Preparation and Characterization of Nanofiber Coatings on Bone Implants for Localized Antimicrobial Activity Based on Sustained Ion Release and Shape-Preserving Design.

Titanium (Ti), as a hard tissue implant, is facing a big challenge for rapid and stable osseointegration owing to its intrinsic bio-inertness. Meanwile, surface-related infection is also a serious threat. In this study, large-scale quasi-vertically aligned sodium titanate nanowire (SNW) arrayed coatings incorporated with bioactive Cu2+ ions were fabricated through a compound process involving acid etching, hydrothermal treatment (HT), and ion exchange (IE). A novel coating based on sustained ion release and a shape-preserving design is successfully obtained. Cu2+ substituted Na+ in sodium titanate lattice to generate Cu-doped SNW (CNW), which maintains the micro-structure and phase components of the original SNW, and can be efficiently released from the structure by immersing them in physiological saline (PS) solutions, ensuring superior long-term structural stability. The synergistic effects of the acid etching, bidirectional cogrowth, and solution-strengthening mechanisms endow the coating with higher bonding strengths. In vitro antibacterial tests demonstrated that the CNW coatings exhibited effective good antibacterial properties against both Gram-positive and Gram-negative bacteria based on the continuous slow release of copper ions. This is an exciting attempt to achieve topographic, hydrophilic, and antibacterial activation of metal implants, demonstrating a paradigm for the activation of coatings without dissolution and providing new insights into insoluble ceramic-coated implants with high bonding strengths.

Low TYROBP expression predicts poor prognosis in multiple myeloma.

BACKGROUND: Multiple myeloma (MM) is the second most common refractory hematologic cancer. Searching for new targets and prognostic markers for MM is significant. METHODS: GSE39754, GSE6477 and GSE24080 were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in MM versus healthy people from GSE39754 and GSE6477 were screened using limma package, and MM-related module genes were chosen with the use of Weighted gene co-expression network analysis (WGCNA), and the two were intersected using ggVennDiagram for obtaining MM-related DEGs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were carried out. Then, protein-protein interactions (PPI) analysis in String database was used to obtain hub genes, while prognosis was analyzed by survival package in GSE24080. Receiver operating characteristic (ROC) curve was adopted for evaluating diagnostic value of hub genes. Besides, univariable/multivariable Cox regression were employed to screen independent prognostic biomarkers. Gene set enrichment analysis (GSEA) was used to find possible mechanism. Finally, western-blotting and reverse transcription-polymerase chain reaction (RT-PCR) verify TYROBP expression within MM and healthy people. We performed cell adhesion and transwell assays for investigating TYROBP function in MM cell adhesion and migration. RESULTS: Through differential analyses, 92 MM-related DEGs were obtained. 10 hub genes were identified by PPI and CytoHubba. Their diagnostic and prognostic significance was analyzed. Down-regulation of genes like TYROBP, ELANE, MNDA, and MPO related to dismal MM prognosis. Upon univariable/multivariable Cox regression, TYROBP independently predicted MM prognosis. GSEA pathway was enriched, indicating that TYROBP expression affected MM development via cell adhesion molecular pathway. Upon Western-blotting and RT-PCR assays, TYROBP expression among MM patients decreased relative to healthy donors. Cell adhesion and transwell migration assays revealed increased MM cell adhesion and decreased migration upon TYROBP up-regulation. CONCLUSION: In summary, TYROBP is a potential prognostic marker for MM.

BM-MSCs display altered gene expression profiles in B-cell acute lymphoblastic leukemia niches and exert pro-proliferative effects via overexpression of IFI6.

