To better understand the creep mechanical behavior of salt rock under very long-term tests and more accurately predict the long-term deformation of the salt caverns, a series of long-term uniaxial ...creep tests lasting for 21000 h (875 days) were carried out. The results show that the creep strain and creep rate of salt rock increase with the increase of axial stress. The initial creep stage under lower stresses lasted for 4.3–8.3 months, which was much higher than that under high stresses. Predicting the true creep rate of the salt cavern based on the test results of the creep rate in this paper is more accurate than the existing research results. A new nonlinear creep-damage constitutive model is proposed by introducing the nonlinear damage body and using the fractional derivative theory. Using the presented model and the classic creep constitutive models to fit the experimental data, it is found that the presented model best characterizes the creep evolution characteristics of salt rock. The fitting function obtained from the experimental data at different times predicts the final creep results, revealing that the longer the test duration, the more accurate the predicted results. The research in this paper provides the necessary basis for intensive investigation and prediction of the long-term creep mechanical behavior of salt storage caverns.
Stability analysis of underground constructions requires a model study of rock masses’ long-term performance. Creep tests under different stress conditions was conducted on intact granite and granite ...samples fractured at 30° and 45° angles. The experimental results indicate that the steady creep strain rates of intact and fractured rock present an exponential increase trend with the increase of stress level. A nonlinear creep model is developed based on the experimental results, in which the initial damage caused by fracture together with the damage caused by constant load have been taken into consideration. The fitting analysis results indicated that the model proposed is more accurate at identifying the full creep regions in fractured granite, especially the accelerated stage of creep deformation. The least-square fit error of the proposed creep model is significantly lower than that of Nishihara model by almost an order of magnitude. An analysis of the effects of elastic modulus, viscosity coefficient, and damage factors on fractured rock strain rate and creep strain is conducted. If no consideration is given to the effects of the damage, the proposed nonlinear creep model can degenerate into to the classical Nishihara model.
Background:
Pregnancy-induced Hypertension (PIH) is a disease that causes serious maternal and fetal morbidity and mortality. Alisma Orientale (AO) has a long history of use as traditional Chinese ...medicine therapy for PIH. This study explores its potential mechanism and biosafety based on network pharmacology, network toxicology, molecular docking and molecular dynamics simulation.
Methods:
Compounds of AO were screened in TCMSP, TCM-ID, TCM@Taiwan, BATMAN, TOXNET and CTD database; PharmMapper and SwissTargetPrediction, GeneCards, DisGeNET and OMIM databases were used to predict the targets of AO anti-PIH. The protein-protein interaction analysis and the KEGG/GO enrichment analysis were applied by STRING and Metascape databases, respectively. Then, we constructed the “herb-compound-target-pathway-disease” map in Cytoscape software to show the core regulatory network. Finally, molecular docking and molecular dynamics simulation were applied to analyze binding affinity and reliability. The same procedure was conducted for network toxicology to illustrate the mechanisms of AO hepatotoxicity and nephrotoxicity.
Results:
29 compounds with 78 potential targets associated with the therapeutic effect of AO on PIH, 10 compounds with 117 and 111 targets associated with AO induced hepatotoxicity and nephrotoxicity were obtained, respectively. The PPI network analysis showed that core therapeutic targets were IGF, MAPK1, AKT1 and EGFR, while PPARG and TNF were toxicity-related targets. Besides, GO/KEGG enrichment analysis showed that AO might modulate the PI3K-AKT and MAPK pathways in treating PIH and mainly interfere with the lipid and atherosclerosis pathways to induce liver and kidney injury. The “herb-compound-target-pathway-disease” network showed that triterpenoids were the main therapeutic compounds, such as Alisol B 23-Acetate and Alisol C, while emodin was the main toxic compounds. The results of molecular docking and molecular dynamics simulation also showed good binding affinity between core compounds and targets.
Conclusion:
This research illustrated the mechanism underlying the therapeutic effects of AO against PIH and AO induced hepato-nephrotoxicity. However, further experimental verification is warranted for optimal use of AO during clinical practice.
Osteoarthritis (OA) is a degenerative disease which serious affects patients. Ligusticum chuanxiong (CX) has been shown to have a certain curative effect on osteoarthritis in traditional Chinese ...medicine therapy. This study is based on network pharmacology and molecular docking technology to explore the potential mechanism of CX.
