Triaxial mechanical behaviours and life cycle assessment of sustainable multi-recycled aggregate concrete.

Multi-recycling of concrete waste presents a promising avenue for carbon-negative development and a circular economy. This study comprehensively assesses the triaxial mechanical performance and environmental impact of multi-recycled concrete (Multi-RAC) through three recycling cycles. The results reveal a triaxial failure mode similar to natural aggregate concrete (NAC). The peak stress and peak strain monotonically increase with confinement stress, showing a significant impact (enlarged by 171.4 % to 280.6 % and 397.4 % to 412.0 %, respectively) from 0 to 20 MPa. All P-values for recycling cycles and confining pressure are less than 0.05, with the confining pressure having a more significant effect. Three best-fit multivariate mixed models predict mechanical properties, and a modified elastoplastic model introduces the recycling cycles factor. Numerical simulations confirm the model's accuracy in predicting the triaxial mechanical properties of Multi-RAC. Comparative analysis reveals that the elastoplastic model-derived non-integral high order failure criterion outperforms the Willam-Warnke failure criterion and other conventional criteria. Regarding environmental impact, all indicators (GWP, POCP, AP, EP, and CED) decrease favourably with the increasing number of recycling cycles, with CED and EP playing the most significant roles. Compared to NAC, the five environmentally favorable indicators for RACIII decrease by 3.24 % to 50.6 %, respectively. These findings provide valuable insights for future research on developing eco-friendlier Multi-RAC for sustainable and green infrastructure.

Detecting small lung tumors in mouse models by refractive-index microradiology.

Refractive-index (phase-contrast) radiology was able to detect lung tumors less than 1 mm in live mice. Significant micromorphology differences were observed in the microradiographs between normal, inflamed, and lung cancer tissues. This was made possible by the high phase contrast and by the fast image taking that reduces the motion blur. The detection of cancer and inflammation areas by phase contrast microradiology and microtomography was validated by bioluminescence and histopathological analysis. The smallest tumor detected is less than 1 mm(3) with accuracy better than 1 × 10(-3) mm(3). This level of performance is currently suitable for animal studies, while further developments are required for clinical application.

[Association between beta3-adrenergic receptor and oxidative stress in chronic heart failure rats].

OBJECTIVE: To investigate the association between beta(3)-adrenergic receptor (beta(3)-AR) and oxidative stress in isoproterenol (ISO)-induced chronic heart failure (HF) rats. METHODS: Seven weight-matched normal adult rats (control), 18 ISO induced heart failure rats and 21 ISO induced heart failure rats treated with specific beta(3)-AR inhibitor, SR59230A for 6 weeks were included in this study. Echocardiography was performed at the end of the study and the myocardial levels of total superoxide dismutase (T-SOD) and lipid peroxidation (LPO) were measured by colorimetry, myocardial expression of beta(3)-AR was detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULT: Compared with control group, the cardiac function was significantly reduced and myocardial beta(3)-AR mRNA expression was significantly increased, LPO level was also significantly enhanced while T-SOD level was significantly reduced in ISO group and these changes could be significantly attenuated by treatment with SR59230A. CONCLUSION: Our results showed that myocardial upregulation of beta(3)-AR is associated with increased oxidative stress in this model and beta(3)-AR inhibitor may be a new therapeutic agent for heart failure treatment.

Probucol attenuates atrial structural remodeling in prolonged pacing-induced atrial fibrillation in dogs.

AIMS: Oxidative stress has recently been implicated in atrial fibrillation (AF); however, the mechanisms remain unclear. Herein, we hypothesize that probucol can attenuate atrial structure remodeling. METHODS: Twenty dogs were randomly divided into sham-operated, control, and probucol-treated groups. We identified apoptosis and histopathological changes in the atria. Oxidative stress was measured by lipid peroxidation and echocardiographic examinations were performed. RESULTS: Atrial apoptosis indexes were dramatically decreased in the probucol-treated group compared to the control group. Relative to the control group, the percentage of myolysis was dramatically decreased in the probucol-treated group (p < 0.01). There was less lipid peroxidation in the probucol-treated group than the control group. Atrial function was dramatically elevated in the probucol-treated group. CONCLUSIONS: The results of this study indicate that the antioxidant probucol suppresses atrial structural remodeling and may act as a new therapy for AF.