BACKGROUND: The tumor microenvironment (TME) is a supportive environment responsible for promoting the growth and proliferation of tumor cells. Current studies have revealed that the bone marrow mesenchymal stem cells (BM-MSCs), a type of crucial stromal cells in the TME, can promote the malignant progression of tumors. However, in the adult B-cell acute lymphoblastic leukemia (B-ALL) microenvironment, it is still uncertain what changes in BM-MSCs are induced by leukemia cells. METHODS: In this study, we mimicked the leukemia microenvironment by constructing a BM-MSC-leukemia cell co-culture system. In vitro cell experiments, in vivo mouse model experiments, lentiviral transfection and transcriptome sequencing analysis were used to investigate the possible change of BM-MSCs in the leukemia niche and the potential factors in BM-MSCs that promote the progression of leukemia. RESULTS: In the leukemia niche, the leukemia cells reduced the MSCs' capacity to differentiate towards adipogenic and osteogenic subtypes, which also promoted the senescence and cell cycle arrest of the MSCs. Meanwhile, compared to the mono-cultured MSCs, the gene expression profiles of MSCs in the leukemia niche changed significantly. These differential genes were enriched for cell cycle, cell differentiation, DNA replication, as well as some tumor-promoting biofunctions including protein phosphorylation, cell migration and angiogenesis. Further, interferon alpha-inducible protein 6 (IFI6), as a gene activated by interferon, was highly expressed in leukemia niche MSCs. The leukemia cell multiplication was facilitated evidently by IFI6 both in vitro and in vivo. Mechanistically, IFI6 might promote leukemia cell proliferation by stimulating SDF-1/CXCR4 axis, which leads to the initiation of downstream ERK signaling pathway. As suggested by further RNA sequencing analysis, the high IFI6 level in MSCs somewhat influenced the gene expression profile and biological functions of leukemia cells. CONCLUSIONS: BM-MSCs in the leukemia niche have varying degrees of changes in biological characteristics and gene expression profiles. Overexpression of IFI6 in BM-MSCs could be a key factor in promoting the proliferation of B-ALL cells, and this effect might be exerted through the SDF-1/CXCR4/ERK signal stimulation. Targeting IFI6 or related signaling pathways might be an important measure to reduce the leukemia cell proliferation.

Nuclear factor Nrf2 promotes glycosidase OGG1 expression by activating the AKT pathway to enhance leukemia cell resistance to cytarabine.

Chemotherapy resistance is the dominant challenge in the treatment of acute myeloid leukemia (AML). Nuclear factor E2-related factor 2 (Nrf2) exerts a vital function in drug resistance of many tumors. Nevertheless, the potential molecular mechanism of Nrf2 regulating the base excision repair pathway that mediates AML chemotherapy resistance remains unclear. Here, in clinical samples, we found that the high expression of Nrf2 and base excision repair pathway gene encoding 8-hydroxyguanine DNA glycosidase (OGG1) was associated with AML disease progression. In vitro, Nrf2 and OGG1 were highly expressed in drug-resistant leukemia cells. Upregulation of Nrf2 in leukemia cells by lentivirus transfection could decrease the sensitivity of leukemia cells to cytarabine, whereas downregulation of Nrf2 in drug-resistant cells could enhance leukemia cell chemosensitivity. Meanwhile, we found that Nrf2 could positively regulate OGG1 expression in leukemia cells. Our chromatin immunoprecipitation assay revealed that Nrf2 could bind to the promoter of OGG1. Furthermore, the use of OGG1 inhibitor TH5487 could partially reverse the inhibitory effect of upregulated Nrf2 on leukemia cell apoptosis. In vivo, downregulation of Nrf2 could increase the sensitivity of leukemia cell to cytarabine and decrease OGG1 expression. Mechanistically, Nrf2-OGG1 axis-mediated AML resistance might be achieved by activating the AKT signaling pathway to regulate downstream apoptotic proteins. Thus, this study reveals a novel mechanism of Nrf2-promoting drug resistance in leukemia, which may provide a potential therapeutic target for the treatment of drug-resistant/refractory leukemia.

Carbonation and serpentinization of diopsidite in the Altun Mountains, NW China.

Mineral carbonation of mafic-ultramafic rocks has been highlighted as a promising way for permanent carbon capture and storage. Carbonatization involves the release of Ca, Mg and Fe from silicate minerals by dissolution and reaction in the aqueous phase to form stable carbonate minerals. Diopside is one of the most abundant mafic minerals in the lithosphere and contributes a portion of Mg and Ca to surface weathering. Here, we present detailed processes of the carbonation-coupled serpentinization of diopsidite from the Yushishan Nb-Ta deposit in the Altun Mountain, northwest China. Diopsidite is the prograde metamorphic product of siliceous dolomitic marble by full decarbonation process. Retrograde serpentinization and carbonation of diopsidite lead to the addition of CO2, H2O, light rare earth elements and fluid-mobile elements but the loss of SiO2. The diopsides are replaced by calcite and chrysotile by mineral alteration to form pseudomorphic textures. Dissolution-precipitation processes significantly affect diopside serpentinization and carbonation. The carbonation of diopside-rich rocks may be suitable for permanent CO2 storage.

