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PURPOSE: Our study aimed to develop and validate a homologous recombination deficiency (HRD) scoring algorithm in the Chinese breast cancer population. METHODS AND MATERIALS: Ninety-six in-house breast cancer (BC) samples and 6 HRD-positive standard cells were analyzed by whole-genome sequencing (WGS). Besides, 122 BCs from the TCGA database were down-sampled to ~ 1X WGS. We constructed an algorithm named AcornHRD for HRD score calculated based on WGS at low coverage as input data to estimate large-scale copy number alteration (LCNA) events on the genome. A clinical cohort of 50 BCs (15 cases carrying BRCA mutation) was used to assess the association between HRD status and anthracyclines-based neoadjuvant treatment outcomes. RESULTS: A 100-kb window was defined as the optimal size using 41 in-house cases and the TCGA dataset. HRD score high threshold was determined as HRD score ≥ 10 using 55 in-house BCs with BRCA mutation to achieve a 95% BRCA-positive agreement rate. Furthermore, the HRD status agreement rate of AcornHRD is 100%, while the ShallowHRD is 60% in standard cells. BRCA mutation was significantly associated with a high HRD score evaluated by AcornHRD and ShallowHRD (p = 0.008 and p = 0.003, respectively) in the TCGA dataset. However, AcornHRD showed a higher positive agreement rate than did the ShallowHRD algorithm (70% vs 60%). In addition, the BRCA-positive agreement rate of AcornHRD was superior to that of ShallowHRD (87% vs 13%) in the clinical cohort. Importantly, the high HRD score assessed by AcornHRD was significantly correlated with a residual cancer burden score of 0 or 1 (RCB0/1). Besides, the HRD-positive group was more likely to respond to anthracycline-based chemotherapy than the HRD-negative group (pCR [OR = 9.5, 95% CI 1.11-81.5, p = 0.040] and RCB0/1 [OR = 10.29, 95% CI 2.02-52.36, p = 0.005]). CONCLUSION: Using the AcornHRD algorithm evaluation, our analysis demonstrated the high performance of the LCNA genomic signature for HRD detection in breast cancers.
Subject(s)
Algorithms , Anthracyclines , Breast Neoplasms , Neoadjuvant Therapy , Humans , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Female , Anthracyclines/therapeutic use , Anthracyclines/administration & dosage , Neoadjuvant Therapy/methods , Middle Aged , China/epidemiology , Adult , Homologous Recombination , Mutation , Aged , DNA Copy Number Variations , BRCA1 Protein/geneticsABSTRACT
CONTEXT: Traditional conductive adhesives based on epoxy resin system often encounter problems such as high brittleness and low heat resistance. Therefore, it is particularly important to improve the thermal and mechanical properties of the conductive adhesive. In this study, the effects of SWCNT-Ag and SWCNT fillers on the thermal properties of DGEBA/DETA/Ag conductive adhesive system were studied by using molecular dynamics to construct different cross-linking models. The final results show that the addition of SWCNT and SWCNT-Ag can significantly improve the thermal properties of the conductive adhesive. However, the nanosilver particles on the surface of SWCNT-Ag act as a bridge for the connection between SWCNT and Ag in the conductive adhesive. Therefore, SWCNT-Ag has a more positive impact on the thermal properties of DGEBA/DETA/Ag conductive adhesive system. METHODS: In this paper, the influence of SWCNT-Ag on the thermal properties of traditional DGEBA/DETA/Ag conductive adhesive system was studied by using Materials Studio software. The volume shrinkage, glass transition temperature, thermal expansion coefficient, and thermal conductivity of the material were calculated based on COMPASS force field. The thermal conductivity is calculated by using reverse non-equilibrium molecular dynamics method. Finally, it is found that SWCNT-Ag has a positive effect on the thermal properties of the conductive adhesive system by comparing several groups of calculation data.
