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With the continuous development of large-scale engineering projects such as construction projects, relief support, and large-scale relocation in various countries, engineering logistics has attracted much attention. This paper addresses a multimodal material route planning problem (MMRPP), which considers the transportation of engineering material from suppliers to the work zones using multiple transport modes. Due to the overall relevance and technical complexity of engineering logistics, we introduce the key processes at work zones to generate a transport solution, which is more realistic for various real-life applications. We propose a multi-objective multimodal transport route planning model that minimizes the total transport cost and the total transport time. The model by using the ε - constraint method that transforms the objective function of minimizing total transportation cost into a constraint, resulting in obtaining pareto optimal solutions. This method makes up for the lack of existing research on the combination of both engineering logistics and multimodal transportation, after which the feasibility of the model and algorithm is verified by examples. The results show that the model solution with the introduction of the key processes at work zones produces more time-efficient and less time-consuming route planning results, and that the results obtained using the ε - constraint method are more reliable than the traditional methods for solving multi-objective planning problems and are more in line with the decision maker's needs.
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Algoritmos , Modelos Teóricos , Meios de Transporte , Meios de Transporte/métodos , Engenharia/métodos , Humanos , Local de TrabalhoRESUMO
Metabolic syndrome (MetS) has a large clinical population nowadays, usually due to excessive energy intake and lack of exercise. During MetS, excess nutrients stress the mitochondria, resulting in relative hypoxia in tissues and organs, even when blood supply is not interrupted or reduced, making mitochondrial dysfunction a central pathogenesis of cardiovascular disease in the MetS. Sodium-glucose cotransporter 2 inhibitors were designed as a hyperglycemic drug that acts on the renal tubules to block sugar reabsorption in primary urine. Recently they have been shown to have anti-inflammatory and other protective effects on cardiomyocytes in MetS, and have also been recommended in the latest heart failure guidelines as a routine therapy. Among these inhibitors, empagliflozin shows better clinical promise due to less influence from glomerular filtration rate. This review focuses on the mitochondrial mechanisms of empagliflozin, which underlie the anti-inflammatory and recover cellular functions in MetS cardiomyocytes, including stabilizing calcium concentration, mediating metabolic reprogramming, maintaining homeostasis of mitochondrial quantity and quality, stable mitochondrial DNA copy number, and repairing damaged mitochondrial DNA.
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Compostos Benzidrílicos , Glucosídeos , Síndrome Metabólica , Miócitos Cardíacos , Inibidores do Transportador 2 de Sódio-Glicose , Animais , Humanos , Compostos Benzidrílicos/farmacologia , Cardiotônicos/farmacologia , Cardiotônicos/uso terapêutico , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Cálcio/metabolismo , Homeostase , Variações do Número de Cópias de DNARESUMO
BACKGROUND: Airway remodelling plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Epithelial-mesenchymal transition (EMT) is a significant process during the occurrence of airway remodelling. Increasing evidence suggests that glucose transporter 3 (GLUT3) is involved in the epithelial mesenchymal transition (EMT) process of various diseases. However, the role of GLUT3 in EMT in the airway epithelial cells of COPD patients remains unclear. METHODS: We detected the levels of GLUT3 in the peripheral lung tissue of COPD patients and cigarette smoke (CS)-exposed mice. Two Gene Expression Omnibus GEO datasets were utilised to analyse GLUT3 gene expression profiles in COPD. Western blot and immunofluorescence were used to detect GLUT3 expression. In addition, we used the AAV9-GLUT3 inhibitor to reduce GLUT3 expression in the mice model. Masson's staining and lung function measurement were used detect the collagen deposition and penh in the mice. A cell study was performed to confirm the regulatory effect of GLUT3. Inhibition of GLUT3 expression with siRNA, Western blot, and immunofluorescence were used to detect the expression of E-cadherin, N-cadherin, vimentin, p65, and ZEB1. RESULTS: Based on the GEO data set analysis, GLUT3 expression in COPD patients was higher than in non-smokers. Moreover, GLUT3 was highly expressed in COPD patients, CS exposed mice, and BEAS-2B cells treated with CS extract (CSE). Further research revealed that down-regulation of GLUT3 significantly alleviated airway remodelling in vivo and in vitro. Lung function measurement showed that GLUT3 reduction reduced airway resistance in experimental COPD mice. Mechanistically, our study showed that reduction of GLUT3 inhibited CSE-induced EMT by down-regulating the NF-κB/ZEB1 pathway. CONCLUSION: We demonstrate that CS enhances the expression of GLUT3 in COPD and further confirm that GLUT3 may regulate airway remodelling in COPD through the NF-κB/ZEB1 pathway; these findings have potential value in the diagnosis and treatment of COPD. The down-regulation of GLUT3 significantly alleviated airway remodelling and reduced airway resistance in vivo. Our observations uncover a key role of GLUT3 in modulating airway remodelling and shed light on the development of GLUT3-targeted therapeutics for COPD.
