Preparation and efficacy of antibacterial methacrylate monomer-based polymethyl methacrylate bone cement containing N-halamine compounds.

Introduction: Our objective in this study was to prepare a novel type of polymethyl methacrylate (PMMA) bone cement, analyze its material properties, and evaluate its safety and antibacterial efficacy. Methods: A halamine compound methacrylate antibacterial PMMA bone cement containing an N-Cl bond structure was formulated, and its material characterization was determined with Fourier transform infrared spectroscopy (FT-IR) and 1H-NMR. The antibacterial properties of the material were studied using contact bacteriostasis and releasing-type bacteriostasis experiments. Finally, in vitro and in vivo biocompatibility experiments were performed to analyze the toxic effects of the material on mice and embryonic osteoblast precursor cells (MC3T3-E1). Results: Incorporation of the antibacterial methacrylate monomer with the N-halamine compound in the new antibacterial PMMA bone cement significantly increased its contact and releasing-type bacteriostatic performance against Staphylococcus aureus. Notably, at 20% and 25% additions of N-halamine compound, the contact and releasing-type bacteriostasis rates of bone cement samples reached 100% (p < 0.001). Furthermore, the new antibacterial bone cement containing 5%, 10%, and 15% N-halamine compounds showed good biocompatibility in vitro and in vivo. Conclusion: In this study, we found that the novel antibacterial PMMA bone cement with N-halamine compound methacrylate demonstrated good contact and releasing-type bacteriostatic properties against S. aureus. In particular, bone cement containing a 15% N-halamine monomer exhibited strong antibacterial properties and good in vitro and in vivo biocompatibility.

Injectable isoniazid-loaded bone cement based on hydrazone bonds achieving long-term release and decent mechanical properties.

A robust and easily manufactured high-strength and long-term release hydrazone-based isoniazid acrylic (HIA) bone cement is reported. The mechanical strength of HIA bone cement is similar to that of normal polymethyl methacrylate (PMMA) bone cement, far surpassing that of traditional isoniazid-containing antibiotic-loaded bone cement (INH bone cement). Isoniazid is connected to the bone cement through bioorthogonal hydrazone chemistry, and it possesses release properties superior to those of INH bone cement, allowing for the sustained release of isoniazid for up to 12 weeks. In vivo and in vitro studies also indicate that HIA cement exhibits better biocompatibility than INH bone cement. The results of this study not only signify progress in the realm of antimicrobial bone cement for addressing bone tuberculosis but also enhance our capacity to create and comprehend high-performing antimicrobial bone cement.

Investigating the in vitro antibacterial efficacy of composite bone cement incorporating natural product-based monomers and gentamicin.

OBJECTIVE: The objective of this study is to investigate the impact of four natural product extracts, namely, aloe-emodin, quercetin, curcumin, and tannic acid, on the in vitro bacteriostatic properties and biocompatibility of gentamicin-loaded bone cement and to establish an experimental groundwork supporting the clinical utility of antibiotic-loaded bone cements (ALBC). METHODS: Based on the components, the bone cement samples were categorized as follows: the gentamicin combined with aloe-emodin group, the gentamicin combined with quercetin group, the gentamicin combined with curcumin group, the gentamicin combined with tannic acid group, the gentamicin group, the aloe-emodin group, the quercetin group, the curcumin group, and the tannic acid group. Using the disk diffusion test, we investigated the antibacterial properties of the bone cement material against Staphylococcus aureus (n = 4). We tested cell toxicity and proliferation using the cell counting kit-8 (CCK-8) and examined the biocompatibility of bone cement materials. RESULTS: The combination of gentamicin with the four natural product extracts resulted in significantly larger diameters of inhibition zones compared to gentamicin alone, and the difference was statistically significant (P < 0.05). Except for the groups containing tannic acid, cells in all other groups showed good proliferation across varying time intervals without displaying significant cytotoxicity (P < 0.05). CONCLUSION: In this study, aloe-emodin, quercetin, curcumin, and tannic acid were capable of enhancing the in vitro antibacterial performance of gentamicin-loaded bone cement against S. aureus. While the groups containing tannic acid displayed moderate cytotoxicity in in vitro cell culture, all other groups showed no discernible cytotoxic effects.