Anti-apoptotic effects of a calpain inhibitor on cardiomyocytes in a canine rapid atrial fibrillation model.

PURPOSE: This study was designed to evaluate the effects of a calpain inhibitor on cardiac muscle apoptosis in rapid pacing canine atrial fibrillation (AF) models. METHODS: Twenty one dogs were divided into three groups: a sham operation group, a control AF group and a calpain inhibitor group. Sustained AF was induced by rapid right atrium pacing at 600 beats per minute. N-Acetyl-Leu-Leu-Met (1.0 mg/kg/day) was administered in the calpain inhibitor group for three weeks. The activity of calpain I and cardiomyocyte apoptosis were measured by fluorometry and TUNEL assay, respectively. Protein expression of caspase-3 was detected by Western blot. The localizations of caspase-3, caspase-8, bcl-2 and ARC were assessed by immunohistochemistry. RESULTS: In comparison to the sham operation group, the activity of calpain I was significantly increased in the control AF group (2.3 fold, p < 0.001), and decreased in the calpain inhibitor group (1.1 fold, p < 0.005). The calpain activity correlated with the apoptosis index (r = 0.9, p < 0.05). The apoptosis index was 1.0 +/- 0.2%, 11.8 +/- 6.8% and 3.5 +/- 2.1% in the sham operation group, control AF group and calpain inhibitor group, respectively. In the sham operation group, control AF group and calpain inhibitor group, the expressions of caspase-3 (13.0 +/- 1.9%, 52.8 +/- 4.3% and 33.6 +/- 3.7%), caspase-8 (40.1 +/- 5.3%, 92.6 +/- 6.5% and 55.3 +/- 5.9%), bcl-2 (65.8 +/- 6.1%, 52.0 +/- 5.7% and 69.9 +/- 5.3%) and ARC (70.2 +/- 8.6%, 68.8 +/- 7.3% and 81.5 +/- 8.8%) were calculated as immunohistochemical indexes, respectively. CONCLUSIONS: The calpain inhibitor N-Acetyl-Leu-Leu-Met attenuated apoptosis through a complicated network of apoptosis-related proteins, which may result in improvement of structural remodeling in atrial fibrillation.

Calpain I inhibition prevents atrial structural remodeling in a canine model with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is accompanied by atrial structural remodeling. Calpain activity is induced during AF. To test a causal relationship between calpain activation and atrial structural changes, N-acetyl-Leu-Leu-Met (ALLM), a calpain inhibitor, was utilized in a canine AF model. METHODS: Fifteen dogs were randomly divided into 3 groups: sham-operated group, control group and calpain inhibitor group; each with 5 dogs. Sustained AF was induced by rapid right atrium pacing at 600 beats per minute for 3 weeks. ALLM was administered at a dosage of 1.0 mg x kg(-1) x d(-1) in the calpain inhibitor group. Three weeks later, the proteolysis, protein expression of TnT and myosin, calpain I localization and expression and structural changes were examined in left atrial free walls, right atrial free walls and the interatrial septum respectively. Atrial size and contractile function were also measured by echocardiography. RESULTS: Long-term rapid atrial pacing induced marked structural changes such as enlarged atrial volume, myolysis, degradation of TnT and myosin, accumulation of glycogen and changes in mitochondrial shape and size, which were paralleled by an increase in calpain activity. The positive correlation between calpain activity and the degree of myolysis (r(s) = 0.90 961, P < 0.0001) was demonstrated. In addition to structural abnormalities, pacing-induced atrial contractile dysfunction was observed in this study. The pacing-induced atrial structural alterations and loss of contractility were partially prevented by the calpain inhibitor ALLM. CONCLUSIONS: Activation of calpain represents key features in the progression towards overt structural remodeling. Calpain inhibitor, ALLM, suppressed the increased calpain activity and reversed structural remodeling caused by sustained atrial fibrillation in the present model. Calpain inhibition may therefore provide a possibility for therapeutic intervention in AF.

