Recent advances in omics techniques have allowed detailed genetic characterization of cortisol-producing adrenal adenoma (CPA). In contrast, the pathophysiology of CPAs has not been elucidated in ...detail on the level of tumor metabolic alterations.
The current study conducted a comprehensive mass spectrometry imaging (MSI) map of CPAs in relation to clinical phenotypes and immunohistochemical profiles of steroidogenic enzymes. The study cohort comprised 46 patients with adrenal tumors including CPAs (n 35) and nonfunctional adenomas (n 11).
Severity of cortisol hypersecretion was significantly correlated with 29 metabolites (adjusted P 0.05). Adrenal androgens derived from the classic androgen pathway were inversely correlated with both cortisol secretion (rs 0.41, adjusted P 0.035) and CYP11B1 expression (rs 0.77, adjusted P 2.00E-08). The extent of cortisol excess and tumor CYP11B1 expression further correlated with serotonin (rs 0.48 and 0.62, adjusted P 0.008 and 2.41E-05). Tumor size was found to be correlated with abundance of 13 fatty acids (adjusted P 0.05) and negatively associated with 9 polyunsaturated fatty acids including phosphatidic acid 38:8 (rs 0.56, adjusted P 0.009).
MSI reveals novel metabolic links between endocrine function and tumorigenesis, which will further support the understanding of CPA pathophysiology.
The homeostasis of NAD
anabolism is indispensable for maintaining the NAD
pool. In mammals, the mainly synthetic pathway of NAD
is the salvage synthesis, a reaction catalyzed by nicotinamide ...mononucleotide adenylyltransferase (NAMPT) and nicotinamide mononucleotide adenylyltransferase (NMNATs) successively, converting nicotinamide (NAM) to nicotinamide mononucleotide (NMN) and NMN to NAD
, respectively. However, the relationship between NAD
anabolism disturbance and diabetic nephropathy (DN) remains elusive. Here our study found that the disruption of NAD
anabolism homeostasis caused an elevation in both oxidative stress and fibronectin expression, along with a decrease in Sirt1 and an increase in both NF-κB P65 expression and acetylation, culminating in extracellular matrix deposition and globular fibrosis in DN. More importantly, through constitutively overexpressing NMNAT1 or NAMPT in human mesangial cells, we revealed NAD
levels altered inversely with NMN levels in the context of DN and, further, their changes affect Sirt1/NF-κB P65, thus playing a crucial role in the pathogenesis of DN. Accordingly, FK866, a NAMPT inhibitor, and quercetin, a Sirt1 agonist, have favorable effects on the maintenance of NAD
homeostasis and renal function in db/db mice. Collectively, our findings suggest that NMN accumulation may provide a causal link between NAD
anabolism disturbance and diabetic nephropathy (DN) as well as a promising therapeutic target for DN treatment.
Rapid urbanization and unplanned development have posed a threat to the thermal environment in a country like China. The urban heat island (UHI) phenomenon is one of the most serious issues because ...of its strong relation to thermal comfort, air pollution, and public health. The water bodies, as an important component of the urban ecosystem, are generally considered a vital resource to mitigate the UHI. This study provides direct evidence with the help of satellite observation and field measurement data using the mono-window algorithm, spatial buffer analysis, and linear regression methods to explore how the stream water affects the local temperature variation. The results showed that Land use/cover change (LUCC) and Land surface temperature (LST) on both banks of the Bahe River changed significantly. The LST of the river was significantly massively reduced within the distance range of 300 to 500 m, and 400 to 600 m, with an average temperature dip from 3.7 to 2.8 °C, and from 3.2 to 1.7 °C respectively were during the summer on east and west river banks. In addition, the surrounding LUCC composition and configuration could strongly affect the maximum cooling scale. The results provide insights for urban planners and managers to arrange the LUCC composition between the river design in urban areas and the cooling effect demands.
