Ferumoxytol-enhanced MR venography for mapping lower-extremity venous networks and evaluating varicose veins in patients with diabetes.

OBJECTIVES: Comprehensive evaluation of lower-extremity varicose veins (VVs) in patients with diabetes is crucial for treatment strategizing. The study aims to assess the feasibility of using ferumoxytol-enhanced MR venography (FE-MRV) for lower-extremity venous mapping and the detection of VVs in patients with diabetes. MATERIALS AND METHODS: As part of a phase II clinical trial of a generic brand of ferumoxytol, documented patients with diabetes were enrolled and underwent FE-MRV on a 3-Τ MRI system. Two observers assessed FE-MRV images for image quality, signal intensity ratio (SIR), perforator (PV) diameter, and luminal signal uniformity in deep-to-superficial venous networks with the assessment of intra- and inter-rater reliability. FE-MRV was used to detect lower-extremity VVs. RESULTS: Eleven patients underwent FE-MRV without adverse events. The average image quality, as scored by the two observers who assessed 275 venous segments, was 3.4 ± 0.6. Two observers strongly agreed on image quality (κ = 0.90) and SIR measurements (interclass correlation coefficient [ICC]: 0.72) and had good agreement on PV diameter (ICC: 0.64). FE-MRV revealed uniform luminal signals in deep and saphenous venous networks (0.13 ± 0.05 vs 0.08 ± 0.03). Below-knee segments exhibited a significantly higher heterogeneity index than above-knee (p = 0.039) segments. Superficial VVs were observed in 55% (12/22) of legs in 64% (7/11) of patients. Calf muscle VVs were present in 64% (14/22) of legs in 9 patients. CONCLUSION: FE-MRV safely and robustly mapped entire lower-extremity venous networks, enabling the detection and pre-treatment evaluation of both superficial, and deep VVs in patients with diabetes. CLINICAL RELEVANCE STATEMENT: Ferumoxytol-enhanced magnetic resonance venography offers a "one-stop" imaging strategy for the detection and pre-operative evaluation of both superficial and deep VVs in diabetic patients. KEY POINTS: Diabetic patients with VVs are at a higher risk of ulcer-related complications. FE-MRV allowed rapid and comprehensive visualization of the lower-limb venous networks and abdominopelvic veins in diabetic patients. This technique allowed for the detection of superficial and deep VVs in diabetic patients before the development of severe peripheral artery disease.

Iron-carbon dots embedded in molybdenum single-atom nanoflowers as multifunctional nanozyme for dual-mode detection of hydrogen peroxide and uric acid.

Single-atom catalysts (SACs) have attracted extensive attention in the field of catalysis due to their excellent catalytic ability and enhanced atomic utilization, but the multi-mode single-atom nanozymes for biosensors remain a challenging issue. In this work, iron-doped carbon dots (Fe CDs) were loaded onto the edges and pores of Mo SACs with nanoflower morphology; accordingly, a composite material Fe CDs/Mo SACs was prepared successfully, which improves the catalytic performance and develops a fluorescence mode without changing the original morphology. The steady-state kinetic data indicates that the material prepared have better affinity for substrates and faster reaction rates under optimized conditions. The specific kinetic parameters Km and Vmax were calculated as 0.39 mM and 7.502×10-7 M·s-1 respectively. The excellent peroxidase-like activity of Fe CDs/Mo SACs allows H2O2 to decompose into •OH, which in turn oxidizes colorless o-phenylenediamine (OPD) to yellow 2,3-diaminophenazine (DAP). At the same time, the fluorescence signal of Fe CDs/Mo SACs quenches obviously by DAP at 460 nm through internal filtration effect (IFE), while the characteristic fluorescence response of DAP gradually increases at 590 nm. Based on this sensing mechanism, a sensitive and accurate dual-mode (colorimetric and ratiometric fluorescent) sensor was constructed to detect H2O2 and uric acid, and the rate of recovery and linearity were acceptable for the detection of UA in human serum and urine samples. This method provides a new strategy for rapid and sensitive detection of UA, and also broadens the development of SACs in the field of biosensors.

Rational Design of High-Performance Electrodes Based on Ferric Oxide Nanosheets Deposited on Reduced Graphene Oxide for Advanced Hybrid Supercapacitors.

