Cubic specimens of granite, marble, and sandstone, with side lengths of 50 mm, were prepared in the laboratory. True triaxial compression tests were conducted on each rock type with minor principal ...stress (σ3) magnitudes of 10, 20, 30, 50, and 100 MPa and the intermediate principal stress (σ2) varying from σ2 = σ3 to σ2 = σ1 (where σ1 represents the major principal stress). The experimental results demonstrated that the failure strength, fracture dip angle, non-linear behavior and failure mode of these rocks under true triaxial conditions were affected by both σ2 and σ3, as well as by the rock lithology. When σ3 was kept constant and σ2 increased, failure strength showed an initial increase followed by a decrease, whereas the fracture dip angle increased monotonically. The non-linear behavior before the peak strength point of granite became more apparent by the increase of σ3, whereas σ2 had an opposite effect on the non-linear behavior of granite under high σ3 (e.g. 100 MPa). The non-linear behavior before the peak strength point was always found in marble and sandstone for all of the stress state conditions. Analyses of fracture dip angle and failure mode showed that when σ3 = 10, 20, and 30 MPa and σ2/σ3 ≥ 5, 7.5, and 10, respectively, the failure mode of granite changed from shear to slabbing, whereas marble and sandstone always fractured in the shear direction. This study confirms that rocks may experience slabbing failure under true triaxial stress, and slabbing failure mode is likely to be induced in high-strength and brittle rocks under low σ3 with the stress ratio of σ2/σ3 exceeding a particular threshold value.
Rapid cut‐off of blood supply in diseases involving thrombosis is a major cause of morbidity and mortality worldwide. However, the current thrombolysis strategies offer limited results due to the ...therapeutics' short half‐lives, low targeting ability, and unexpected bleeding complications. Inspired by the innate roles of platelets in hemostasis and pathological thrombus, platelet membrane‐camouflaged polymeric nanoparticles (nanoplatelets) are developed for targeting delivery of the thrombolytic drug, recombinant tissue plasminogen activator (rt‐PA), to local thrombus sites. The tailor‐designed nanoplatelets efficiently accumulate at the thrombi in pulmonary embolism and mesenteric arterial thrombosis model mice, eliciting a significantly enhanced thrombolysis activity compared to free rt‐PA. In addition, the nanoplatelets exhibit improved therapeutic efficacy over free rt‐PA in an ischemic stroke model. Analysis of in vivo coagulation indicators suggests the nanoplatelets might possess a low risk of bleeding complications. The hybrid biomimetic nanoplatelets described offer a promising solution to improve the efficacy and reduce the bleeding risk of thrombolytic therapy in a broad spectrum of thrombosis diseases.
Tailor‐designed platelet membrane‐camouflaged polymeric nanoparticles (designated as nanoplatelet) for targeting delivery of the thrombolytic drug (rt‐PA) are developed to navigate multiple acute thrombosis diseases. This nanoplatform can efficiently target to clot sites and dissolve thrombus, simultaneously overcoming the main disadvantages of existing thrombolysis therapy (i.e., life‐threatening bleeding risk, a narrow therapeutic time window, and extremely low drug circulation time).
Gold nanoparticles (GNPs) are attracting more and more attention for their great potential value in biomedical application. Currently, no study has been reported on the chronic cardiac toxicity of ...GNPs after repeated administration. Here we carried out a comprehensive evaluation of the chronic cardiac toxicity of GNPs to the heart. Polyethylene glycol (PEG) -coated GNPs at three different sizes (10, 30 and 50 nm) or PBS was administrated to mice via tail vein for 14 consecutive days. Then the mice were euthanized at 2 weeks, 4 weeks or 12 weeks after the first injection. The accumulation of GNPs in the mouse heart and their effects on cardiac function, structure, fibrosis and inflammation were analysized. GNPs with smaller size showed higher accumulation and faster elimination. None of the three sizes of GNPs affected cardiac systolic function. The LVIDd (left ventricular end-diastolicinner-dimension), LVMass (left ventricular mass) and HW/BW (heart weight/body weight) were significantly increased in the mice receiving 10 nm PEG-GNPs for 2 weeks, but not for 4 weeks or 12 weeks. These results indicated that the accumulation of small size GNPs can induce reversible cardiac hypertrophy. Our results provide the basis for the further biomedical applications of GNPs in cardiac diseases.
