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In this study, a lignin-based aerogel (LA) was prepared through acid precipitation of BPBL, followed by sol-gel method and freeze-drying. Additionally, a one-step activation-carbonization method was used to acquire nitrogen-doped lignin-based activated carbon aerogel (NLACA). The adsorption and catalytic degradation performance for malachite green (MG) were examined. The specific surface area of NLACA after N-doping was 2644.5 m2/g. The adsorption capacity for MG was increased to 3433 mg/g with the presence of nitrogenous functional groups on surface of NLACA compared without N-doping. Meanwhile, non-radical singlet oxygen is the primary active substance and degradation efficiency arrives at 91.8% after the catalytic degradation within 20 min and it has good stability and reuse. Three possible degradation pathways during degradation were analyzed by LC-MS technique. The adsorption isotherm and kinetic data demonstrated conformity with both the Langmuir model and the pseudo-second-order kinetic model. The primary mechanisms of the adsorption for MG dyes on NLACA include hydrogen bonding, π-π interactions, attraction of electrostatic and pore filling. Hence, NLACA derived from BPBL acts as a cost-effective and high-performance adsorbent and catalyst for removal of MG in dye wastewater. This concept introduces an innovative approach of "treatment of waste with waste" for developing a low-consumption, high-efficiency dye wastewater treatment and provides significant reference to treatment dye wastewater.
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Infection is a common medical problem at present. Different pathogens can lead to different infections. Severe infections can ultimately lead to sepsis, resulting in multiple organ dysfunction and the high mortality of patients. Therefore, studying the occurrence and development of severe infections is essential to improve the survival rate of patients. More and more studies have revealed the important role of connection between intestine and liver in infectious diseases. The maintenance of intestinal mechanical barrier and biological barrier function and the regulation of intestinal flora metabolites can reduce infectious liver injury. Bile acids are important metabolites in the liver, which can inhibit the progression of certain infectious intestinal injuries and promote intestinal damage caused by certain pathogens. In this article, the mechanism of action of the intestinal-liver axis in infection was reviewed to find a new target for the treatment of clinical infection.
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Intestinos , Fígado , Humanos , Fígado/metabolismo , Ácidos e Sais Biliares/metabolismo , Hepatopatias/metabolismo , Hepatopatias/etiologia , Mucosa Intestinal/metabolismo , Microbioma GastrointestinalRESUMO
Background: Peripheral neuropathy (PN) is a prevalent complication of multiple myeloma (MM), due to the disease itself or its treatment. Despite extensive research, the optimal treatment for multiple myeloma peripheral neuropathy (MMPN) remains unclear. Clinical practice has shown the potential efficacy of acupuncture in managing MMPN. This study aimed to conduct a comprehensive analysis of the literature to assess the effectiveness and safety of acupuncture as a treatment for MMPN. Methods: The PubMed, Web of Science, MEDLINE, Cochrane Library, and Embase databases were comprehensively searched from inception to November 1, 2023 to identify relevant studies pertaining to the use of acupuncture to treat MMPN. Results: A total of five studies, encompassing 97 patients diagnosed with drug-related PN, were ultimately included in this analysis. The literature lacks any reports pertaining to the utilization of acupuncture for disease-related PN. ST36, LI4, SP6, and EX-LE-10 were found to be the most frequently chosen acupoints. Following acupuncture treatment, there was a consistent reduction in scores on the Visual Analogue Scale (VAS), Neuropathic Pain Scale (NPS), Brief Pain Inventory-Short Form (BPI-SF), and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) among MMPN patients. The results of Nerve Conduction Velocity (NCV) tests yielded conflicting results. No severe adverse effects were reported. Conclusion: The use of acupuncture for disease-related PN has not been studied to date. Acupuncture is safe for drug-related PN and is helpful for relieving pain. But uncertainty exists regarding the efficacy of this approach because there is substantial heterogeneity with respect to acupuncture treatment regimens, and more high-quality studies on this topic are warranted.
