Existing numerical simulation studies show that confining pressure has a negative effect on the efficiency of percussion drilling. However, the corresponding systematic experimental studies ...considering confining pressure have rarely been reported. In this study, single drop weight impact tests were performed on granite samples and the influence of the confining pressure on the crater parameters was analyzed. Besides, the fluorescent approach was adopted to observe the cracks in the damaged samples. The results indicate that confining pressure has a significant adverse effect on rock fragmentation. For instance, the average volume of crater under confining pressure of 20 MPa is 91.5% smaller than that without confining pressure. Meanwhile, the higher the confining pressure, the shorter the cracks. The confining pressure can inhibit the propagation of side cracks around the crater and hinder the expansion of radial cracks to the free surface. Knowing these phenomena and conclusions, we may be able to eliminate or reduce the negative effect of the confining pressure by optimizing the working parameters of the drilling tools and the layout structure of the buttons on the bit.
•The dynamic rock fragmentation performance with confining pressure has been systematically studied by experiments.•The influence of the confining pressure on the crater parameters is quantitatively analyzed.•Crack evolution under confining pressure was revealed by the fluorescent approach.•Confining pressure has a significant adverse effect on dynamic rock fragmentation.
Display omitted
•The studied BIF deposits were formed in the Early Cambrian (516–520 Ma).•The studied BIF deposits were formed in a back-arc basin.•High- to low-T hydrothermal fluids, seawater and ...minor clastic input all contribute to the studied BIF deposits.•The studied BIF deposits formed in a stratified seawater column.
Large amounts of magnetite-rich banded iron formation (BIF) deposits, located in the Western Kunlun orogenic belt (WKOB), are hosted within the greenschist- to amphibolite-facies metamorphosed Bulunkuole complex. The iron (Fe) orebodies of these BIF deposits are interlayered with biotite-quartz schist and amphibolite, indicating that they are temporally closely associated. Analyses of the contents and ratios of major and trace elements indicate that the protoliths of the amphibolite should be basalt and andesite. LA-ICP-MS U-Pb dating of zircons from three representative amphibolite samples suggests that the studied BIF deposits were formed in the Early Cambrian (516–520 Ma). Based on regional geology and geochemistry of the amphibolite, we propose that these BIF deposits were formed in a back-arc basin setting. A wide range of Ce and Eu anomalies for Fe ores indicate that the studied BIF deposits were formed in both oxygenated surface seawater and deeper suboxic to anoxic seawater. Linking the tectonic setting with geochemical characteristics of bulk-rock Fe ores, we propose Fe and Si are predominantly seafloor-derived, with pulsed contribution of high- to low-T hydrothermal fluids that were closely associated with the extension of back-arc basin. In addition, we postulate that periodically upwelled metalliferous hydrothermal fluids were subsequently oxidized by surface seawater and mixed with detrital components, which ultimately led to the rhythmic precipitation of the Fe-rich and Si-rich layers.
To address the issue of insufficient deep contextual information mining in the semantic segmentation task of multiple defects in concrete bridges, due to the diversity in texture, shape, and scale of ...the defects as well as significant differences in the background, we propose the Concrete Bridge Apparent Multi-Defect Segmentation Network (PID-MHENet) based on a PID encoder and multi-feature fusion. PID-MHENet consists of a PID encoder, skip connection, and decoder. The PID encoder adopts a multi-branch structure, including an integral branch and a proportional branch with a “thick and long” design principle and a differential branch with a “thin and short” design principle. The PID Aggregation Enhancement (PAE) combines the detail information of the proportional branch and the semantic information of the differential branch to enhance the fusion of contextual information and, at the same time, introduces the self-learning parameters, which can effectively extract the information of the boundary details of the lesions, the texture, and the background differences. The Multi-Feature Fusion Enhancement Decoding Block (MFEDB) in the decoding stage enhances the information and globally fuses the different feature maps introduced by the three-channel skip connection, which improves the segmentation accuracy of the network for the background similarity and the micro-defects. The experimental results show that the mean Pixel accuracy (mPa) and mean Intersection over Union (mIoU) values of PID-MHENet on the concrete bridge multi-defect semantic segmentation dataset improved by 5.17% and 5.46%, respectively, compared to the UNet network.
The novel coronavirus disease 2019 (COVID-19) pandemic has tested the ability of universities to provide a high-quality, safe educational experience for students due to campuses shutting down. As a ...result, online learning could shift from a traditional classroom teaching mode and make education accessible to students. Previous studies have used individual online teaching cases to exploit a variety of online learning tools to ensure the continuation of medical education during this difficult time in China. However, for the first time, we have conducted a systematic review of local online teaching approaches, existing challenges, and potential solutions.
We present the issues and experience of conducting online medical teaching practices in China with the aim of communicating them to our peers in other countries or regions when examining the transition to e-learning during the COVID-19 pandemic and beyond.
We searched the keywords below from public databases and reviewed relevant publications reporting on medical online teaching in China during the COVID-19 pandemic to analyze and summarize the online tools, modalities, and challenges.