[Influence of oxidative stress on atrial myocardium pathohistological and ultrastructural changes in atrial fibrillation: experiment with dogs].

OBJECTIVE: To evaluate the effects of oxidative stress on the protein expression of atrial calpain I and pathohistological and ultrastructural changes of atrial myocardium in atrial fibrillation (AF). METHODS: Twenty dogs were all implanted with pacemaker in a subcutaneous pocket and attached to a screw-in epicardial lead in right atrial appendage. They were randomly divided into 3 groups: sham-operation group (n = 6 without pacing), control group (n = 7 per minutes for 6 weeks), and probucol group (n = 7, pacing 1 week after recovery for 6 weeks, and administration of probucol 100 mg x kg(-1) x d(-1) 1 week before pacing till the end of pacing). One thin silicon plaque containing 4 pairs of electrodes were sutured to the right atrium. The dogs in control group, probucol group were paced at 400 beats per minutes for 6 weeks. Then the dogs were killed with their hearts taken out. The expression of atrial calpain I was measured by Western-blotting and immunohistochemistry. The pathohistological and ultrastructural changes in atrial tissue were tested by light and electron microscopy. The inducibility and duration of AF were measured in the control group and probucol group. The indexes of oxidative stress total anti-oxidation capability (T-AOC), malonyldiadehyde (MDA), and scavenging activities of superoxide anion (O2-) radical were measured by colorimetric method. RESULTS: The percentage of myolysis in the left and right atria of the control group were (53.6 +/- 11.8)% and. (58.5 +/- 9.2)% respectively, significantly higher than those of the sham operation group [(4.4 +/- 3.1)% and (4.1 +/- 2.9)% respectively, both P < 0.01]. The percentage of myolysis in the left and right atria of the probucol group were (12.3 +/- 3.2)% and (12.0 +/- 2.6)% respectively, both significantly lower than those of the control group (both P < 0.01). The protein expression of calpain I of the control group was significantly higher than that of the sham-operation group, and the protein expression of calpain I of the probucol group was significantly lower than that of the control group. The AF inducibility rate after pacing of the probucol group was 60%, significantly lower than that of the control group (92.9%, P < 0.01). The average AF duration time after pacing of the probucol group was (601 +/- 328) s, significantly shorter than that of the control group (1458 +/- 498) s. The indexes of oxidative stress in probucol group were lower than the level in control group. The MDA levels of the probucol group was (3.08 +/- 0.20) mmol/mg protein, significantly lower than that of the control group (4.15 +/- 0.23) mmol/mg protein). The anti-O2- and T-AOC level of the probucol group were 279 +/- 20 U/g protein and 30.5 +/- 1.3 nmol/mg protein, both significantly higher than those of the control group (215 +/- 16 U/g protein and 25.6 +/- 1.5 nmol/mg protein respectively, both P < 0.01). There were more sarcomere vacuolization and dissolution in atrial myocytes in the control group than in the sham operation group. And the pathohistological and ultrastructural changes of the probucol were lighter than those of the control group. CONCLUSION: Probucol prevents the pathohistological and ultrastructural changes in atrial myocardium by inhibiting calpain I expression, thus suppressing atrial structural remodeling, and preventing the induction and promotion of AF.

[Effect of calpain 1 on structural remodeling and contractile dysfunction in atrial fibrillation: experiment with dogs].

