIVE: To explore pathogenesis of glucocortocoid-induced osteoporosis(GIOP) based on label-free mass proteomics. METHODS: Twevle female Sprague-Dawley(SD) rats were randomly divided into two groups, named as sham group and GIOP group. After one-week adaptive feeding, the rats of GIOP group were administered with dexamethasone via intramuscular injection according to 2.5 mg/kg weighting, while the rats of sham group were administered with the same amount of saline, twice a week. The tibias of each group were collected after 8-week modeling and made pathological sections to confirm the success of modeling. Three samples of each group were picked up to perform label-free mass proteomics. After quality control, differentially expressed proteins were identified according to qualitative and quantitative analyses. Then gene ontology(GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, cluster analysis as well as protein-protein interaction analysis were performed using bioinformatics analysis. RESULTS: Compared with sham group, the structure of bone trabecular in GIOP group showed abnormal arrangement, uneven distribution and obvious fragmentation, which could demonstrate successful modeling. A total of 47 differentially expressed proteins (DEPs) were identified including 20 up-regulated and 27 down-regulated proteins. The expression of protein nucleophosmin 1(NPM1), adipocyte plasma membrane associated protein (APMAP), cytochromec oxidase subunit 6A1 (COX6A1) and tartrate-resistant acid phosphatase (ACP5) showed a significant difference between two groups. KEGG results showed DEPs were enriched on metabolism-related pathways, immune-related pathways and AMP-activated kinase (AMPK) signaling pathway. CONCLUSION: Protein NPM1, APMAP, COX6A1 and ACP5 showed a close relationship with pathogenesis of GIOP, which could serve as potential biomarkers of GIOP. AMPK signaling pathway played an important role in the occurrence and development of GIOP, which could be regarded as potential signaling pathway to treatment GIOP.

Anisotropic Etching of InGaN Thin Films with Photoelectrochemical Etching to Form Quantum Dots.

Traditional methods for synthesizing InGaN quantum dots (QDs), such as the Stranski-Krastanov growth, often result in QD ensembles with low density and non-uniform size distribution. To overcome these challenges, forming QDs using photoelectrochemical (PEC) etching with coherent light has been developed. Anisotropic etching of InGaN thin films is demonstrated here with PEC etching. InGaN films are etched in dilute H2SO4 and exposed to a pulsed 445 nm laser with a 100 mW/cm2 average power density. Two potentials (0.4 V or 0.9 V) measured with respect to an AgCl|Ag reference electrode are applied during PEC etching, resulting in different QDs. Atomic force microscope images show that while the QD density and sizes are similar for both applied potentials, the heights are more uniform and match the initial InGaN thickness at the lower applied potential. Schrodinger-Poisson simulations show that polarization-induced fields in the thin InGaN layer prevent positively charged carriers (holes) from arriving at the c-plane surface. These fields are mitigated in the less polar planes resulting in high etch selectivity for the different planes. The higher applied potential overcomes the polarization fields and breaks the anisotropic etching.

GPX4 utilization by selenium is required to alleviate cadmium-induced ferroptosis and pyroptosis in sheep kidney.

Cadmium (Cd), a persistent and harmful heavy metal in the environment, can accumulate in the kidneys and cause nephrotoxicity. Selenium (Se) is a beneficial natural element that alleviates the toxicity of Cd. To ascertain the relationship between the protective mechanism of Se against Cd nephrotoxicity and ferroptosis and pyroptosis, we randomly divided 48 sheep into four groups and treated them with Cd chloride and/or sodium selenite for 50 days. The data confirmed that Cd apparently resulted in impaired kidney histology and function, depletion of GSH and nicotinamide adenine dinucleotide phosphate contents and CAT and SOD activities, elevation of MDA level, as well as the reduction in selenoprotein mRNA (GPX1, GPX4, TXNRD1, SELP) levels and GPX4 protein level and immunofluorescence intensity. Meanwhile, Cd induced ferroptosis by causing iron overload, up-regulating PTGS2, NCOA4, TFR1, and LC3B mRNA levels and PTGS2 and LC3B-II/LC3B-I protein levels, reducing SLC7A11 and FTH1 mRNA and protein levels, and enhancing the immunofluorescence co-localization of FTH1/LC3B. Moreover, it was also found that Cd triggered pyroptosis, which was evidenced by the increase of NLRP3 immunohistochemical positive signal, GSDMD-N immunofluorescence intensity, IL-1ß and IL-18 release and the levels of pyroptosis-related mRNA (NLRP3, ASC, Caspase-1, GSDMD, IL-1ß and IL-18) and proteins (NLRP3, Caspase-1p20, GSDMD-N, IL-1ß and IL-18). Notably, Se increased the expression level of GPX4 and the transcription factors TFAP2c and SP1, and ameliorated Cd-induced changes in aforementioned factors. In conclusion, GPX4 utilization by Se might be required to alleviate Cd-induced ferroptosis and pyroptosis in sheep kidney.

