•Ecological impact coefficients and land use protection coefficients are proposed.•The system dynamic model was developed to analyze land space changes under different scenarios.•The coordinated ...symbiotic scenario would be in a better state compared with the other development scenarios.
Simulation of future land space changes in urban agglomerations is a powerful means to optimize regional spatial structure and improve human well-being. This study highlights the equilibrium between urban development and ecological protection and introduces ecological impact coefficient and land use protection coefficient to measure the degree of sustainable land development. The system dynamic model was used to simulate the dynamics of urban development space, ecological space, and urban agricultural space in the Changsha-Zhuzhou-Xiangtan urban agglomeration from 2019 to 2035. Four development scenarios were used in the simulation, namely, status-quo, economic-centric, environment-centric, and coordinated equilibrium. Simulation results show that for the year 2035, urban development space scale would increase by 678.91 km2 under the status quo, increase by 870.12 km2 under the economic-centric scenario, increase by 740.98 km2 under an environment-centric setting, and increase by 775.54 km2 with coordinated equilibrium. The various scenarios would have significant differences in ecological impact and land use protection coefficients, with the environment-centric scenario yielding the highest values for these indicators. The approach presented in this study shows that the needs for urban development can be achieved while also protecting ecological and urban agricultural spaces and that allocation of production, living, and ecological spaces can be optimized using multi-scenario simulation. The development of ecological impact coefficients and land use protection coefficients, as well as the use of different development scenarios, can be used as reference for the more efficient use of land resources areas and the formulation of land-use and spatial planning.
The recently determined C. elegans P‐glycoprotein (Pgp) structure revealed significant deviations compared to the original mouse Pgp structure, which suggested possible misinterpretations in the ...latter model. To address this concern, we generated an experimental electron density map from single‐wavelength anomalous dispersion phasing of an original mouse Pgp dataset to 3.8 Å resolution. The map exhibited significantly more detail compared to the original MAD map and revealed several regions of the structure that required de novo model building. The improved drug‐free structure was refined to 3.8 Å resolution with a 9.4 and 8.1% decrease in Rwork and Rfree, respectively, (Rwork = 21.2%, Rfree = 26.6%) and a significant improvement in protein geometry. The improved mouse Pgp model contains ∼95% of residues in the favorable Ramachandran region compared to only 57% for the original model. The registry of six transmembrane helices was corrected, revealing amino acid residues involved in drug binding that were previously unrecognized. Registry shifts (rotations and translations) for three transmembrane (TM)4 and TM5 and the addition of three N‐terminal residues were necessary, and were validated with new mercury labeling and anomalous Fourier density. The corrected position of TM4, which forms the frame of a portal for drug entry, had backbone atoms shifted >6 Å from their original positions. The drug translocation pathway of mouse Pgp is 96% identical to human Pgp and is enriched in aromatic residues that likely play a collective role in allowing a high degree of polyspecific substrate recognition.
PDB Code(s): 4M1M, 4M2S, 4M2T
This paper is concerned with numerical algorithms for Biot model. By introducing an intermediate variable, the classical 2-field Biot model is written into a 3-field formulation. Based on such a ...3-field formulation, we propose a coupled algorithm, some time-extrapolation based decoupled algorithms, and an iterative decoupled algorithm. Our focus is the analysis of the iterative decoupled algorithm. It is shown that the convergence of the iterative decoupled algorithm requires no extra assumptions on physical parameters or stabilization parameters. Numerical experiments are provided to demonstrate the accuracy and efficiency of the proposed method.
Pansharpening is a fundamental and crucial image processing task for many remote sensing applications, which generates a high-resolution multispectral image by fusing a low-resolution multispectral ...image and a high-resolution panchromatic image. Recently, vision transformers have been introduced into the pansharpening task for utilizing global contextual information. However, long-range and local dependencies modeling and multiscale feature learning are all essential to the pansharpening task. Learning and exploiting these various information raises a big challenge and limits the performance and efficiency of existing pansharpening methods. To solve this issue, we propose a pansharpening network based on multiscale embedding and dual attention transformers (MDPNet). Specifically, a multiscale embedding block is proposed to embed multiscale information of the images into vectors. Thus, transformers only need to process a multispectral embedding sequence and a panchromatic embedding sequence to efficiently use multiscale information. Furthermore, an additive hybrid attention transformer is proposed to fuse the embedding sequences in an additive injection manner. Finally, a channel self-attention transformer is proposed to utilize channel correlations for high-quality detail generation. Experiments over QuickBird and WorldView-3 datasets demonstrate the proposed MDPNet outperforms state-of-the-art methods visually and quantitatively with low running time. Ablation studies further verify the effectiveness of the proposed multiscale embedding and transformers in pansharpening.
