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Achieving diffraction-limited performance in fourth-generation synchrotron radiation sources demands monochromator crystals that can preserve the wavefront across an unprecedented extensive range. There is an urgent need for techniques of absolute crystal diffraction wavefront measurement. At the Beijing Synchrotron Radiation Facility (BSRF), a novel edge scan wavefront metrology technique has been developed. This technique employs a double-edge tracking method, making diffraction-limited level absolute crystal diffraction wavefront measurement a reality. The results demonstrate an equivalent diffraction surface slope error below 70â nrad (corresponding to a wavefront phase error of 4.57% λ) r.m.s. within a nearly 6â mm range for a flat crystal in the crystal surface coordinate. The double-edge structure contributes to exceptional measurement precision for slope error reproducibility, achieving levels below 15â nrad (phase error reproducibility < λ/100) even at a first-generation synchrotron radiation source. Currently, the measurement termed double-edge scan (DES) has already been regarded as a critical feedback mechanism in the fabrication of next-generation crystals.
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A novel insertion device is introduced, designated as the Mango wiggler, designed for synchrotron radiation (SR) imaging that provides a large field of view. This innovative device is constructed from two orthogonal planar wigglers with a small difference in their period lengths, eliciting the phase difference of the magnetic fields to incrementally transitions from 0 to π/2. Such a configuration enlarges the vertical divergence of the light source, as with the horizontal divergence. The appellation `Mango wiggler' derives from the distinctive mango-shaped contour of its radiation field. A comprehensive suite of theoretical analyses and simulations has been executed to elucidate the radiation properties of the Mango wiggler, employing SPECTRA and Mathematica as calculation tools. In conjunction with the ongoing construction of the High Energy Photon Source in Beijing a practical Mango wiggler device has been fabricated for utilization in SR imaging applications. Theoretical analyses were applied to this particular Mango wiggler to yield several theoretical conclusions, and several simulations were performed according to the measured magnetic field results.
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We consider an SEIR epidemic model on a network also allowing random contacts, where recovered individuals could either recover naturally or be diagnosed. Upon diagnosis, manual contact tracing is triggered such that each infected network contact is reported, tested and isolated with some probability and after a random delay. Additionally, digital tracing (based on a tracing app) is triggered if the diagnosed individual is an app-user, and then all of its app-using infectees are immediately notified and isolated. The early phase of the epidemic with manual and/or digital tracing is approximated by different multi-type branching processes, and three respective reproduction numbers are derived. The effectiveness of both contact tracing mechanisms is numerically quantified through the reduction of the reproduction number. This shows that app-using fraction plays an essential role in the overall effectiveness of contact tracing. The relative effectiveness of manual tracing compared to digital tracing increases if: more of the transmission occurs on the network, when the tracing delay is shortened, and when the network degree distribution is heavy-tailed. For realistic values, the combined tracing case can reduce R0 by 20%-30%, so other preventive measures are needed to reduce the reproduction number down to 1.2-1.4 for contact tracing to make it successful in avoiding big outbreaks.
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Número Básico de Reprodução , Busca de Comunicante , Epidemias , Busca de Comunicante/métodos , Humanos , Epidemias/prevenção & controle , Epidemias/estatística & dados numéricos , Número Básico de Reprodução/estatística & dados numéricos , Modelos Epidemiológicos , Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/transmissãoRESUMO
Breast cancer is the leading cause of cancer-related deaths in women worldwide, with Hormone Receptor (HR)+ being the predominant subtype. Tamoxifen (TAM) serves as the primary treatment for HR+ breast cancer. However, drug resistance often leads to recurrence, underscoring the need to develop new therapies to enhance patient quality of life and reduce recurrence rates. Artemisinin (ART) has demonstrated efficacy in inhibiting the growth of drug-resistant cells, positioning art as a viable option for counteracting endocrine resistance. This study explored the interaction between artemisinin and tamoxifen through a combined approach of bioinformatics analysis and experimental validation. Five characterized genes (ar, cdkn1a, erbb2, esr1, hsp90aa1) and seven drug-disease crossover genes (cyp2e1, rorc, mapk10, glp1r, egfr, pgr, mgll) were identified using WGCNA crossover analysis. Subsequent functional enrichment analyses were conducted. Our findings confirm a significant correlation between key cluster gene expression and immune cell infiltration in tamoxifen-resistant and -sensitized patients. scRNA-seq analysis revealed high expression of key cluster genes in epithelial cells, suggesting artemisinin's specific impact on tumor cells in estrogen receptor (ER)-positive BC tissues. Molecular target docking and in vitro experiments with artemisinin on LCC9 cells demonstrated a reversal effect in reducing migratory and drug resistance of drug-resistant cells by modulating relevant drug resistance genes. These results indicate that artemisinin could potentially reverse tamoxifen resistance in ER-positive breast cancer.
