High-resolution myelin-water fraction and quantitative relaxation mapping using 3D ViSTa-MR fingerprinting

Purpose: This study aims to develop a high-resolution whole-brain multi-parametric quantitative MRI approach for simultaneous mapping of myelin-water fraction (MWF), T1, T2, and proton-density (PD), all within a clinically feasible scan time. Methods: We developed 3D ViSTa-MRF, which combined Visualization of Short Transverse relaxation time component (ViSTa) technique with MR Fingerprinting (MRF), to achieve high-fidelity whole-brain MWF and T1/T2/PD mapping on a clinical 3T scanner. To achieve fast acquisition and memory-efficient reconstruction, the ViSTa-MRF sequence leverages an optimized 3D tiny-golden-angle-shuffling spiral-projection acquisition and joint spatial-temporal subspace reconstruction with optimized preconditioning algorithm. With the proposed ViSTa-MRF approach, high-fidelity direct MWF mapping was achieved without a need for multi-compartment fitting that could introduce bias and/or noise from additional assumptions or priors. Results: The in-vivo results demonstrate the effectiveness of the proposed acquisition and reconstruction framework to provide fast multi-parametric mapping with high SNR and good quality. The in-vivo results of 1mm- and 0.66mm-iso datasets indicate that the MWF values measured by the proposed method are consistent with standard ViSTa results that are 30x slower with lower SNR. Furthermore, we applied the proposed method to enable 5-minute whole-brain 1mm-iso assessment of MWF and T1/T2/PD mappings for infant brain development and for post-mortem brain samples. Conclusions: In this work, we have developed a 3D ViSTa-MRF technique that enables the acquisition of whole-brain MWF, quantitative T1, T2, and PD maps at 1mm and 0.66mm isotropic resolution in 5 and 15 minutes, respectively. This advancement allows for quantitative investigations of myelination changes in the brain.Comment: 38 pages, 12 figures and 1 tabl

Fangchinoline Inhibits Human Immunodeficiency Virus Type 1 Replication by Interfering with gp160 Proteolytic Processing

The introduction of highly active antiretroviral therapy has led to a significant reduction in the morbidity and mortality of acquired immunodeficiency syndrome patients. However, the emergence of drug resistance has resulted in the failure of treatments in large numbers of patients and thus necessitates the development of new classes of anti-HIV drugs. In this study, more than 200 plant-derived small-molecule compounds were evaluated in a cell-based HIV-1 antiviral screen, resulting in the identification of a novel HIV-1 inhibitor (fangchinoline). Fangchinoline, a bisbenzylisoquinoline alkaloid isolated from Radix Stephaniae tetrandrae, exhibited antiviral activity against HIV-1 laboratory strains NL4-3, LAI and BaL in MT-4 and PM1 cells with a 50% effective concentration ranging from 0.8 to 1.7 µM. Mechanism-of-action studies showed that fangchinoline did not exhibit measurable antiviral activity in TZM-b1 cells but did inhibit the production of infectious virions in HIV-1 cDNA transfected 293T cells, which suggests that the compound targets a late event in infection cycle. Furthermore, the antiviral effect of fangchinoline seems to be HIV-1 enve1ope-dependent, as the production of infectious HIV-1 particles packaged with a heterologous envelope, the vesicular stomatitis virus G glycoprotein, was unaffected by fangchinoline. Western blot analysis of HIV envelope proteins expressed in transfected 293T cells and in isolated virions showed that fangchinoline inhibited HIV-1 gp160 processing, resulting in reduced envelope glycoprotein incorporation into nascent virions. Collectively, our results demonstrate that fangchinoline inhibits HIV-1 replication by interfering with gp160 proteolytic processing. Fangchinoline may serve as a starting point for developing a new HIV-1 therapeutic approach

Effect of aging process on combustion and mechanical performance of nitroguanidine propellants

The effect of different aging times (1 day, 3 days, 5 days and 7 days) on the combustion performance and mechanical properties of nitroguanidine propellants was studied.Through the mechanical properties test of impact and compression and closed bomb test of the prepared propellants, it was found that the relative steepness of the propellants aged for 3 days under normal and low temperature conditions was all less than 1;Under normal and low temperature conditions, the impact strength of propellants aged for 5 days was the largest;Propellants aged for 7 days had the highest compressive strength at low temperatures and propellants aged for 1 day had the highest compression rate at low temperatures.Comprehensive research results show that aging time of three days has a better improvement in the combustion performance and mechanical properties of the propellants

