Arylsulfatase B Mediates the Sulfonation-Transport Interplay in Human Embryonic Kidney 293 Cells Overexpressing Sulfotransferase 1A3

ABSTRACT Elucidating the intricate relationships between metabolic and transport pathways contributes to improved predictions of in vivo drug disposition and drug-drug interactions. Here we reported that inhibited excretion of conjugative metabolites [i.e., hesperetin 39-O-sulfate (H39S) and hesperetin 7-O-sulfate (H7S)] by MK-571 led to reduced metabolism of hesperetin (a maximal 78% reduction) in human embryonic kidney 293 cells overexpressing sulfotransferase 1A3 (named SULT293 cells). The strong dependence of cellular sulfonation on the efflux transport of generated sulfated metabolites revealed an interplay of sulfonation metabolism with efflux transport (or sulfonation-transport interplay). Polymerase chain reaction (PCR) and Western blot analyses demonstrated that SULT293 cells expressed multiple sulfatases such as arylsulfatase A (ARSA), ARSB, and ARSC. Of these three desulfonation enzymes, only ARSB showed significant activities toward hesperetin sulfates. The intrinsic clearance values for the hydrolysis of H39S and H7S were estimated at 0.6 and 0.5 ml/h/mg, respectively. Furthermore, knockdown of ARSB attenuated the regulatory effect of efflux transporter on cellular sulfonation, whereas overexpression of ABSB enhanced the transporter effect. Taken together, the results indicated that ARSB mediated the sulfonation-transport interplay in SULT293 cells

Application of circulating tumour DNA in terms of prognosis prediction in Chinese follicular lymphoma patients

Background: Follicular lymphoma (FL), an indolent non-Hodgkin lymphoma (NHL), is generally incurable. Favourable prognosis and durable remission are crucial for FL patients. The genetic mutation spectrum provides novel biomarkers for determining the prognosis of FL patients, but its detection is easily affected by the collection of tumour tissue biopsies. In this study, we aimed to describe the mutational landscape of FL using circulating tumour DNA (ctDNA) samples and to explore the relationship between mutations and prognostic indicators of clinical outcome in patients with newly diagnosed follicular lymphoma and the prognostic value of such mutations.Methods: A total of 28 patients with newly diagnosed FL were included in this study. A targeted NGS-based 59-gene panel was used to assess the ctDNA mutation profiles. Differences in clinical factors between patients carrying mutations and those without mutations were analysed. We also explored the relationship between gene mutation status, mean VAFs (variant allele frequencies) and clinical factors. The Kaplan‒Meier method was applied to analyse the overall survival (OS) and progression-free survival (PFS) of patients carrying mutations and those without mutations.Results: ctDNA mutations were detectable in 21 (75%) patients. The most commonly mutated genes were CREBBP (54%, 15/28), KMT2D (50%, 14/28), STAT6 (29%, 8/28), CARD11 (18%, 5/28), PCLO (14%, 4/28), EP300 (14%, 4/28), BCL2 (11%, 3/28), and TNFAIP3 (11%, 3/28), with a mutation frequency of >10%. Patients with detectable ctDNA mutation tended to present with advanced Ann Arbor stage (III-IV) (p = 0.009), high FLIPI risk (3–5) (p = 0.023) and severe lymph node involvement (No. of involved areas ≥5) (p = 0.02). In addition, we found that the mean VAF was significantly higher in patients with advanced Ann Arbor stage, high-risk FLIPI, elevated lactate dehydrogenase (LDH: 0–248U/L), advanced pathology grade, bone marrow involvement (BMI) and lymph node involvement. Additionally, KMT2D, EP300, and STAT6 mutations were associated with inferior PFS (p < 0.05).Conclusion: We described the ctDNA mutation landscapes in Chinese patients with newly diagnosed FL and found that ctDNA VAF means reflect tumour burden. Moreover, PFS was shorter in patients with KMT2D, EP300 and STAT6 mutations

High Resolution Genome Wide Association Studies Reveal Rich Genetic Architectures of Grain Zinc and Iron in Common Wheat (Triticum aestivum L.)