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Amidation of lactobionic acid with N,N-dimethylaminopropyltriamine was conducted to obtain N-(3'-dimethylaminopropyl)-lactamido-3-aminopropane (DDLPD), which was quaternized with bromoalkanes of different carbon chain lengths to synthesize double-stranded lactosylamide quaternary ammonium salt N-[N'[3-(lactosylamide)]propyl-N'-alkyl] propyl-N,N-dimethyl-N-alkylammonium bromide (CnDDLPB, n = 8, 10, 12, 14, 16). The surface activity and the adsorption and aggregation behaviors of the surfactants were investigated via equilibrium surface tension, dynamic light scattering, and cryo-electron microscopy measurements in an aqueous solution. The application properties of the products in terms of wettability, emulsification, foam properties, antistatic, salt resistance, and bacteriostatic properties were tested. CnDDLPB exhibited a low equilibrium surface tension of 27.82 mN/m. With an increase in the carbon chain length, the critical micellar concentration of CnDDLPBD decreased. Cryo-electron microscopy revealed that all products except C8DDLPB formed stable monolayer, multi-layer, and multi-compartmental vesicle structures in an aqueous solution. C14DDLPB has the best emulsification performance on soybean oil, with a time of 16.6 min; C14DDLPB has good wetting and spreading properties on polytetrafluoroethylene (PTFE) when the length of carbon chain is from 8 to 14, and the contact angle can be lowered to 33°~40°; CnDDLPB has low foam, which is typical of low-foaming products; C8DDLPB and C10DDLPB both show good antistatic properties. C8DDLPB and C14DDLPB have good salt resistance, and C12DDLPB has the best antimicrobial property, with the inhibition rate of 99.29% and 95.28% for E. coli and Gluconococcus aureus, respectively, at a concentration of 350 ppm.
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Tumor microenvironment (TME)-responsive size-changeable and biodegradable nanoplatforms for multimodal therapy possess huge advantages in anti-tumor therapy. Hence, we developed a hyaluronic acid (HA) modified CuS/MnO2 nanosheets (HCMNs) as a multifunctional nanoplatform for synergistic chemodynamic therapy (CDT)/photothermal therapy (PTT)/photodynamic therapy (PDT). The prepared HCMNs exhibited significant NIR light absorption and photothermal conversion efficiency because of the densely deposited ultra-small sized CuS nanoparticles on the surface of MnO2 nanosheet. They could precisely target the tumor cells and rapidly decomposed into small sized nanostructures in the TME, and then efficiently promote intracellular ROS generation through a series of cascade reactions. Moreover, the local temperature elevation induced by photothermal effect also promote the PDT based on CuS nanoparticles and the Fenton-like reaction of Mn2+, thereby enhancing the therapeutic efficiency. Furthermore, the T1-weighted magnetic resonance (MR) imaging was significantly enhanced by the abundant Mn2+ ions from the decomposition process of HCMNs. In addition, the CDT/PTT/PDT synergistic therapy using a single NIR light source exhibited considerable anti-tumor effect via in vitro cell test. Therefore, the developed HCMNs will provide great potential for MR imaging and multimodal synergistic cancer therapy.
Subject(s)
Copper , Hyaluronic Acid , Magnetic Resonance Imaging , Manganese Compounds , Oxides , Photochemotherapy , Tumor Microenvironment , Manganese Compounds/chemistry , Manganese Compounds/pharmacology , Tumor Microenvironment/drug effects , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacology , Oxides/chemistry , Oxides/pharmacology , Humans , Copper/chemistry , Copper/pharmacology , Particle Size , Nanostructures/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Phototherapy , Nanoparticles/chemistry , Cell Survival/drug effects , Surface Properties , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Drug Screening Assays, Antitumor , AnimalsABSTRACT
With the development of microelectronics products with high density and high power, it is urgent to improve the electrical and thermal conductivity of electronic paste to achieve the new requirements of packaging materials. In this work, a new synthesis method of Ag-MWCNTs was designed: Firstly, carboxylated MWCNTs and stannous chloride were used as raw materials to prepare high-loading-rate Sn-MWCNT composite material to ensure the high loading rate of metal on the MWCNT surface. Then, Ag-MWCNT composite material was prepared by the chemical displacement method to solve the problem of the low loading rate of silver nanoparticles on the MWCNT surface. On the basis of this innovation, we analyzed and compared the electrical, thermal, and mechanical properties of Ag-MWCNT composite electronic paste. Compared with the electronic paste without adding Ag-MWCNTs, the resistivity was reduced by 77%, the thermal conductivity was increased by 66%, and the shear strength was increased by 15%. Therefore, the addition of Ag-MWCNTs effectively improves the electrical, thermal, and mechanical properties of the paste, making it a promising and competitive choice for new packaging materials in the future.