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Artemisininas , Neoplasias da Mama , Biologia Computacional , Resistencia a Medicamentos Antineoplásicos , Receptores de Estrogênio , Tamoxifeno , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico , Humanos , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Resistencia a Medicamentos Antineoplásicos/genética , Biologia Computacional/métodos , Receptores de Estrogênio/metabolismo , Antineoplásicos Hormonais/farmacologia , Antineoplásicos Hormonais/uso terapêutico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Linhagem Celular Tumoral , Simulação de Acoplamento Molecular , Proliferação de Células/efeitos dos fármacosRESUMO
The excessive elevation of angiotensin II (ANG II) is closely associated with the occurrence and development of aortic dissection (AD)-related acute lung injury (ALI), through its binding to angiotensin II receptor type I (AT1R). MiR-145-5p is a noncoding RNA that can be involved in a variety of cellular physiopathological processes. Transfection with miR-145-5p was found to downregulated the expression of A disintegrin and metalloprotease 17 (ADAM17) and reduced the levels of angiotensin-converting enzyme 2 (ACE2) in lung tissue, while concurrently increasing plasma ACE2 levels in the AD combined with ALI mice. ADAM17 was proved to be a target of miR-145-5p. Transfection with miR-145-5p decreased the shedding of ACE2 and alleviated the inflammatory response induced by ANG II through targeting ADAM17 and inhibiting the AT1R/ADAM17 pathway in A549 cells. In conclusion, our present study demonstrates the role and mechanism of miR-145-5p in alleviating ANG II-induced acute lung injury, providing a new insight into miRNA therapy for reducing lung injury in patients with aortic dissection.
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Lesão Pulmonar Aguda , Dissecção Aórtica , MicroRNAs , Humanos , Animais , Camundongos , Enzima de Conversão de Angiotensina 2/genética , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Células Epiteliais Alveolares/metabolismo , Proteína ADAM17/genética , Angiotensina II/farmacologia , Angiotensina II/metabolismo , MicroRNAs/genética , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/metabolismoRESUMO
Background: Ovarian cancer (OC) has the highest mortality rate among gynecological malignancies. Current treatment options are limited and ineffective, prompting the discovery of reliable biomarkers. Exosome lncRNAs, carrying genetic information, are promising new markers. Previous studies only focused on exosome-related genes and employed the Lasso algorithm to construct prediction models, which are not robust. Methods: 420 OC patients from the TCGA datasets were divided into training and validation datasets. The GSE102037 dataset was used for external validation. LncRNAs associated with exosome-related genes were selected using Pearson analysis. Univariate COX regression analysis was used to filter prognosis-related lncRNAs. The overlapping lncRNAs were identified as candidate lncRNAs for machine learning. Based on 10 machine learning algorithms and 117 algorithm combinations, the optimal predictor combinations were selected according to the C index. The exosome-related LncRNA Signature (ERLS) model was constructed using multivariate COX regression. Based on the median risk score of the training datasets, the patients were divided into high- and low-risk groups. Kaplan-Meier survival analysis, the time-dependent ROC, immune cell infiltration, immunotherapy response, and immune checkpoints were analyzed. Results: 64 lncRNAs were subjected to a machine-learning process. Based on the stepCox (forward) combined Ridge algorithm, 20 lncRNA were selected to construct the ERLS model. Kaplan-Meier survival analysis showed that the high-risk group had a lower survival rate. The area under the curve (AUC) in predicting OS at 1, 3, and 5 years were 0.758, 0.816, and 0.827 in the entire TCGA cohort. xCell and ssGSEA analysis showed that the low-risk group had higher immune cell infiltration, which may contribute to the activation of cytolytic activity, inflammation promotion, and T-cell co-stimulation pathways. The low-risk group had higher expression levels of PDL1, CTLA4, and higher TMB. The ERLS model can predict response to anti-PD1 and anti-CTLA4 therapy. Patients with low expression of PDL1 or high expression of CTLA4 and low ERLS exhibited significantly better survival prospects, whereas patients with high ERLS and low levels of PDL1 or CTLA4 exhibited the poorest outcomes. Conclusion: Our study constructed an ERLS model that can predict prognostic risk and immunotherapy response, optimizing clinical management for OC patients.