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Fumar Cigarros , Doença Pulmonar Obstrutiva Crônica , Humanos , Camundongos , Animais , NF-kappa B/metabolismo , Remodelação das Vias Aéreas , Fumar Cigarros/efeitos adversos , Transportador de Glucose Tipo 3/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Transição Epitelial-Mesenquimal , Células Epiteliais/metabolismo , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genéticaRESUMO
Elastomeric polymers have gained significant attention in the field of flexible electronics. The investigation of the electro-mechanical response relationship between polymer structure and flexible electronics is in increasing demand. This study investigated the factors that affect the performance of flexible capacitive pressure sensors using the finite element method (FEM). The sensor employed a porous elastomeric polymer as the dielectric layer. The results indicate that the sensor's performance was influenced by both the structural and material characteristics of the porous elastomeric polymer. In terms of structural characteristics, porosity was the primary factor influencing the performance of sensors. At a porosity of 76%, the sensitivity was 42 times higher than at a porosity of 1%. In terms of material properties, Young's modulus played a crucial role in influencing the performance of the sensors. In particular, the influence on the sensor became more pronounced when Young's modulus was less than 1 MPa. Furthermore, porous polydimethylsiloxane (PDMS) with porosities of 34%, 47%, 67%, and 72% was fabricated as the dielectric layer for the sensor using the thermal expansion microsphere method, followed by sensing capability testing. The results indicate that the sensor's sensitivity was noticeably influenced within the high porosity range, aligning with the trend observed in the simulation.
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Background: Camrelizumab has been demonstrated to be a feasible treatment option for locally advanced esophageal squamous cell carcinoma (ESCC) when combined with neoadjuvant chemotherapy. This trial was conducted to investigate the effectiveness and safety of camrelizumab-containing neoadjuvant therapy in patients with ESCC in daily practice. Methods: This prospective multicenter observational cohort study was conducted at 13 tertiary hospitals in Southeast China. Patients with histologically or cytologically confirmed ESCC [clinical tumor-node-metastasis (cTNM) stage I-IVA] who had received at least one dose of camrelizumab-containing neoadjuvant therapy were eligible for inclusion. Results: Between June 1, 2020 and July 13, 2022, 255 patients were enrolled and included. The median age was 64 (range, 27 to 82) years. Most participants were male (82.0%) and had clinical stage III-IVA diseases (82.4%). A total of 169 (66.3%) participants underwent surgical resection; 146 (86.4%) achieved R0 resection, and 36 (21.3%) achieved pathological complete response (pCR). Grades 3-5 adverse events (AEs) were experienced by 14.5% of participants. Reactive cutaneous capillary endothelial proliferation occurred in 100 (39.2%) of participants and all were grade 1 or 2. Conclusions: Camrelizumab-containing neoadjuvant therapy has acceptable effectiveness and safety profiles in real-life ESCC patients.