The core strategy for constructing ultra-high-performance hybrid supercapacitors is the design of reasonable and effective electrode materials. Herein, a facile solvothermal-calcination strategy is developed to deposit the phosphate-functionalized Fe2O3 (P-Fe2O3) nanosheets on the reduced graphene oxide (rGO) framework. Benefiting from the superior conductivity of rGO and the high conductivity and fast charge storage dynamics of phosphate ions, the synthesized P-Fe2O3/rGO anode exhibits remarkable electrochemical performance with a high capacitance of 586.6 F g-1 at 1 A g-1 and only 4.0% capacitance loss within 10 000 cycles. In addition, the FeMoO4/Fe2O3/rGO nanosheets are fabricated by utilizing Fe2O3/rGO as the precursor. The introduction of molybdates successfully constructs open ion channels between rGO layers and provides abundant active sites, enabling the excellent electrochemical features of FeMoO4/Fe2O3/rGO cathode with a splendid capacity of 475.4 C g-1 at 1 A g-1. By matching P-Fe2O3/rGO with FeMoO4/Fe2O3/rGO, the constructed hybrid supercapacitor presents an admirable energy density of 82.0 Wh kg-1 and an extremely long working life of 95.0% after 20 000 cycles. Furthermore, the continuous operation of the red light-emitting diode for up to 30 min demonstrates the excellent energy storage properties of FeMoO4/Fe2O3/rGO//P-Fe2O3/rGO, which provides multiple possibilities for the follow-up energy storage applications of the iron-based composites.

Enhancing catalytic performance of Fe and Mo co-doped dual single-atom catalysts with dual-enzyme activities for sensitive detection of hydrogen peroxide and uric acid.

Single-atom catalysts (SACs) have attracted much attention due to their excellent catalytic activity, but the improvement of atomic loading which means that weight fraction (wt%) of metal atom was still facing great challenges. In this work, iron and molybdenum co-doped dual single-atom catalysts (Fe/Mo DSACs) was prepared for the first time by using the soft template sacrifice strategy, which improved significantly the atomic load and exhibited both the oxidase-like (OXD) activity and the dominant peroxidase-like (POD) activity. Further experiments reveal that Fe/Mo DSACs can not only catalyze O2 to generate O2•- and 1O2, but also catalyze H2O2 to generate a large number of •OH, which caused 3, 3', 5, 5'-tetramethylbenzidine (TMB) to be oxidized to oxTMB, accompanied by the color changing from colorless to blue. The steady-state kinetic test showed that Michaelis-Menten constant (Km) values and the maximum initial velocity values (Vmax) of the POD activity of Fe/Mo DSACs were 0.0018 mM and 12.6 × 10-8 M s-1, respectively. The corresponding catalytic efficiency was tens of times higher than Fe SACs and Mo SACs, which proves that the synergistic effect between Fe and Mo has significantly improved the catalytic ability. Based on the excellent POD activity of Fe/Mo DSACs, a colorimetric sensing platform combined with TMB was proposed to realize the sensitive detection of H2O2 and uric acid (UA) in a wide range, with limits of detection as low as 0.13 and 0.18 µM, respectively. Finally, accurate and reliable results were obtained in the detection of H2O2 in cells, and of UA in human serum and urine.

Improving the Therapeutic Effect of Ultrasound Combined With Microbubbles on Muscular Tumor Xenografts With Appropriate Acoustic Pressure.

Ultrasound combined with microbubbles (USMB) is a promising antitumor therapy because of its capability to selectively disrupt tumor perfusion. However, the antitumor effects of repeated USMB treatments have yet to be clarified. In this study, we established a VX2 muscular tumor xenograft model in rabbits, and performed USMB treatments at five different peak negative acoustic pressure levels (1.0, 2.0, 3.0, 4.0, or 5.0 MPa) to determine the appropriate acoustic pressure. To investigate whether repeated USMB treatments could improve the antitumor effects, a group of tumor-bearing rabbits was subjected to one USMB treatment per day for three consecutive days for comparison with the single-treatment group. Contrast-enhanced ultrasonic imaging and histological analyses showed that at an acoustic pressure of 4.0 MPa, USMB treatment contributed to substantial cessation of tumor perfusion, resulting in severe damage to the tumor cells and microvessels without causing significant effects on the normal tissue. Further, the percentages of damaged area and apoptotic cells in the tumor were significantly higher, and the tumor growth inhibition effect was more obvious in the multiple-treatment group than in the single USMB treatment group. These findings indicate that with an appropriate acoustic pressure, the USMB treatment can selectively destroy tumor vessels in muscular tumor xenograft models. Moreover, the repeated treatments strategy can significantly improve the antitumor effect. Therefore, our results provide a foundation for the clinical application of USMB to treat solid tumors using a novel therapeutic strategy.