Display omitted
•Li mostly occurs as adsorption or ion exchange in clay minerals.•The depositional environment of the No. 2 coal alternates between a hydrostatic reducing condition and an anoxic ...reducing environment.•Multiple geological effects influence the dissolution and migration of element-enriched minerals, resulting in the enrichment of stable components.
In order to study the enrichment mechanism and depositional environment of valuable elements, this paper reports new geochemistry and mineralogy data on the No. 2 and No. 5 coals of the Nangou Mine, Ningwu Coalfield. Clay minerals and calcite are the dominant minerals in both the No. 2 and No. 5 coals. Additionally, small amounts of pyrite, quartz, rutile, and zircon are observed under scanning electron microscopy in the No. 5 coal. The studied coals in Nangou Mine are enriched in Li (CC = 8.50 and 5.80, respectively in the No. 2 and No. 5 coal), Zr (CC = 21.87 and 5.53), Nb (CC = 16.97 and 2.54), Hf (CC = 14.00 and 4.19), Ga (CC = 2.56 and 2.41). Li mostly occurs as adsorption or ion exchange in clay minerals, Nb, Zr, Hf, and Ga have organic affinities, rare earth elements and Y are mostly found in residue and organic binding states. The sediment source of the Nangou Mine is characterized by a multi-source area, with the dissolution and migration of element-enriched minerals under the influence of multiple geological effects, leading to the enrichment of valuable elements (Li, Nb, Zr, Ga, and REY).
Pregnancy is known to be a risk factor for venous thromboembolism (VTE). We report the case of a pregnant patient with difficult to diagnose iliac vein thrombosis, establishing a definite diagnosis ...by clues of great saphenous vein reflux.
A 37-year-old G1P0 woman at 35 weeks of assisted twin gestation presented with a complaint of persistent left lower limb edema and tenderness. A vascular ultrasound was used to examine the bilateral lower limb. Doppler of left lower extremity revealed continuous great saphenous vein reflux. Right saphenofemoral veins demonstrated venous stasis and no reflux. Unilateral continuous great saphenous vein reflux suggested left iliac veins obstruction or extrinsic compression. Anterograde venography showed a completely occlusive filling defect of the left external iliac vein, which is the definitive diagnosis of acute deep venous thrombosis. The patient underwent a cesarean delivery following inferior vena cava filter (IVCF) placement, and no signs of deep venous thrombosis (DVT) or pulmonary embolism (PE) were reported after delivery.
In pregnant women with suspected deep vein thrombosis, it is imperative to assess the presence of unilateral continuous great saphenous vein reflux.
To understand the functions of secretory proteins in odontogenesis and to further the understanding of the different molecular events during odontogenesis and osteogenesis, we induced the ...odonto/osteogenic differentiation of stem cells from dental apical papilla (SCAPs) and bone marrow-derived stem cells (BMSCs)
and compared the expression of secretory proteins during early odonto/osteogenic differentiation using high-performance liquid chromatography with tandem mass spectrometry. The results revealed significant changes by at least 50% in 139 SCAP proteins and 203 BMSC proteins during differentiation. Of these, 92 were significantly upregulated and 47 were significantly downregulated during the differentiation of SCAPs. Most of these proteins showed the same trend during the differentiation of BMSCs. Among the proteins that showed significantly changes during the differentiation of SCAPs and BMSCs, we found that transforming growth factor-β2 (TGFβ2) is a key protein in the network with powerful mediation ability. TGFβ2 was secreted more by SCAPs than BMSCs, was significantly upregulated during the differentiation of SCAPs and was significantly downregulated during the differentiation of BMSCs. Furthermore, the effects of recombinant human TGFβ2 and TGFβ1 on the odonto/osteogenic differentiation of SCAPs and BMSCs were investigated. Real-time reverse transcription polymerase chain reaction (RT-PCR) and western blotting data revealed that TGFβ2 enhanced the odontogenic-related markers dentin sialophosphoprotein (DSPP), dentin matrix protein 1 (DMP1) and inhibited the osteogenic-related marker bone sialoprotein (BSP) in SCAPs, whereas TGFβ1 enhanced the BSP expression and inhibited the DSPP and DMP1 expression at early odonto/osteogenic differentiation of SCAPs. However, in BMSCs, TGFβ2 enhanced the expression of alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), DSPP, and DMP1, whereas TGFβ1 enhanced the expression of ALP and RUNX2, with no significant intergroup difference of DSPP at the early odonto/osteogenic differentiation of BMSCs. TGFβ2 is a potentially important molecule with a distinct function in the regulation of odontogenesis and osteogenesis.
Much of the volume of solid tumors typically exists in a chronically hypoxic microenvironment that has been shown to result in both chemotherapy and radiation therapy resistance. The purpose of this ...study was to use localized microbubble delivery to overcome hypoxia prior to therapy.
