Cyclic wetting and drying processes have been considered as important factors that accelerate the weathering process and have deteriorative effects on rock properties. In the present study, a fully ...nondestructive and noninvasive testing approach utilizing micro-CT and ultrasonic wave velocity tests was employed to investigate the microstructure of slate under wetting and drying cycles. We studied variations in the physical properties, including the dry weight and the velocities of P- and S-waves versus the number of wetting and drying cycles. The internal microstructural distributions were visualized and quantified by the 3D reconstruction and hybrid image segmentation of CT images. The degree of deterioration caused by wetting and drying cycles was reflected by exponential decreases of physical properties, including dry weight and velocities of the P- and S-waves. Parameters relating to the microfracture diameter, volume, etc. were quantified. The nondestructive and noninvasive testing approach utilizing micro-CT and ultrasonic wave velocity tests has potential for the detection and visualization of the internal microstructure of rock under wetting and drying cycles.
With the widespread application of machine learning methods, the continuous improvement of forecast accuracy has become an important task, which is especially crucial for landslide displacement ...predictions. This study aimed to propose a novel prediction model to improve accuracy in landslide prediction, based on the combination of multiple new algorithms. The proposed new method includes three parts: data preparation, multi-swarm intelligence (MSI) optimization, and displacement prediction. In the data preparation, the complete ensemble empirical mode decomposition (CEEMD) is adopted to separate the trend and periodic displacements from the observed cumulative landslide displacement. The frequency component and residual component of reconstructed inducing factors that related to landslide movements are also extracted by the CEEMD and
-test, and then picked out with edit distance on real sequence (EDR) as input variables for the support vector regression (SVR) model. MSI optimization algorithms are used to optimize the SVR model in the MSI optimization; thus, six predictions models can be obtained that can be used in the displacement prediction part. Finally, the trend and periodic displacements are predicted by six optimized SVR models, respectively. The trend displacement and periodic displacement with the highest prediction accuracy are added and regarded as the final prediction result. The case study of the Shiliushubao landslide shows that the prediction results match the observed data well with an improvement in the aspect of average relative error, which indicates that the proposed model can predict landslide displacements with high precision, even when the displacements are characterized by stepped curves that under the influence of multiple time-varying factors.
Cepharanthine (CEP) is a biscoclaurine alkaloid extracted from Stephania cepharantha and has been shown to have an anti-tumour effect on different types of cancers. However, the anti-cancer effect of ...CEP on human breast cancer cells is still unclear.
We used MTT, clone formation, in vitro scratch, invasion and migration assays to confirm the inhibitory role of CEP on the proliferation of breast cancer cells. Flow cytometry, plasmid construction and western blot analysis were used to study the detailed mechanisms.
Our study showed that CEP could inhibit cell proliferation by inducing autophagy, apoptosis, and G0/G1 cell cycle arrest of breast cancer cells. Furthermore, we found that CEP induced autophagy and apoptosis by inhibiting the AKT/mTOR signalling pathway.
We found that CEP could inhibit growth and motility of MCF-7 and MDA-MB-231 breast cancer cell. Our study revealed an anti-tumour effect of CEP on breast cancer cells and suggests that CEP could be a potential new clinical therapy for breast cancer.
Calcium oxalate (CaOx) crystal can trigger kidney injury, which contributes to the pathogenesis of nephrocalcinosis. The phenotypes of infiltrating macrophage may impact CaOx-mediated kidney ...inflammatory injury as well as crystal deposition. How aryl hydrocarbon receptor (AhR) regulates inflammation and macrophage polarization is well understood; however, how it modulates CaOx nephrocalcinosis remains unclear. Methods: Mice were intraperitoneally injected with glyoxylate to establish CaOx nephrocalcinosis model with or without the treatment of AhR activator 6-formylindolo(3,2-b)carbazole (FICZ). Positron emission tomography computed tomography (PET-CT) imaging, Periodic acid-Schiff (PAS) staining, and polarized light optical microscopy were used to evaluate kidney injury and crystal deposition in mice kidney. Western blotting, immunofluorescence, chromatin immunoprecipitation, microRNA-fluorescence in situ hybridization, and luciferase reporter assays were applied to analyze polarization state and regulation mechanism of macrophage. Results: AhR expression was significantly upregulated and negatively correlated with interferon-regulatory factor 1 (IRF1) and hypoxia inducible factor 1-alpha (HIF-1α) levels in a murine CaOx nephrocalcinosis model following administration of FICZ. Moreover, AhR activation suppressed IRF1 and HIF-1α levels and decreased M1 macrophage polarization in vitro. In terms of the mechanism, bioinformatics analysis and chromatin immunoprecipitation assay confirmed that AhR could bind to miR-142a promoter to transcriptionally activate miR-142a. In addition, luciferase reporter assays validated that miR-142a inhibited IRF1 and HIF-1α expression by directly targeting their 3'-untranslated regions. Conclusions: Our results indicated that AhR activation could diminish M1 macrophage polarization and promote M2 macrophage polarization to suppress CaOx nephrocalcinosis via the AhR-miR-142a-IRF1/HIF-1α pathway.