[Clinical Effect of Tyrosine Kinase Inhibitors in the Treatment of P230 Chronic Myeloid Leukemia].

OBJECTIVE: To observe the curative efficacy of tyrosine kinase inhibitors (TKIs) in the treatment of e19a2 transcript (P230) CML chronic phase (CML-CP) patients. METHODS: The clinical data of 11 P230 CML-CP patients were collected from July 2008 to December 2019. Blood routine examination, bone marrow cytology, chromosome, and BCR-ABL qualitative and quantitative tests were performed at initial diagnosis. After TKIs treatment, BCR-ABL (P230)/ABL in peripheral blood was regularly detected to evaluate molecular response by real-time quantitative PCR. RESULTS: There were 11 patients (7 males and 4 females) in chronic phase from 6 domestic hospitals enrolled, their median age was 46 years old (range from 19 to 56 years old). Among 4 patients treated with imatinib (400 mg, qd) firstly, 3 cases switched to nilotinib (400 mg, bid) and 1 case switched to dasatinib (100 mg, qd) due to failure to achieve best molecular response at the landmark time or mutation of ABL kinase. Then major molecular response (MMR) was obtained within 1 year. In addition, 5 patients were treated with nilotinib (300 mg, bid) and 2 patients with dasatinib (100 mg, qd) as first-line treatment, all of them got MMR within 6 months. CONCLUSION: For intolerance or resistance to imatinib, second-generation TKIs can enable P230 CML patients to achieve deeper molecular response, and MMR in a short time.

Mesenchymal Stem Cells With Cancer-Associated Fibroblast-Like Phenotype Stimulate SDF-1/CXCR4 Axis to Enhance the Growth and Invasion of B-Cell Acute Lymphoblastic Leukemia Cells Through Cell-to-Cell Communication.

Background: Bone marrow mesenchymal stem cells (BM-MSCs) are the stromal cells in the leukemia microenvironment, and can obtain cancer-associated fibroblast (CAF)-like phenotype under certain conditions to further promote leukemia progression. However, the mechanism of MSCs with CAF-like phenotype interacting with leukemia cells in B-cell acute lymphoblastic leukemia (B-ALL) and promoting the progression of B-ALL remains unclear. Methods: Mesenchymal stem cells with CAF-like phenotype were obtained by treating MSCs with recombinant human transforming growth factor-ß (rhTGF-ß), hereafter referred to as TGF-ß conditioned MSCs. In vivo mouse model experiments, in vitro transwell chamber experiments, three-dimensional (3D) cell culture models, lentiviral transfection and other experimental methods were used to investigate the possible mechanism of the interaction between TGF-ß conditioned MSCs and leukemia cells in promoting the growth, migration and invasion of B-ALL cells. Results: Compared with untreated MSCs, TGF-ß conditioned MSCs significantly promoted the growth and proliferation of leukemia cells in mice, and increased the expression of CXCR4 in tumor tissues. In vitro cell experiments, TGF-ß conditioned MSCs obviously promoted the migration and invasion of Nalm-6/RS4;11 cells, which were effectively blocked by the CXCR4 inhibitor AMD3100, thereby inhibiting the secretion of MMP-9 in TGF-ß conditioned MSCs and inhibiting the activation of the PI3K/AKT signaling pathway in leukemia cells. Further, findings were made that the interaction between TGF-ß conditioned MSCs and leukemia cells were mediated by the interaction between the integrin receptor α5ß1 on the surface of leukemia cells and the increased expression of fibronectin on TGF-ß conditioned MSCs. AMD3100 could weaken such effect by reducing the expression of integrin α5ß1 on leukemia cells. Further regulation of integrin ß1 could effectively interfere with the interaction between TGF-ß conditioned MSCs and leukemia cells. Conclusion: Mesenchymal stem cells with CAF-like phenotype could be a key factor in promoting the growth and invasion of B-ALL cells, and the SDF-1/CXCR4 axis might be a significant factor in mediating the communication of MSCs with CAF-like phenotype and leukemia cells. To prevent the progression of B-ALL cells, blocking the SDF-1/CXCR4 axis with AMD3100 or targeting integrin ß1 might be a potential therapeutic strategy.