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Background: The role of cardiopulmonary exercise testing (CPET) parameters in evaluating the functional severity of coronary disease remains unclear. The aim of this study was to quantify the O2-pulse morphology and investigate its relevance in predicting the functional severity of coronary stenosis, using Murray law-based quantitative flow ratio (µQFR) as the reference. Methods: CPET and µQFR were analyzed in 138 patients with stable coronary artery disease (CAD). The O2-pulse morphology was quantified through calculating the O2-pulse slope ratio. The presence of O2-pulse plateau was defined according to the best cutoff value of O2-pulse slope ratio for predicting µQFR ≤ 0.8. Results: The optimal cutoff value of O2-pulse slope ratio for predicting µQFR ≤ 0.8 was 0.4, with area under the curve (AUC) of 0.632 (95 % CI: 0.505-0.759, p = 0.032). The total discordance rate between O2-pulse slope ratio and µQFR was 27.5 %, with 13 patients (9.4 %) being classified as mismatch (O2-pulse slope ratio > 0.4 and µQFR ≤ 0.8) and 25 patients being classified as reverse-mismatch (O2-pulse slope ratio ≤ 0.4 and µQFR > 0.8). Angiography-derived microvascular resistance was independently associated with mismatch (OR 0.07; 95 % CI: 0.01-0.38, p = 0.002) and reverse-mismatch (OR 9.76; 95 % CI: 1.47-64.82, p = 0.018). Conclusion: Our findings demonstrate the potential of the CPET-derived O2-pulse slope ratio for assessing myocardial ischemia in stable CAD patients.
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In a fiber-based optical tweezer system, it is a common practice to insert the fiber probe into the sample solution to perform the tweezer function. Such a configuration of the fiber probe may lead to unwanted contamination and/or damage to the sample system and is thus potentially invasive. Here, we propose a completely non-invasive method for cell manipulation by combining a microcapillary microfluidic device and an optical fiber tweezer. We demonstrate that Chlorella cells inside the microcapillary channel can be successfully trapped and manipulated by an optical fiber probe located outside of the microcapillary, thus making the process completely non-invasive. The fiber does not even invade the sample solution. To our knowledge, this is the first report of such a method. The speed of stable manipulation can reach the 7â µm/s scale. We found that the curved walls of the microcapillaries worked like a lens, which helped to boost the light focusing and trapping efficiency. Numerical simulation of optical forces under medium settings reveals that the optical forces can be enhanced by up to 1.44 times, and the optical forces can change direction under certain conditions.
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Current methods for the early detection and minimal residual disease (MRD) monitoring of urothelial carcinoma (UC) are invasive and/or possess suboptimal sensitivity. We developed an efficient workflow named urine tumor DNA multidimensional bioinformatic predictor (utLIFE). Using UC-specific mutations and large copy number variations, the utLIFE-UC model was developed on a bladder cancer cohort (n = 150) and validated in The Cancer Genome Atlas (TCGA) bladder cancer cohort (n = 674) and an upper tract urothelial carcinoma (UTUC) cohort (n = 22). The utLIFE-UC model could discriminate 92.8% of UCs with 96.0% specificity and was robustly validated in the BLCA_TCGA and UTUC cohorts. Furthermore, compared to cytology, utLIFE-UC improved the sensitivity of bladder cancer detection (p < 0.01). In the MRD cohort, utLIFE-UC could distinguish 100% of patients with residual disease, showing superior sensitivity compared to cytology (p < 0.01) and fluorescence in situ hybridization (FISH, p < 0.05). This study shows that utLIFE-UC can be used to detect UC with high sensitivity and specificity in patients with early-stage cancer or MRD. The utLIFE-UC is a cost-effective, rapid, high-throughput, noninvasive, and promising approach that may reduce the burden of cystoscopy and blind surgery.