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Objective: Here, we aimed to explore the effect of LBP in combination with Oxaliplatin (OXA) on reversing drug resistance in colon cancer cells through in vitro and in vivo experiments. We also aimed to explore the possible mechanism underlying this effect. Finally, we aimed to determine potential targets of Lycium barbarum polysaccharide (LBP) in colon cancer (CC) through network pharmacology and molecular docking. Methods: The invasion ability of colon cancer cells was assessed using the invasion assay. The migration ability of these cells was assessed using the migration assay and wound healing assay. Cell cycle analysis was carried out using flow cytometry. The expression levels of phosphomannose isomerase (PMI) and ATP-binding cassette transport protein of G2 (ABCG2) proteins were determined using immunofluorescence and western blotting. The expression levels of phosphatidylinositol3-kinase (PI3K), protein kinase B (AKT), B-cell lymphoma 2 (Bcl-2), and BCL2-Associated X (Bax) were determined using western blotting. Forty BALB/c nude mice purchased from Weitong Lihua, Beijing, for the in vivo analyses. The mice were randomly divided into eight groups. They were administered HCT116 and HCT116-OXR cells to prepare colon cancer xenograft models and then treated with PBS, LBP (50 mg/kg), OXA (10 mg/kg), or LBP + OXA (50 mg/kg + 10 mg/kg). The tumor weight and volume of treated model mice were measured, and organ toxicity was evaluated using hematoxylin and eosin staining. The expression levels of PMI, ABCG2, PI3K, and AKT proteins were then assessed using immunohistochemistry. Moreover, PMI and ABCG2 expression levels were analyzed using immunofluorescence and western blotting. The active components and possible targets of LBP in colon cancer were explored using in silico analysis. GeneCards was used to identify CC targets, and an online Venn analysis tool was used to determine intersection targets between these and LBP active components. The PPI network for intersection target protein interactions and the PPI network for interactions between the intersection target proteins and PMI was built using STRING and Cytoscape. To obtain putative targets of LBP in CC, we performed GO function enrichment and KEGG pathway enrichment analyses. Results: Compared with the HCT116-OXR blank treatment group, both invasion and migration abilities of HCT116-OXR cells were inhibited in the LBP + OXA (2.5 mg/mL LBP, 10 µΜ OXA) group (p < 0.05). Cells in the LBP + OXA (2.5 mg/mL LBP, 10 µΜ OXA) group were found to arrest in the G1 phase of the cell cycle. Knockdown of PMI was found to downregulate PI3K, AKT, and Bcl-2 (p < 0.05), while it was found to upregulate Bax (p < 0.05). After treatment with L. barbarum polysaccharide, 40 colon cancer subcutaneous tumor models showed a decrease in tumor size. There was no difference in the liver index after LBP treatment (p > 0.05). However, the spleen index decreased in the OXA and LBP + OXA groups (p < 0.05), possibly as a side effect of oxaliplatin. Immunohistochemistry, immunofluorescence, and western blotting showed that LBP + OXA treatment decreased PMI and ABCG2 expression levels (p < 0.05). Moreover, immunohistochemistry showed that LBP + OXA treatment decreased the expression levels of PI3K and AKT (p < 0.05). Network pharmacology analysis revealed 45 active LBP components, including carotenoids, phenylpropanoids, quercetin, xanthophylls, and other polyphenols. It also revealed 146 therapeutic targets of LBP, including AKT, SRC, EGFR, HRAS, STAT3, and MAPK3. KEGG pathway enrichment analysis showed that the LBP target proteins were enriched in pathways, including cancer-related signaling pathways, PI3K/AKT signaling pathway, and IL-17 signaling pathways. Finally, molecular docking experiments revealed that the active LBP components bind well with ABCG2 and PMI. conclusion: Our in vitro experiments showed that PMI knockdown downregulated PI3K, AKT, and Bcl-2 and upregulated Bax. This finding confirms that PMI plays a role in drug resistance by regulating the PI3K/AKT pathway and lays a foundation to study the mechanism underlying the reversal of colon cancer cell drug resistance by the combination of LBP and OXA. Our in vivo experiments showed that LBP combined with oxaliplatin could inhibit tumor growth. LBP showed no hepatic or splenic toxicity. LBP combined with oxaliplatin could downregulate the expression levels of PMI, ABCG2, PI3K, and AKT; it may thus have positive significance for the treatment of advanced metastatic colon cancer. Our network pharmacology analysis revealed the core targets of LBP in the treatment of CC as well as the pathways they are enriched in. It further verified the results of our in vitro and in vivo experiments, showing the involvement of multi-component, multi-target, and multi-pathway synergism in the drug-reversing effect of LBP in CC. Overall, the findings of the present study provide new avenues for the future clinical treatment of CC.