Protic/aprotic ionic liquids for effective CO2 separation using supported ionic liquid membrane.

Four ionic liquids (ILs) namely, 1-butylsulfonate-3-methylimidazolium P-toluene sulfonate ([BSmim][tos]), 1-butylsulfonate pyridine P-toluene sulfonate ([BSmpy][tos]), 1-butyl-3-methylimidazolium chloride ([Bmim][Cl]) and 1-butylpyridine chloride ([Bpy][Cl]) were synthesized for the effective separation of gases CO2/N2 and CO2/CH4 through supported ionic liquid membranes (SILMs). ILs were confirmed by NMR and FTIR spectroscopy, and their characteristics and physical properties were studied. The ILs were immobilized on the porous hydrophobic 200 µm thick polyvinylidene difluoride (PVDF) support. Pure and mixed gas separation performances of the prepared SILMs were analyzed in a custom-built gas permeation unit. The SILMs were stable up to 0.6 MPa at room temperature without leaching the ionic liquid. [BSmim][tos] was recorded to have the highest solubility coefficient and permeability for CO2, among other ILs. At 0.5 MPa, for pure CO2/N2 and CO2/CH4, IL [BSmim][tos] was observed with selectivities of 56.2 and 47.5, respectively. Based on the SILMs separation performance, the ILs synthesized for this work can be ranked as [BSmim][tos] > [BSmpy][tos] > [Bmim][Cl] > [Bpy][Cl]. Moreover, the exceptionally high selectivity values of [BSmim][tos] and [BSmpy][tos] confirms the potential use of ILs for CO2 separation through SILMs.

Towards understanding corrosion inhibition of sulfonate/carboxylate functionalized ionic liquids: An experimental and theoretical study.

The inhibition performance of ionic liquids, abbreviated as [(CH2)COOHMIm][HSO4], [(CH2)2COOHMIm][HSO4], and [(CH2)3SO3HMIm][HSO4] was investigated for carbon steel in 0.5 M HCl solution. Results indicated that these ionic liquids could act as effective inhibitors by adsorption onto the steel surface, and the inhibition efficiency increases with cation alkyl chain length and concentration up to a limit. The inhibition efficiency of a sulfonate-type ionic liquid with a longer alkyl chain is higher than those of the carboxylate-type ionic liquids. Besides, the order of inhibition efficiency was verified by both computational calculation and electrochemical experimental observations.

Green Brönsted acid ionic liquids as novel corrosion inhibitors for carbon steel in acidic medium.

New ionic liquids with multiple Brönsted acid sites were synthesized in ≥98% yield, and their inhibiting properties for the corrosion of carbon steel in 0.5 M HCl solution had been evaluated using electrochemical impedance spectroscopy, potentiodynamic polarization and weight loss method, finally the possible inhibiting mechanism was proposed according to UV-visible spectroscopic measurements and surface analysis including SEM and XPS techniques. The designed cation structure of Brönsted acid ionic liquids (BAILs), with one phenyl and two imidazolium rings, makes them good mixed-type inhibitors via the adsorption of BAILs on the steel surface to suppress both anodic and cathodic processes, obeying Langmuir adsorption isotherm. As potential acid catalysts, BAILs show nice corrosion inhibiting performance in acidic medium regardless of their Brönsted acidity, which is of great significance to enlarge the industry applications of BAILs.

Latcripin-13 domain induces apoptosis and cell cycle arrest at the G1 phase in human lung carcinoma A549 cells.