Comparison of antibacterial activity and biocompatibility of non-leaching nitrofuran bone cement loaded with vancomycin, gentamicin, and tigecycline.

BACKGROUND: Non-leaching antibacterial bone cement can generate long-term antibacterial activity, it cannot treat serious infections that have occurred like antibiotic-loaded bone cement. Currently, the antibacterial activity and biocompatibility of non-leaching cement when loaded with antibiotics have yet to be determined. METHODS: Non-leaching antibacterial nitrofuran bone cement (NFBC) specimens were prepared with low-dose and high-dose antibiotics. The antibacterial activity and biocompatibility of NFBC loaded with vancomycin, gentamicin, and tigecycline were compared. The agar diffusion method was employed to observe the inhibition zone of the samples against two bacterial strains from day one to day seven. The CCK-8 assay and acute liver and kidney toxicity test were conducted to assess the effects of the samples on mouse embryo osteoblast precursor cells and C57 mice, respectively. RESULTS: Gentamicin-loaded cement exhibited the most potent antibacterial activity, effectively inhibiting both bacterial strains at a low dose. Tigecycline-loaded cement demonstrated superior biocompatibility, showing no acute liver and kidney toxicity in mice and minimal cytotoxicity to osteoblasts. CONCLUSIONS: NFBC loaded with gentamicin, vancomycin, and tigecycline not only maintains sustained antibacterial activity but also exhibits excellent biocompatibility.

ß-catenin-IRP2-primed iron availability to mitochondrial metabolism is druggable for active ß-catenin-mediated cancer.

BACKGROUND: Although ß-catenin signaling cascade is frequently altered in human cancers, targeting this pathway has not been approved for cancer treatment. METHODS: High-throughput screening of an FDA-approved drug library was conducted to identify therapeutics that selectively inhibited the cells with activated ß-catenin. Efficacy of iron chelator and mitochondrial inhibitor was evaluated for suppression of cell proliferation and tumorigenesis. Cellular chelatable iron levels were measured to gain insight into the potential vulnerability of ß-catenin-activated cells to iron deprivation. Extracellular flux analysis of mitochondrial function was conducted to evaluate the downstream events of iron deprivation. Chromatin immunoprecipitation, real-time quantitative PCR and immunoblotting were performed to identify ß-catenin targets. Depletion of iron-regulatory protein 2 (IRP2), a key regulator of cellular iron homeostasis, was carried out to elucidate its significance in ß-catenin-activated cells. Online databases were analyzed for correlation between ß-catenin activity and IRP2-TfR1 axis in human cancers. RESULTS: Iron chelators were identified as selective inhibitors against ß-catenin-activated cells. Deferoxamine mesylate, an iron chelator, preferentially repressed ß-catenin-activated cell proliferation and tumor formation in mice. Mechanically, ß-catenin stimulated the transcription of IRP2 to increase labile iron level. Depletion of IRP2-sequered iron impaired ß-catenin-invigorated mitochondrial function. Moreover, mitochondrial inhibitor S-Gboxin selectively reduced ß-catenin-associated cell viability and tumor formation. CONCLUSIONS: ß-catenin/IRP2/iron stimulation of mitochondrial energetics is targetable vulnerability of ß-catenin-potentiated cancer.

The Lnc-RNA APPAT Suppresses Human Aortic Smooth Muscle Cell Proliferation and Migration by Interacting With MiR-647 and FGF5 in Atherosclerosis.