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We aimed to evaluate the association between air pollutants and mortality risk in patients with acute aortic dissection (AAD) in a longitudinal cohort and to explore the potential mechanisms of adverse prognosis induced by fine particulate matter (PM2.5). Air pollutants data, including PM2.5, PM10.0, nitrogen dioxide (NO2), carbon monoxide (CO), sulfur dioxide (SO2), and ozone (O3), were collected from official monitoring stations, and multivariable Cox regression models were applied. Single-cell sequencing and proteomics of aortic tissue were conducted to explore the potential mechanisms. In total, 1,267 patients with AAD were included. Exposure to higher concentrations of air pollutants was independently associated with an increased mortality risk. The high-PM2.5 group carried approximately 2 times increased mortality risk. There were linear associations of PM10, NO2, CO, and SO2 exposures with long-term mortality risk. Single-cell sequencing revealed an increase in mast cells in aortic tissue in the high-PM2.5 exposure group. Enrichment analysis of the differentially expressed genes identified the inflammatory response as one of the main pathways, with IL-17 and TNF signaling pathways being among the top pathways. Analysis of proteomics also identified these pathways. This study suggests that exposure to higher PM2.5, PM10, NO2, CO, and SO2 are associated with increased mortality risk in patients with AAD. PM2.5-related activation and degranulation of mast cells may be involved in this process.
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Poluentes Atmosféricos , Poluição do Ar , Dissecção Aórtica , Ozônio , Humanos , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Dióxido de Nitrogênio/análise , Proteômica , Material Particulado/análise , Ozônio/análise , Dióxido de Enxofre , Exposição Ambiental/análise , ChinaRESUMO
Background: The public health burden of cardiomyopathies and competency in their management by health agencies in China are not well understood. Methods: This study adopted a multi-stage sampling method for hospital selection. In the first stage, nationwide tertiary hospital recruitment was performed. As a result, 88 hospitals with the consent of the director of cardiology and access to an established electronic medical records system, were recruited. In the second stage, we sampled 66 hospitals within each geographic-economic stratification through a random sampling process. Data on (1) the outpatient and inpatient visits for cardiomyopathies between 2017 and 2021 and (2) the competency in the management of patients with cardiomyopathies, were collected. The competency of a hospital to provide cardiomyopathy care was evaluated using a specifically devised scale. Findings: The outpatient and inpatient visits for cardiomyopathies increased between 2017 and 2021 by 38.6% and 33.0%, respectively. Most hospitals had basic facilities for cardiomyopathy assessment. However, access to more complex procedures was limited, and the integrated management pathway needs improvement. Only 4 (6.1%) of the 66 participating hospitals met the criteria for being designated as a comprehensive cardiomyopathy center, and only 29 (43.9%) could be classified as a primary cardiomyopathy center. There were significant variations in competency between hospitals with different administrative and economic levels. Interpretation: The health burden of cardiomyopathies has increased significantly between 2017 and 2021 in China. Although most tertiary hospitals in China can offer basic cardiomyopathy care, more advanced facilities are not yet universally available. Moreover, inconsistencies in the management of cardiomyopathies across hospitals due to differing administrative and economic levels warrants a review of the nation allocation of medical resources. Funding: This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2023-I2M-1-001) and the National High Level Hospital Clinical Research Funding (2022-GSP-GG-17).