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Background: This study aims to investigate the association between immune cells and the development of COPD, while providing a new method for the diagnosis of COPD according to the changes in immune microenvironment. Methods: In this study, the "CIBERSORT" algorithm was used to estimate the tissue infiltration of 22 types of immune cells in GSE20257 and GSE10006. The "limma" package was used for differentially expressed analysis. The key modules associated with vital immune cells were identified using WGCNA. GO and KEGG enrichment analysis revealed the biological functions of the candidate genes. Ultimately, a novel diagnostic prediction model was constructed via machine learning methods and multivariate logistic regression analysis based on GSE20257. Furthermore, we examined the stability of the model on one internal test set (GSE10006), three external test sets (GSE8545, GSE57148 and GSE76925), one single-cell transcriptome dataset (GSE167295), macrophages (THP-M cells) and lung tissue from COPD patients. Results: M0 macrophages (AUC > 0.7 in GSE20257 and GSE10006) were considered as the most important immune cells through exploring the immune microenvironment landscapes in COPD patients and healthy controls. The differentially expressed genes from GSE20257 and GSE10006 were divided into six and five modules via WGCNA, respectively. The green module in GSE20257 (cor = 0.41, P < 0.001) and the brown module in GSE10006 (cor = 0.67, P < 0.001) were highly correlated with M0 macrophages and were selected as key modules. Forty-one intersected genes obtained from two modules were primarily involved in regulation of cytokine production, regulation of innate immune response, specific granule, phagosome, lysosome, ferroptosis, and other biological processes. On the basis of the candidate genetic markers further characterized via the "Boruta" and "LASSO" algorithm for COPD, a diagnostic model comprising CLEC5A, FTL and SLC2A3 was constructed, which could accurately distinguish COPD patients from healthy controls in multiple datasets. GSE20257 as the training set has an AUC of 0.916. The AUCs of the internal test set and three external test sets were 0.873, 0.932, 0.675 and 0.688, respectively. Single-cell sequencing analysis suggested that CLEC5A, FTL and SLC2A3 were expressed in macrophages from COPD patients. The expressions of CLEC5A, FTL and SLC2A3 were up-regulated in THP-M cells and lung tissue from COPD patients. Conclusion: According to the variations of immune microenvironment in COPD patients, we constructed and validated a novel macrophage M0-associated diagnostic model with satisfactory predictive value. CLEC5A, FTL and SLC2A3 are expected to be promising targets of immunotherapy in COPD.
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Introduction: Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD), which can worsen the prognosis and increase the mortality of COPD patients. Circular RNA (circRNA) has been discovered to participate in the occurrence and progression of PH in COPD and may have significant prospects for advanced diagnostics and prognosis evaluation. However, the expression profile of circRNAs in human lung tissues with definite diagnosis of COPD-PH remains to be further explored and validated. Methods: Twelve human lung tissue samples (6 each from COPD-PH and control groups) were collected and subjected to high-throughput sequencing. QRT-PCR was performed to validate the differential expression levels of the top 10 dysregulated circRNAs in patients' plasma samples, HPAECs and HPASMCs. Functional and pathway enrichment analysis on target genes was performed to explore the potential functions and pathways of those circRNAs. Hub genes obtained after conducting bioinformatics analysis on the predicted target mRNAs were verified by qRT-PCR in HPAECs and HPASMCs, and then we selected VCAN as a potential key gene involved in the pathogenesis of COPD-PH for immunohistochemistry validation in lung tissue. Results: A total of 136 circRNAs (39 up-regulated and 97 down-regulated) were differentially expressed between the two groups. Following qRT-PCR validation, two circRNAs (hsa_circ_0007608 and hsa_circ_0064656) were believed to be involved in the pathogenesis. GO and KEGG pathway analysis suggested that these two DECs were mainly related to the celluar proliferation, migration and EndMT. PPI network revealed 11 pairs of key mRNAs. VCAM1, VCAN and THBS1, three hub mRNAs with the highest reliability among all, were validated and proven to be up-regulated in COPD-PH. We innovatively found that VCAN may be involved in COPD-PH. Conclusion: This study identified the functional circRNAs, providing insights into the molecular mechanisms and predictions of COPD-PH, and may provide potential diagnostic biomarkers or therapeutic targets for COPD-PH.