ZeXie decoction alleviates non-alcoholic fatty liver disease in rats: the study of genes, lipids, and gut microbiotas.

Recently, with increasing awareness of health issues, non-alcoholic fatty liver disease (NAFLD) has become an epidemic attracting global attention. As a serious chronic disease, NAFLD is clinically managed with pharmacological interventions that are usually associated with poor long-term efficacy and adverse effects. In this scenario, traditional Chinese medicine (TCM) characterized by "multiple ingredients-multiple targets-multiple pathways" shows promise as a potential option to treat NAFLD. Zexie decoction (ZXD) is a classical TCM formula that possesses favorable lipid-lowering and anti-inflammatory activities. Accumulating evidence indicates that ZXD displays robust efficacy in treating NAFLD. The effectiveness of ZXD against NAFLD has been evaluated in our previous studies. This study further examines its probable mechanism of action in an in-depth manner using multi-omic analysis based on the gut-liver axis and sheds light on the potential relationship among genes, hepatic lipid metabolites, and gut microbiotas. Totally, 71 differentially expressed genes (34 upregulated and 37 downregulated genes), 31 differential lipid molecules (8 upregulated and 23 downregulated), and 56 differential gut microbiotas (37 upregulated and 19 downregulated) were identified in the ZXD-treated group rats compared with the negative control group rats. Of these, owing to their key role in the association analysis, g_Blautia, g_Romboutsia, and g_Lactobacillus were hypothesized to be crucial gut microbiotas in the ZXD-mediated treatment of NAFLD. These microbiotas were found to synergize with key genes, such as AKR1B8, CCN1, and TNKS2, and hepatic lipid metabolites, such as glycerophospholipid and sphingomyelin, which might play a therapeutic role by regulating fatty acid synthesis, correcting lipid metabolism disorder, or reducing the inflammatory response. Overall, the present study provides fresh insights into the ZXD-mediated treatment of NAFLD, which, in turn, is expected to give a push to the modernization of TCM.

Qualitative Analysis of Drug-Containing Plasma and its Application to Quantitative Analysis and Pharmacokinetic Study of Zexie Decoction Using UPLC-MS/MS.

ZeXie Decoction (ZXD) is one of the traditional Chinese medicine formulas (TCMFs) comprising Alisma orientalis (Sam.) Juzep. (ZX) and Atractylodes macrocephala Koidz. (BZ) in 5:2 ratios and is widely employed in clinical applications since ancient times. In this study, UHPLC-QE-Orbitrap-MS was used for qualitative analysis of ZXD in rats' plasma after a single oral dose of 750 mg/kg body weight. Afterward, UHPLC-Q-TRAP-MS/MS was used for simultaneous analysis of three bioactive chemical compounds including alisol A, alisol B, and alisol A 24-acetate in ZXD's ethanol extract. Subsequently, the pharmacokinetic profiles of the three analytes were investigated in rat plasma utilizing UHPLC-Q-TRAP-MS/MS. The multiple reaction monitoring (MRM) mode for the three analytes were at m/z 508.4→383.2 for alisol A, m/z 490.4→365.2 for alisol B, and m/z 550.4→515.5 for alisol A 24-acetate. The analysis method was validated in terms of its accuracy, stability, repeatability, linearity, spiked recovery and matrix effect. As a result, twenty-five chemical constituents of ZXD were putatively identified in plasma, and rapid, sensitive, and accurate methods were established for the quantitative analysis and pharmacokinetic study of ZXD. The findings of this study can provide a scientific base for further study of in vivo pharmacokinetics of TCMFs.

Selenium protects against cadmium-induced cardiac injury by attenuating programmed cell death via PI3K/AKT/PTEN signaling.

Cadmium (Cd) is an environmental pollutant that has an enormous influence on agricultural production, but selenium (Se) can alleviate its toxicity. The present study aimed to illustrate the effects of Se on Cd-induced heart injury. All 40 rabbits were randomly divided into four groups: control group, Se [0.5 mg kg-1 ·body weight (BW)] group, Cd (1 mg kg-1 ·BW) group, and Se + Cd group. After 30 days of feeding, morphological changes, the levels of oxidative stress and myocardial enzyme, the content of cardiac troponin T, programmed cell death (pyroptosis, autophagy and apoptosis), and PI3K/AKT/PTEN transduction capacity were observed. The results showed that Cd destroyed the physiological balance of trace elements and caused myocardial damage, increased the cardiac oxidative damage and led to programmed cell death. Coadministration of Se prominently ameliorated histological lesions and improved cardiac function of hearts in Cd-induced rabbits. Furthermore, Se exerted detoxification and oxidation resistance, maintained trace element homeostasis, and alleviated the changes of mRNA and protein levels of pyroptosis-, autophagy- and apoptosis-controlling factors and PI3K/AKT/PTEN signal molecules caused by Cd. In conclusion, Se might protect against Cd-induced pyroptosis, autophagy and apoptosis by interfering with PI3K/AKT/PTEN signaling in heart.