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Punicalagin (PUN) is a polyphenol derived from the pomegranate peel. It has been reported to have many beneficial effects, including anti-inflammatory, anti-oxidant, and anti-proliferation. However, the role of PUN in macrophage phagocytosis is currently unknown. In this study, we found that pre-treatment with PUN significantly enhanced phagocytosis by macrophages in a time- and dose-dependent manner in vitro. Moreover, KEGG enrichment analysis by RNA-sequencing showed that differentially expressed genes following PUN treatment were significantly enriched in phagocyte-related receptors, such as the C-type lectin receptor signaling pathway. Among the C-type lectin receptor family, Mincle (Clec4e) significantly increased at the mRNA and protein level after PUN treatment, as shown by qRT-PCR and western blotting. Small interfering RNA (siRNA) mediated knockdown of Mincle in macrophages resulted in down regulation of phagocytosis. Furthermore, western blotting showed that PUN treatment enhanced the phosphorylation of nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) in macrophages at the early stage. Mincle-mediated phagocytosis by PUN was inhibited by PDTC (a NF-κB inhibitor) and SB203580 (a p38 MAPK inhibitor). In addition, PUN pre-treatment enhanced phagocytosis by peritoneal and alveolar macrophages in vivo. After intraperitoneal injection of Escherichia coli (E.coli), the bacterial load of peritoneal lavage fluid and peripheral blood in PUN pre-treated mice decreased significantly. Similarly, the number of bacteria in the lung tissue significantly reduced after intranasal administration of Pseudomonas aeruginosa (PAO1). Taken together, our results reveal that PUN enhances bacterial clearance in mice by activating the NF-κB and MAPK pathways and upregulating C-type lectin receptor expression to enhance phagocytosis by macrophages.
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Taninos Hidrolisáveis , Macrófagos , NF-kappa B , Camundongos , Animais , NF-kappa B/metabolismo , Transdução de Sinais , Fagocitose , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Antioxidantes/farmacologia , Lectinas Tipo C/metabolismoRESUMO
Mixed systems of betaines and anionic surfactants can have a significant synergistic effect and greatly reduce the interfacial tension (IFT), which has attracted an extensive amount of attention. However, this synergistic effect requires an anionic surfactant and betaine molecular size matching, which limits the scope of its application. In this work, we studied three mixed systems of sodium dialkyl sulfosuccinate (AOT) and betaines with different sizes by molecular dynamics simulation and an IFT experiment and explored the interfacial behavior and synergistic mechanism of AOT in single and mixed systems. The hydrophobic tail chain center angle, average rising height of carbon atoms, stretch degree and distance between the terminal carbon atoms of AOT, and tilt angles of betaine were calculated and analyzed in detail. Simulation results showed that the hydrophobic tail chain center angle of AOT in the single system was smaller, and it tended to extend into the oil phase. After being mixed with different betaines, AOT can adjust its size according to the interfacial vacancies of different betaine systems by changing the alkyl chain orientation and forming tighter interfacial films. The IFT experiment showed that betaine/AOT mixed systems achieved a lower IFT value compared with that of the single system, indicating that AOT showed a synergistic effect with betaines with different structures. This study will be importantly instructively significant for the design and research of betaine mixed systems in crude oil exploitation.
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We describe a 45-year-old patient who was diagnosed with hypertrophic obstructive cardiomyopathy (HOCM) after the aortic valve replacement surgery. Enlarged left atria, thickened ventricular septum, left ventricular outflow tract stenosis, moderate mitral regurgitation and mild tricuspid regurgitation in the echocardiography were found. We offered the patient the new minimally invasive treatment modality: percutaneous intra-myocardial septal radiofrequency ablation (PIMSRA). We demonstrate the safety and efficacy with pictures. One month after surgery, the patient recovered well with improved symptoms of chest tightness, and no LVOT obstruction or arrhythmia.