Abstract
Impaired oxidative metabolism is one of multi-variate factors leading to exercise intolerance in heart failure patients. The purpose of the study was to demonstrate the use of dynamic
31
P ...magnetic resonance spectroscopy (MRS) and
31
P magnetic resonance imaging (MRI) techniques to measure PCr resynthesis rate post-exercise as a biomarker for oxidative metabolism in skeletal muscle in HF patients and controls. In this prospective imaging study, we recruited six HF patients and five healthy controls. The imaging protocol included
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P-MRS, spectrally selective 3D turbo spin echo for
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P-MRI, and Dixon multi-echo GRE for fat–water imaging on a 3 T clinical MRI scanner. All the subjects were scanned pre-exercise, during plantar flexion exercise, and post-exercise recovery, with two rounds of exercise for
31
P -MRS and
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P-MRI, respectively. Unpaired t-tests were used to compare
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P-MRS and
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P-MRI results between the HF and control cohorts. The results show that PCr resynthesis rate was significantly slower in the HF cohort compared to the controls using
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P-MRS (
P
= 0.0003) and
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P-MRI (
P
= 0.0014).
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P-MRI showed significant differences between the cohorts in muscle groups (soleus (
P
= 0.0018), gastrocnemius lateral (
P
= 0.0007) and gastrocnemius medial (
P
= 0.0054)). The results from this study suggest that
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P-MRS/
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P-MRI may be used to quantify lower leg muscle oxidative metabolism in HF patients, with
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P-MRI giving an additional advantage of allowing further localization of oxidative metabolism deficits. Upon further validation, these techniques may serve as a potentially useful clinical imaging biomarker for staging and monitoring therapies in HF-patients.
In this work, the advanced all solid-state block copolymer electrolytes (SBCPEs) for lithium-ion batteries with double conductive phases, poly(ethylene oxide)-
-poly(trimethyl-
...-((2-(dimethylamino)ethyl methacrylate)-7-propyl)-ammonium bis(trifluoromethanesulfonyl) imide) (PEO-
-PDM-dTFSI)/LiTFSI, were fabricated, in which the charged PDM-dTFSI block contained double quaternary ammonium cations and the PEO block was doped with LiTFSI. The disordered (DIS) and ordered lamellae (LAM) phase structures were achieved by adjusting the composition of the block copolymer and the doping ratio
. In addition, the presence of the hard PDM-dTFSI block and the formation of the LAM phase structure resulted in a good mechanical strength of the solid PEO-
-PDM-dTFSI/LiTFSI electrolyte, and it could maintain a high level of 10
Pa at 100 °C, which was around 10,000 times stronger than that of the PEO/LiTFSI electrolyte. Based on the good mechanical and electrochemical properties, the PEO-
-PDM-dTFSI/LiTFSI SBCPE exhibited excellent long-term galvanostatic cycle performance, indicating the strong ability to suppress lithium dendrites.
Chronic atrophic gastritis is a significant premalignant lesion of gastric carcinoma. There is a great need to prevent the progression to gastric carcinoma through early intervention and treatment ...for chronic atrophic gastritis. Weifuchun, a famous Chinese patent drug, has been widely used for chronic atrophic gastritis in China. However, it remains unclear whether Weifuchun is effective for atrophic gastritis.
To determine the effectiveness and safety of Weifuchun for chronic atrophic gastritis.
We systematically retrieved seven databases (Cochrane Library, EMBASE, PubMed, China National Knowledge Infrastructure, Wanfang database, Chinese Scientific Journals Database, and Chinese Biological Medical Database) from their inception to October 5, 2022. Methodological quality was examined using the Cochrane Risk of bias tool. We also used RevMan 5.4 software for statistical analysis to examine the effectiveness and safety of Weifuchun.
Fifteen studies with 1,488 patients were enrolled in this meta-analysis. The study indicated that Weifuchun was more effective (RR 1.52; 95% CI 1.41, 1.63; p<0.00001) than Western medicine and other Chinese patent medicine. In addition, Weifuchun was more effective in improving gastric mucosal under gastroscopy, improving histopathologic changes of gastric mucosal, and inhibiting Helicobacter pylori. However, no significant difference in safety was examined between Weifuchun and the control group (RR 2.83; 95% CI 0.85, 9.38; P = 0.09).
The meta-analysis revealed a significant statistical difference with Weifuchun in effectiveness compared to the control group. However, there was no significant difference in safety. Thus, more high-quality clinical studies are needed in the future.
