Magnetic resonance imaging contrast agents are frequently used in clinics to enhance the contrast between diseased and normal tissues. The previously reported poly(acrylic acid) stabilized ...exceedingly small gadolinium oxide nanoparticles (ES‐GdON‐PAA) overcame the problems of commercial Gd chelates, but limitations still exist, i.e., high r2/r1 ratio, long blood circulation half‐life, and no data for large scale synthesis and formulation optimization. In this study, polymaleic acid (PMA) is found to be an ideal stabilizer to synthesize ES‐GdONs. Compared with ES‐GdON‐PAA, the PMA‐stabilized ES‐GdON (ES‐GdON‐PMA) has a lower r2/r1 ratio (2.05, 7.0 T) and a lower blood circulation half‐life (37.51 min). The optimized ES‐GdON‐PMA‐9 has an exceedingly small particle size (2.1 nm), excellent water dispersibility, and stability. A facile, efficient, and environmental friendly synthetic method is developed for large‐scale synthesis of the ES‐GdONs‐PMA. The weight of the optimized freeze–dried ES‐GdON‐PMA‐26 synthesized in a 20 L of reactor reaches the kilogram level. The formulation optimization is also finished, and the concentrated ES‐GdON‐PMA‐26 formulation (CGd = 100 mm) after high‐pressure steam sterilization possesses eligible physicochemical properties (i.e., pH value, osmolality, viscosity, and density) for investigational new drug application.
A polymaleic acid‐stabilized exceedingly small gadolinium oxide nanoparticle with superhigh r1 , ultralow r2/r1 and low blood circulation half‐life is developed to be a T1‐weighted magnetic resonance imaging contrast agent, which can be synthesized up to kilogram level by a facile, efficient and environmental friendly method and possesses eligible physicochemical properties for investigational new drug application.
Developing a cost-effective and highly efficient electrocatalyst with superior catalytic activity is crucial for clean and green water splitting, including the hydrogen evolution reaction (HER), the ...oxygen evolution reaction (OER), and the oxygen reduction reaction (ORR). The single-atom catalyst (SAC) is a breakthrough in industrial catalysis because of the advantages of maximum metal atom utilization, single active sites, strong metal–support interactions, and great potential to accomplish high catalytic performance and selectivity. Herein, we investigate the electrocatalytic performance of a series of SACs supported on a phosphomolybdic acid (PMA) cluster for the HER, OER, and ORR by using first-principles-based calculations. It has been found that the most plausible binding site for the single-metal adatoms is the 4-fold hollow (4H) site over the PMA cluster. Due to the higher stability and catalytic activity of single-metal adatoms, fast electron transfer kinetics is permissible through catalysis. Mainly, Pt1/PMA, Ru1/PMA, V1/PMA, and Ti1/PMA realized decent catalytic performance toward the HER due to nearly ideal (ΔG H* = 0) ΔG H* values via the Volmer–Heyrovsky pathway. The Co1/PMA (0.45 V) and Pt1/PMA (0.49 V) can be active and selective catalysts for the OER with their overpotentials comparable those of to MoC2, IrO2, and RuO2. Among the considered candidates, a non-noble metal Fe1/PMA SAC is a promising electrocatalyst for the ORR with an overpotential of 0.42 V, which is lower than that for the most favorable Pt (0.45 V) catalyst. Furthermore, Pt1/PMA is an auspicious multifunctional electrocatalyst for overall water splitting (−0.02 V for the HER and 0.49 V for the OER) and a metal-air battery (0.79 V for the ORR) catalyst. The current study is further extended to calculate the kinetic potential energy barrier for the excellent catalytic performance of Co1 for the OER and Fe1 for the ORR. The results suggest that the kinetic activation barrier values in all proton-coupled electron transfer steps are in good agreement with the thermodynamic results. It was revealed that the PMA cluster is a promising single-atom support for the HER, OER, and ORR and provides low-cost and highly efficient electrocatalytic activity under normal reaction conditions.