Latcripin-13 domain, isolated from the transcriptome of Lentinula edodes C91-3, contains a regulator of chromosome condensation (RCC1) domain/ß-lactamase-inhibitor protein II (BLIP-II) and a plant homeodomain (PHD). Latcripin-13 domain has been shown to have antitumor effects. However, the underlying molecular pharmacology is largely unknown. We report here that Latcripin-13 domain induced cell cycle arrest in the G1 phase and caused the apoptosis of human lung carcinoma A549 cells via the GSK3ß-cyclin D1 and caspase-8/NF-κB signaling pathways. Western blot analysis showed that Latcripin-13 domain decreased cyclin D1 and cyclin-dependent kinase 4 (CDK4), while it increased the ratio of GSK3ß/phosphorylated GSK3ß. Importantly, Latcripin-13 domain induced nuclear fragmentation and chromatin condensation in the A549 cells. In addition, treatment of the A549 cells with Latcripin-13 domain resulted in the loss of mitochondrial membrane potential, accompanied by an increase in the Bax/Bcl-2 ratio and activation of caspase-3, -8, and -9. Intriguingly, western blot analysis revealed that NF-κB was significantly downregulated by Latcripin-13 domain. These results demonstrated that Latcripin-13 domain induced apoptosis and cell cycle arrest at G1 phase in the A549 cells, providing a mechanism for the antitumor effects of Latcripin-13 domain.

The lateral boundary of a metamorphic core complex: The Moutsounas shear zone on Naxos, Cyclades, Greece.

We describe the structure, microstructures, texture and paleopiezometry of quartz-rich phyllites and marbles along N-trending Moutsounas shear zone at the eastern margin of the Naxos metamorphic core complex (MCC). Fabrics consistently indicate a top-to-the-NNE non-coaxial shear and formed during the main stage of updoming and exhumation between ca. 14 and 11 Ma of the Naxos MCC. The main stage of exhumation postdates the deposition of overlying Miocene sedimentary successions and predates the overlying Upper Miocene/Pliocene conglomerates. Detailed microstructural and textural analysis reveals that the movement along the Moutsounas shear zone is associated with a retrograde greenschist to subgreenschist facies overprint of the early higher-temperature rocks. Paleopiezometry on recrystallized quartz and calcite yields differential stresses of 20-77 MPa and a strain rate of 10-15-10-13 s-1 at 350 °C for quartz and ca. 300 °C for calcite. Chlorite geothermometry of the shear zone yields two temperature regimes, 300-360 °C, and 200-250 °C. The lower temperature group is interpreted to result from late-stage hydrothermal overprint.

Structures, microfabrics and textures of the Cordilleran-type Rechnitz metamorphic core complex, Eastern Alps.

Rechnitz window group represents a Cordilleran-style metamorphic core complex, which is almost entirely located within nearly contemporaneous Neogene sediments at the transition zone between the Eastern Alps and the Neogene Pannonian basin. Two tectonic units are distinguished within the Rechnitz metamorphic core complex (RMCC): (1) a lower unit mainly composed of Mesozoic metasediments, and (2) an upper unit mainly composed of ophiolite remnants. Both units are metamorphosed within greenschist facies conditions during earliest Miocene followed by exhumation and cooling. The internal structure of the RMCC is characterized by the following succession of structure-forming events: (1) blueschist relics of Paleocene/Eocene age formed as a result of subduction (D1), (2) ductile nappe stacking (D2) of an ophiolite nappe over a distant passive margin succession (ca. E-W to WNW-ESE oriented stretching lineation), (3) greenschist facies-grade metamorphism annealing dominant in the lower unit, and (4) ductile low-angle normal faulting (D3) (with mainly NE-SW oriented stretching lineation), and (5) ca. E to NE-vergent folding (D4). The microfabrics are related to mostly ductile nappe stacking to ductile low-angle normal faulting. Paleopiezometry in conjunction with P-T estimates yield high strain rates of 10- 11 to 10- 13 s- 1, depending on the temperature (400-350 °C) and choice of piezometer and flow law calibration. Progressive microstructures and texture analysis indicate an overprint of the high-temperature fabrics (D2) by the low-temperature deformation (D3). Phengitic mica from the Paleocene/Eocene high-pressure metamorphism remained stable during D2 ductile deformation as well as preserved within late stages of final sub-greenschist facies shearing. Chlorite geothermometry yields two temperature groups, 376-328 °C, and 306-132 °C. Chlorite is seemingly accessible to late-stage resetting. The RMCC underwent an earlier large-scale coaxial deformation accommodated by a late non-coaxial shear with ductile low-angle normal faulting, resulting in subvertical thinning in the extensional deformation regime. The RMCC was rapidly exhumed during ca. 23-18 Ma.