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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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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.
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Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Carcinoma de Células Transicionales/diagnóstico , Carcinoma de Células Transicionales/genética , Carcinoma de Células Transicionales/patología , Hibridación Fluorescente in Situ/métodos , Variaciones en el Número de Copia de ADN , Neoplasia Residual/diagnóstico , Neoplasia Residual/genética , ADN , Sensibilidad y EspecificidadRESUMEN
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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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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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.
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Insuficiencia Cardíaca , MicroARNs , ARN Circular , Humanos , Apoptosis/genética , Inflamación/genética , MicroARNs/genética , Proteínas Quinasas Activadas por Mitógenos , Oxígeno/metabolismo , ARN Circular/genéticaRESUMEN
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.
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Estenosis Coronaria , Diabetes Mellitus , Reserva del Flujo Fraccional Miocárdico , Humanos , Angiografía Coronaria/métodos , Estudios Retrospectivos , Hemoglobina Glucada , Ultrasonografía Intervencional/métodos , Diabetes Mellitus/diagnóstico por imagen , Vasos Coronarios/diagnóstico por imagen , Valor Predictivo de las Pruebas , Índice de Severidad de la EnfermedadRESUMEN
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.
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Enfermedad de la Arteria Coronaria/epidemiología , Vasos Coronarios/diagnóstico por imagen , Infarto del Miocardio/epidemiología , Revascularización Miocárdica/estadística & datos numéricos , Ultrasonografía Intervencional , Remodelación Vascular , Anciano , Velocidad del Flujo Sanguíneo , Enfermedad de la Arteria Coronaria/terapia , Estenosis Coronaria/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Placa Aterosclerótica/diagnóstico por imagen , Estudios RetrospectivosRESUMEN
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.
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Plaquetas/efectos de los fármacos , Terapia Antiplaquetaria Doble , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/administración & dosificación , Pruebas de Función Plaquetaria , Infarto del Miocardio con Elevación del ST/terapia , Anciano , Aspirina/administración & dosificación , Biomarcadores/sangre , Plaquetas/metabolismo , Moléculas de Adhesión Celular/sangre , China , Clopidogrel/administración & dosificación , Sustitución de Medicamentos , Terapia Antiplaquetaria Doble/efectos adversos , Terapia Antiplaquetaria Doble/mortalidad , Femenino , Hemorragia/inducido químicamente , Humanos , Masculino , Proteínas de Microfilamentos/sangre , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Fosfoproteínas/sangre , Inhibidores de Agregación Plaquetaria/efectos adversos , Valor Predictivo de las Pruebas , Estudios Prospectivos , Recurrencia , Medición de Riesgo , Factores de Riesgo , Infarto del Miocardio con Elevación del ST/diagnóstico , Infarto del Miocardio con Elevación del ST/mortalidad , Ticagrelor/administración & dosificación , Factores de Tiempo , Resultado del TratamientoRESUMEN
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.
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Sedimentos Geológicos/análisis , Sedimentos Geológicos/química , Lagos/análisis , Isótopos de Carbono/análisis , China , Monitoreo del Ambiente , Humanos , Lagos/química , Metales Pesados/análisis , Isótopos de Nitrógeno/análisis , Ríos , Estaciones del Año , Agua , Contaminantes Químicos del Agua/análisisRESUMEN
Picroside II (P-II), one of the main active components of scrophularia extract, which have anti-oxidative, anti-inflammatory effects, but its effect on hyperhomocysteinemia (HHcy) induced endothelial injury remains to be determined. Here, we test whether P-II protects HHcy-induced endothelial dysfunction against oxidative stress, inflammation and cell apoptosis. In vitro study using HUVECs, and in hyperhomocysteinemia mouse models, we found that HHcy decreased endothelial SIRT1 expression and increased LOX-1 expression, subsequently causing reactive oxygen species generation, up-regulation of NADPH oxidase activity and NF-κB activation, thereby promoting pro-inflammatory response and cell apoptosis. Blockade of Sirt1 with Ex527 or siRNASIRT1 increased LOX-1 expression, whereas overexpression of SIRT1 decreased LOX-1 expression markedly. P-II treatment significantly increased SIRT1 expression and reduced LOX-1 expression, and protected against endothelial cells from Hcy-induced oxidative injury, inflammation and apoptosis. However, blockade of SIRT1 or overexpression of LOX-1 attenuated the therapeutic effects of P-II. In conclusion, our results suggest that P-II prevents the Hcy induced endothelial damage probably through regulating the SIRT1/LOX-1 signaling pathway.