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Exossomos , Neoplasias Ovarianas , RNA Longo não Codificante , Humanos , Feminino , RNA Longo não Codificante/genética , Antígeno CTLA-4 , Exossomos/genética , Prognóstico , Biomarcadores , Imunoterapia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/terapiaRESUMO
Epidemiological studies have reported a positive association between chronic inflammation and cancer risk. However, the causal association between chronic inflammation and breast cancer (BC) risk remains unclear. Here, we performed a Mendelian randomization study to investigate the etiological role of chronic inflammation in BC risk. We acquired data regarding C-reactive protein (CRP), interleukin (IL)-1a, IL-1b, and IL-6 expression and BC related to single nucleotide polymorphisms (SNPs) from two larger consortia (the genome-wide association studies and the Breast Cancer Association Consortium). Next, we conducted the two-sample Mendelian randomization study to investigate the relationship of the abovementioned inflammatory factors with the incidence of BC. We found that genetically predicted CRP, IL-6, and IL-1a levels did not increase BC incidence (odds ratio (OR)CRP 1.06, 95% confidence interval (CI) 0.98-1.12, P = 0.2059, ORIL-6 1.05, 95% CI 0.95-1.16, P = 0.3297 and ORIL-1a 1.01, 95% CI 0.99-1.03, P = 0.2167). However, in subgroup analysis, genetically predicted IL-1b levels increased ER + BC incidence (OR 1.15, 95% CI 1.03-1.27, P = 0.0088). Our study suggested that genetically predicted IL-1b levels were found to increase ER + BC susceptibility. However, due to the support of only one SNP, heterogeneity and pleiotropy tests cannot be performed, which deserves further research.
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Neoplasias Inflamatórias Mamárias , Interleucina-1alfa , Humanos , Interleucina-1beta , Proteína C-Reativa , Interleucina-6 , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , InflamaçãoRESUMO
Excessive or uncontrolled mitophagy may result in a drastic shortage of healthy mitochondrial for ATP supply after reperfusion, leading to irreversible myocardial damage. Melatonin, a hormone produced by the pineal gland, has been proven to ameliorate myocardial ischemia-reperfusion (I/R) injury via regulating mitophagy. However, its underlying mechanism has not been fully elucidated. The present study focused on the role of mitophagy in the cardioprotective effects of melatonin by using the myocardial I/R rat model. The rats were pretreated with or without the apelin inhibitor ML221, the sirtuin 3 (SIRT3) inhibitor 3-TYP and then subjected to I/R injury, with melatonin administrated 10 min before reperfusion. The effects of melatonin on myocardial infarct size, biomarkers of myocardial injury, oxidative stress, and mitochondrial function were detected, and the expression of apelin, SIRT3, and mitophagy-related proteins were also measured. Excessive mitophagy was activated after I/R injury and was correlated with oxidative stress and mitochondrial dysfunction. Melatonin pretreatment ameliorated myocardial injury by decreasing oxidative stress, restoring mitochondrial function, and inhibiting excessive mitophagy. However, ML221 or 3-TYP disrupted these beneficial effects of melatonin on I/R injury. Taken together, these results suggest that melatonin pretreatment ameliorates myocardial I/R injury through regulating the apelin/SIRT3 pathway to inhibit excessive mitophagy.