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Cardiomiopatia Hipertrófica , Insuficiência da Valva Mitral , Humanos , Pessoa de Meia-Idade , Valva Aórtica/cirurgia , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/cirurgia , Ecocardiografia , Miocárdio , Insuficiência da Valva Mitral/cirurgia , Resultado do TratamentoRESUMO
The highly strained, phenylene-derived organic cages are typically regarded as very rigid entities, yet their deformation potential and supramolecular properties remain underexplored. Herein, we report a pliable conjugated phenylene nanocage by synergistically merging rigid and flexible building blocks. The anisotropic cage molecule contains branched phenylene chains capped by a calix[6]arene moiety, the delicate conformational changes of which endow the cage with a remarkably deformable cavity. When complexing with fullerene guests, the cage showcases excellent guest-adaptivity, with its cavity volume capable of swelling by as much as 85 %.
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OBJECTIVE: To generate a mouse model carrying TTNtv Y4370* simulating the newly discovered human heterozygous nonsense TTNtv c.13254T>G (p.Tyr4418Ter) to supplement and improve the functional evidence of pathogenic mutation TTNtv c.13254T>G on the pathogenic type of dilated cardiomyopathy. METHODS: We generated 4 mice carrying TTNtv p. Y4370* through CRISPR/Cas-mediated genome engineering. Monthly serological detection, bimonthly echocardiography, and histology evaluation were carried out to observe and compare alterations of cardiac structure and function between 4 TTN+/- mice and 4 wild-type (WT) mice. RESULTS: For the two-month-old TTN+/- mice, serum glutamic-oxalacetic transaminase (AST), lactic dehydrogenase (LDH), and creatine kinase (CK) were significantly increased, the diastolic Left Ventricular Systolic Anterior Wall (LVAW), and the LV mass markedly rose, with the left ventricular volume displaying an increasing trend and Ejection Fraction (EF) and Fractional Shortening (FS) showing a decreasing trend. Besides, the histological evaluation showed that cardiac fibrosis level and positive rate of cardiac mast cell of TTN+/- mice were obviously increased compared with WT mice. CONCLUSIONS: TTNtv Y4370* could lead to cardiac structure and function alterations in mice, supplementing the evidence of TTNtv c.13254T>G pathogenicity in human.
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Cardiomiopatias , Cardiomiopatia Dilatada , Animais , Humanos , Lactente , Camundongos , Cardiomiopatias/genética , Conectina/genética , Coração , MutaçãoRESUMO
"Improbable" rotaxanes consisting of interlocked conjugated components represent non-trivial synthetic targets, not to mention those with all-benzene scaffolds. Herein, a modular synthetic strategy has been established using an isolable azo-linked pre-rotaxane as the core module, in which the azo group functions as a tracelessly removable template to direct mechanical bond formations. Through versatile connections of the pre-rotaxane and other customizable modules, [2]- and [3]rotaxanes derived from all-benzene scaffolds have been accomplished, demonstrating the utility and potential of the synthetic design for all-benzene interlocked supramolecules.
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Objective: Myofibrillar myopathies (MFM) are a group of sporadic and inherited progressive skeletal muscle disorders that can lead to physical disability and premature death. To date, pathogenic variants in different genes are associated with MFM. MFM induced by variants in the Desmin (DES) gene is the most common subtype of MFM. Case presentation: A 15-year-old boy with MFM was described, whose symptoms first presented as cardiac symptoms. Enlarged right and left atria, thickened ventricular septal (IVS) and mild mitral (MR) and tricuspid regurgitation (TR) in the echocardiography were found. Atrial fibrillation, intermittent atrioventricular (AV) block, ST-T changes in the dynamic electrocardiogram (ECG) were shown. Mild myopathic changes in the electromyographic exam were detected. Ultrastructural analysis found slight Z-line changes and a few small myolysis lesions, but no abnormal inclusion bodies. Genetic testing detected a heterozygous missense variant (c.1216C > T) of DES, and 2 rare variants: TNNI3K (c.1102C > G) and PRDM16 (c.3074G > A). The patient's parents didn't show skeletal and cardiac muscle disorders. DNA sequencing analysis showed no variant of DES was carried by them. Thus, we detected a case of MFM caused by de novo DES variant c.1216C > T/p.Arg406Trp with predominantly myocardial alterations.