PURPOSE: LncRNA-Atherosclerotic plaque pathogenesis-associated transcript (APPAT) could be detected in circulating blood and has been demonstrated to correlate with the development of atherosclerosis in our previous work. It could be a potential noninvasive biomarker for earlier diagnoses of clinical cardiovascular disease. Moreover, the expression of miR-647 increased in ox-LDL-treated vascular smooth muscle cells and peripheral blood of patients with coronary heart disease. A negative correlation between APPAT and miR-647 was confirmed, and FGF5 was screened as molecular target of miR-647. However, it is largely unclear how APPAT, miR-647, and FGF5 interact and function in disease development. Here, we aim to explore the underlying molecular mechanism in this progression. MATERIALS AND METHODS: APPAT, miR-647, and FGF5 expression levels were detected by quantitative reverse transcription polymerase chain reaction; cell proliferation was detected by EdU incorporation assay; cell migration was detected by wound-healing assay; the molecular interaction of APPAT/FGF5 with miR-647 was verified by dual-luciferase reporter assay; the western blot was performed to determine the gene expression at protein levels; subcellular localizations of APPAT and miR-647 were observed by fluorescence in situ hybridization; cytosolic and nucleus fractionation assay was performed to further detect the distribution of miR-647. RESULTS: APPAT and miR-647 have inverse effects on human aortic smooth muscle cells' (HASMCs) proliferation and migration. APPAT negatively regulated the cell activity, whereas miR-647 did it in a positive way (p<0.05). Three pairs of molecular interplay were found: mutual negative regulation between APPAT and miR-647, APPAT downregulated FGF5, miR-647 regulation on FGF5 (p<0.05). Subcellular location assay confirmed the molecular interaction of APPAT and miR-647. CONCLUSIONS: APPAT could suppress the migration and proliferation of ox-LDL-treated HASMCs via interacting with miR-647 and FGF5. We revealed a nontypical competing endogenous RNA mechanism of long noncoding RNA in the progression of atherosclerosis.

eIF4A1 Inhibitor Suppresses Hyperactive mTOR-Associated Tumors by Inducing Necroptosis and G2/M Arrest.

Aberrantly activated mechanistic target of rapamycin (mTOR) signaling pathway stimulates translation initiation/protein synthesis and eventually causes tumors. Targeting these processes thus holds potential for treating mTOR-associated diseases. We tested the potential of eFT226, a sequence-selective inhibitor of eIF4A-mediated translation, in the treatment of mTOR hyperactive cells caused by the deletion of tuberous sclerosis complex 1/2 (TSC1/2) or phosphatase and TENsin homology (PTEN). eFT226 preferentially inhibited the proliferation of Tsc2- and Pten-deficient cells by inducing necroptosis and G2/M phase arrest. In addition, eFT226 blocked the development of TSC2-deficient tumors. The translation initiation inhibitor is thus a promising regimen for the treatment of hyperactive mTOR-mediated tumors.

Laboratory characteristics analysis of the efficacy of levothyroxine on subclinical hypothyroidism during pregnancy: a single-center retrospective study.

To reassess the efficacy of levothyroxine on subclinical hypothyroidism (SCH, 4.0 mIU/L ≤ TSH (thyroid stimulating hormone) <10 mIU/L with normal free T4) during pregnancy. 165 levothyroxine-treated pregnant women experiencing SCH were screened. And controls were randomly selected using euthyroidism (EU) women, matched by age, gravidity, and parity in the EU group (n = 660). We evaluated laboratory characteristics and pregnancy outcomes during follow-ups. Compared with the EU group, the SCH group displayed higher inadequate maternal gestational weight gain, premature delivery, low birth weight offspring and infant offspring small for their gestational age. After levothyroxine treatment, the SCH group displayed lower total cholesterol, low-density lipoprotein levels, and higher serum homocysteine levels before delivery. Pregnant women with SCH still exhibit adverse pregnancy outcomes after levothyroxine treatment. Taken together, we believe that besides levothyroxine, vitamin B12 and folic acid could be added to the treatment of pregnant women with SCH. In addition, regular monitoring of blood sugar levels, lipid and homocysteine levels, and intervention gestational weight gain could alleviate the adverse effects of SCH on pregnancy outcomes.

Association between maternal gestational weight gain and preterm birth according to body mass index and maternal age in Quzhou, China.