OBJECTIVE: To test the causal relationship between calpain activation and atrial structural changes during atrial fibrillation (AF). METHODS: The tip of a spiral mono-polar pacing lead was fixed to the right atrial appendages of 15 dogs randomly divided into 3 equal groups: calpain inhibitor group, undergoing continuous pacing with the impulse of 600 beats/min for 3 weeks and intravenous injection of N-acetyl-Leu-Leu-Met (ALLM), a calpain inhibitor for 3 weeks; control group, undergoing continuous pacing and intravenous injection of dimethyl sulfoxide (DMSO; and sham operation group, given DMSO injection without pacing. Ultrasonography was used to observe the changes of the structures of left atrium and left atrial appendage and the heart function as well. Specimens of atrial muscles were obtained. Calpain 1 activity was detected by Suc-Leu-Leu-Val-Tyr-7-amino-4-methyl-coumarin method. HE staining was conducted to observe the myolysis. Western blotting was used to detect the protein expression of troponin I (TnI) and myosin. RESULTS: The left atrial ejection fraction (LAEF) of the ALLM group was (41 +/- 6)%, significantly higher than that of the control group [(34 +/- 9)%, P < 0.05]. The left atrial appendage ejection fraction (LAAEF) of the ALLM group was (41 +/- 6)%, significantly higher than that of the control group [(35 +/- 6)%, P < 0.05]. Myolysis was extensive in the control group [(71.5 +/- 10.2)%], relatively rare in the ALLM group [(12.3 +/- 16.5)%], and was not seen in the sham operation group, with significantly differences among the 3 groups (all P < 0.01). The calpain 1 activity was positively correlated with the degree of myolysis (r(s) = 0.90 961, P < 0.01). The TnI level of the control group was (43 +/- 12)% that of the sham operation group (P = 0.001), the TnI level of the ALLM group was (51 +/- 11)% that of the sham operation group (P = 0.002) and was significant higher than that of the control group (P = 0.01). The level of myosin of the control group was (51 +/- 11)% that of the sham operation group (P = 0.002), and that of the ALLM group was (149 +/- 33)% that of the control group (P = 0.005). CONCLUSION: Activation of and upregulation of expression of calpain participate in the structural remodeling of left atrial cardiac muscle and contractile dysfunction. Calpain inhibitor suppresses the increased calpain activity and reverses the structural remodeling of sustained atrial fibrillation. Calpain inhibition may therefore provide a possibility for therapeutic intervention in AF.

[Calpain I inhibition prevents pacing-induced structural remodeling for atrial fibrillation in canine].

OBJECTIVE: To study the relation of the structural remodeling processes and activation of calpain I. METHODS: Fifteen dogs were randomly divided into three groups. The dogs in pacing group (n=5) and inhibitor group (n=5) were subjected to 3 weeks of rapid atrial pacing at 600 beats/min, control dogs (n=5) were in sham-operated group. The dogs in inhibitor group were administered intravenous N-Acetyl-Leu-Leu-Met (ALLM), a calpain inhibitor, and in pacing group and sham-operated group were administered intravenous DMSO. The activity of calpain I was measured by hydrolyzing Suc-Leu-Leu-Val-Tyr-7-amino-4-methyl-coumarin. The ultrastructure of atrium was examined by light and electron microscopy. TnT expression was assessed by Western blot. Echocardiography examination was performed in all the three groups. RESULTS: Calpain I activity was significantly increased in pacing group (2.3-fold, P<0.01), and decreased in inhibitor group (1.1-fold, P>0.05), compared to sham-operated group respectively. The percentages of myolysis were (76.7 +/- 5.9)% and (20.8 +/- 8.1)% in pacing group and inhibitor group respectively (P<0.01). TnT expression decreased in the rapid pacing-induced persistent atrial fibrillation, and these effects were inhibited by calpain I inhibitor ALLM. The area and volume of left atrium tended to increase after 3 weeks ALLM treatment in inhibitor group, but the change was not as prominent as in pacing group (P<0.05). CONCLUSIONS: ALLM can decrease calpain I activity, and prevent canine atrial cardiomyocyte structural remodeling during atrial fibrillation. This study provided a capacity of atrial cardiomyocyte protection.