Epilepsy is a severe and chronic neurological disease. Edaravone is an effective free radical scavenger and has been reported to prevent neuronal loss induced by Kainate (KA). However, the molecular ...mechanisms by which edaravone inhibits KA-induced neuron injury remain elusive. Seventy adult male Wistar rats were randomly divided into 7 groups. For KA treatment, Kainate (4 μg/kg) were administrated in the right hippocampus CA3 region with sereotactic technique. And for edaravone treatment, the rats were intraperitoneal injection with edaravone (10 mg kg - 1 d – 1). All rats were sacrificed on the seven day after the injection of KA. Histological changes of the hippocampus, CA1, CA3 and CA4 were observed under thionine staining. Histological changes of CA1 and CA3 were divided into the following 4 grades (histological grade,HG) under light microscope. The release of inflammatory cytokines was measured by ELISA assay. The inflammatory proteins and Nrf2 and HO-1 expression were determined by quantitative real time PCR (qRT-PCR) and Western blots analysis. Treatment with edaravone increased the neuronal density and decreased the neuronal damage degree in the CA1, CA3 subfield induced by KA. Besides, edaravone reduced the downregulation of the mRNA and protein expression levels of Nrf2 and HO-1 induced by KA. Moreover, edaravone decreased the levels of NF-κB (P65) and proinflammatory cytokines TNF-α, IL-1β and IL-6 and the inflammatory proteins expression levels, HMGB1, nNOS, iNOS and eNOS in the hippocampus. However, introduction of Nrf2-siRNA and HO-1 inhibitor (Znpp) reversed the effects of edaravone on KA-injected rats. Edaravone can protect hippocampal neurons from damage in KA-induced epilepsy rats through Nrf2/HO-1 pathway.
•Edaravone decreased KA-induced hippocampal neuron damage via Nrf2/HO-1 signaling.•Edaravone protected against KA-induced inflammation in the hippocampus through Nrf2/HO-1 signaling.•Under edaravone treatment, HO-1 was a downstream signaling of Nrf2 in KA-injected rats.
Danshensu, the effective ingredient of the plant Salvia miltiorrhiza (Danshen), has been widely used for treatment of cardiovascular diseases. Cardiac fibrosis is an important process in pathological ...cardiac remodeling and leads to heart failure. We investigated the effect of Danshensu on β-adrenergic receptor (β-AR)-mediated cardiac fibrosis and the involved signaling transduction. Danshensu inhibited cardiofibroblast proliferation and collagen I synthesis induced by isoproterenol (ISO), a selective β-AR agonist. Phosphorylation of p38 mitogen-activated protein kinase (MAPK), which mediates ISO-induced cardiac fibrosis, was negatively regulated in this process. The negative regulation depended on the ISO inhibition of reactive oxygen species (ROS) production. Taken together, Danshensu may inhibit β-AR-mediated cardiac fibrosis by negative regulation of ROS-p38 MAPK signaling.
Abstract Objective Acute acromioclavicular (AC) joint dislocation is a common orthopedic injury that can significantly impair shoulder function and reduce quality of life. Effective treatment methods ...are essential to restore function and alleviate pain. To investigate the short-term clinical efficacy of the minimally invasive closed-loop double endobutton fixation assisted by orthopaedic surgery robot positioning system (TiRobot) in the treatment of AC joint dislocation, and to evaluate its feasibility and safety. Methods The clinical data of 19 patients with AC joint dislocation who underwent treatment with closed-loop double Endobutton fixation assisted by TiRobot between May 2020 and December 2022 were retrospectively analyzed. Visual Analog Scale (VAS) pain scores, the Constant Murley Score (CMS), and shoulder abduction range of motion were assessed and compared preoperatively and at the last follow-up. Computed tomography (CT) parameters of the acromioclavicular joint, including acromioclavicular distance (ACD), the distance between the upper and lower Endobutton (DED), the horizontal distance between the anterior edge of the distal clavicle and the anterior edge of the acromion (DACC), the diameter of the clavicular tunnel (DCT), and coracoid tunnel diameter (DC), were compared at 2 days, and 1 month after surgery, as well as at the last follow-up, along with the evaluation of intraoperative and postoperative complications. Results The postoperative VAS, CMS, and shoulder-abduction range of motion were significantly improved compared with the preoperative (all, P <0.05). The statistical analysis showed no significant difference in the CT image parameters of the acromioclavicular joint at 2 days and 1 month after surgery(all, P >0.05). Comparisons of DCT and DC revealed statistically significant differences between the last follow-up and 1 month after surgery ( P <0.05), and no statistically significant difference was found in ACD, DED, and DACC(all, P >0.05). There were no complications such as infection or vascular or neurological damage, no cases of rostral or clavicle fractures, loss of reduction, heterotopic ossification, shoulder stiffness, and no loosening or breaking of internal fixations. Conclusion Closed-loop double endobutton internal fixation assisted by TiRobot is an ideal method for the treatment of acute acromioclavicular (AC) joint dislocation. This method has the advantages of relatively simple operation, more accurate localization of bone tunnel during operation, less surgical trauma, and good recovery of shoulder function.