The aim of this study is to investigate the association between maternal gestational weight gain (GWG) and preterm birth according to pre-pregnancy body mass index (BMI) and maternal age. We did a cohort, hospital-based study in Quzhou, South China, from 1 Jan 2018 to 30 June 2019. We selected 4274 singleton live births in our analysis, 315 (7.4%) of which were preterm births. In the overall population, excess GWG was significantly associated with a decreased risk of preterm birth compared with adequate GWG (adjusted OR 0.81 [95% CI 0.72-0.91]), and the risk varied by increasing maternal age and pre-pregnancy BMI. Interestingly, underweight women who older than 35 years with excess GWG had significantly increased odds of preterm birth compared with adequate GWG in underweight women aged 20-29 years (2.26 [1.06-4.85]) and normal weight women older than 35 years (2.23 [1.13-4.39]). Additionally, low GWG was positively and significantly associated with preterm birth overall (1.92 [1.47-2.50]). Among normal weight women category, compared with adequate GWG women aged 20-29 years did, those older than 20 years with low GWG, had significantly higher odds of preterm birth, which increased with maternal age (1.80 [1.16-2.79] in 20-29 years, 2.19 [1.23-3.91] in 30-34 years, 3.30 [1.68-6.46] in ≫ 35 years). In conclusion, maternal GWG was significantly associated with the risk of preterm birth, but the risk varied by pre-pregnancy BMI and maternal age.

Chemerin-induced macrophages pyroptosis in fetal brain tissue leads to cognitive disorder in offspring of diabetic dams.

BACKGROUND: Chemerin is highly expressed in the serum, placenta tissue, and umbilical cord blood of diabetic mother; however, the impact of chemerin on cognitive disorders of offspring from mothers with diabetes in pregnancy remains unclear. METHODS: A diabetic phenotype in pregnant mice dams was induced by streptozocin (STZ) injection or intraperitoneal injection of chemerin. Behavioral changes in offspring of diabetic dams and nondiabetic controls were assessed, and changes in chemerin, two receptors of chemerin [chemerin receptor 23 (ChemR23) and chemokine (C-C motif) receptor-like 2 (CCRL2)], macrophages, and neurons in the brain tissue were studied to reveal the underlying mechanism of the behavioral changes. RESULTS: Chemerin treatment mimicked the STZ-induced symptom of maternal diabetes in mice along with the altered behavior of offspring in the open field test (OFT) assay. In the exploring process for potential mechanism, the brain tissues of offspring from chemerin-treated dams were observed with an increase level of macrophage infiltration and a decrease number of neuron cells. Moreover, an increased level of NOD-like receptor family pyrin domain containing 3 (NLRP3) and apoptosis-associated speck-like (Asc) protein as well as pyroptosis [characterized by increased active caspase-1 content and secretion of cytokines such as interleukin (IL) 1 beta (IL-1ß) and IL-18] more activated in macrophages is also observed in the brain of these diabetic dam's offspring, in the presence of ChemR23. In vitro, it was found that pyroptosis activation was increased in macrophages separated from the abdominal cavity of normal mice, after chemerin treatment. However, depletion of CCRL2 decreased the level of chemerin in the brain tissues of diabetic dams' offspring; depletion of ChemR23 decreased macrophage pyroptosis, and depletion of either receptor reversed chemerin-mediated neurodevelopmental deficits and cognitive impairment of offspring of diabetic pregnant dams. CONCLUSIONS: Chemerin induced diabetic pregnant disease and CCRL2 were required to enrich chemerin in the brain of offspring. Aggregation of chemerin could lead to macrophage recruitment, activation of pyroptosis, the release of inflammatory cytokines, a decrease in the number of neurons, and cognitive impairment in offspring in a ChemR23-dependent manner. Targeting CCRL2 and/or ChemR23 could be useful for treating neuropsychological deficits in offspring of dams with diabetes in pregnancy.