•Uniaxial PMA in Si/SiO2//W/MgAl2O4/CoFeMnSi/W/CoFeMnSi/MgAl2O4/W stacks at specified annealing temperature (TA).•Robust PMA energy (Keff ≈ 1.604 × 106 erg/cc) is observed with a low Ms⊥ of ≈ 514 ...emu/cc.•Enhanced thermal stability with PMA is maintained at 450 °C.•PMA could solely be attributed to the Co-O bond, as supported by FTIR studies.
In this study, we achieved the improvement of uniaxial out-of-plane/perpendicular magnetic anisotropy (PMA) in the W/MgAl2O4/CoFeMnSi/W/CoFeMnSi/MgAl2O4/W heterostructure by manipulating the annealing temperature (TA) 350 °C, 450 °C, and 550 °C. We observed a maximum effective PMA energy density (Keff) of ≈ 1.604 × 106 erg/cc with low saturation magnetization (Ms) at the specified TA. The enhancement of Keff with Ms is significantly influenced by structural variations at the interfaces of CoFeMnSi and MgAl2O4, attributed to sufficient interfacial oxidation dependent on the TA. The TA was identified as a critical factor affecting the surface morphology, grain size, and surface roughness of the multilayer. Fourier-transform infrared (FT-IR) measurements were employed to confirm the presence of Co-O or Fe-O bond in the multilayer structures, elucidating the true origin of PMA. The control of interfacial oxidation at the interface during annealing is crucial for regulating the strength of PMA. Therefore, this double CoFeMnSi/MgAl2O4-based multilayer presents a promising avenue, serving as a favorable candidate for future p-MTJs-based spintronic devices with enhanced thermal stability.
Listeria monocytogenes and Salmonella are common pathogens in milk products that cause foodborne illness. Rapid and accurate detection is essential for effective control of their infections. In this ...study, the bioinformatics method was used to screen highly specific primers for L. monocytogenes (AX10_RS05385) and Salmonella (SEEPA511_RS03120), which were combined to construct a dual qPCR system. On this basis, propidium monoazide (PMA) was used to compensate the inability of qPCR to distinguish between viable and non-viable cells. The addition of sodium deoxycholate (SD) was utilized to maximally improve the inhibition efficiency of PMA. The gold nanoparticles (AuNPs) enhanced about 20% fluorescence signal of the qPCR system, thereby establishing a rapid, highly specific, and sensitive AuNPs-SD-PMA-qPCR detection technology. This method could accurately detect as low as 5 × 101 CFU/g L. monocytogenes and Salmonella in milk products after 6 h enrichment. Therefore, the AuNPs-SD-PMA-qPCR provided significant application value for simultaneous detection of viable L. monocytogenes and Salmonella in food.
•New specific targets for simultaneous detection of L. monocytogenes and Salmonella.•SD combined with PMA to exclude the interference from 107 CFU/mL non-viable cells.•AuNPs enhanced 20% of the fluorescent signal to improve sensitivity of qPCR system.•101 CFU/g L. monocytogenes and Salmonella in milk products could be detected.