Ball-sealer in-stage diversion in horizontal wells is a key technique to realize the uniform stimulation of fractured sections in tight oil and gas reservoirs. So far, however, there are fewer ...research results on the propagation morphologies of multi-cluster fractures after the implementation of different ball-sealer in-stage diversion processes during the fracturing treatment, which results in less theoretical support for the preparation of field ball-sealer in-stage diversion process and measures and impacts its application effects in the fracturing field. To deal with this situation, this paper established a fully coupled “wellbore–perforation–fracture propagation” model of horizontal wells on the basis of the boundary element method. Then, a method for calculating the allocation of ball sealers was proposed. Finally, the number of ball sealers, diversion time and number of diversions during the intra-stage temporary plugging and diversion under the condition of initial heterogeneous stress field and their effects on the propagation of multi-cluster fractures were simulated. And the following research results were obtained. First, the flow restriction of perforation friction can counterbalance the intake difference caused by the induced stress interference so that the friction difference applied on the fluid flow in each fracture cluster is reduced. Second, when the effect of the heterogeneous distribution of the initial stress field is taken into consideration, the liquid intake of each fracture cluster changes greatly and even ineffective perforation clusters without liquid incoming appear in the high-stress region. And after the ball is injected, new fractures are initiated from the ineffective perforation clusters. Third, when the initial minimum horizontal principal stress difference (Δσh) is higher than 3 MPa, it is beneficial to reduce the non-uniform propagation of each fracture cluster by increasing the number of ball sealers appropriately in the middle stage of the construction (over half of the total perforations of each stage) or carrying out temporary plugging in the early–middle stage (including ball injection in batches in the early–middle stage). Fourth, when Δσh is lower than 2 MPa, it is necessary to reduce the number of ball sealers or inject balls in the middle–late stage, or the non-uniform propagation of each fracture cluster will be aggravated.
Expanded newborn screening facilitates early identification and intervention of patients with inborn errors of metabolism (IEMs), There is a lack of disease spectrum data for many areas in China. To ...determine the disease spectrum and genetic characteristics of IEMs in Xi'an city of Shaanxi province in northwest China, 146152 newborns were screening by MSMS from January 2014 to December 2019 and 61 patients were referred to genetic analysis by next generation sequencing (NGS) and validated by Sanger sequencing. Seventy-five newborns and two mothers were diagnosed with IEMs, with an overall incidence of 1:1898 (1:1949 without mothers). There were 35 newborns with amino acidemias (45.45%, 1:4176), 28 newborns with organic acidurias (36.36%, 1:5220), and 12 newborns and two mothers with FAO disorders (18.18%; 1:10439 or 1:12179 without mothers). Phenylketonuria and methylmalonic acidemia were the two most common disorders, accounting for 65.33% (49/75) of all confirmed newborn. Some hotspot mutations were observed for several IEMs, including PAH gene c.728G>A for phenylketonuria; MMACHC gene c.609G>A and c.567dupT, MMUT gene c.323G>A for methylmalonic acidemia and SLC25A13 gene c.852_855del for citrin deficiency. Our study provides effective clinical guidance for the popularization and application of expanded newborn screening, genetic screening, and genetic counseling of IEMs in this region.
The formation of complex fracture networks through the fracturing technology is a crucial operation used to improve the production capacity of tight gas/oil. In this study, physical simulation ...experiments of hydraulic fracturing were conducted with a true triaxial test system on cubic shale oil samples from the Yanchang Formation, China. The fractures were scanned by CT both before and after the experiments and then reconstructed in 3D. The complexity of fracture networks was investigated quantitatively by the fractal theory with topology. Finally, the effect of the horizontal stress ratio, fluid viscosity, and natural fractures on the complexity of the fracture networks was discussed. The results indicate that the method based on fractal theory and topology can effectively characterize the complexity of the fracture network. The change rates of the fractal dimension (K) are 0.45–3.64%, and the fractal dimensions (DNH) of the 3D fracture network after fracturing are 1.9522–2.1837, the number of connections per branch after fracturing (CB) are 1.57–2.0. The change rate of the fractal dimension and the horizontal stress ratio are negatively correlated. However, the change rate of the fractal dimension first increases and then decreases under increasing fluid viscosities, and a transition occurs at a fluid viscosity of 5.0 mPa·s. Whether under different horizontal stress ratios or fluid viscosities, the complexity of the fracture networks after fracturing can be divided into four levels according to DNH and CB. Complex fracture networks are more easily formed under a lower horizontal stress ratio and a relatively low fluid viscosity. A fracturing fluid viscosity that is too low or too high limits the formation of a fracture network.