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Melatonina , Traumatismo por Reperfusão Miocárdica , Traumatismo por Reperfusão , Sirtuína 3 , Ratos , Animais , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Traumatismo por Reperfusão Miocárdica/metabolismo , Sirtuína 3/metabolismo , Melatonina/farmacologia , Melatonina/uso terapêutico , Melatonina/metabolismo , Mitofagia , ApelinaRESUMO
BACKGROUND: Emergence agitation (EA) is a prevalent complication in children following general anesthesia. Several studies have assessed the relationship between melatonin or its analogs and the incidence of pediatric EA, yielding conflicting results. This meta-analysis aims to assess the effects of premedication with melatonin or its analogs on preventing EA in children after general anesthesia. METHODS: PubMed, EMBASE, the Cochrane Library, ProQuest Dissertations & Theses Global, Web of Science, CNKI, Wanfang Data, clinicaltrials.gov, and WHO International Clinical Trials Registry Platform were searched until 25 November 2022. We included randomized controlled trials that assessed EA in patients less than 18 years old who underwent general anesthesia. We excluded studies that did not use a specific evaluation to assess EA. RESULTS: Nine studies (951 participants) were included in this systematic review. Melatonin significantly reduced the incidence of EA compared with placebos (risk ratio 0.40, 95% CI 0.26 to 0.61, P < 0.01) and midazolam (risk ratio 0.48, 95% CI 0.32 to 0.73, P < 0.01). Dexmedetomidine remarkably decreased the incidence of EA compared with melatonin (risk ratio 2.04, 95% CI 1.11 to 3.73, P = 0.02). CONCLUSIONS: Melatonin premedication significantly decreases the incidence of EA compared with placebos and midazolam. Dexmedetomidine premedication has a stronger effect than melatonin in preventing EA. Nevertheless, further studies are warranted to reinforce and validate the conclusion on the efficacy of melatonin premedication in mitigating EA in pediatric patients.
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Dexmedetomidina , Delírio do Despertar , Melatonina , Éteres Metílicos , Criança , Humanos , Adolescente , Midazolam , Dexmedetomidina/uso terapêutico , Delírio do Despertar/prevenção & controle , Delírio do Despertar/tratamento farmacológico , Melatonina/uso terapêutico , Sevoflurano , Pré-MedicaçãoRESUMO
Ferroptosis, a regulated form of cell death, is characterized by iron-dependent lipid peroxidation leading to oxidative damage to cell membranes. Cell sensitivity to ferroptosis is influenced by factors such as iron overload, lipid metabolism, and the regulation of the antioxidant system. Melatonin, with its demonstrated capacity to chelate iron, modulate iron metabolism proteins, regulate lipid peroxidation, and regulate antioxidant systems, has promise as a potential therapeutic agent in mediating ferroptosis. The availability of approved drugs targeting ferroptosis is limited; therefore, melatonin is a candidate for broad application due to its safety and efficacy in attenuating ferroptosis in noncancerous diseases. Melatonin has been demonstrated to attenuate ferroptosis in cellular and animal models of noncancerous diseases, showcasing effectiveness in organs such as the heart, brain, lung, liver, kidney, and bone. This review outlines the molecular mechanisms of ferroptosis, investigates melatonin's potential effects on ferroptosis, and discusses melatonin's therapeutic potential as a promising intervention against diseases associated with ferroptosis. Through this discourse, we aim to lay a strong foundation for developing melatonin as a therapeutic strategy to modulate ferroptosis in a variety of disease contexts.