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Inspired by the drawstring structure in daily life, here we report the development of a drawstring-mimetic supramolecular complex at the molecular scale. This complex consists of a rigid figure-of-eight macrocyclic host molecule and a flexible linear guest molecule which could interact through three-point non-covalent binding to form a highly selective and efficient host-guest assembly. The complex not only resembles the drawstring structure, but also mimics the properties of a drawstring with regard to deformations under external forces. The supramolecular drawstring can be utilized as an interlocked crosslinker for poly(methyl acrylate), and the corresponding polymer samples exhibit comprehensive enhancement of macroscopic mechanical performance including stiffness, strength, and toughness.
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BACKGROUND: Although endometrial cancer represents a frequently diagnosed malignancy of the female reproductive tract, we know very little about the factors that control endometrial cancer. OBJECTIVE: Our study was presented to investigate the function of MCU in endometrial tumorigenesis and the molecular mechanisms involved. MATERIALS AND METHODS: A total of 94 endometrial cancer patients were recruited into our cohort. MCU and VDAC1 expression was examined in tumor and normal tissues via immunohistochemistry and immunofluorescence. Associations of MCU and VDAC1 expression with clinicopathological characteristics were evaluated. After transfection with shRNA targeting MCU or full-length MCU plasmids, clone formation, wound healing, transwell and MitoTracker Red staining were separately presented in Ishikawa and RL95-2 cells. Moreover, Western blotting or immunofluorescence was utilized to examine the expression of MCU, VDAC1, Na+/Ca2+/Li+ exchanger (NCLX), and ß-catenin under VDAC1 knockdown and/or MCU overexpression or knockdown. RESULTS: MCU and VDAC1 expression were prominently up-regulated in endometrial cancer tissues and were significantly associated with histological grade, depth of myometrial invasion and lymph node status. MCU up-regulation enhanced clone formation, migration, and mitochondrial activity of endometrial cancer cells. The opposite results were investigated when MCU was silenced. MCU or VDAC1 silencing reduced the expression of MCU, VDAC1, NCLX, and ß-catenin. Moreover, VDAC1 knockdown alleviated the promoting effect of MCU overexpression on the above proteins. CONCLUSION: This investigation demonstrated that MCU-induced mitochondrial calcium uptake plays a critical role in endometrial tumorigenesis through interaction with VDAC1.
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Canais de Cálcio , Cálcio , Neoplasias do Endométrio , Feminino , Humanos , beta Catenina/metabolismo , Cálcio/metabolismo , Carcinogênese , Neoplasias do Endométrio/genética , Processos Neoplásicos , Canal de Ânion 1 Dependente de Voltagem/metabolismoRESUMO
OBJECTIVE: To measure the preoperative uric acid (UA) concentration in patients with type A aortic dissection (TAAD), and to assess its value in predicting in-hospital mortality. METHODS: A total of 747 patients with TAAD between January 2016 and December 2022 were enrolled. The patients were divided into a survivor group and a non-survivor group. The clinical data of the two groups were compared. Univariate and multiple logistic regression analyses were performed to determine risk factors related to in-hospital mortality. RESULTS: Compared with survivors, non-survivors had significantly higher serum uric acid levels (486.84 ± 127.59 vs 419.49 ± 141.02, P = 0.040). The incidence of in-hospital death increased along with higher UA levels (3.8% vs 0.7%, P = 0.007). Serum UA ≥ 373.5 µmol/L had 89.5% sensitivity and 41.3% specificity for predicting in-hospital death (area under the curve = 0.659, 95% CI: 0.554-0.765, P < 0.05). In the multivariable logistic model, Serum UA ≥ 373.5 µmol/L was independently associated with in-hospital mortality (OR = 1.022, 95% CI: 1.000-1.044, P = 0.048). CONCLUSION: Serum UA resulted as an independent predictor of adverse prognosis in patients with TAAD, and thus could be used as an effective tool for the risk-stratification of patients with TAAD.