Subject(s)
Carcinoma, Transitional Cell , Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology , Carcinoma, Transitional Cell/diagnosis , Carcinoma, Transitional Cell/genetics , Carcinoma, Transitional Cell/pathology , In Situ Hybridization, Fluorescence/methods , DNA Copy Number Variations , Neoplasm, Residual/diagnosis , Neoplasm, Residual/genetics , DNA , Sensitivity and SpecificityABSTRACT
The upsurge of new materials that can be used for near-infrared (NIR) photodetectors operated without cooling is crucial. As a novel material with a small bandgap of ≈0.28 eV, the topological crystalline insulator SnTe has attracted considerable attention. Herein, this work demonstrates self-driven NIR photodetectors based on SnTe/Si and SnTe:Si/Si heterostructures. The SnTe/Si heterostructure has a high detectivity D* of 3.3 × 1012 Jones. By Si doping, the SnTe:Si/Si heterostructure reduces the dark current density and increases the photocurrent by ≈1 order of magnitude simultaneously, which improves the detectivity D* by ≈2 orders of magnitude up to 1.59 × 1014 Jones. Further theoretical analysis indicates that the improved device performance may be ascribed to the bulk photovoltaic effect (BPVE), in which doped Si atoms break the inversion symmetry and thus enable the generation of additional photocurrents beyond the heterostructure. In addition, the external quantum efficiency (EQE) measured at room temperature at 850 nm increases by a factor of 7.5 times, from 38.5% to 289%. A high responsivity of 1979 mA W-1 without bias and fast rising time of 8 µs are also observed. The significantly improved photodetection achieved by the Si doping is of great interest and may provide a novel strategy for superior photodetectors.
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The aim of this study was to investigate the effect of circSnap47 on heart failure (HF) and its potential mechanisms. Quantitative real-time PCR (qRT-PCR) was performed to detect the mRNA expression levels of circSnap47 and miR-233-3p. The viability and apoptosis of H9C2 cells were assessed using CCK-8 and TUNEL assays. The expressions of interleukin (IL)-6, IL-1ß, IL-18, and tumor necrosis factor-alpha were determined using ELISA and qRT-PCR. In addition, the expression of apoptosis-related proteins and mitogen-activated protein kinase (MAPK) signaling pathway-related proteins was analyzed using western blot. Moreover, HF-related circRNAs and miRNAs were predicted via bioinformatics analysis. The relationship between circSnap47 and miR-233-3p was further confirmed using a dual-luciferase reporter gene assay. In HF tissues and H9C2 cells treated with oxygen-glucose deprivation (OGD), circSnap47 was upregulated. Silencing circSnap47 increased cell viability and inhibited apoptosis. Besides, silencing circSnap47 alleviated OGD-induced inflammation in H9C2 cells. Moreover, we found that miR-233-3p was the downstream target gene of circSnap47. Our results also revealed that silencing circSnap47 relieved OGD-induced H9C2 cell damage by inactivating the miR-223-3p/MAPK axis. We confirmed that circSnap47 silencing inhibited HF progression via regulation of miR-223/MAPK axis, which will provide for a new therapeutic direction for the treatment of HF.
Subject(s)
Heart Failure , MicroRNAs , RNA, Circular , Humans , Apoptosis/genetics , Inflammation/genetics , MicroRNAs/genetics , Mitogen-Activated Protein Kinases , Oxygen/metabolism , RNA, Circular/geneticsABSTRACT
BACKGROUND: Data regarding the performance of computational fractional flow reserve in patients with diabetes mellitus (DM) remain scarce. This study sought to explore the impact of DM on quantitative flow ratio (QFR) and its association with intravascular ultrasound (IVUS)-derived anatomical references.MethodsâandâResults: IVUS and QFR were retrospectively analyzed in 237 non-diabetic and 93 diabetic patients with 250 and 102 intermediate lesions, respectively. Diabetics were further categorized based on adequate (HbA1c <7.0%: 47 patients with 53 lesions) or poor (HbA1c ≥7.0%: 46 patients with 49 lesions) glycemic control. Lesions with QFR ≤0.8 or minimum lumen area (MLA) ≤4.0 mm2and plaque burden (PB, %) ≥70 were considered functionally or anatomically significant, respectively. PB increased, and MLA decreased stepwise across non-diabetics, diabetics with adequate glycemic control and those with poor glycemic control. In contrast, QFR was similar among the 3 groups. PB correlated significantly with the QFR for lesions in non-diabetics, but not for lesions in diabetics. DM was independently correlated with the functionally non-significant lesions (QFR >0.8) with high-risk IVUS features (MLA ≤4.0 mm2and PB ≥70; OR 2.053, 95% CI: 1.137-3.707, P=0.017). When considering the effect of glycemic control, HbA1c was an independent predictor of anatomical-functional discordance (OR 1.347, 95% CI: 1.089-1.667, P=0.006). CONCLUSIONS: Anatomical-functional discordance of intermediate coronary lesions assessed by IVUS and QFR is exacerbated in patients with diabetes, especially when glycemia is poorly controlled.