Sparganium longifolium was reported as a hybrid between S. emersum and S. gramineum based on its intermediate type or the common characteristics of its parent species. Its hybrid origin needs to be ...confirmed using molecular technology. We investigated the origin of S. longifolium based on 10 populations of S. emersum, S. gramineum and S. longifolium from five lakes in European Russia, using sequences of six nuclear loci and one chloroplast DNA fragment. Haplotype network, principal coordinate analysis and genetic clustering based on data of nuclear loci confirmed that S. longifolium is the hybrid between S. emersum and S. gramineum. We found that the natural hybridization between S. emersum and S. gramineum is bidirectional but asymmetrical, and the latter mainly acts as maternal species. We also found that all samples of S. longifolium were F1 generations, and thus hypothesized that S. emersum and S. gramineum could likely maintain their species boundary through the post-zygote reproductive isolation mechanism of F1 generation sterility.
Nano secondary ion mass spectrometry (nanoSIMS) imaging is a rapidly growing field in biological sciences, which enables investigators to describe the chemical composition of cells and tissues with ...high resolution. One of the major challenges of nanoSIMS is to identify specific molecules or organelles, as these are not immediately recognizable in nanoSIMS and need to be revealed by SIMS-compatible probes. Few laboratories have generated such probes, and none are commercially available. To address this, we performed a systematic study of probes initially developed for electron microscopy. Relying on nanoscale SIMS, we found that antibodies coupled to 6 nm gold particles are surprisingly efficient in terms of labeling specificity while offering a reliable detection threshold. These tools enabled accurate visualization and sample analysis and were easily employed in correlating SIMS with other imaging approaches, such as fluorescence microscopy. We conclude that antibodies conjugated to moderately sized gold particles are promising tools for SIMS imaging.
In order to obtain a targeting drug carrier system, magnetic polylactic acid (PLA) microspheres loading curcumin were synthesized by the classical oil-in-water emulsion solvent-evaporation method. In ...the Fourier transform infrared spectra of microspheres, the present functional groups of PLA were all kept invariably. The morphology and size distribution of magnetic microspheres were observed with scanning electron microscopy and dynamic light scattering, respectively. The results showed that the microspheres were regularly spherical and the surface was smooth with a diameter of 0.55–0.75
μm. Magnetic Fe
3O
4 was loaded in PLA microspheres and the content of magnetic particles was 12
wt% through thermogravimetric analysis. The magnetic property of prepared microspheres was measured by vibrating sample magnetometer. The results showed that the magnetic microspheres exhibited typical superparamagnetic behavior and the saturated magnetization was 14.38
emu/g. Through analysis of differential scanning calorimetry, the curcumin was in an amorphous state in the magnetic microspheres. The drug loading, encapsulation efficiency and releasing properties of curcumin in vitro were also investigated by ultraviolet–visible spectrum analysis. The results showed that the drug loading and encapsulation efficiency were 8.0% and 24.2%, respectively. And curcumin was obviously slowly released because the cumulative release percentage of magnetic microspheres in the phosphate buffer (pH=7.4) solution was only 49.01% in 72
h, and the basic release of curcumin finished in 120
h.
► We prepare magnetic polylactic acid microspheres loading curcumin. ► The classical oil-in-water emulsion solvent-evaporation method is used. ► The magnetic microspheres are regularly spherical with a diameter of 0.55–0.75
μm. ► They show a certain sustained release effect on in vitro drug releasing.
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