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Dissecção Aórtica , Ácido Úrico , Humanos , Mortalidade Hospitalar , Estudos Retrospectivos , Dissecção Aórtica/cirurgiaRESUMO
Vascular smooth muscle cells (VSMCs) are the major contributor to vascular repair and remodeling, which showed high level of phenotypic plasticity. Abnormalities in VSMC plasticity can lead to multiple cardiovascular diseases, wherein alternative splicing plays important roles. However, alternative splicing variants in VSMC plasticity are not fully understood. Here we systematically characterized the long-read transcriptome and their dysregulation in human aortic smooth muscle cells (HASMCs) by employing the Oxford Nanopore Technologies long-read RNA sequencing in HASMCs that are separately treated with platelet-derived growth factor, transforming growth factor, and hsa-miR-221-3P transfection. Our analysis reveals frequent alternative splicing events and thousands of unannotated transcripts generated from alternative splicing. HASMCs treated with different factors exhibit distinct transcriptional reprogramming modulated by alternative splicing. We also found that unannotated transcripts produce different open reading frames compared to the annotated transcripts. Finally, we experimentally validated the unannotated transcript derived from gene CISD1, namely CISD1-u, which plays a role in the phenotypic switch of HASMCs. Our study characterizes the phenotypic modulation of HASMCs from an insight of long-read transcriptome, which would promote the understanding and the manipulation of HASMC plasticity in cardiovascular diseases.
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Doenças Cardiovasculares , MicroRNAs , Nanoporos , Humanos , Processamento Alternativo , Músculo Liso Vascular/metabolismo , Doenças Cardiovasculares/metabolismo , MicroRNAs/genética , Análise de Sequência de RNA , Miócitos de Músculo Liso/metabolismoRESUMO
In this paper, the interfacial properties of extended surfactants with different oxypropylene (PO) groups were comprehensively investigated by using interfacial dilational rheology. The differences in molecular orientation, spatial configuration, and relaxation process were compared at the gas-water interface and oil-water interface. The influences of the PO groups on the interface viscoelasticity were analyzed, providing important theoretical support for the wide application of extended surfactants. Experimental results show that the lower number of PO groups in extended surfactants does not cause differences in their presence states on the interface; however, once it increases, the longer PO segment will spiral up in the direction perpendicular to the interface, forming a spatial configuration like a thin cylinder. Compared with air, the PO group has better solubility in the oil phase. The chain segment can still maintain a helical extension from the beginning to the end as a result. However, the upper layer of the thin cylinder will collapse to a certain extent at the surface. Moreover, the orientation of the hydrophobic side has a dynamic process of "tilting to upright" with the increase of adsorption amount or in response to interfacial dilation and compression. The increase of PO number or the insertion of oil molecules has little effect on dilational modulus, and the interfacial film strength is generally relatively low. That is to say, the better emulsifying and solubilizing ability of PO-containing extended surfactants may be more attributed to the matching steric effect at interface or better packing action in bulk phase than to higher film strength.
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The photosensitizers (PSs) for photodynamic therapy (PDT) mostly possess conjugated skeletons that are over-sized and poorly water-soluble to be encapsulated by conventional macrocyclic receptors. Herein, we report that two fluorescent hydrophilic cyclophanes, AnBox·4Cl and ExAnBox·4Cl, can effectively bind hypocrellin B (HB), a pharmaceutically active natural PS for PDT, with binding constants of the 107 level in aqueous solutions. The two macrocycles feature extended electron-deficient cavities and can be facilely synthesized through photo-induced ring expansions. The corresponding supramolecular PSs (HBâAnBox4+ and HBâExAnBox4+) exhibit desirable stability, biocompatibility, and cellular delivery, as well as excellent PDT efficiency against cancer cells. In addition, living cell imaging results indicate that HBâAnBox4+ and HBâExAnBox4+ have different delivery effects at the cellular level.