We listed common online teaching tools and described a variety of online teaching modalities, as well as possible challenges. We also discussed potential solutions for those challenges, as well as the impact of the transition to online teaching on traditional education.
By investigating local online medical teaching in China, we present useful tools and modalities that have been successfully exploited in education during the difficult time of COVID-19, although some challenges remain. The exploration of the transition to online teaching or learning will likely continue to have a profound impact on traditional classroom teaching.
•The feasibility of using fractal dimension theory to analyze impact cracks is studied.•The impact crack patterns are classified and explained systematically.•The distribution area of the impact ...cracks near the borehole is divided, and the evolution law of the impact cracks is revealed.•The function relation between fractal dimension of impact cracks and surface crack porosity is given.
Impact cracks near the borehole are beneficial to geothermal energy development in many aspects, such as hydraulic fracturing, perforation and so on. However, the quantitative evaluation of the impact cracks near the borehole has not been studied. In the present paper, the fractal dimension of the impact crack has been calculated by the box-counting method to capture the complexity and irregularity of the impact crack pattern. The results show that the impact crack has fractal characteristics, which proves that it is feasible to use the fractal dimension method to quantitatively evaluate the impact cracks. The fractal dimension of the impact cracks is between 1.27 and 1.64. Moreover, the variation of fractal dimension with the increase of the dimensionless distance shows a remarkable regionalization. Simultaneously, the impact crack patterns are classified and divided into seven kinds according to their shape characteristics, and T-shaped, Y-shaped, and wave-shaped cracks are the main kinds of impact cracks. Finally, the surface crack porosity parameter is introduced to characterize the actual content of impact cracks, and the maximum surface crack porosity is 15.9%. Through the comprehensive evaluation of fractal dimension and surface crack porosity, it can be estimated that the influence of percussion drilling on rocks near the borehole ranges from about 1.5 times to 1.7 times the diameter of the borehole. The concept of fractal dimension provides a new perspective for a quantitative understanding of impact cracks, and the presented experimental results can be a useful reference for building numerical models.
Elongation of very long-chain fatty acids protein 6 (ELOVL6) played crucial roles in regulating energy expenditure and fatty acid metabolism. Many studies have performed to investigate the ...physiological roles and regulatory mechanisms of
in fish and animals, while few studies were reported in crustaceans.
Here we reported on the molecular cloning, tissue distribution and expression profiles in response to dietary fatty acids, ambient salinity and starvation stress in
by using rapid amplification of cDNA ends (RACE) and quantitative real-time PCR.
Three
isoforms (named
and
) were isolated from
in the present study. The complete sequence of
was 1345 bp, the full-length sequence of
was 1419 bp, and the obtained
sequence was 1375 bp in full length. The
and
encoded 287, 329 and 301 amino acids respectively, and exhibited the typical structural features of ELOVL protein family members. Phylogenetic analysis showed that the ELOVL6a from
clustered most closely to ELOVL6 from
and
, while the ELOVL6b and ELOVL6c from
gathered alone into a single branch. Quantitative real-time PCR exhibited that the relatively abundant expression of
was observed in intestine and stomach, and the
and
were highly expressed in hepatopancreas. In addition, studies found that replacing fish oil with soybean oil could significantly increase the transcriptional levels of three
in hepatopancreas of
, and the expression of
and
in hepatopancreas were more sensitive to dietary fatty acids than the
. Compared with the normal sea water group (27‰), the expression of sterol-regulatory element binding protein1c
and
were upregulated in the low salinity groups, particularly in 7‰. On the contrary, the starvation stress suppressed the expression of
and
.
These results may contribute to understand the functions of
in fatty acid synthesis and regulatory mechanisms in crustaceans.
Immune checkpoint inhibition targeting the PD-1/PD-L1 pathway has become a powerful clinical strategy for treating cancer, but its efficacy is complicated by various resistance mechanisms. One of the ...reasons for the resistance is the internalization and recycling of PD-L1 itself upon antibody binding. The inhibition of lysosome-mediated degradation of PD-L1 is critical for preserving the amount of PD-L1 recycling back to the cell membrane. In this study, we find that Hsc70 promotes PD-L1 degradation through the endosome-lysosome pathway and reduces PD-L1 recycling to the cell membrane. This effect is dependent on Hsc70-PD-L1 binding which inhibits the CMTM6-PD-L1 interaction. We further identify an Hsp90α/β inhibitor, AUY-922, which induces Hsc70 expression and PD-L1 lysosomal degradation. Either Hsc70 overexpression or AUY-922 treatment can reduce PD-L1 expression, inhibit tumor growth and promote anti-tumor immunity in female mice; AUY-922 can further enhance the anti-tumor efficacy of anti-PD-L1 and anti-CTLA4 treatment. Our study elucidates a molecular mechanism of Hsc70-mediated PD-L1 lysosomal degradation and provides a target and therapeutic strategies for tumor immunotherapy.
Objectives
Autophagy is divided into three phases: autophagosome engulfment of intracellular organelles and proteins, autophagosome fusion with lysosomes, and autolysosome degradation. The farnesyl ...pyrophosphate synthase inhibitor ibandronate (IBAN) has in vivo cardioprotective properties, potentially via anti-oxidant effects. Whether autophagy is involved in the cardioprotective effect of IBAN remains unexplored.