It is acknowledged that most surrounding rocks of underground engineering are subjected to biaxial static stresses and various dynamic fatigue loads. In most cases, the dynamic loads have a point or ...local acting area, which affect the failure properties of rocks greatly. To reveal the failure mechanism of rocks under the combined effects of biaxial static stress and dynamic fatigue loads, a series of biaxial compression tests and point/local fatigue-induced failure tests on cubic granite specimens with a side length of 50 mm were conducted out. In the biaxial compression tests (the maximum principal stress
σ
1
> the intermediate principal stress
σ
2
> the minimum principal stress
σ
3
= 0), the biaxial compressive strength of granite presents a monotonous increasing trend with the
σ
2
increasing from 0 to 40 MPa, while the increasing rate of biaxial compressive strength increases firstly and then decreases with the increase in
σ
2
. The rock failure induced by point/local fatigue loads with 5 kHz frequency was analyzed in this study. It shows that the fatigue life of granite is much shorter than that in the traditional full-section fatigue tests, which increases with the increase in
σ
2
and decreases as the upper level of the fatigue stress or predefined stress of
σ
1
increase. From the acoustic emission properties, the failure of rocks under biaxial confinements induced by point/local static or fatigue loads are mainly because of tensile cracks. Meanwhile, the application of a disturbance bar with a smaller cross-sectional area induces rock broken more quickly. It seems that the following measures can be used to improve rock breakage efficiency: increasing the predefined stress in the breaking direction, reducing the lateral confinement, using the breaking bar with a small cross-sectional area, and changing the static loading into the dynamic loading of the breaking force.
To evaluate the short-term clinical efficacy and advantages of surgery robot positioning system for insertion of Femoral Neck System (FNS) in the treatment of femoral neck fractures.
The clinical ...data of 52 patients with Femoral neck fracture (FNF) who had been treated with FNS between June 2020 and September 2021 were retrospectively analyzed. Among them, 26 patients were treated with traditional FNS (control group), while 26 additional patients were treated with FNS assisted by an orthopaedic robot positioning system (study group). The operation duration, frequency of key-guide needle placement, intraoperative blood loss, incision length, fracture healing rate, fracture healing time, and the Harris scores at the last follow-up were calculated and compared between the 2 groups.
The study group had shorter operation duration, fewer numbers of placing the key-guide needle, less intraoperative blood loss, and smaller surgical incisions than the control group (all, P < 0.05). There was no significant difference in the rate of fracture healing rate between the 2 groups (P = 0.47), while the fracture healing duration of the study group was shorter than that of the control group (P = 0.03). At the last follow-up, compared with the control group, the Harris score and the number of excellent and good ratings were significantly higher in the study group (all, P < 0.05).
Using orthopaedic surgery robot positioning system-assisted FNS in the treatment of FNFs can effectively improve the efficiency of surgery, shorten operation time, and reduce the number of placing the key-guide needle, intraoperative blood loss, and operative trauma. Simultaneously, it shortens the duration of fracture healing and improves the recovery of hip function.