Subject(s)
Coronary Stenosis , Diabetes Mellitus , Fractional Flow Reserve, Myocardial , Humans , Coronary Angiography/methods , Retrospective Studies , Glycated Hemoglobin , Ultrasonography, Interventional/methods , Diabetes Mellitus/diagnostic imaging , Coronary Vessels/diagnostic imaging , Predictive Value of Tests , Severity of Illness IndexABSTRACT
Optimizing the performance of front silver paste is of great significance in improving the efficiency of the photoelectric conversion of crystalline silicon solar cells. As a conductive functional phase of silver paste, the structure and performance of silver powder have an important influence on the sintering process of silver paste and the conductivity of silver electrodes. Because of their two-dimensional structure, flake silver powders can effectively increase the contact area with other silver powders and silicon cells before sintering. Additionally, flake silver particles have higher surface energy and sintering activity than spherical silver particles of the same particle size. However, recent research has mainly focused on the influence of the particle size of silver powder. This paper fills the research gap regarding the morphology of silver powders and clarifies the influence of flake silver powders on the performance of silver paste. The influence of the ratio of spherical silver powder to flake silver powder in silver paste on the sheet resistance, adhesion, and specific contact resistivity of silver film after sintering at 800 °C was studied, and the optimal ratio was determined according to a cross-sectional contact picture of the silver film. The results showed that with the increase in the mass fraction of the flake silver powder, the sheet resistance of the sintered silver film gradually increased, the adhesion first increased and then decreased, and the specific contact resistance first decreased and then increased. When the flake silver powder content was 0%, the minimum sheet resistance of the silver film was 2.41 m Ω/â. When the flake silver powder content was 30%, the maximum adhesion of the silver film was 6.07 N. When the flake silver powder content was 50%, the minimum specific contact resistivity of the silver film was 0.25 Ω·cm2. In conclusion, when the flake silver powder content was 30%, the comprehensive performance of the silver film was the best.
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BACKGROUND: Treatment of coronary intermediate lesions remains a controversy, and the role of arterial remodeling patterns determined by intravascular ultrasound in intermediate lesion is still not well known. The aim of this study was to investigate the impact of arterial remodeling of intermediate coronary lesions on long-term clinical outcomes. METHODS: Arterial remodeling patterns were assessed in 212 deferred intermediate lesions from 162 patients after IVUS examination. Negative, intermediate, and positive remodeling was defined as a remodeling index of <0.88, 0.88â¼1.0, and >1.0, respectively. The primary endpoint was the composite vessel-oriented clinical events, defined as the composition of target vessel-related cardiac death, target vessel-related myocardial infarction, and target vessel revascularization. Quantitative flow ratio was assessed for evaluating the functional significance of intermediate lesions. RESULTS: 72 intermediate remodeling lesions were present in 66 patients, whereas 77 negative remodeling lesions were present in 71 patients, and 63 positive remodeling lesions were present in 55 patients. Negative remodeling lesions had the smallest minimum lumen area (4.16 ± 1.03 mm2 vs. 5.05 ± 1.39 mm2 vs. 4.85 ± 1.76 mm2; P < 0.01), smallest plaque burden (63.45 ± 6.13% vs. 66.12 ± 6.82% vs. 71.17 ± 6.45%; P < 0.01), and highest area stenosis rate (59.32% ± 10.15% vs. 54.61% ± 9.09% vs. 51.67% ± 12.96%; P < 0.01). No significant difference was found in terms of quantitative flow ratio among three groups. At 5 years follow-up, negative remodeling lesions had a higher rate of composite vessel-oriented clinical event (14.3%), compared to intermediate (1.4%, P=0.004) or positive remodeling lesions (4.8%, P=0.06). After adjusting for multiple covariates, negative remodeling remained an independent determinant for vessel-oriented clinical event (HR: 4.849, 95% CI 1.542-15.251, P=0.007). CONCLUSION: IVUS-derived negative remodeling is associated with adverse long-term clinical outcome in stable patients with intermediate coronary artery stenosis.