Foodborne outbreaks are a serious public health and food safety concern worldwide. There is a great demand for rapid, sensitive, specific, and accurate methods to detect microbial pathogens in foods. ...Conventional methods based on cultivation of pathogens have been the gold standard protocols; however, they take up to a week to complete. Molecular assays such as polymerase chain reaction (PCR), sequencing, microarray technologies have been widely used in detection of foodborne pathogens. Among molecular assays, PCR technology conventional and real-time PCR (qPCR) is most commonly used in the foodborne pathogen detection because of its high sensitivity and specificity. However, a major drawback of PCR is its inability to differentiate the DNA from dead and viable cells, and this is a critical factor for the food industry, regulatory agencies and the consumer. To remedy this shortcoming, researchers have used biological dyes such as ethidium monoazide and propidium monoazide (PMA) to pretreat samples before DNA extraction to intercalate the DNA of dead cells in food samples, and then proceed with regular DNA preparation and qPCR. By combining PMA treatment with qPCR (PMA-qPCR), scientists have applied this technology to detect viable cells of various bacterial pathogens in foods. The incorporation of PMA into PCR-based assays for viability detection of pathogens in foods has increased significantly in the last decade. On the other hand, some downsides with this approach have been noted, particularly to achieve complete suppression of signal of DNA from the dead cells present in some particular food matrix. Nowadays, there is a tendency of more and more researchers adapting this approach for viability detection; and a few commercial kits based on PMA are available in the market. As time goes on, more scientists apply this approach to a broader range of pathogen detections, this viability approach (PMA or other chemicals such as platinum compound) may eventually become a common methodology for the rapid, sensitive, and accurate detection of foodborne pathogens. In this review, we summarize the development in the field including progress and challenges and give our perspective in this area.
In this research, the synthesis of pyrido2,3‐d:5,6‐d′dipyrimidines by CuFe2O4/KCC‐1/PMA magnetic nanoparticles was reported. Synthesis of pyrido2,3‐d:5,6‐d′dipyrimidines was performed under ...solvent‐free conditions with good to excellent yields. The prepared nanocatalyst was synthesized in three steps and also was characterized by Fourier transform infrared (FT‐IR) spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy‐dispersive X‐ray spectroscopy (EDX), X‐ray diffraction (XRD), vibrating sample magnetometry (VSM), and N2 adsorption–desorption measurement (Brunauer–Emmett–Teller BET) analyses. In addition, the reusability studies of CuFe2O4/KCC‐1/PMA showed that the recovered catalyst could be used for several times.
Preparation of CuFe2O4/KCC‐1/PMA as a novel catalyst. The synthesized nanocomposite exhibited high efficiency for the production of pyrido2,3‐d:5,6‐d′dipyrimidines. The catalyst was fully characterized by various spectroscopic techniques.
Polymalate (PMA) produced by the whole genome duplicated strain Aureobasidium melanogenum OUC had a high molecular weight (Mw) of 3.9 × 105 Da while the Mw of PMA produced by A. melanogenum ATCC62921 ...was 3.8 × 104 Da. Therefore, the purified PMA produced by A. melanogenum OUC could form hydrogel and film and the precipitated Ca2+-PMA looked like noodle whereas the purified PMA produced by A. melanogenum ATCC62921 could not form such a hydrogel and a film and the precipitated PMA was powder-like. The high Mw PMA biosynthesis in A. melanogenum OUC was also controlled by the PMA synthetase. However, it was still unclear why the PMA synthetase in A. melanogenum OUC could catalyze the high Mw PMA biosynthesis. Both removal of two copies of the PKS genes and overexpression of the PYC1 gene, the VGB gene and the CRZ2 gene rendered the new transformant Crz46 to produce 34.6 ± 0.3 g/L of extracellular Ca2+-PMA with Mw of 4.9 × 105 Da while its native A. melanogenum OUC only produced 17.2 ± 0.3 g/L of Ca2+-PMA. During the 10-Liter fermentation, 35.6 ± 1.2 g/L of Ca2+-PMA and 13.9 g/Lof cell mass were produced within 168 h, leading to the yield of 0.36 g/g of glucose and the productivity of 0.21 g/L/h. This was the first time to report that the whole genome duplicated strain A. melanogenum OUC and its engineered mutants could produce the high Mw PMA.
•The PMA produced by the engineered strain of A. melanogenum OUC had 4.9 × 105 Da.•The high Mw PMA could form hydrogel and film and the precipitated PMA looked like noodle.•Biosynthesis of the high Mw PMA was also controlled by the PMA synthetase.•It had highly potential applications in biomaterials, food, pharmaceutical and agricultural industries.