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•Distinct grain size characteristics of fine-grained gas/non-gas hydrate-bearing sediments are documented.•Correlation between grain-size parameters and gas hydrate saturation is ...presented.•Increased coarse fraction/particle size favours reservoir property by improving initial permeability.•Seismic and C-M patterns indicate fine-grained turbidites as potential favored host for gas hydrate.
Fine-grained gas hydrate (GH) reservoirs are extensively studied worldwide, among which the Shenhu Area (located on the northern slope of the South China Sea) is a world-class GH exploration area. However, the lithology, physical properties, and depositional origins of the fine-grained GH reservoirs are not well known. Understanding how sediment grain-size parameters affect the fine-grained GH reservoir quality could provide and important breakthrough for reservoir evaluation. Eight cores, recovered from various expeditions of the Guangzhou Marine Geological Survey, can be combined with 2D/3D seismic data to provide a rare opportunity to systematically investigate the grain-size characteristics of the GH reservoir, as well as the surrounding sediments.
A combination of lithology, grain size characteristics (mean size, sorting, skewness, kurtosis), high-resolution seismic features, and associated bivariate and cluster analysis results support the identification of two distinct intervals of fine-grained sediments that were deposited by different sedimentary processes. There is a relatively higher content of coarser silt in the lower interval than in the upper interval, and their boundary depths are highly consistent with those of the GH-bearing layer and the overlying non-GH-bearing layer. With respect to the unconsolidated GH-bearing sediments from Well G, both the porosity (52%–64%) and sorting coefficient (1.68–2.2) have limited variation, while high GH saturation (>30%) occurs at the top layer. The positive correlation between saturation and the coarsest one-percentile grain size (R = 0.55) reveals that an increase in the coarse fraction/particle size favours the development of a larger pore throat diameter and improves the initial permeability and reservoir properties.
The seismic features and cross-plots of the coarsest one-percentile and median values indicate that the lower thin-bedded fine-grained sediments with hydrate may be fine-grained turbidite complexes, including channels/levees/lobes and mass transport deposits. If this is the case, then it may be inferred that turbidite sediments provide good reservoir physical properties, favourable for GH formation and accumulation. These insights into the relationship between the Quaternary fine-grained turbidites and GH saturation may promote a clearer understanding of the characteristics and development of fine-grained GH reservoirs globally, including in the Shenhu Area of the South China Sea.
Background and Purpose
Cardiac fibrosis is a common feature of advanced coronary heart disease and is characteristic of heart disease. However, currently available drugs against cardiac fibrosis are ...still very limited. Here, we have assessed the role of isopropyl 3‐(3,4‐dihydroxyphenyl)‐2‐hydroxylpropanoate (IDHP), a new metabolite of Danshen Dripping Pills, in cardiac fibrosis mediated by the β‐adrenoceptor agonist, isoprenaline, and its underlying mechanisms.
Experimental Approach
Identification of IDHP was identified by mass spectrometry, and proton and carbon nuclear magnetic resonance spectra. Myocardial collagen was quantitatively assessed with Picrosirius Red staining. Expression of mRNA for collagen was evaluated with real‐time PCR. Phosphorylated and total p38 MAPK, NADPH oxidase (NOX) and superoxide dismutase (SOD) were analysed by Western blot. Generation of reactive oxygen species (ROS) generation was evaluated by dihydroethidium (DHE) fluorescent staining. NOX2 was knocked down using specific siRNA.
Key Results
IDHP attenuated β‐adrenoceptor mediated cardiac fibrosis in vivo and inhibited isoprenaline‐induced proliferation of neonatal rat cardiac fibroblasts (NRCFs) and collagen I synthesis in vitro. Phosphorylation of p38 MAPK, which is an important mediator in the pathogenesis of isoprenaline‐induced cardiac fibrosis, was inhibited by IDHP. This inhibition of phospho‐p38 by IDHP was dependent on decreased generation of ROS. These effects of IDHP were abolished in NRCFs treated with siRNA for NOX2.
Conclusions and Implications
IDHP attenuated the cardiac fibrosis induced by isoprenaline through a NOX2/ROS/p38 pathway. These novel findings suggest that IDHP is a potential pharmacological candidate for the treatment of cardiac fibrosis, induced by β‐adrenoceptor agonists.
Linked Articles
This article is part of a themed section on Chinese Innovation in Cardiovascular Drug Discovery. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-23
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