Subject(s)
Coronary Artery Disease/epidemiology , Coronary Vessels/diagnostic imaging , Myocardial Infarction/epidemiology , Myocardial Revascularization/statistics & numerical data , Ultrasonography, Interventional , Vascular Remodeling , Aged , Blood Flow Velocity , Coronary Artery Disease/therapy , Coronary Stenosis/diagnostic imaging , Female , Humans , Male , Middle Aged , Plaque, Atherosclerotic/diagnostic imaging , Retrospective StudiesABSTRACT
Discrepancy between coronary lesion severity and functional significance has always been a relevant issue in the management of patients undergoing coronary angiography and/or revascularization. We sought to investigate the relationship between quantitative flow ratio (QFR)-derived microcirculatory indices and anatomical-functional mismatch/reverse mismatch in intermediate coronary lesions. Intravascular ultrasound (IVUS) imaging and QFR were analyzed in 117 de novo intermediate coronary lesions. Lesions with QFR ≤ 0.8 were considered hemodynamically significant. Anatomical significance of the lesions was defined according to the best cutoff value of combined IVUS parameters for predicting QFR ≤ 0.8. QFR-derived microcirculatory indices including contrast-flow QFR minus fixed-flow QFR (cQFR-fQFR), hyperemic flow velocity and angiography-derived index of microcirculatory resistance (IMRangio) were calculated. The best cutoff values of IVUS parameters for predicting QFR ≤ 0.8 were minimum lumen area (MLA) 3.1mm2 and plaque burden (PB) 70%, with area under the curve of 0.635 and 0.703, respectively. The total discordance rate of lesion functional significance between IVUS and QFR assessments was 26.5%, with 21 lesions (17.9%) being classified as mismatch (MLA ≤ 3.1mm2 and PB ≥ 70% and QFR > 0.8) and 10 lesions (8.5%) as reverse-mismatch (MLA > 3.1 mm2 or PB < 70% and QFR ≤ 0.8). At multivariate analysis, IMRangio was identified as an independent predictor of mismatch (OR1.675, 95%CI:1.176-2.386, P = 0.004), whereas hyperemic flow velocity was identified as an independent predictor of reverse-mismatch (OR 1.233, 95%CI:1.073-1.416, P = 0.003). In intermediate coronary lesions, although MLA 3.1mm2 and PB 70% determined by IVUS are predictive of QFR-defined functional significance, the discordance rate remains substantial. QFR-derived microcirculatory indices are independently associated with anatomical-functional discordance between IVUS and QFR assessments.
Subject(s)
Coronary Stenosis , Fractional Flow Reserve, Myocardial , Coronary Angiography , Coronary Stenosis/diagnostic imaging , Coronary Vessels/diagnostic imaging , Humans , Microcirculation , Predictive Value of Tests , Severity of Illness Index , Ultrasonography, InterventionalABSTRACT
Heart failure (HF) is a serious threat to human health. Long noncoding RNAs (lncRNAs) are critical regulators of HF. The aim of the study was to investigate the molecular mechanism of MALAT1 in HF rats. MALAT1 expression was detected in serum of normal volunteers and HF patients, HF rats and isoproterenol (ISO)induced H9C2 cells, and its diagnostic value was evaluated in HF patients. Indexes related to cardiac functions and hemodynamics, myocardial injury, lipid metabolism, lipid oxidation, and inflammation were detected. Moreover, the downstream mechanism of MALAT1 was predicted and verified and in vivo experiments were further performed in ISOinduced H9C2 cells to verify the effects of MALAT1 in HF. MALAT1 was highly expressed in serum of HF patients, HF rats and ISOinduced H9C2 cells and was valuable in predicting HF. Inhibition of MALAT1 increased cardiac function and antiinflammation and alleviated myocardial injury, lipid metabolism, lipid oxidation and apoptosis rates. Inhibition of MALAT1 reduced H9C2 cell injury. MALAT1 competitively bound to microRNA (miR)5323p to upregulate LDLR protein. Inhibition of miR5323p weakened the protective effect of downregulated MALAT1 against H9C2 cell injury. We concluded that MALAT1 upregulated LDLR expression by competitively binding to miR5323p, thereby increasing pathological injury in HF.