Enzyme Commission Number Prediction and Benchmarking with Hierarchical Dual-core Multitask Learning Framework

Enzyme commission (EC) numbers, which associate a protein sequence with the biochemical reactions it catalyzes, are essential for the accurate understanding of enzyme functions and cellular metabolism. Many ab initio computational approaches were proposed to predict EC numbers for given input protein sequences. However, the prediction performance (accuracy, recall, and precision), usability, and efficiency of existing methods decreased seriously when dealing with recently discovered proteins, thus still having much room to be improved. Here, we report HDMLF, a hierarchical dual-core multitask learning framework for accurately predicting EC numbers based on novel deep learning techniques. HDMLF is composed of an embedding core and a learning core; the embedding core adopts the latest protein language model for protein sequence embedding, and the learning core conducts the EC number prediction. Specifically, HDMLF is designed on the basis of a gated recurrent unit framework to perform EC number prediction in the multi-objective hierarchy, multitasking manner. Additionally, we introduced an attention layer to optimize the EC prediction and employed a greedy strategy to integrate and fine-tune the final model. Comparative analyses against 4 representative methods demonstrate that HDMLF stably delivers the highest performance, which improves accuracy and F1 score by 60% and 40% over the state of the art, respectively. An additional case study of tyrB predicted to compensate for the loss of aspartate aminotransferase aspC, as reported in a previous experimental study, shows that our model can also be used to uncover the enzyme promiscuity. Finally, we established a web platform, namely, ECRECer (https://ecrecer.biodesign.ac.cn), using an entirely could-based serverless architecture and provided an offline bundle to improve usability

Effect of Temperature and Acidification on Reinjection of Geothermal Water into Sandstone Geothermal Reservoirs: Laboratory Study

Geothermal reinjection is a new method of geothermal development which can maintain regional geothermal reservoir pressure, and it is conducive to the sustainable development and utilization of geothermal heat. However, geothermal reinjection blockage has always been a problem that restricts geothermal development and utilization, causing geothermal reservoirs, especially the attenuation of sandstone geothermal reservoirs. Considering an example of a typical sandstone geothermal reservoir in Binzhou, in this study, in situ geothermal fluids and borehole cores were collected to conduct automatic rotary reactor experiments under different temperature and acidification conditions in laboratory studies. The chemical compositions of geothermal fluids and core samples before and after the experiment were compared. The results show that both temperature and acid have significant effects on the water–rock interaction. The effect of temperature is mainly shown on mineral solubility, while the effect of acidification is shown in the increased dissolution of calcite and feldspar minerals. Compared with high temperature (65 °C) reinjection conditions, the calcite precipitation at a low temperature (45 °C) is largely reduced, but with larger total mineral volume changes, mainly due to the formation of montmorillonite. Therefore, from the laboratory studies, it is recommended to preform reinjection using a low-temperature fluid, without adding acids

Permeability and Porosity Changes in Sandstone Reservoir by Geothermal Fluid Reinjection: Insights from a Laboratory Study

Geothermal energy is a clean and environmentally friendly energy source that can be used sustainably; however, attention towards geothermal energy has been intermittent during the last 40 years as a function of the crisis of oil price. However, geothermal reinjection and clogging has been a challenge limiting geothermal development and utilization. In China, widely distributed sandstone geothermal reservoirs have reduced production due to technical constraints such as excessive reinjection pressure and blockage. In this paper, we took the Binzhou sandstone geothermal field in North China as an example and conducted displacement experiments under different temperature and flow rate conditions by collecting in situ geothermal fluid and core rock to obtain changes in sandstone permeability. By comparing the variation in geochemical and mineral composition of geothermal fluids and cores before and after the experiments, combined with a water–rock interaction simulation, we investigated the reasons for the changes in permeability and porosity. The results show that high temperature and low flow rate have relatively minimal displacement pressure, and a flow rate of 1.0 mL/min at 45 °C shows a minimal effect on permeability, while 1.0 mL/min at 55 °C and 0.5 mL/min at 45 °C show a minimal effect on porosity. Flow rate is the main factor controlling permeability, while temperature demonstrated a relatively minor effect. The shift in permeability and porosity is mainly caused by the precipitation of quartz and the conversion of albite to montmorillonite. The injection of fluids at 55 °C may have dissolved additional minerals with a minimal change in porosity. However, the permeability reduction at 55 °C is greater than that at 45 °C, indicating that the blockage, which led to the permeability reduction, contains multiple causes, such as chemical and physical blockages. From the laboratory studies, we recommended that reinjected geothermal water be cooled or kept below the reservoir temperature before reinjection and at moderate flow conditions