Components of CX to treat osteoarthritis were screened in the TCMSP database and targets were predicted by the PharmMapper database, the osteoarthritis targets were collected from the GeneCards database, and intersection genes were found to be the possible targets of CX anti-OA. The STRING database and Cytoscape software were utilized for protein-protein interaction analysis and further screening of core targets. The Metascape database was used for KEGG and GO enrichment analyses. Then, the top 10 pathways were selected to construct "drug-compound-target-pathway-disease" network analysis. Finally, molecular docking was used to analyze the binding affinity of seven compounds with core targets and TNF-α.
Seven compounds with 253 non-repetitive targets of CX were screened from the TCMSP database and 60 potential intersection targets of CX anti-OA were found. PPI network analysis showed that the core targets were ALB, AKT1, IGF1, CASP3, MAPK1, ANXA5, and MAPK14, while GO and KEGG pathway enrichment analyses showed that the relevant biological processes involved in the treatment of osteoarthritis by CX might include the MAPK cascade and reactive oxygen species metabolic process. The KEGG pathway analysis result was mainly associated with the MAPK signaling pathway and PI3K-AKT signaling pathway. We further docked seven ingredients with MAPK1 and MAPK14 enriched in the MAPK pathway, and TNF-α as the typical inflammatory cytokine. The results also showed good binding affinity, especially FA, which may be the most important component of CX anti-OA.
Our research revealed the potential mechanism of CX in the treatment of OA, and our findings can also pave the way for subsequent basic experimental verification and a new research direction.
ObjectiveThe association between haemoglobin-to-red blood cell distribution width ratio (HRR) and all-cause mortality remains poorly understood. This study aimed to examine the influence of HRR at ...the time of admission mortality over 1 year and 30 days in patients with sepsis.DesignThis was a secondary analysis.SettingThis study was conducted in intensive care units (ICUs).ParticipantsAdult patients with sepsis were identified and included from an intensive care database based on eligibility criteria.Primary outcome and measureThe primary outcome was the rate of death within 1 year. The secondary outcome was the death rate within 30 days.ResultsA total of 4233 patients with sepsis who met the inclusion criteria were analysed, excluding those ineligible. These participants were divided into quartiles based on their HRR at admission. The overall mortality rates at 1 year and 30 days were 42.9% and 25.5%, respectively. A significant inverse association was observed between HRR quartiles and all-cause mortality (p<0.001). Pairwise comparisons using Kaplan-Meier analysis showed significant differences in 1-year mortality rates across the quartiles. However, no significant difference was detected in 30-day mortality between the Q3 and Q4 groups (p=0.222). Multivariate Cox regression analysis demonstrated that a higher HRR at ICU admission was independently associated with reduced mortality at 1 year (HR, 0.935; 95% CI 0.913 to 0.958; p<0.001) and 30 days (HR, 0.969; 95% CI 0.939 to 0.999; p=0.043). Furthermore, restricted cubic spline models indicated a non-linear relationship between HRR and mortality at both 1 year and 30 days (p<0.001 for both).ConclusionsThis retrospective analysis demonstrated that the HRR at the time of admission was a significant prognostic marker for long-term mortality in patients with sepsis.
A tracheal foreign body is a common airway aspiration that creates an emergency, which often causes unobserved respiratory problems and requires management. Iatrogenic tracheal foreign bodies are ...rarely observed, which results in tracheal obstruction. If the foreign body were removed from the tracheobronchial system, it would save lives. A similar case of a tracheal foreign body was focused on, which was caused by medical glue used during preoperative computed tomography localization of pulmonary nodules.
The foreign body was deposited in the right upper bronchi, accidentally discovered after anesthesia when a double-lumen tube was located by fiber bronchoscopy. Following a video-assisted thoracoscopic surgery, the foreign body was removed using a respiratory endoscopy without subsequent adverse consequences for the patient.
There is a risk of complications from iatrogenic airway foreign bodies for preoperative localization of pulmonary nodules by injecting cyanoacrylate glue.