Subject(s)
Heart Failure/metabolism , Lipid Metabolism , Myocarditis/metabolism , Myocardium/metabolism , RNA, Long Noncoding/metabolism , Aged , Animals , Cell Line , Female , Heart Failure/pathology , Humans , Inflammation/metabolism , Inflammation/pathology , Male , Middle Aged , Myocarditis/pathology , Myocardium/pathology , Rats , Rats, Sprague-DawleyABSTRACT
BACKGROUND: The clinical relevance of moderate coronary stenosis is determined by its morphological characteristics and physiological significance. We investigated the relationship between high-risk plaque characteristics detected by intravascular ultrasound and functional significance assessed with quantitative flow ratio (QFR) in intermediate coronary lesions. METHODS: QFR was retrospectively analyzed in 352 intermediate lesions from 330 patients undergoing intravascular ultrasound examination. The functional significance was defined as QFR ≤0.8. High-risk plaque morphologies including plaque rupture, echo-lucent, echo-attenuation, and spotty calcification were identified, and attenuation indices including maximum angle, attenuation length, and superficial attenuation were determined. Clinically relevant echo-attenuation was defined as an attenuation with a minimum lumen area ≤4.0 mm2 and plaque burden ≥70%. RESULTS: The prevalence of echo-attenuation was higher (63.0% vs. 37.6%, P=0.001) and attenuation length was longer (12.8±10.3 vs. 8.0±5.8 mm, P=0.015) in lesions with QFR ≤0.8 compared to those with QFR >0.8, associated with a higher rate of clinically relevant echo-attenuation (35.2% vs. 10.4%, P<0.001). On multivariable analysis, the presence of echo-attenuation was an independent predictor of QFR ≤0.8 [odds ratio (OR) 3.162, 95% confidence interval (CI): 1.263-7.917, P=0.014], whereas attenuation length was weakly correlated with QFR value (ß=-0.185, B=-0.002, 95% CI: -0.004 to -0.001, P=0.001). Receiver-operating characteristic curve analysis revealed that the best cutoff of QFR in predicting clinically relevant echo-attenuation was 0.82 [area under the curve (AUC) =0.696, 95% CI: 0.616-0.775, P<0.001]. CONCLUSIONS: The presence of intravascular ultrasound-derived echo-attenuation confers an increased risk of QFR-defined functional significance in intermediate coronary lesions. KEYWORDS: Coronary artery disease; intermediate coronary lesion; quantitative flow ratio (QFR); intravascular ultrasound (IVUS); echo-attenuation.
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BACKGROUND: Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor has become the standard of care to reduce thrombotic events in patients with acute coronary syndrome or after percutaneous coronary intervention (PCI). The role of routine platelet function testing (PFT) in patients treated with DAPT after PCI remains controversial and evidence of PFT-guided antiplatelet therapy for patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI is limited. METHODS: We analyzed 1,353 consecutive STEMI patients undergoing primary PCI. PFT was performed 72 hr postprocedure using a vasodilator-stimulated phosphoprotein assay. The primary endpoint of major adverse cardio-cerebral events (MACCEs) was defined as a composite of all-cause death, cardiac death, nonfatal myocardial infarction, target vessel revascularization, and ischemic stroke. Patients with high platelet reactivity (HPR) were randomized to receive an intensified antiplatelet strategy by switching from clopidogrel to ticagrelor (HPR switch group) or to continue on clopidogrel (HPR nonswitch group). One-year clinical outcomes were compared among the groups. RESULTS: The baseline clinical characteristics were comparable across all groups (all p > .05). At the 1-year clinical follow-up, the primary endpoint of MACCE was significantly higher in the HPR nonswitch group than in the non-HPR and HPR switch groups (19.49% vs. 10.20% or 8.57%, p < .05), which was mainly caused by higher mortality (14.87% vs. 4.51% or 5.71%, p < .05). Major bleeding events were comparable across the groups. CONCLUSIONS: In STEMI patients with HPR, identified by vasodilator stimulated phosphoprotein (VASP)-determined PFT, switching clopidogrel to ticagrelor could significantly improve 1-year clinical outcomes without increasing the risk of bleeding.