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Ferroptose , Melatonina , Animais , Melatonina/farmacologia , Melatonina/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Ferro/metabolismo , Morte Celular , Peroxidação de LipídeosRESUMO
BACKGROUND: The treatment of triple-negative breast cancer (TNBC) is one of the main focuses and key difficulties because of its heterogeneity, and the source of this heterogeneity is unclear. METHODS: Single-cell RNA (scRNA) and transcriptomics data of TNBC and normal breast samples were retrieved from Gene Expression Omnibus (GEO) database and TCGA-BRCA database. These cells were clustered using the t-SNE and UMAP method, and the marker genes for each cluster were found. We annotated the clusters using the published literature, CellMarker database and "SingleR" R package. RESULTS: A total of 1535 cells and 21785 genes from 6 TNBC patients and 2068 cells and 15868 genes from 3 normal breast tissues were used for downstream analyses. The scRNA data were divided into 14 clusters labeled into 8 cell types, including epithelial cells, immunocytes, CAFs/fibroblasts and etc. In the TNBC samples, CAFs were divided into three clusters and labelled as prCAFs, myCAFs and emCAFs, and the marker genes were DCN, FAP and RGS5, respectively. The prCAF subgroup is functionally characterized by promoting proliferation and multi drug resistance; myCAF subgroup is involved in constituting the extracellular matrix and collagen production, matrix composition and collagen production, and the emCAF functionally characterized by energy metabolism. CONCLUSIONS: TNBC has inter- and intra-tumor heterogeneity, and CAF is one of the sources of this heterogeneity. CD74, SASH3, CD2, TAGAP and CCR7 served as significant marker genes with prognostic and therapeutic value.
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Fibroblastos Associados a Câncer , Neoplasias de Mama Triplo Negativas , Humanos , RNA-Seq , Neoplasias de Mama Triplo Negativas/genética , Análise da Expressão Gênica de Célula Única , Colágeno , Microambiente Tumoral/genéticaRESUMO
Hypoxemia is one of the most common complications in patients after Stanford type A acute aortic dissection surgery. The aim of this study was to investigate the association of circulating ANG II level with postoperative hypoxemia and to identify the risk factors for postoperative hypoxemia in Stanford type A acute aortic dissection patients. In this study, 88 patients who underwent Stanford type A acute aortic dissection surgery were enrolled. Postoperative hypoxemia is defined by the oxygenation index (OI). Perioperative clinical data were collected and the serum ANG II and sACE2 levels were measured. The differences in the basic characteristics, intraoperative details, biochemical parameters, laboratory test data and clinical outcomes were compared between the hypoxemia group and the non-hypoxemia group by univariate analysis. Multivariate logistic regression analysis was performed on the variables with P < .1 in univariate analysis or that were considered clinically important to identify risk factors for postoperative hypoxemia. Twenty-five patients (28.4%) were considered to have postoperative hypoxemia (OI ≤ 200 mm Hg). The ANG II concentration remained a risk factor associated with postoperative hypoxemia [OR = 1.018, 95% CI (1.003-1.034), P = .022]. The other risk factors remaining in the logistic regression model were BMI [OR = 1.417, 95% CI (1.159-1.733), P = .001] and cTnI [OR = 1.003, 95% CI (1.000-1.005), P = .032]. Elevated levels of ANG II, BMI and cTnI are risk factors for postoperative hypoxemia in patients with Stanford type A acute aortic dissection.