Biofortification is a sustainable strategy to alleviate micronutrient deficiency in humans. It is necessary to improve grain zinc (GZnC) and iron concentrations (GFeC) in wheat based on genetic knowledge. However, the precise dissection of the genetic architecture underlying GZnC and GFeC remains challenging. In this study, high-resolution genome-wide association studies were conducted for GZnC and GFeC by three different models using 166 wheat cultivars and 373,106 polymorphic markers from the wheat 660K and 90K single nucleotide polymorphism (SNP) arrays. Totally, 25 and 16 stable loci were detected for GZnC and GFeC, respectively. Among them, 17 loci for GZnC and 8 for GFeC are likely to be new quantitative trait locus/loci (QTL). Based on gene annotations and expression profiles, 28 promising candidate genes were identified for Zn/Fe uptake (8), transport (11), storage (3), and regulations (6). Of them, 11 genes were putative wheat orthologs of known Arabidopsis and rice genes related to Zn/Fe homeostasis. A brief model, such as genes related to Zn/Fe homeostasis from root uptake, xylem transport to the final seed storage was proposed in wheat. Kompetitive allele-specific PCR (KASP) markers were successfully developed for two major QTL of GZnC on chromosome arms 3AL and 7AL, respectively, which were independent of thousand kernel weight and plant height. The 3AL QTL was further validated in a bi-parental population under multi-environments. A wheat multidrug and toxic compound extrusion (MATE) transporter TraesCS3A01G499300, the ortholog of rice gene OsPEZ2, was identified as a potential candidate gene. This study has advanced our knowledge of the genetic basis underlying GZnC and GFeC in wheat and provides valuable markers and candidate genes for wheat biofortification

Flow Field and Temperature Field in a Four-Strand Tundish Heated by Plasma

Tundish plasma heating is an effective method for achieving steady casting with low superheat and constant temperature. In order to study the flow field, temperature field in tundish heated by plasma, a three-dimensional transient mathematical model was established in the present work. A four-strand T-type tundish in a steelmaking plant was used to explore the changes in the flow field and temperature field of molten steel in the tundish under different plasma heating powers. The results showed that plasma heating affected the flow state of molten steel. It could eliminate the short-circuit flow at outlet. When the plasma heating was 500 kW, the molten steel had an obvious upward flow. The turbulence intensity was improved and distributed evenly with an increase in plasma heating power. In the prototype tundish, the temperature of the outlet was dropped by nearly 2–3 K within 300 s. With the increase of plasma heating power, the low temperature area in the tundish gradually was decreased. When the heating power was 1000 kW, the temperature difference of two outlets was 0.5 K and the overall temperature distribution was more uniform. The research results have a certain guiding significance for the selection of the actual plasma heating power on site

Pitting Corrosion of Steel Induced by Al2O3 Inclusions

To study the effect of Al2O3 inclusions on pitting corrosion in steel, our researchers utilized industrial pure iron as the raw material with the addition of a proper amount of pure aluminum powder to form Al2O3 inclusions. Corrosion experiments were performed by exposing the samples to a 6% FeCl3 solution at room temperature (25 °C) for different lengths of time. Microscopic corrosion morphology was observed by scanning electron microscope (SEM), and the size change of the inclusions was quantitatively analyzed with Image Pro Plus. The experimental results showed that pitting corrosion arose preferentially around the Al2O3 inclusions, and that pitting corrosion initiated at the junction of the Al2O3 inclusions. The steel matrix dissolved and micro-cracks occurred as the Al2O3 inclusions that were buried shallowly below the surface of the steel matrix promoted corrosion of the steel matrix. As corrosion progressed, the shallowly buried Al2O3 inclusions began to appear on the surface, and the small, shallow inclusions fell off and formed micro pits. Furthermore, the clustered distribution of alumina inclusions had a greater effect on pitting initiation than the alumina inclusions distributed alone

Influence of Plasma Heating on the Metallurgical Effects of a Continuous Casting Tundish

Steel products have experienced long-standing problems such as unstable product quality and low product homogeneity. In the continuous casting process, realizing constant-temperature pouring is an effective way to improve product homogeneity. Plasma heating can compensate for the temperature drop during casting with a tundish and maintain a stable degree of superheating of the molten steel in the tundish. Plasma heating has a certain impact on the cleanliness of the molten steel and on the tundish covering flux in the tundish while compensating for the temperature drop. This paper uses SEM-EDS, XRD and FactSage to analyze the cleanliness of molten steel and the characteristics of the tundish covering flux before and after plasma heating. The results show that the number density of inclusions in the tundish is significantly lower after heating, improving the floating removal of small-sized inclusions; after heating, the surface morphology of the tundish covering flux sample appears transparent and glassy, with uniform morphology. XRD results show that the tundish covering flux after plasma heating exhibits no crystal precipitation and is amorphous and that there is a certain regularity before and after heating; there are no obvious changes in the composition of the tundish covering flux in the liquid phase area