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Hipertensão Pulmonar , Hipertensão , MicroRNAs , Doença Pulmonar Obstrutiva Crônica , Humanos , RNA Circular/genética , Reprodutibilidade dos Testes , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Biomarcadores , MicroRNAs/genéticaRESUMO
Background: Proteasome 26S subunit ATPase 2 (PSMC2) is a part of the 19S regulatory complex, which catalyzes the unfolding and transport of substrates into the 20S proteasome. Our previous research demonstrated that PSMC2 participates in the tumorigenesis and progression of pancreatic cancer (PC). However, no systematic analysis has been conducted to conclude its expression pattern and correlation with tumor immunity. Aim: To investigate the expression level of PSMC2 in PC, its prognostic value and its relationship with tumor immunity. Methods: In numerous public and internal cohorts, the expression, prognostic significance, and immunological connections of PSMC2 in PC were investigated. Additionally, using data from The Cancer Genome Atlas (TCGA), a pan-cancer analysis was carried out to examine PSMC2's immunological assocaition, and the predictive power of PSMC2 for immunotherapy was also evaluated in numerous public cohorts. Results: PSMC2 was overexpressed in tumor tissues and linked to unfavorable prognosis in PC. PSMC2 was not only positively correlated with TIICs, also positively correlated with immune checkpoints in PC. In addition to PC, PSMC2 was expected to be an indicator of high immunogenicity in most cancer types. Importantly, PSMC2 could predict the immunotherapeutic responses in various cancer types, including urothelial carcinoma and breast cancer. Conclusion: From PC to pan-cancer analysis, we report that PSMC2 is a novel prognostic biomarker in multiple cancer types. PSMC2 is related to the immuno-hot phenotype and predicts the outcome of immunotherapy. Therefore, the current study emphasizes that cancer patients with high PMSC2 expression should actively receive immunotherapy to improve their prognosis.
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Lung cancer, with non-small cell lung cancer (NSCLC) being the main subtype, is the leading cause of cancer death worldwide, which is mainly due to the cancer metastasis. Glutathione peroxidase 2 (GPX2), an antioxidant enzyme, is involved in tumor progression and metastasis. Nevertheless, the role of GPX2 in NSCLC metastasis has not been clarified. In this study, we found that GPX2 expression was elevated in NSCLC tissues and high GPX2 expression was correlated with poor prognosis in patients with NSCLC. In addtion, GPX2 expression was related to the patient's clinicopathological features, including lymph node metastasis, tumor size, and TNM stage. Overexpression of GPX2 promoted epithelial-mesenchymal transition (EMT), migration, and invasion of NSCLC cells in vitro. Knockdown of GPX2 showed the opposite effects in vitro and inhibited the metastasis of NSCLC cells in nude mice. Furthermore, GPX2 reduced reactive oxygen species (ROS) accumulation and activated the PI3K/AKT/mTOR/Snail signaling axis. Therefore, our results indicate that GPX2 promotes EMT and metastasis of NSCLC cells by activating the PI3K/AKT/mTOR/Snail signaling axis via the removal of ROS. GPX2 may be an effective diagnostic and prognostic biomarker for NSCLC.