Registration number CRD42022365703.
RAD51 promotes homology-directed repair (HDR), replication fork reversal, and stalled fork protection. Defects in these functions cause genomic instability and tumorigenesis but also generate ...hypersensitivity to cancer therapeutics. Here we describe the identification of RADX as an RPA-like, single-strand DNA binding protein. RADX is recruited to replication forks, where it prevents fork collapse by regulating RAD51. When RADX is inactivated, excessive RAD51 activity slows replication elongation and causes double-strand breaks. In cancer cells lacking BRCA2, RADX deletion restores fork protection without restoring HDR. Furthermore, RADX inactivation confers chemotherapy and PARP inhibitor resistance to cancer cells with reduced BRCA2/RAD51 pathway function. By antagonizing RAD51 at forks, RADX allows cells to maintain a high capacity for HDR while ensuring that replication functions of RAD51 are properly regulated. Thus, RADX is essential to achieve the proper balance of RAD51 activity to maintain genome stability.
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•RADX (CXorf57) is a single-strand DNA binding protein related to RPA•RADX prevents MUS81-dependent replication fork collapse•RADX antagonizes RAD51 to prevent excessive replication fork remodeling•RADX deletion restores fork protection and chemoresistance to BRCA2-deficient cells
Dungrawala et al. identify RADX as an RPA-like single-strand DNA binding protein enriched at replication forks. RADX antagonizes RAD51 accumulation at forks, thereby preventing aberrant fork remodeling. RADX deletion confers fork protection and chemoresistance to BRCA2 mutant cells without affecting homologous recombination repair of double-strand breaks.
Since the occurrence of coronavirus disease 2019 (COVID-19) in Wuhan, China in December 2019, COVID-19 has been quickly spreading out to other provinces and countries. Considering that traditional ...Chinese medicine (TCM) played an important role during outbreak of SARS and H1N1, finding potential alternative approaches for COVID-19 treatment is necessary before vaccines are developed. According to previous studies, Maxing Shigan decoction (MXSGD) present a prominent antivirus effect and is often used to treat pulmonary diseases. Furthermore, we collected 115 open prescriptions for COVID-19 therapy from the National Health Commission, State Administration of TCM and other organizations, MXSGD was identified as the key formula. However, the underlying molecular mechanism of MXSGD against COVID-19 is still unknown.
The present study aimed to evaluate the therapeutic mechanism of MXSGD against COVID-19 by network pharmacology and in vitro experiment verification, and screen the potential components which could bind to key targets of COVID-19 via molecular docking method.
Multiple open-source databases related to TCM or compounds were employed to screen active ingredients and potential targets of MXSGD. Network pharmacology analysis methods were used to initially predict the antivirus and anti-inflammatory effects of MXSGD against COVID-19. IL-6 induced rat lung epithelial type Ⅱ cells (RLE-6TN) damage was established to explore the anti-inflammatory damage activity of MXSGD. After MXSGD intervention, the expression level of related proteins and their phosphorylation in the IL-6 mediated JAK-STAT signaling pathway were detected by Western blot. Molecular docking technique was used to further identify the potential substances which could bind to three key targets (ACE2, Mpro and RdRp) of COVID-19.
In this study, 105 active ingredients and 1025 candidate targets were selected for MXSGD, 83 overlapping targets related to MXSGD and COVID-19 were identified, and the protein-protein interaction (PPI) network of MXSGD against COVID-19 was constructed. According to the results of biological enrichment analysis, 63 significant KEGG pathways were enriched, and most of them were related to signal transduction, immune system and virus infection. Furthermore, according the relationship between signal pathways, we confirmed MXSGD could effectively inhibit IL-6 mediated JAK-STAT signal pathway related protein expression level, decreased the protein expression levels of p-JAK2, p-STAT3, Bax and Caspase 3, and increased the protein expression level of Bcl-2, thereby inhibiting RLE-6TN cells damage. In addition, according to the LibDock scores screening results, the components with strong potential affinity (Top 10) with ACE2, Mpro and RdRp are mainly from glycyrrhiza uralensis (Chinese name: Gancao) and semen armeniacae amarum (Chinese name: Kuxingren). Among them, amygdalin was selected as the optimal candidate component bind to all three key targets, and euchrenone, glycyrrhizin, and glycyrol also exhibited superior affinity interactions with ACE2, Mpro and RdRp, respectively.
This work explained the positive characteristics of multi-component, multi-target, and multi-approach intervention with MXSGD in combating COVID-19, and preliminary revealed the antiviral and anti-inflammatory pharmacodynamic substances and mechanism of MXSGD, which might provide insights into the vital role of TCM in the prevention and treatment of COVID-19.
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