Effect of adding yttrium on precipitation behaviors of inclusions in E690 ultra high strength offshore platform steel

The mechanism of inclusions precipitation of the E690 offshore platform steel, with and without addition of yttrium, was studied using the thermodynamic calculation method. The results show that in the E690 steel in the absence of yttrium, the MnS inclusions were precipitated in the liquid phase at the solidification front. By adding the yttrium, MnS inclusions were replaced by spindle and spherical yttrium-containing oxide and sulfide complex inclusions, and the precipitation sequence of yttrium-containing inclusions in the liquid steel was Y2O3, Y2O2S, and YS. However, Y2S3 inclusions cannot be precipitated in the liquid steel under the experimental conditions. It was also found that Al2O3 inclusions can be formed in the liquid steel with and without addition of yttrium. The thermodynamic calculation results are in accordance with the experimental results

Optimization of Corrugated Sheet Packing Structure Based on Analysis of Falling Film Flow Characteristics

The falling film flow characteristics of a liquid on the surface of corrugated sheet packing are crucial for its mass transfer performance in various industrial applications. In this study, a falling film flow experiment with laser-induced fluorescence technology was conducted to validate the flow characteristics of a falling film simulated using computational fluid dynamics (CFD). The influences of Reynolds number (Re) and the packing structure on flow characteristics were analyzed with quantitative film thickness and wetted area obtained through three-dimensional simulation. The results show that the CFD model can accurately predict the liquid falling–film flow behavior and calculate the characteristic parameters. For sinusoidal corrugated sheets, when Re reaches 500, the groove flow changes into a rivulet flow along the adjacent ripples and the wetted area is at its largest, about 0.022 m2. However, relative to the geometric area of the corrugated sheet, the wetted area can only reach 20% of the surface area, and the overall wetting performance is still poor. Triangular and trapezoidal corrugated sheets were further proposed and proved to improve the wetting area compared with the sinusoidal sheet, with maximum increases of 23% and 9%, respectively. On this basis, extensive research was carried out on the corrugation angle. The results show that a triangular corrugated sheet with a 75° corrugated angle was more conducive to the flow of the liquid film, and the wetted area was 38.8% of the surface area

Deep-Sea Natural Products from Extreme Environments: Cold Seeps and Hydrothermal Vents

The deep sea has been proven to be a great treasure for structurally unique and biologically active natural products in the last two decades. Cold seeps and hydrothermal vents, as typical representatives of deep-sea extreme environments, have attracted more and more attention. This review mainly summarizes the natural products of marine animals, marine fungi, and marine bacteria derived from deep-sea cold seeps and hydrothermal vents as well as their biological activities. In general, there were 182 compounds reported, citing 132 references and covering the literature from the first report in 1984 up to March 2022. The sources of the compounds are represented by the genera Aspergillus sp., Penicillium sp., Streptomyces sp., and so on. It is worth mentioning that 90 of the 182 compounds are new and that almost 60% of the reported structures exhibited diverse bioactivities, which became attractive targets for relevant organic synthetic and biosynthetic studies

Flow behavior and heat transfer of molten steel in a two-strand tundish heated by plasma

Tundish plasma heating could achieve constant temperature and low superheat pouring of molten steel, which is conductive for improving the efficiency of continuous casting, enhancing the internal quality of slab. The flow behavior and heat transfer of molten steel in tundish heated by plasma are essential for understanding this process. In the present study, numerical and physical simulation were conducted to investigate the temperature filed and flow characteristics of molten steel in two-strand tundish heated by plasma with different plasma heating powers. Based on the conducted simulation, it was stated that the temperature field of molten steel in tundish was significantly improved by plasma heating. The outlet temperature in 500 kW was increased by 3.05 K compared with non-plasma heating. The physical simulation demonstrated that the dead volume of tundish was reduced by 18.89% in 6 kg/h compared with non-plasma heating. The flow characteristics in the tundish with plasma heating were better than that without plasma heating. With an increase in heating power, the effect of plasma heating was considerably improved