[IL-10 gene modification on immature dendritic cells induces antigen-specific tolerance in experimental autoimmune myocarditis].

OBJECTIVE: To investigate whether IL-10 gene modification on immature dendritic cells (iDC) could induce autoimmune tolerance in rat experimental autoimmune myocarditis (EAM). METHODS: EAM was induced by cardiac myosin immunization on day 0 and day 7 in rats. A total of 2 x 10(6) mature DC (mDC), iDC, pcDNA3 transfected iDC, pcDNA3-IL-10 transfected iDC or PBS were injected intravenously at 5th immunization day. Three weeks later, echocardiography and HE staining were performed to observe the cardiac function and myocardial inflammation. Th1/Th2 cytokines were detected by ELISA and MHC-II molecules, costimulatory molecules were identified by flow cytometry. In vitro T lymphocyte proliferation assay and adoptive transfer of DCs were performed to determine the antigen specific tolerance induced by IL-10 gene modification on iDCs. RESULTS: EAM rats treated with pcDNA3-IL-10 transfected iDC showed improved cardiac function and reduced inflammatory cells infiltration into myocardium. Moreover, lower Th1 and higher Th2-type response was induced, MHC-II and costimulatory molecules down-regulated and antigen specific immunological responses towards cardiac myosin inhibited in pcDNA3-IL-10-iDC treated EAM rats. CONCLUSION: Treatment with IL-10 gene modified iDCs could ameliorates EAM by inducing Th2 polarization and down-regulation of MHC-II molecules and costimulatory molecule expressions.

Plasma microRNAs as potential noninvasive biomarkers for in-stent restenosis.

OBJECTIVE: To investigate whether microRNAs (miRs) can serve as novel biomarkers for in-stent restenosis (ISR). METHODS: This retrospective, observational single-centre study was conducted at the cardiovascular department of a tertiary hospital centre in the north of China. Follow-up coronary angiography at 6 to 12 months was performed in 181 consecutive patients implanted with drug-eluting stents. Fifty-two healthy volunteers served as the control group. The plasma miRs levels were analyzed by quantitative real-time PCR. Receiver-operating characteristic curve (ROC) analysis was performed to investigate the characters of these miRs as potential biomarkers of ISR. RESULTS: MiR-21 levels in ISR patients were significantly higher than those in non-ISR patients and healthy controls (P<0.05), while miR-100 (P<0.05), miR-143 (P<0.001) and miR-145 (P<0.0001) levels were significantly decreased in ISR patients. Further analysis showed that miR-21 levels were remarkably increased (P = 0.045), while miR-100 (P = 0.041), miR-143 (P = 0.029) and miR-145 (P<0.01) levels were dramatically decreased in patients with diffuse ISR compared to those with focal ISR. ROC analysis demonstrated that the area under curve of miR-145, miR-143, miR-100 and miR-21 were 0.880 (95% confidence interval; CI = 0.791-0.987, P<0.001), 0.818 (95% confidence interval; CI = 0.755-0.963, P<0.001), 0.608 (95% confidence interval; CI = 0.372-0.757, P<0.05) and 0.568 (95% confidence interval; CI = 0.372-0.757, P<0.05), with specificity of 83.1%, 80.1%, 68.9% and 68.6%, and sensitivity of 88.7%, 82.1%, 60.2% and 50.1%, respectively. CONCLUSIONS: Circulating miR-143 and miR-145 levels are associated with the occurrence of ISR and can serve as novel noninvasive biomarkers for ISR.

Probucol attenuates atrial autonomic remodeling in a canine model of atrial fibrillation produced by prolonged atrial pacing.