Selenium triggers Nrf2-AMPK crosstalk to alleviate cadmium-induced autophagy in rabbit cerebrum.

Cadmium (Cd) is a toxic heavy metal that accumulates in the brain and causes a series of histopathological changes. Selenium (Se) exerts a crucial function in protecting damage caused by toxic heavy metals, but its potential mechanism is rarely studied. The main purpose of this study is to explore the protective effects of Se on Cd-induced oxidative stress and autophagy in rabbit cerebrum. Forty rabbits were randomly divided into four groups and treated as follows: Control group, Cd (1 mg/kg⋅BW) group, Se (0.5 mg/kg⋅BW) group and Cd (1 mg/kg⋅BW)+Se (0.5 mg/kg⋅BW) group, with 30 days feeding management. Our results suggested that Se treatment significantly suppressed the Cd-induced degenerative changes including cell necrosis, vacuolization, and atrophic neurons. In addition, Se decreased the contents of MDA and H2O2 and increased the activities of CAT, SOD, GST, GSH and GSH-Px, alleviating the imbalance of the redox system induced by Cd. Furthermore, Cd caused the up-regulation of the mRNA levels of autophagy-related genes (ATG3, ATG5, ATG7, ATG12 and p62), AMPK (Prkaa1, Prkaa2, Prkab1, Prkab2, Prkag2, Prkag3) and Nrf2 (Nrf2, HO-1 and NQO1) signaling pathway, and the expression levels of LC3II/LC3I, p-AMPK/AMPK, Beclin-1, Nrf2 and HO-1 proteins, which were alleviated by Se, indicated that Se inhibited Cd-induced autophagy and Nrf2 signaling pathway activation. In conclusion, our study found that Se antagonized Cd-induced oxidative stress and autophagy in the brain by generating crosstalk between AMPK and Nrf2 signaling pathway.

Efflux Pumps of Burkholderia thailandensis Control the Permeability Barrier of the Outer Membrane.

Burkholderia comprises species that are significant biothreat agents and common contaminants of pharmaceutical production facilities. Their extreme antibiotic resistance affects all classes of antibiotics, including polycationic polymyxins and aminoglycosides. The major underlying mechanism is the presence of two permeability barriers, the outer membrane with modified lipid A moieties and active drug efflux pumps. The two barriers are thought to be mechanistically independent and act synergistically to reduce the intracellular concentrations of antibiotics. In this study, we analyzed the interplay between active efflux pumps and the permeability barrier of the outer membrane in Burkholderia thailandensis We found that three efflux pumps, AmrAB-OprA, BpeEF-OprC, and BpeAB-OprB, of B. thailandensis are expressed under standard laboratory conditions and provide protection against multiple antibiotics, including polycationic polymyxins. Our results further suggest that the inactivation of AmrAB-OprA or BpeAB-OprB potentiates the antibacterial activities of antibiotics not only by reducing their efflux, but also by increasing their uptake into cells. Mass spectrometry analyses showed that in efflux-deficient B. thailandensis cells, lipid A species modified with 4-amino-4-deoxy-l-aminoarabinose are significantly less abundant than in the parent strain. Taken together, our results suggest that changes in the outer membrane permeability due to alterations in lipid A structure could be contributing factors in antibiotic hypersusceptibilities of B. thailandensis cells lacking AmrAB-OprA and BpeAB-OprB efflux pumps.

Remediation of Cr(VI)-Contaminated Soil Using the Acidified Hydrazine Hydrate.

Acidified hydrazine hydrate was used to remediate Cr(VI)-contaminated soil. The content of water-soluble Cr(VI) in contaminated soil was 4977.53 mg/kg. The optimal initial pH of hydrazine hydrate solution, soil to solution ratio and molar ratio of Cr(VI) to hydrazine hydrate for remediation of Cr(VI)-contaminated soil were 5.0, 3:1 and 1:3, respectively. Over 99.50 % of water-soluble Cr(VI) in the contaminated soil was reduced at the optimal condition within 30 min. The remediated soil can keep stable within 4 months. Meanwhile the total phosphorus increased from 0.47 to 4.29 g/kg, indicating that using of acidified hydrazine hydrate is an effective method to remediate Cr(VI)-contaminated soil.