Salinity mediates the effects of nitrogen enrichment on the growth, photosynthesis, and biochemical composition of Ulva prolifera.

To study the combined effects of multiple nitrogen (N) sources and salinity on the growth and physiology on macroalgae, we cultured Ulva prolifera under three N levels (N0, 0.1235 mg L-1; N1, 0.6 mg L-1; and N2, 4.4 mg L-1; the ratios were 18:74:8 for NH4-N, NO3-N, and NO2-N, respectively) and three salinity conditions (15, 25, and 35). Then, the growth, pigment content, photosynthetic performance, superoxide dismutase (SOD) activity, and contents of soluble protein and carbohydrates were measured. The results showed the following: (1) Compared to that grown at salinity 25, the growth of U. prolifera decreased under salinity 35, especially under the N0 and N2 levels, but there were no significant effects of salinity 15 under any of the N levels. (2) There were no significant effects of salinity on the chlorophyll a (Chla) content, but compared to the content at salinity 25, the chlorophyll b (Chlb) content was enhanced by salinity 15 and 35; lower ratio values between Chla and carotenoids (Car) occurred under the salinity 25 treatment. Under each salinity condition, the pigments were enhanced by a high N level. (3) A relatively higher salinity level decreased the photosynthetic oxygen evolution rate, while a higher N level increased this value. Compared to the rate at salinity 25, the dark respiration rate (Rd) significantly increased at salinity 15 under the N0 condition. (4) SOD activity was enhanced by a high N level, but no significant effects of salinity were observed. (5) The carbohydrate content was enhanced at salinity 35 under the N0 and N1 levels, and under salinity 15, this value increased with increasing N levels. In conclusion, although the growth of U. prolifera decreased at high N levels under high salinity conditions, a high N level induced an increase in photosynthesis, while no significant decrease in growth occurred. These findings indicate that low salinity and high N levels may be nonnegligible reasons why this species thrives, and low salinity was the better choice when this species was used for wastewater treatment.

Photoperiod mediates the effects of elevated CO2 on the growth and physiological performance in the green tide alga Ulva prolifera.

Ulva spp., an increasingly important food, are the dominant species of the large-scale green tides. In this study, both the growth and the physiological responses of the Ulva prolifera were studied after cultured in three different light and dark regimes (12:12, 14:10 and 16:8-h light/dark) in combination with current (420 µatm; LC) and increased (1000 µatm; HC) levels of atmospheric CO2. Grown rate of U. prolifera was significantly enhanced by increased CO2 under the three light:dark regimes, especially under 16:8 h-light:dark, indicating that growth was C-unsaturated at present CO2 levels. U. prolifera showed a significantly higher growth rate and lower dark respiration rate (Rd) at 16:8 h-light:dark treatment than at 12:12 h-light/dark treatment, regardless of the CO2 treatment. The photochemical performance was largely unaffected by elevated CO2 and daylength. These results suggest that U. prolifera in a future CO2 enriched coastal water, seems to be resilient to higher CO2 concentrations, and this could be enhanced by longer daylength.

TCMAnalyzer: A Chemo- and Bioinformatics Web Service for Analyzing Traditional Chinese Medicine.

Traditional Chinese medicine (TCM) has been widely used and proven effective in long term clinical practice. However, the molecular mechanism of action for many TCMs remains unclear due to the complexity of many ingredients and their interactions with biological receptors. This is one of the major roadblocks in TCM modernization. In order to solve this problem, we have developed TCMAnalyzer, which is a free web-based toolkit allowing a user to (1) identify the potential compounds that are responsible for the bioactivities for a TCM herb through scaffold-activity relation searches using structural search techniques, (2) investigate the molecular mechanism of action for a TCM herb at the systemic level, and (3) explore the potentially targeted bioactive herbs. The toolkit can result in TCM networks that demonstrate the relations among natural product molecules (small molecular ligands), putative protein targets, pathways, and diseases. These networks are graphically depicted to reveal the mechanism of actions for a TCM herb or to identify new molecular scaffolds for new chemotherapies. TCMAnalyzer is freely available at http://www.rcdd.org.cn/tcmanalyzer .