Effect of Temperature and Acidification on Reinjection of Geothermal Water into Sandstone Geothermal Reservoirs: Laboratory Study

Geothermal reinjection is a new method of geothermal development which can maintain regional geothermal reservoir pressure, and it is conducive to the sustainable development and utilization of geothermal heat. However, geothermal reinjection blockage has always been a problem that restricts geothermal development and utilization, causing geothermal reservoirs, especially the attenuation of sandstone geothermal reservoirs. Considering an example of a typical sandstone geothermal reservoir in Binzhou, in this study, in situ geothermal fluids and borehole cores were collected to conduct automatic rotary reactor experiments under different temperature and acidification conditions in laboratory studies. The chemical compositions of geothermal fluids and core samples before and after the experiment were compared. The results show that both temperature and acid have significant effects on the water–rock interaction. The effect of temperature is mainly shown on mineral solubility, while the effect of acidification is shown in the increased dissolution of calcite and feldspar minerals. Compared with high temperature (65 °C) reinjection conditions, the calcite precipitation at a low temperature (45 °C) is largely reduced, but with larger total mineral volume changes, mainly due to the formation of montmorillonite. Therefore, from the laboratory studies, it is recommended to preform reinjection using a low-temperature fluid, without adding acids

Permeability and Porosity Changes in Sandstone Reservoir by Geothermal Fluid Reinjection: Insights from a Laboratory Study

Geothermal energy is a clean and environmentally friendly energy source that can be used sustainably; however, attention towards geothermal energy has been intermittent during the last 40 years as a function of the crisis of oil price. However, geothermal reinjection and clogging has been a challenge limiting geothermal development and utilization. In China, widely distributed sandstone geothermal reservoirs have reduced production due to technical constraints such as excessive reinjection pressure and blockage. In this paper, we took the Binzhou sandstone geothermal field in North China as an example and conducted displacement experiments under different temperature and flow rate conditions by collecting in situ geothermal fluid and core rock to obtain changes in sandstone permeability. By comparing the variation in geochemical and mineral composition of geothermal fluids and cores before and after the experiments, combined with a water–rock interaction simulation, we investigated the reasons for the changes in permeability and porosity. The results show that high temperature and low flow rate have relatively minimal displacement pressure, and a flow rate of 1.0 mL/min at 45 °C shows a minimal effect on permeability, while 1.0 mL/min at 55 °C and 0.5 mL/min at 45 °C show a minimal effect on porosity. Flow rate is the main factor controlling permeability, while temperature demonstrated a relatively minor effect. The shift in permeability and porosity is mainly caused by the precipitation of quartz and the conversion of albite to montmorillonite. The injection of fluids at 55 °C may have dissolved additional minerals with a minimal change in porosity. However, the permeability reduction at 55 °C is greater than that at 45 °C, indicating that the blockage, which led to the permeability reduction, contains multiple causes, such as chemical and physical blockages. From the laboratory studies, we recommended that reinjected geothermal water be cooled or kept below the reservoir temperature before reinjection and at moderate flow conditions

Fangchinoline reduces functional Env expression by interfering with gp160 processing.

<p>(A) HIV-1 NL4-3-infected MT-4 cells were pretreated with 1 µM IDV alone (left panel) or 1 µM IDV plus 2.5 µM fangchinoline (right panel) for 24 hours and then cocultured with C8166 cells. After 24 hours of cocultivation, syncytium formation was examined using light microscopy. (B) 293T cells were transfected with pNL4-3 and treated with the indicated concentration of fangchinoline. The Env protein expression in transfected cells was analyzed by Western blot using a polyclonal antibody directed against HIV-1 gp120 48 hours post-transfection. (C) 293T cells were transfected with pNL4-3. At 3 hours post-transfection, the cell supernatant was removed and fresh medium with or without 10 µM fangchinoline was added. After 24 hours, the cells were labeled for 1 h and chased for indicated times in the presence or absence of fangchinoline. After biotinylated, the newly synthesized protein was collected with streptavidin-coupled magnetic beads. Processing of newly synthesized gp160 was examined by Western blot analysis.</p