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Background: Obesity is a common and highly convincing risk factor for many cancers, including liver cancer. Sex disparities in the body composition and regulatory mechanisms involved in energy homeostasis may contribute to the difference in the incidence of cancer. However, evidence on the gender-specific association between body composition and liver cancer incidence is limited. We performed this study to investigate the linear and non-linear associations of body composition with liver cancer risk by gender. Materials and methods: This prospective analysis included 4,75,659 participants free of cancer, based on the UK Biobank. We used Cox proportional hazard models to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) after adjusting for potential confounders. Restricted cubic spline was performed to investigate the potential non-linear associations. Results: During a median follow-up, 275 cases (174 male patients and 101 female patients) of liver cancer were identified. Male patients in the highest body fat percentage group are more likely to develop liver cancer (HR = 1.89, 95% CI: 1.17-3.03) compared with those in the lowest group. The one-unit increase of whole-body fat mass, arm fat mass, and trunk fat mass was associated with 1.03-, 1.14-, and 1.05-fold increased risk of liver cancer in male subjects, respectively. U-shaped associations of body composition with liver cancer risk were observed in the female subjects. Both high and low levels of whole-body fat-free mass, particularly in the arm and trunk, were associated with an increased risk of liver cancer. Conclusion: This study found a gender-specific association between body composition and liver cancer risk and provided evidence for individualized weight management for the prevention of liver cancer.
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Background: M2 polarized macrophages are involved in the occurrence and development of emphysema in COPD patients. However, the molecular mechanism of M2 macrophage polarization is still unclear. This study investigated the molecular mechanism of let-7 differentially expressed in bronchial epithelial cells of COPD patients participating in COPD emphysema by regulating the expression of IL-6 and inducing M2 polarization of alveolar macrophages (AM). Materials and Methods: We measured let-7c expression in human lung tissue, serum and the lung tissue of cigarette smoke (CS)-exposed mice by qRTâPCR. We observed the M1/M2 AM polarization in the lungs of COPD patients and COPD model mice by immunofluorescence analysis. Western blotting was used to determine the expression of MMP9/12 in the lung tissue of COPD patients and CS-exposed mice. An in vitro experiment was performed to determine the molecular mechanism of let-7c-induced macrophage polarization. Results: Let-7c expression was downregulated in COPD patients, CS-exposed mice, and CS extract (CSE)-treated human bronchial epithelial (HBE) cells. AMs in COPD patients and CS-exposed mice were dominated by the M2 type, and the release of MMP9/12 was increased. In vitro, the transfection of mimics overexpressing let-7 or the use of tocilizumab to block signal transduction between HBE cells and macrophages inhibited the IL-6/STAT3 pathway. M2 macrophage polarization was inhibited, and MMP9/12 release was reduced. Conclusion: Our results indicate that CS decreased let-7c expression in HBE cells, and M2 AM polarization was dominant in COPD. In HBE cells, let-7c could inhibit M2 polarization of AMs through the IL-6/STAT3 pathway, providing potential diagnostic and therapeutic value for slowing COPD emphysema.
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Enfisema , MicroRNAs , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Animais , Humanos , Camundongos , Interleucina-6/metabolismo , Macrófagos/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/metabolismo , Enfisema Pulmonar/genética , Enfisema Pulmonar/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , NicotianaRESUMO
Background: Most gastric cancer (GC) patients were diagnosed in the advanced stages without obvious symptoms, which resulted in the increased risk of death. Although the combination therapies have showed survival benefit of patients, there is still urgent need to explore the underlying mechanisms of GC development and potential novel targets for clinical applications. Numerous studies have reported the upregulation of Wnt signaling pathway in human GC, which play important role during GC development and progression. However, the current understanding of Wnt signaling pathway is still limited due to its complexity and contradictory effect on different stages of GC tumor microenvironment. Method: We used The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset to screen Wnt signaling pathway-associated genes by ssGSEA and correlation analysis. Three molecular subtypes were constructed based on a consistent clustering analysis. The key Wnt-related genes were screened through univariate cox analysis, lasso, and stepwise regression. In addition, the Gene Set Enrichment Analysis (GSEA) were performed to explore potential molecular pathways regulated by the Wnt-related gene signatures. ESTIMATE was utilized for evaluating the immune cell populations in GC tumor microenvironment. Results: Three molecular subtypes associated to Wnt were identified, and 7 key Wnt-related genes were screened to establish a predictive RiskScore model. These three molecular subtypes showed significant prognostic differences and distinct functional signaling pathways. We also found the downregulated immune checkpoint expression in the clust1 with good prognosis. The RiskScore model was successfully validated in GSE26942 dataset. Nomogram based on RiskScore and Gender had better prognostic predictive ability. Conclusion: In summary, our study showed that the Wnt-related genes could be used to predict prognosis of GC patients. The risk model we established showed high accuracy and survival prediction capability.