Subject(s)
Blood Platelets/drug effects , Dual Anti-Platelet Therapy , Percutaneous Coronary Intervention , Platelet Aggregation Inhibitors/administration & dosage , Platelet Function Tests , ST Elevation Myocardial Infarction/therapy , Aged , Aspirin/administration & dosage , Biomarkers/blood , Blood Platelets/metabolism , Cell Adhesion Molecules/blood , China , Clopidogrel/administration & dosage , Drug Substitution , Dual Anti-Platelet Therapy/adverse effects , Dual Anti-Platelet Therapy/mortality , Female , Hemorrhage/chemically induced , Humans , Male , Microfilament Proteins/blood , Middle Aged , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/mortality , Phosphoproteins/blood , Platelet Aggregation Inhibitors/adverse effects , Predictive Value of Tests , Prospective Studies , Recurrence , Risk Assessment , Risk Factors , ST Elevation Myocardial Infarction/diagnosis , ST Elevation Myocardial Infarction/mortality , Ticagrelor/administration & dosage , Time Factors , Treatment OutcomeABSTRACT
Lithium-ion capacitors possess excellent power and energy densities, and they can combine both of those advantages from supercapacitors and lithium-ion batteries, leading to novel generation hybrid devices for storing energy. This study synthesized one three-dimensional (3D) hierarchical structure, self-assembled from CoS nanosheets, according to a simple and efficient manner, and can be used as an anode for lithium ion capacitors. This CoS anode, based on a conversion-type Li+ storage mechanism dominated by diffusion control, showed a large reversible capacity, together with excellent stability for cycling. The CoS shows a discharge capacity ≈434 mA h/g at 0.1 A/g. The hybrid lithium-ion capacitor, which had the CoS anode as well as the biochar cathode, exhibits excellent electrochemical performance with ultrahigh energy and power densities of 125.2 Wh/kg and 6400 W/kg, respectively, and an extended cycling life of 81.75% retention after 40â¯000 cycles. The CoS with self-assembled 3D hierarchical structure in combination with a carbon cathode offers a versatile device for future applications in energy storage.
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This study discusses changes in connected water systems in Chagan Lake induced by the interference of natural and human activities, based on the analysis of sediment characteristics. In this study, the following sediment characteristics were investigated in the lake area, the natural supply area, and the lake drainage area: mineral composition; particle size distribution; magnetic susceptibility; nutrient content; content of isotopes δ13Corg and δ15N; and content of heavy metals and of metallic oxides. The results showed that silicate minerals quartz, orthoclase, and anorthose were abundant in the whole lake water system. Quartz accumulated more easily in the lake area, while carbonate masses in the lake mainly came from the Huolinhe River. Moving from the lake area to the water diversion and drainage areas, fine particles clearly decreased, while coarse particles significantly increased due to the increase in hydraulic erosion. The main sources of nutrients and of organic matter are: the residual of the drainage from the Qianguo irrigated areas; the surrounding villages and the tourist area; and the decomposition of aquatic organisms. A large number of anthropogenic heavy metals, such as Hg, Cu, and As, were accumulated in the artificial water diversion area and in the farmland drainage area. This study indicates that recovering the original connected water system during the wet season, while at the same time enhancing water supply during the dry season could improve the ecological quality of Chagan Lake.
Subject(s)
Geologic Sediments/analysis , Geologic Sediments/chemistry , Lakes/analysis , Carbon Isotopes/analysis , China , Environmental Monitoring , Humans , Lakes/chemistry , Metals, Heavy/analysis , Nitrogen Isotopes/analysis , Rivers , Seasons , Water , Water Pollutants, Chemical/analysisABSTRACT
PURPOSE: Myocardial delivery of magnetic iron oxide nanoparticles (MNPs) might produce iron overload-induced myocardial injury, and the oxidative stress was regarded as the main mechanism. Therefore, we speculated antioxidant modification might be a reasonable strategy to mitigate the toxicity of MNPs. METHODS AND RESULTS: Antioxidant N-acetylcysteine (NAC) was loaded into magnetic mesoporous silica coated Fe3O4 nanoparticles. Neonatal rat hypoxia/reoxygenation (H/R) cardiomyocytes were incubated with nanoparticles for 24 hrs. NAC can effectively mitigate iron-induced oxidative injury of cardiomyocytes, evidenced by reduced production of MDA, 8-iso-PGF2α, and 8-OHDG and maintained concentrations of SOD, CAT, GSH-Px, and GSH in ELISA and biochemical tests; downregulated expression of CHOP, GRP78, p62, and LC3-II proteins in Western Blot, and less cardiomyocytes apoptosis in flow cytometric analysis. CONCLUSIONS: NAC modifying could suppress the toxic effects of Fe3O4 nanoparticles in H/R cardiomyocytes model in vitro, indicating a promising strategy to improve the safety of iron oxide nanoparticles.