Methods
Human umbilical vein endothelial cells (HUVECs) were treated in vitro with IBAN to assess autophagy induction. Lysosomal activation and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling were assessed using a LysoTracker assay, acridine orange staining and western blotting. An MTS assay was used to assess cellular proliferation. Autophagy was inhibited using chloroquine or RNA silencing of autophagy-related 7 (Atg7) expression.
Results
IBAN induced autophagy in HUVECs. Moreover, IBAN activated lysosomal function, which is pivotal to autophagy induction. PI3K/AKT/mTOR activity was inhibited in IBAN-treated HUVECs, indicating the involvement of this pathway in IBAN-induced autophagy. Inhibition of autophagy using either chloroquine or Atg7 siRNA potentiated inhibition of HUVEC growth by IBAN, suggesting the involvement of non-autophagy pathways in the antiproliferative effects of IBAN.
Conclusions
These findings provide insights into the role of autophagy in the cardioprotective effects of IBAN and the molecular mechanisms underlying autophagy induction by IBAN.
•A novel technique of hydraulic fracturing assisted by the DTH-hammer-induced impact fractures is proposed.•Complex fracture networks can be formed near the wellbore.•The novel technique can ...significantly reduce the fracturing pressure and improve the permeability near the wellbore.
Hydraulic fracturing is one of the key technologies in geothermal development of hot-dry-rock (HDR) geothermal energy. How to reduce the fracturing pressure and enhance the fractures connectivity of HDR has become a hot issue. In this paper, we propose to use a down-the-hole (DTH) hammer to impact granite, which assist to create new artificial fractures similar to natural fractures or widen the existing fractures near the wellbore, consequently enhancing the connectivity of fractures during hydraulic fracturing. A series of experiments were conducted to verify the feasibility of this stimulation technique, including the observation and quantification of impact fractures, and the determination of fracturing pressure. In addition, numerical simulation of impact stress wave was carried out to explain the distribution of fractures. The results showed that the granite rock mass damage caused by percussive rotary drilling was about 5–7 times larger than that caused by diamond rotary drilling. Meanwhile, the distribution of fractures was characterized by regionalization, which was mainly attributed to the attenuation of impact stress wave, and the numerical results were consistent with the experimental observations. Laboratory experiment results of hydraulic fracturing indicated that the fracturing pressure of granite samples near the wellbore after percussive drilling had been greatly reduced, which was nearly 50% lower than that of conventional drilling. It indicates that the proposed multi-fractured stimulation technique of hydraulic fracturing assisted by the impact fractures induced by a DTH hammer can be a potential solution to solve the problems of hydraulic fracturing.
As rate-limiting enzymes of β-oxidation of fatty acids in mitochondria, the carnitine palmitoyltransferase (CPT) played an important role in regulating energy homeostasis of aquatic animals. However, ...there was very little research on β-oxidation of fatty acids in crustaceans. In the present study, the full-length cDNA sequences of cpt-1a , cpt-1b and cpt-2 were isolated from the hepatopancreas of Scylla paramamosain , and contained 4206, 5303 and 3486 bp respectively. Sequence analysis showed that the CPT-1A, CPT-1B and CPT-2 encoded proteins with 777, 775 and 672 amino acids respectively, and only the CPT-1A possessed a transmembrane region. In addition, both the CPT-1B and CPT-2 contained conservative functional domains like N-terminal domain and acyltransferases choActase 2, while the CPT-1A lacked. The results of phylogenetic tree indicated that the CPT-1A, CPT-1B and CPT-2 of S. paramamosain gathered together with their corresponding orthologues from crustaceans. The tissue distribution exhibited that the cpt-1a was highly expressed in hepatopancreas, followed by muscle, eyestalk and cranial ganglia, and the muscle, eyestalk and heart were main expressed tissues of cpt-1b . Furthermore, the high expression levels of cpt-2 were mainly detected in hepatopancreas, muscle and heart. The transcriptional levels of cpt-1a , cpt-1b and cpt-2 were significantly up-regulated under chronic low salinity stress. Besides, at the acute low salinity stress condition, the expression levels of cpt-1a , cpt-1b and cpt-2 in hepatopancreas were dramatically increased in 14‰ and 4‰ salinity groups at the 6h and 48h, while the transcriptional levels of cpt-1a , cpt-1b and cpt-2 in muscle were signally up-regulated in 14‰ and 4‰ salinity groups at the 12h and 24h, showing an alternate response pattern. Similarly, the present study found that fasting could markedly increase the expression levels of cpt-1a , cpt-1b and cpt-2 in hepatopancreas and muscle, especially cpt-1a in hepatopancreas as well as cpt-1a and cpt-1b in muscle. The results above indicated that the cpt-1a , cpt-1b and cpt-2 played a crucial part in providing energy for coping with fasting and salinity stress. These results would contribute to enhancing the knowledge of cpt phylogenetic evolution and their roles in energy metabolism of crustaceans.
PDF