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BACKGROUND: Colonic duplication refers to a spherical or tubular cavity which shows similar properties with the native colon and is attached to the mesenteric side of the alimentary tract. It is the rarest in alimentary tract duplications. Based upon anatomic feature, colonic duplications can be classified as spherical (cystic) or tubular, with the latter being less common (approximately 20%). Symptoms of colonic duplication are dependent on the duplication site and extent, and patient age, etc. Usually, patients with colonic duplication manifest typical intestinal obstruction, potentially accompanied by recurrent dark or bright red bloody stool, varying degrees of anemia-related symptoms, and body wasting. CASE SUMMARY: A young male patient was admitted to our hospital due to recurrent abdominal pain. No definite diagnosis was achieved by computed tomography (CT) or electronic colonoscopy, and the bowel preparation efficacy was suboptimal. Hirschsprung disease was suspected, and thus laparoscopic exploration was performed. An approximately 60-cm-long inverted duplicated colon with severe edema and dilation was identified. It originated from the mesenteric side of the transverse colon and ended in the terminal part of the descending colon with a blind end. The parallel native colon had a thickened colonic wall, became stiff, and was poor in peristalsis. The patient then underwent subtotal colectomy and was discharged 7 d after the surgery. From 3 mo post-surgery to date, the patient had regular bowel movement once daily and a steady increase in body weight. CONCLUSION: Tubular colonic duplication is a rare type of alimentary tract duplication that can be detected by ultrasonography, CT, or magnetic resonance imaging based on the actual clinical situation. Surgical resection of aberrant colon (including the duplicated colonic segment and other potentially involved colonic segments) is the only approach to cure this medical condition.
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The in-depth study of the interplay and cooperation between multiple organelles is an important biological task. Single fluorescent probes for separate visualization of multiple organelles is a desirable molecular tool, but the construction of such a probe is extremely difficult owing to the lack of valid strategies. In this work, utilizing the reversible cyclization reaction and intermolecular π stacking mechanism, a robust fluorescent probe is constructed to discriminatively illuminate lipid droplets (LDs), mitochondria, and lysosomes with blue, green, and red emission colors, respectively. Using the probe, the interplays and cooperation between LDs, mitochondria, and lysosomes are successfully studied, and the critical roles of lysosomes and LDs during mitochondrial fission are successfully revealed. Furthermore, this unique probe reveals the sequential damage of mitochondria and lysosomes during apoptosis through the successive fading of green and red emission. Thereby, the probe enables the discrimination of health state, early apoptosis, and late apoptosis of cells with three different sets of fluorescent signals. Overall, the robust probe is a desirable molecular tool to reveal the interactions between the three organelles, and investigate cell apoptosis and relative areas.
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Corantes Fluorescentes , Organelas , Lisossomos , Mitocôndrias , ApoptoseRESUMO
Heterostructure materials, as newborn electrode materials for rechargeable batteries, are attracting increasing attention due to their robust architectures and superior electrochemical performances. It is widely believed that the inner electric field induced at the interface can improve the electric conductivity and ion diffusion kinetics, thus enhancing the long-term stability and high-rate performance of the batteries. Although much progress is made on heterostructure construction, the performance of the batteries is still far from satisfying the commercial applications. In this work, a new type of SnO2/SnSx (x = 1, 1.5) heterostructure embedded in carbon framework (C@SnO2/SnSx) is constructed via a facile sulfidation process. Compared to a single heterojunction, the multi-heterojunctions generated at SnO2/SnSx interface can induce an intensified built-in electric field, which promotes charge transportation and reaction kinetics of the electrode for Na-ions storage. Upon the sodiation process, the induced intensified electric field drives Na ions from Sn2S3 or SnO2 to SnS, while an inverse transportation of Na ions are accelerated upon the desodation process. As a result, C@SnO2/SnSx exhibits an outstanding reversible capacity of 510 mA h g-1 after 300 cycles at 200 mA g-1.