BACKGROUND: We hypothesize that increased atrial oxidative stress and inflammation may play an important role in atrial nerve sprouting and heterogeneous sympathetic hyperinnervation during atrial fibrillation (AF). To test the hypothesis, we examined whether the antioxidant and anti-inflammatory treatment with probucol attenuates atrial autonomic remodeling in a canine model of AF produced by prolonged rapid right atrial pacing. METHODS: Twenty-one dogs were divided into a sham-operated group, a control group and a probucol group. Dogs in the control group and probucol group underwent right atrial pacing at 400 beats per minute for 6 weeks, and those in the probucol group received probucol 1 week before rapid atrial pacing until pacing stopped. After 6-week rapid atrial pacing, general properties including left atrial structure and function, atrial hemodynamics and the inducibility and duration of AF were measured in all the groups. Atrial oxidative stress markers and serum C-reactive protein (CRP) concentration were estimated. The degree of nerve sprouting and sympathetic innervation at the right atrial anterior wall (RAAW) and the left atrial anterior wall (LAAW) were quantified by immunohistochemistry, atrial norepinephrine contents were also detected. Atrial beta-nerve growth factor (beta-NGF) mRNA and protein expression at the RAAW and LAAW were assessed by real-time quantitative RT-PCR and Western blotting respectively. RESULTS: Atrial tachypacing induced significant nerve sprouting and heterogeneous sympathetic hyperinnervation, and the magnitude of nerve sprouting and hyperinnervation was higher in the RAAW than in the LAAW. Atrial beta-NGF mRNA and protein levels were significantly increased at the RAAW and LAAW, and the upregulation of beta-NGF expression was greater at the RAAW than at the LAAW in the control group. The beta-NGF protein level was positively correlated with the density of sympathetic nerves in all groups. Probucol decreased the increase of CRP concentration and attenuated atrial oxidative stress caused by atrial tachypacing. In addition, probucol could effectively inhibit atrial beta-NGF upregulation, significantly attenuate atrial nerve sprouting and heterogeneous sympathetic hyperinnervation, and dramatically reduce the inducibility and duration of AF. CONCLUSIONS: The atrial over-expression of beta-NGF possibly caused by increased oxidative stress and inflammation may be the main mechanism underlying atrial autonomic remodeling during AF. Probucol attenuates atrial autonomic remodeling possibly by its antioxidant and anti-inflammatory actions.

[Reversal of multidrug resistance of human hepatocellular carcinoma cells by wild-type p53 gene and related mechanisms].

BACKGROUND & OBJECTIVE: The mechanism of cell apoptosis plays an important role in tumor multidrug resistance (MDR). Wild-type p53 (wt-p53) gene is an activator of cell apoptosis, and is closely related to tumor MDR. This study was to explore the effect of p53 gene on the reversal of MDR of human hepatocellular carcinoma (HCC) and related mechanisms. METHODS: The eukaryotic expression plasmid pCR 3.1-p53 was constructed and transfected into human HCC cell line Bel-7402. Proliferation and chemosensitivity of Bel-7402 cells to vincristine (VCR) were measured by MTT assay. The morphology of transfected Bel-7402 cells was observed. The expression of P-glycoprotein (P-gp) was detected by immunochemistry. The expression of multidrug resistance gene 1 (mdr1), multidrug resistance related protein (MRP), glutathione S-transferase pi (GST pi), and topoisomerase II alpha (Topo II alpha) were detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The growth of wt-p53-transfected Bel-7402 cells was obviously slower than that of untransfected cells. After transfection with wt-p53, the chemosensivity of Bel-7402 cells to VCR was enhanced at the concentration of 0.01, 0.1, 1.0, 10, and 25 microg/ml. The optimal concentration was 1.0 microg/ml. After wt-p53 transfection and VCR treatment, the number of Bel-7402 cells was decreased; the cells were swollen severely with irregular projections; pyknosis, karyorrhexis and karyolysis were observed. After wt-p53 transfection, the expression of mdr1 and P-gp in Bel-7402 cells was down-regulated remarkably, and the expression of Topo II alpha was up-regulated. CONCLUSION: Wild-type p53 gene raises chemosensitivity of Bel-7402 cells to VCR, which may be partly related to the down-regulation of mdr1 and up-regulation of Topo II alpha.