Expression status and clinical significance of lncRNA APPAT in the progression of atherosclerosis.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been reported to modulate cardiovascular diseases, and expression dynamics of lncRNAs in the bloodstream were proposed to be potential biomarkers for clinical diagnosis. However, few cardiovascular diseases-related circulating lncRNAs were identified and their prediction power has not been investigated in depth. Here we report a new circulating lncRNA, atherosclerotic plaque pathogenesis associated transcript (APPAT), and evaluated its role and predicting ability in atherosclerotic development. METHODS: APPAT was analyzed and screened by high-throughput sequencing, and then detected in vitro and in vivo. Immunofluorescence-fluorescence in situ hybridization (IF-FISH) was utilized to explore distribution and subcellular location of APPAT. The expressing alteration of APPAT in samples of healthy and pathological coronary artery was explored further. We also assessed the level of circulating APPAT in blood samples from healthy individuals, and patients with angina pectoris (AP) or myocardial infarction (MI). Additionally, we predicted and validated microRNA targets of APPAT, then showed the expression level of a candidate target which was primarily measured in human VSMCs cell line, coronary artery, and blood samples. Lastly, we examined the potential indicating ability of APPAT for the risk of AP or MI. RESULTS: APPAT showed significant reduction in ox-LDL treated human VSMCs in vitro. It enriched in contractile VSMCs of artery tunica media and mainly existed in cytoplasm. Significant down-regulation of APPAT was found in coronary artery samples with severe stenosis. More importantly, we observed decreased expression of APPAT in blood samples accompanying disease progression. ROC and correlation analyses further verified the relatively high predicting ability of APPAT. We also observed the predicted miRNA exhibited opposite expression direction to that of APPAT. CONCLUSIONS: This study revealed that circulating lncRNA-APPAT may perform an important function and have some indicating ability on the development of atherosclerosis.

Effects of Copper Pollution on the Phenolic Compound Content, Color, and Antioxidant Activity of Wine.

The effects of copper pollution on the polyphenol content, color, and antioxidant activity of wine, as well as correlations among these factors, were investigated. Copper had clear influences on wine polyphenol content. At low copper concentrations, the concentrations of nearly all polyphenols increased, and the antioxidant activity values of the wine also increased. When the copper concentration reached the lowest level of the medium copper range (9.6~16 mg/L), most of the indices also improved. When the copper concentrations reached the latter part of the medium copper range (19.2 and 22.4 mg/L), many of the tested indices began to decrease. Furthermore, when the copper concentration reached the high ranges (32, 64, and 96 mg/L), the polyphenol content, CIELAB color parameters, and antioxidant activity of wine were substantially decreased, indicating the need to control increasing copper content in grape must.

Manipulating topological states by imprinting non-collinear spin textures.

Topological magnetic states, such as chiral skyrmions, are of great scientific interest and show huge potential for novel spintronics applications, provided their topological charges can be fully controlled. So far skyrmionic textures have been observed in noncentrosymmetric crystalline materials with low symmetry and at low temperatures. We propose theoretically and demonstrate experimentally the design of spin textures with topological charge densities that can be tailored at ambient temperatures. Tuning the interlayer coupling in vertically stacked nanopatterned magnetic heterostructures, such as a model system of a Co/Pd multilayer coupled to Permalloy, the in-plane non-collinear spin texture of one layer can be imprinted into the out-of-plane magnetised material. We observe distinct spin textures, e.g. vortices, magnetic swirls with tunable opening angle, donut states and skyrmion core configurations. We show that applying a small magnetic field, a reliable switching between topologically distinct textures can be achieved at remanence.

A single rolled-up Si tube battery for the study of electrochemical kinetics, electrical conductivity, and structural integrity.

A lab-on-chip device is demonstrated for probing the electrochemical kinetics, electrical properties, and structure integrity of a single Si rolled-up tube as the anode in lithium-ion batteries. Cyclic voltammetry of the tube exhibits better-resolved peaks than of the planar film due to the enhanced diffusion. The tube is wrinkled after cycling. The tube could be used as a promising ultra-microelectrode for other voltammetry research.

Imaging of buried 3D magnetic rolled-up nanomembranes.