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Helicobacter pylori (H.pylori) infection caused by gastric mucosal inflammation plays a pivotal role in the progression of gastric diseases. The recruitment and attachment of monocytes to the gastric mucosal epithelium are a major event in the early stages of H. pylori-associated gastric diseases. Everolimus is a mechanistic/mammalian target of rapamycin (mTOR) inhibitor used to prevent tumor growth by inhibiting the PI3K signaling pathway. Here, we examined the pharmacological role of Everolimus against H.pylori-induced damage in gastric epithelial cells. Firstly, we found that Everolimus ameliorated H.pylori-induced oxidative stress by reducing reactive oxygen species (ROS) and malondialdehyde (MDA). Secondly, Everolimus significantly reduced the expressions of the pro-inflammatory cytokines interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and IL-8. Moreover, it decreased the production of the pro-inflammatory chemokines C-X-C motif ligand 1 (CXCL1) and macrophage chemoattractant protein-1 (MCP-1). Importantly, Everolimus suppressed the induction of the adhesion molecule intracellular adhesion molecule-1 (ICAM-1) and the attachment of THP-1 monocytes to gastric epithelial AGS cells. Our data also shows that Everolimus inhibited the activation of the NF-κB signaling pathway. Therefore, we conclude that Everolimus could protect gastric epithelial cells by mitigating H.pylori-induced inflammatory response and the attachment of monocytes to epithelial cells.
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Infecções por Helicobacter , Helicobacter pylori , Células Epiteliais/metabolismo , Everolimo/metabolismo , Everolimo/farmacologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/metabolismo , Helicobacter pylori/metabolismo , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interleucina-8/metabolismo , Fosfatidilinositol 3-Quinases/metabolismoRESUMO
The opening of mitochondrial permeability transition pore (mPTP) plays a fundamental role in cell apoptosis regulation, ischemia-reperfusion injury, and neurodegenerative disorders. However, the molecular tools for detecting mPTP open in cellular native status have not been reported yet. Herein, we de novo designed a robust fluorescent probe mPTP-F to monitor mPTP opening in cellular native status for the first time. The membrane-permeable probe could accumulate into mitochondria and convert to a product poorly permeable to biomembranes, which was trapped in mitochondria to form near-infrared (NIR)-emissive aggregates. After mPTP opening, the product was released from mitochondria through the pore to form green-emissive monomers. Significantly, with mPTP-F, we discovered that formaldehyde, a signaling molecule, could induce mPTP opening. Therefore, the new probe could serve as a desirable molecular tool for the study of ischemia-reperfusion injury, cell apoptosis, and relative areas.
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Poro de Transição de Permeabilidade Mitocondrial , Traumatismo por Reperfusão , Humanos , Mitocôndrias Cardíacas , Proteínas de Transporte da Membrana Mitocondrial , PermeabilidadeRESUMO
RATIONALE: The incidence of pure arterial malformations is relatively low, and few cases have been reported. Only 2 cases with pure arterial malformation have been reported to receive surgery or endovascular treatment. PATIENT CONCERNS: We report 3 cases and review the relevant literatures. The head examinations of the patients suggested the presence of high-density shadows in front of the pons and midbrain, the dilation of the supraclinoid segment of the right internal carotid artery, and moyamoya in the left brain with an aneurysm-like expansion located on the left posterior communicating artery respectively. After admission, head digital subtraction angiography (DSA) was performed. DIAGNOSES: Digital subtraction angiography (DSA) for these 3 patients showed that the left posterior communicating artery, the supraclinoid segment of the right internal carotid artery, and the left posterior communicating artery appeared dilated, tortuous, and spirally elongated. In addition, the lesions in the latter 2 patients were accompanied with local aneurysmal changes. INTERVENTIONS: Two patients were given conservative treatment, and another patient was given endovascular treatment. A head DSA was reviewed 6 months after therapy. OUTCOMES: The prognosis status of the 3 patients was good. Two patients in the conservative treatment group showed no changes in the lesions on head DSA examination. The DSA examination of the third patient indicated that the vascular remodeling of the diseased vessels was good, the blood vessels were unobstructed, and the aneurysms had disappeared. LESSONS: Pure arterial malformations mostly occur in young women and may involve any blood vessels in the brain. It can be accompanied with local aneurysms and calcification. The patients are often given conservative treatment but need to be reviewed regularly. However, it is beneficial to give endovascular treatment to the patients with local aneurysms.