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Apoptosis/efectos de los fármacos , Cinamatos/farmacología , Endotelio/efectos de los fármacos , Hiperhomocisteinemia/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Glucósidos Iridoides/farmacología , Estrés Oxidativo/efectos de los fármacos , Animales , Antioxidantes/metabolismo , Línea Celular , Endotelio/metabolismo , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Hiperhomocisteinemia/metabolismo , Inflamación/metabolismo , Ratones , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Sirtuina 1/metabolismo , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Effective magnetic fields have enabled unprecedented manipulation of neutral particles including photons. In most studied cases, the effective gauge fields are defined through the phase of mode coupling between spatially discrete elements, such as optical resonators and waveguides in the case for photons. Here, in the paradigm of Bloch-wave modulated photonic crystals, we show the creation of effective magnetic fields for photons in conventional dielectric continua for the first time, via Floquet band engineering. By controlling the phase and wave vector of Bloch waves, we demonstrated the anomalous quantum Hall effect for light with distinct topological band features due to delocalized wave interference. Based on a cavity-free architecture, in which Bloch-wave modulations can be enhanced using guided resonances in photonic crystals, the study here opens the door to the realization of effective magnetic fields at large scales for optical beam steering and topological light-matter phases with broken time-reversal symmetry.
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Gap junctions play a critical role in electrical synchronization and exchange of small molecules between neighboring cells; connexins are a family of structurally related transmembrane proteins that assemble to form vertebrate gap junctions. Hyperglycemia changes the structure gap junction proteins and their expression, resulting in obstruction of neural regeneration, vascular function and wound healing, and also promoting vascular atherosclerosis. These pathogenic factors would cause diabetic foot ulcers. This article reviews the involvement of connexins in pathogenesis of diabetic foot.
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Conexinas/metabolismo , Pie Diabético/patología , Uniones Comunicantes/metabolismo , Aterosclerosis , Humanos , Hiperglucemia/fisiopatología , Regeneración , Cicatrización de HeridasRESUMEN
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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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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This study summarizes the significance of microRNA-134 (miRNA-134) in the pathophysiology, diagnosis, and treatment of depression, a disease still under investigation due to its complexity. miRNA-134 is an endogenous short non-coding RNA that can bind to the 3' untranslated region (3'UTR) of miRNA-134, inhibiting gene translation and showing great potential in the regulation of mood, synaptic plasticity, and neuronal function. This study included 15 articles retrieved from four English-language databases: PubMed, Embase, The Cochrane Library, and Web of Science, and three Chinese literature databases: CNKI, Wanfang, and Chinese Science and Technology Periodical Database (VIP).We evaluated each of the 15 articles using the Critical Appraisal Skills Program (CASP) tool.The standard integrates analyzes of genomic, transcriptomic, neuroimaging, and behavioral data analyses related to miRNA-134 and depression. A multidimensional framework based on standardized criteria was used for quality assessment. The main findings indicate that miRNA-134 significantly affects synaptic plasticity and neurotransmitter regulation, in particular the synthesis and release of serotonin and dopamine. miRNA-134 shows high sensitivity and specificity as a biomarker for the diagnosis of depression and has therapeutic potential for the targeted treatment of depression. miRNA-134 plays a crucial role in the pathogenesis of depression, providing valuable insights for early diagnosis and the development of targeted therapeutic strategies. This work highlights the potential of miRNA-134 as a focal point for advancing personalized medicine approaches for depression.
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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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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.
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Cobre , Ácido Hialurónico , Imagen por Resonancia Magnética , Compuestos de Manganeso , Óxidos , Fotoquimioterapia , Microambiente Tumoral , Compuestos de Manganeso/química , Compuestos de Manganeso/farmacología , Microambiente Tumoral/efectos de los fármacos , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Óxidos/química , Óxidos/farmacología , Humanos , Cobre/química , Cobre/farmacología , Tamaño de la Partícula , Nanoestructuras/química , Antineoplásicos/farmacología , Antineoplásicos/química , Fototerapia , Nanopartículas/química , Supervivencia Celular/efectos de los fármacos , Propiedades de Superficie , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Ensayos de Selección de Medicamentos Antitumorales , AnimalesRESUMEN
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.
Asunto(s)
Algoritmos , Antraciclinas , Neoplasias de la Mama , Terapia Neoadyuvante , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Femenino , Antraciclinas/uso terapéutico , Antraciclinas/administración & dosificación , Terapia Neoadyuvante/métodos , Persona de Mediana Edad , China/epidemiología , Adulto , Recombinación Homóloga , Mutación , Anciano , Variaciones en el Número de Copia de ADN , Proteína BRCA1/genéticaRESUMEN
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.
RESUMEN
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.