Synergic Anti-Pruritus Mechanisms of Action for the Radix Sophorae Flavescentis and Fructus Cnidii Herbal Pair.

Radix Sophorae Flavescentis (RSF) and Fructus Cnidii (FC) compose a typical herbal synergic pair in traditional Chinese medicine (TCM) for pruritus symptom treatments. The mechanisms of action for the synergy are not understood. This paper aims at predicting the anti-pruritus targets and the main active ingredients for the RSF and FC herbal pair. We demonstrate that the RSF-FC herbal pair can be elucidated by mining the chemical structures of compounds derived from RSF and FC. Based on chemical structure data, the putative targets for RSF and FC were predicted. Additional putative targets that interact with the anti-pruritus targets were derived by mapping the putative targets onto a PPI network. By examining the annotations of these proteins, we conclude that (1) RSF's active compounds are mainly alkaloids and flavonoids. The representative putative targets of the alkaloids are inflammation-related proteins (MAPK14, PTGS2, PTGS2, and F2) and pruritus-related proteins (HRH1, TRPA1, HTR3A, and HTR6). The representative putative targets of the flavonoids are inflammation-related proteins (TNF, NF-κB, F2, PTGS2, and PTGS2) and pruritus-related proteins (NR3C1 and IL2). (2) FC's active compounds are mainly coumarins. Their representative putative targets are CNS-related proteins (AChE and OPRK1) and inflammation-related proteins (PDE4D, TLR9, and NF-κB). (3) Both RSF and FC display anti-inflammatory effects, though they exhibit their anti-pruritus effects in different ways. Their synergy shows that RSF regulates inflammation-related pruritus and FC regulates CNS-related pruritus.

TAT-OSBP-1-MKK6(E), a novel TAT-fusion protein with high selectivity for human ovarian cancer, exhibits anti-tumor activity.

To improve the selectivity of TAT-fusion proteins for targeted cancer therapy, we developed a novel TAT-based target-specific fusion protein, TAT-OSBP-1-MKK6(E), and evaluated its selectivity and anti-tumor activity in vitro and in vivo. The fusion protein containing TAT-OSBP-1-MKK6(E) has three functional domains: (1) the protein transduction domain of TAT, (2) the human ovarian cancer HO8910 cell-specific binding peptide (OSBP-1) and (3) the potential anti-tumor effector domain of MKK6(E). The transduction efficiency, selectivity, cytotoxicity and apoptotic effect of TAT-OSBP-1-MKK6(E) were examined using immunofluorescence, CCK8 assay and flow cytometry. The in vivo anti-tumor efficacy and target specificity of the fusion protein were evaluated using a nude mouse model with subcutaneous xenografts of human ovarian cancer HO8910 cells. Tumor-bearing mice were divided into three treatment groups that received tail vein injections of TAT-OSBP-1-MKK6(E), TAT-OSBP-1 or normal saline. Tumor growth inhibition was determined by tumor volume, weight and morphology. The distribution and apoptotic effect of TAT-OSBP-1-MKK6(E) were assessed by immunohistochemical staining and TUNEL assays. TAT-OSBP-1-MKK6(E) can be selectively internalized into human ovarian cancer HO8910 cells, rather than normal ovarian OSE cells. In vivo, the fusion protein was mainly expressed in the tumor xenograft, but not in ovary or liver tissues. As a result, TAT-OSBP-1-MKK6(E) significantly induced growth inhibition and apoptosis of tumor cells in vitro and in vivo, with limited effects in normal cells and tissues. TAT-OSBP-1-MKK6(E) treatment can selectively target HO8910 cells in vitro and in vivo, leading to growth inhibition and apoptosis of tumor cells. As such, TAT-OSBP-1-MKK6(E) may be a potential approach for ovarian cancer target therapy.