In this study, surfactant-shelled oxygen microbubbles were fabricated and injected intravenously to locally elevate tumor oxygen levels when triggered by noninvasive ultrasound in mice with human breast cancer tumors. Changes in oxygen and sensitivity to radiation therapy were then measured.
In this work, we show that oxygen-filled microbubbles successfully and consistently increase breast tumor oxygenation levels in a murine model by 20 mmHg, significantly more than control injections of saline solution or untriggered oxygen microbubbles (P < .001). Using photoacoustic imaging, we also show that oxygen delivery is independent of hemoglobin transport, enabling oxygen delivery to avascular regions of the tumor. Finally, we show that overcoming hypoxia by this method immediately prior to radiation therapy nearly triples radiosensitivity. This improvement in radiosensitivity results in roughly 30 days of improved tumor control, providing statistically significant improvements in tumor growth and animal survival (P < .03).
Our findings demonstrate the potential advantages of ultrasound-triggered oxygen delivery to solid tumors and warrant future efforts into clinical translation of the microbubble platform.
Nasopharyngeal carcinoma (NPC) is a malignant tumor that is highly prevalent in Southeast Asia, especially in South China. The pathogenesis of NPC is complex, and genetic alterations of tumor ...suppressors and proto-oncogenes play important roles in NPC carcinogenesis. p53 is unexpectedly highly expressed in NPC and possesses an uncommon mutation of R280T, which is different from a high frequency of hotspot mutations or low expression in other tumors. However, the mechanism of p53 loss of function and its correlation with R280T in NPC are still unclear. In this study, p53 amyloid aggregates were found to be widespread in NPC and can be mainly induced by the R280T mutation. Aggregated p53-R280T impeded its entry into the nucleus and was unable to initiate the transcription of downstream target genes, resulting in decreased NPC cell cycle arrest and apoptosis. In addition, NPC cells with p53-R280T amyloid aggregates also contributed aggressively to tumor growth in vivo. Transcriptome analysis suggested that p53 amyloid aggregation dysregulated major signaling pathways associated with the cell cycle, proliferation, apoptosis, and unfolded protein response (UPR). Further studies revealed that Hsp90, as a key molecular chaperone in p53 folding, was upregulated in NPC cells with p53-R280T aggregation, and the upregulated Hsp90 facilitated p53 aggregation in turn, forming positive feedback. Therefore, Hsp90 inhibitors could dissociate p53-R280T aggregation and restore the suppressor function of p53 in vitro and in vivo. In conclusion, our study demonstrated that p53-R280T may misfold to form aggregates with the help of Hsp90, resulting in the inability of sequestered p53 to initiate the transcription of downstream target genes. These results revealed a new mechanism for the loss of p53 function in NPC and provided novel mechanistic insight into NPC pathogenesis.
Abstract
Background
Proteolytic cleavage of von Willebrand factor (VWF) by a plasma a disintegrin and metalloproteinase with a thrombospondin type 1 motifs, member 13 (ADAMTS13) is regulated by ...shear stress and binding of coagulation factor VIII, platelets or platelet glycoprotein 1b, and ristocetin to VWF.
Objective
Current study aims to identify novel VWF binding partners that may modulate VWF functions under physiological conditions.
Methods
A deoxyribonucleic acid aptamer-based affinity purification of VWF, followed by tandem mass spectrometry, functional, and binding assays was employed.
Results
Apolipoprotein B100/low-density lipoprotein (apoB100/LDL) was identified as a novel VWF-binding partner. Purified apoB100/LDL was able to accelerate the proteolytic cleavage of VWF by ADAMTS13 under shear in a concentration-dependent manner. This rate-enhancing activity was dramatically reduced when apoB100/LDL was oxidized. More interestingly, the oxidized apoB100/LDL appeared to compete with native apoB100/LDL for its enhancing activity on VWF proteolysis under shear. As a control, a purified apoA1/high-density lipoprotein (apoA1/HDL) or apoB48 exhibited a minimal or no activity enhancing VWF proteolysis by ADAMTS13 under the same conditions. Both VWF and ADAMTS13 were able to bind native or oxidized apoB100/LDL with high affinities. No binding interaction was detected between VWF (or ADAMTS13) and apoA1/HDL (or apoB48). Moreover, apoB100/LDL but not its oxidized products inhibited the adhesion of platelets to ultra large VWF released from endothelial cells under flow. Finally, significantly reduced ratios of high to low molecular weight of VWF multimers with increased levels of plasma VWF antigen were detected in
LDLR
−/−
mice fed with high cholesterol diet.
Conclusion
These results indicate that apoB100/LDL may be a novel physiological regulator for ADAMTS13-VWF functions.
PDF