The human monocytic THP-1 cell line is the most routinely employed in vitro model for studying monocyte-to-macrophage differentiation. Despite the wide use of this model, differentiation protocols ...using phorbol 12-myristate-13-acetate (PMA) or 1,25-dihydroxyvitamin D3 (1,25D3) vary drastically between studies. Given that differences in differentiation protocols have the potential to impact the characteristics of the macrophages produced, we aimed to assess the efficacy of three different THP-1 differentiation protocols by assessing changes in morphology and gene- and cell surface macrophage marker expression. THP-1 cells were differentiated with either 5 nM PMA, 10 nM 1,25D3, or a combination thereof, followed by a rest period. The results indicated that all three protocols significantly increased the expression of the macrophage markers, CD11b (p < 0.001) and CD14 (p < 0.010). Despite this, THP-1 cells exposed to 1,25D3 alone did not adopt the morphological and expression characteristics associated with macrophages. PMA was required to produce these characteristics, which were found to be more pronounced in the presence of 1,25D3. Both PMA- and PMA with 1,25D3−differentiated THP-1 cells were capable of M1 and M2 macrophage polarization, though the gene expression of polarization-associated markers was most pronounced in PMA with 1,25D3−differentiated THP-1 cells. Moreover, the combination of PMA with 1,25D3 appeared to support the process of commitment to a particular polarization state.
•1,25D3 does not differentiate THP-1 cells into macrophages, based on morphology and gene expression•Low concentrations of PMA can produce THP-1-derived macrophages•1,25D3 combined with PMA augments macrophage characteristics in THP-1 cells•1,25D3 combined with PMA enables THP-1-derived macrophage commitment to both M1 and M2 polarization states
Vibrio parahaemolyticus is an important human pathogen causing a variety of life-threatening diseases and is widely distributed in marine and estuarine environments. The objective of this study was ...to develop a sensitive, specific, and accurate method by using sodium deoxycholate (SD)-propidium monoazide (PMA)-qPCR (SD-PMA-qPCR) for selective detection of viable V. parahaemolyticus cells in shrimp. A qPCR assay was developed by targeting a unique fragment in the toxR gene in V. parahaemolyticus. The qPCR assay demonstrated superior specificity (100%) on V. parahaemolyticus strains (n = 70) and non-V. parahaemolyticus strains (n = 37) examined in the inclusivity and exclusivity tests; and the limit of detection (LOD) of the assay reached 5 × 101 CFU/ml. To remedy the drawback of PCR, SD-PMA treatment was incorporated with the qPCR assay. The optimized PMA treatment conditions were determined as follows, 40 μM PMA and 3-min light exposure at 40 w. The maximum removal efficiency of non-viable cell DNA was achieved by an optimal amplicon (262 bp) of qPCR for PMA treatment with SD at an optimal concentration (0.02% wt/vol). Furthermore, we have applied the SD-PMA-qPCR assay for detection of viable V. parahaemolyticus cells in shrimp. Consequently, the SD-PMA-qPCR assay could accurately detect as low as 5 × 101 CFU/g of V. parahaemolyticus in the presence of a large number of non-viable cells (5 × 107 CFU/g) in spiked shrimp with a 4-h enrichment. In summary, the qPCR assay based on the target gene, toxR, is sensitive and specific; treatment of non-viable cells with SD and PMA improved the removal efficiency of DNA of non-viable cells; and the SD-PMA-qPCR assay developed in this study is a specific and accurate detection method for viable V. parahaemolyticus, providing an effective and rapid means for detection of viable V. parahaemolyticus in food.
•Specific primers and probe were assessed for detection of V. parahaemolyticus by qPCR.•The optimal conditions for treatment of V. parahaemolyticus with SD and PMA were investigated.•A SD-PMA-qPCR assay was proved to be specific and sensitive for detection viable cells from mixtures of cells.•The assay has been applied to detect V. parahaemolyticus in spiked shrimp samples.
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