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Aneurisma/diagnóstico por imagem , Angiografia Digital/métodos , Mesencéfalo/diagnóstico por imagem , Doença de Moyamoya/diagnóstico por imagem , Ponte/diagnóstico por imagem , Adolescente , Adulto , Aneurisma/patologia , Aneurisma/terapia , Vasos Sanguíneos/anormalidades , Artéria Carótida Interna/anormalidades , Artéria Carótida Interna/diagnóstico por imagem , Angiografia Cerebral/métodos , Criança , Pré-Escolar , Tratamento Conservador/métodos , Embolização Terapêutica/métodos , Procedimentos Endovasculares/métodos , Feminino , Humanos , Lactente , Doenças Arteriais Intracranianas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Masculino , Mesencéfalo/irrigação sanguínea , Mesencéfalo/patologia , Pessoa de Meia-Idade , Doença de Moyamoya/terapia , Ponte/irrigação sanguínea , Ponte/patologia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Adulto JovemRESUMO
The primitive trigeminal artery is an anastomotic vessel of the carotid-basilar artery system that occurs only transiently during the embryonic period. Persistent primitive trigeminal artery occurs in approximately 0.1-0.6% of the population. Here, we report the case of a 60-year-old woman with Fisher II grade subarachnoid haemorrhage. Computed tomography angiography demonstrated a lateral, Saltzman type I persistent primitive trigeminal artery with three cerebral aneurysms, including one anterior communicating artery aneurysm, one suspicious right anterior choroidal artery aneurysm and one distal basilar artery aneurysm supplied by the persistent primitive trigeminal artery. All three aneurysms were treated with coil embolisation. At the 8-month follow-up, the anterior communicating artery aneurysm had a neck remnant, the other two aneurysms exhibited complete occlusion. Persistent primitive trigeminal artery with multiple cerebral aneurysms is extremely rare, and only seven cases of persistent primitive trigeminal artery with multiple cerebral aneurysms have previously been reported in publications that included information on treatment. Most aneurysms were treated by open surgery. This is the first report of coil embolisation treatment of multiple aneurysms in persistent primitive trigeminal artery patients with follow-up results, and provides relevant and valuable information about the persistent primitive trigeminal artery and the endovascular treatment of multiple aneurysms in persistent primitive trigeminal artery patients.
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Artérias Cerebrais/anormalidades , Embolização Terapêutica/métodos , Aneurisma Intracraniano/terapia , Angiografia Digital , Angiografia Cerebral , Angiografia por Tomografia Computadorizada , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
A silver-catalyzed three-component difunctionalization of alkenes by using 2-amino- and 2-hydroxy-1,4-naphthoquinone derivatives as the radical-trapping reagents is reported. Various alkenes and 2-amino- or 2-hydroxy-1,4-naphthoquinones with diverse structures and electronic properties are applied to the reaction. The methodology provides an alternative method to access CF3-functionalized alkyl-substituted quinone derivatives which are prevalent structures in bioactive molecules. Furthermore, a plausible radical pathway for the reaction is proposed based on results from primary control experiments.