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Dissecção Aórtica , Humanos , Fatores de Risco , Dissecção Aórtica/cirurgia , Gasometria , Modelos Logísticos , Período Pós-Operatório , Troponina IRESUMO
Background: The treatment of platinum-resistant recurrent ovarian cancer (PROC) is a clinical challenge and a hot topic. Tumor microenvironment (TME) as a key factor promoting ovarian cancer progression. Macrophage is a component of TME, and it has been reported that macrophage phenotype is related to the development of PROC. However, the mechanism underlying macrophage polarization and whether macrophage phenotype can be used as a prognostic indicator of PROC remains unclear. Methods: We used ESTIMATE to calculate the number of immune and stromal components in high-grade serous ovarian cancer (HGSOC) cases from The Cancer Genome Atlas database. The differential expression genes (DEGs) were analyzed via protein-protein interaction network, Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) analysis to reveal major pathways of DEGs. CD80 was selected for survival analysis. IL-6 was selected for gene set enrichment analysis (GSEA). A subsequent cohort study was performed to confirm the correlation of IL-6 expression with macrophage phenotype in peripheral blood and to explore the clinical utility of macrophage phenotype for the prognosis of PROC patients. Results: A total of 993 intersecting genes were identified as candidates for further survival analysis. Further analysis revealed that CD80 expression was positively correlated with the survival of HGSOC patients. The results of GO and KEGG analysis suggested that macrophage polarization could be regulated via chemokine pathway and cytokine-cytokine receptor interaction. GSEA showed that the genes were mainly enriched in IL-6-STAT-3. Correlation analysis for the proportion of tumor infiltration macrophages revealed that M2 was correlated with IL-6. The results of a cohort study demonstrated that the regulation of macrophage phenotype by IL-6 is bidirectional. The high M1% was a protective factor for progression-free survival. Conclusion: Thus, the macrophage phenotype is a prognostic indicator in PROC patients, possibly via a hyperactive IL-6-related pathway, providing an additional clue for the therapeutic intervention of PROC.
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Interleucina-6 , Neoplasias Ovarianas , Feminino , Humanos , Antígeno B7-1 , Carcinoma Epitelial do Ovário , Estudos de Coortes , Interleucina-6/genética , Macrófagos , Neoplasias Ovarianas/genética , Prognóstico , Microambiente Tumoral/genéticaRESUMO
BACKGROUND: While adjuvant endocrine therapy (ET) may decrease the mortality rate of estrogen receptor-positive (ER+) breast cancer (BC), the likelihood of relapse and metastasis due to ET resistance remains high. Cuproptosis is a recently discovered regulated cell death (RCD), whose role in tumors has yet to be elucidated. Thus, there is a need to study its specific regulatory mechanism in resistance to ET in BC, to identify novel therapeutic targets. METHODS: The prognostic cuproptosis-related genes (CRGs) in ER+ BC were filtered by undergoing Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses in TCGA-BRCA, and a CRGs risk signature was constructed using the correlation coefficient. Immune infiltration analysis, immune function analysis, tumor microenvironment (TME) analysis, immune checkpoint analysis, immunotherapy response analysis, drug sensitivity analysis, and pathway activation analysis were carried out among the high- and low-risk groups in turn. The central CRG of cuproptosis in ER+ BC resistance to ET was acquired through the intersection of protein interaction network (PPI) analysis, genes differentially expressed (DEGs) between human BC cells LCC9 and MCF-7 (GSE159968), and CRGs with prognostic significance in TCGA-BRCA ER+ BC. The miRNAs upstream of the core CRGs were predicted based on the intersection of 4 databases, miRDB, RNA22, miRWalk, and RNAlnter. Candidate miRNAs consisted of the intersection of predicted miRNAs and miRNAs differentially expressed in the LCC9 and MCF-7 cell lines (GSE159979). Candidate lncRNAs were the intersection of the differential lncRNAs from the LCC9 and MCF-7 cell lines and the survival-related lncRNAs obtained from a univariate Cox regression analysis. Pearson's correlation analysis was performed between mRNA-miRNA, miRNA-lncRNA, and mRNA-lncRNA expression separately. RESULTS: We constructed A risk signature of 4-CRGs to predict the prognosis of ER+ BC in TCGA-BRCA, a risk score = DLD*0.378 + DBT*0.201 + DLAT*0.380 + ATP7A*0.447 was used as the definition of the formula. There were significant differences between the high- and low-risk groups based on the risk score of 4-CRGs in aspects of immune infiltration, immune function, expression levels of immune checkpoint genes, and signaling pathways. DLD was determined to be the central CRG of cuproptosis in ER+ BC resistance to ET through the intersection of the PPI network analysis, DEGs between LCC9 and MCF-7 and 4-CRGs. Two miRNAs hsa-miR-370-3p and hsa-miR-432-5p were found taking DLD mRNA as a target, and the lncRNA C6orf99 has been hypothesized to be a competitive endogenous RNA that regulates DLD mRNA expression by sponging off hsa-miR-370-3p and hsa-miR-432-5p. CONCLUSION: This study built a prognostic model based on genes related to cuproptosis in ER+ BC. We considered DLD to be the core gene associated with resistance to ET in ER+ BC via copper metabolism. The search for promising therapeutic targets led to the establishment of a cuproptosis-related ceRNA network C6orf99/hsa-miR-370-3p and hsa-miR-432-5p/DLD.