Increasing performance and enabling novel functionalities of microelectronic devices, such as three-dimensional (3D) on-chip architectures in optics, electronics, and magnetics, calls for new approaches in both fabrication and characterization. Up to now, 3D magnetic architectures had mainly been studied by integral means without providing insight into local magnetic microstructures that determine the device performance. We prove a concept that allows for imaging magnetic domain patterns in buried 3D objects, for example, magnetic tubular architectures with multiple windings. The approach is based on utilizing the shadow contrast in transmission X-ray magnetic circular dichroism (XMCD) photoemission electron microscopy and correlating the observed 2D projection of the 3D magnetic domains with simulated XMCD patterns. That way, we are not only able to assess magnetic states but also monitor the field-driven evolution of the magnetic domain patterns in individual windings of buried magnetic rolled-up nanomembranes.

Magnetic microstructure of rolled-up single-layer ferromagnetic nanomembranes.

The magnetic microstructure of rolled-up magnetic nanomembranes is revealed both theoretically and experimentally. Two types of nanomembranes are considered, one with a non-magnetic spacer layer and the other without. Experimentally, by using different materials and tuning the dimensions of the rolled-up nanomembranes, domain patterns consisting of spiral-like and azimuthally magnetized domains are observed, which are in qualitative agreement with the theoretical predictions.

A nanomembrane-based wavelength-tunable high-speed single-photon-emitting diode.

We demonstrate an all-electrically operated wavelength-tunable on demand single-photon source for the first time. The device consists of a light-emitting diode in the form of a semiconductor nanomembrane containing self-assembled quantum dots integrated onto a piezoelectric crystal. Triggered single photons are generated via injection of ultrashort electrical pulses into the diode, while their energy can be precisely tuned over a broad range by varying the voltage applied to the piezoelectric crystal. High speed operation of this single-photon-emitting diode up to 0.8 GHz is demonstrated. These results represent an important step toward the realization of electrically driven sources of indistinguishable photons on demand.

Magnetoresistive emulsion analyzer.

We realize a magnetoresistive emulsion analyzer capable of detection, multiparametric analysis and sorting of ferrofluid-containing nanoliter-droplets. The operation of the device in a cytometric mode provides high throughput and quantitative information about the dimensions and magnetic content of the emulsion. Our method offers important complementarity to conventional optical approaches involving ferrofluids, and paves the way to the development of novel compact tools for diagnostics and nanomedicine including drug design and screening.

Geometry-induced spin-ice structures prepared by self-organization on the nanoscale.

We use non-close packed colloidal lithography to prepare hexagonal magnetic antidot arrays with varying diameters at a period of 205 nm. Smaller antidots are attractive for applications as spin waveguides in magnonics. Larger antidots form a magnetically frustrated system, i.e. Kagome spin-ice, as we prove by magnetic force microscopy. The simple but effective approach successfully extends the limits of top-down lithography previously used to study spin-ice configurations and emergent magnetic monopoles towards smaller structures.

Fuel-free locomotion of Janus motors: magnetically induced thermophoresis.

We present fuel-free locomotion of magnetic spherical Janus motors driven by magnetically induced thermophoresis--a self-diffusive propulsion of an object in any liquid media due to a local temperature gradient. Within this approach an ac magnetic field is applied to induce thermophoretic motion of the objects via heating a magnetic cap of the particles, while an additional dc magnetic field is used to orient Janus motors and guide their motion on a long time scale. Full control over the motion is achieved due to specific properties of ultrathin 100-nm-thick Permalloy (Py, Fe19Ni81 alloys) magnetic films resulting in a topologically stable magnetic vortex state in the cap structure of Janus motors. Realized here magnetically induced thermophoretic locomotion does not require catalytic chemical reactions that imply toxic reagents. In this respect, we addressed and successfully solved one of the main shortcomings in the field of artificial motors, namely being fully controlled and remain biocompatible. Therefore, our approach is attractive for biotechnological in vitro assays and even in vivo operations, since the functioning of Janus motors offers low toxicity; it is not dependent on the presence of the fuel molecules in solution. Furthermore, the suggested magnetic ac excitation is superior compared to the previously proposed optically induced heating using lasers as it does not require transparent packaging.