With the increase in energy demand, energy engineering has gradually developed to go deeper, accompanied by a complex geological environment, such as the coupling of stress and seepage. Limestone is ...widely found in underground rock engineering, and its stress–seepage coupling characteristics have a great influence on the safety and stability of related engineering projects. In order to study the permeability characteristics and damage evolution of limestone during the deformation and failure process under stress–seepage coupling conditions, permeability and acoustic emission tests on limestone were performed in this paper. The results showed that: the stress–strain curve demonstrated periodicity, as did the permeability change. The change in permeability in different deformation stages of axial strain and lateral strain was similar, but it was more appropriate to reflect the permeability evolution in terms of lateral strain. The permeability of the limestone slightly decreased in the volumetric compression stage, and tended to saturate after a sudden increase in the expansion stage. The presence of the confining pressure reduced the permeability of the rock. In the process of limestone deformation and failure, the level of acoustic emission activity can reflect the degree of fracture development. The permeability characteristics and acoustic emission characteristics had a good corresponding relationship. The greater the confining pressure, the higher the acoustic emission activity. The deformation and damage process of limestone experienced three stages: damage stable growth, damage acceleration development, and damage saturation.
Multi-rotor unmanned aerial vehicles (UAVs) for plant protection are widely used in China's agricultural production. However, spray droplets often drift and distribute nonuniformly, thereby harming ...its utilization and the environment. A variable spray system is designed, discussed, and verified to solve this problem. The distribution characteristics of droplet deposition under different spray states (flight state, environment state, nozzle state) are obtained through computational fluid dynamics simulation. In the verification experiment, the wind velocity error of most sample points is less than 1 m/s, and the deposition ratio error is less than 10%, indicating that the simulation is reliable. A simulation data set is used to train support vector regression and back propagation neural network with multiple parameters. An optimal regression model with the root mean square error of 6.5% is selected. The UAV offset and nozzle flow of the variable spray system can be obtained in accordance with the current spray state by multi-sensor fusion and the predicted deposition distribution characteristics. The farmland experiment shows that the deposition volume error between the prediction and experiment is within 30%, thereby proving the effectiveness of the system. This article provides a reference for the improvement of UAV intelligent spray system.
ObjectiveTo explore the association between dynamic changes in red blood cell distribution width to platelet count ratio (RPR) during hospitalisation and short-term mortality in patients with ...sepsis.DesignA retrospective cohort study using propensity score matching.SettingIntensive care units (ICUs) of Beth Israel Deaconess Medical Center.ParticipantsA total of 8731 adult patients with sepsis were included in the study. The patients were identified from the ICU of the Medical Information Mart for Intensive Care database. The observed group included patients who experienced an increase in RPR of more than 30% during the first week of ICU admission, whereas the control group included the rest.Main outcome and measureUsing propensity score matching, a matched control group was created. The primary outcome was 28-day mortality, and the length of hospital stay and in-hospital mortality were the secondary outcomes.ResultsThe difference was evident in 28-day mortality between the two groups (85.8% vs 74.5%, p<0.001, Kaplan-Meier analysis, and HR=1.896, 95% CI=1.659 to 2.168, p<0.001, Cox regression). In the secondary outcomes, there was a significant difference in in-hospital mortality (p<0.001). In addition, the study discovered that the observed groups had a significantly longer hospital stay (p<0.001). Meanwhile, the results of subgroup analyses were consistent with those of the primary analyses.ConclusionsIn patients with sepsis, a significantly increased RPR is positively associated with the short-term death rate. Continuous RPR monitoring could be a valuable measure for predicting short-term mortality in patients with sepsis.
Staphylococcus aureus
(
S. aureus
) is the most common cause of hospital and community-acquired infections. The current clinical treatment is limited by the emergence of drug-resistant strains. We ...previously developed a chimeric ClyC that effectively inhibited
S. aureus
strains. Nonetheless, an efficient delivery system to provide sustained release of ClyC to infected site is needed. Thus, we engineered a chimeric ClyC loaded alginate hydrogel (ClyC-AH) to improve the therapeutic outcomes against
S. aureus
. ClyC-AH retained the stability and activity of ClyC while providing a sustained release of ClyC and a continuous antibacterial effect against
S. aureus.
Compared to ClyC alone, the use of ClyC-AH was relatively safe, as there was no significant cytotoxicity to BHK-21 cells at a ClyC concentration≤250 μg/ml. Furthermore, in a
S. aureus
infected mouse model of osteomyelitis, ClyC-AH reduced bacterial burden in the femur and surrounding tissues, with a reduction of 2 log
10
(CFU/ml) in viable bacterial number. Based on these results, hydrogel-delivered chimeric lysin ClyC provides a promising future in the
S.aureus
targeting therapy.
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