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Apoptose , MicroRNAs , RNA Longo não Codificante , Humanos , Adjuvantes Imunológicos , Terapia Combinada , MicroRNAs/genética , Recidiva Local de Neoplasia , RNA Longo não Codificante/genética , Microambiente Tumoral , CobreRESUMO
BACKGROUND: Platinum-based chemotherapy is one of the most common treatments for many cancers; however, the effect of chemotherapy varies from individual to individual. Excision repair cross complementation group 1 (ERCC1) is widely recognized as a key gene regulating nucleotide excision repair (NER) and is closely associated with platinum response. Many studies have yielded conflicting results regarding whether ERCC1 polymorphisms can affect the response to platinum and overall survival (OS). Therefore, it is necessary to perform a meta-analysis of patients with specific races and cancer types. METHODS: Eight databases (EMBASE, PubMed, Cochrane Library, Chinese National Knowledge Infrastructure, Scopus, VIP, China Biology Medicine disc and Wanfang databases) were searched. Results were expressed in terms of odds ratios (ORs), hazard ratios (HRs) and 95% CIs. RESULTS: In this study, rs11615, rs2298881 and rs3212986 SNPs were studied. In the comparison between CT and TT on the response to platinum, esophageal cancer [I2 = 0%, OR = 6.18, 95% CI(1.89,20.23), P = 0.003] and ovarian cancer [I2 = 0%, OR = 4.94, 95% CI(2.21,11.04), P<0.001] showed that the rs11615 CT genotype predicted a better response. In the comparison between CC and TT, ovarian cancer [I2 = 48.0%, OR = 6.15, 95% CI (2.56,14.29), P<0.001] indicated that the CC genotype predicted a better response. In the meta-analysis of OS, the CC genotype was related to longer OS than TT in ovarian cancer [TT vs CC: I2 = 57.7%, HR = 1.71, 95% CI (1.18, 2.49), P<0.001]. CONCLUSION: The ERCC1 rs11615 polymorphism was related to the response to platinum and OS, but the correlation is based on specific cancer types in the Asian population.
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Neoplasias Ovarianas , Platina , Feminino , Humanos , Platina/uso terapêutico , Genótipo , Polimorfismo de Nucleotídeo Único , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , China , Endonucleases/genética , Proteínas de Ligação a DNA/genéticaRESUMO
Background: Ovarian cancer tends to metastasize to the omentum, which is an organ mainly composed of adipose tissue. Many studies have found that fatty acid metabolism is related to the occurrence and metastasis of cancers. Therefore, it is possible that fatty acid metabolism-related genes (FAMRG) affect the prognosis of ovarian cancer patients. Methods: First, profiles of ovarian cancer and normal ovarian tissue transcriptomes were acquired from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. A LASSO regression predictive model was developed via the "glmnet" R package. The nomogram was created via the "regplot." Gene Set Variation Analysis (GSVA), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO) analyses were conducted to determine the FAMRGs' roles. The percentage of immunocyte infiltration was calculated via CIBERSORT. Using "pRRophetic," the sensitivity of eight regularly used medications and immunotherapy was anticipated. Results: 125 genes were determined as different expression genes (DEGs). Based on RXRA, ECI2, PTGIS, and ACACB, a prognostic model is created and the risk score is calculated. Analyses of univariate and multivariate regressions revealed that the risk score was a distinct prognostic factor (univariate: HR: 2.855, 95% CI: 1.756-4.739, P < 0.001; multivariate: HR: 2.943, 95% CI: 1.800-4.812, P < 0.001). The nomogram demonstrated that it properly predicted the 1-year survival rate. The expression of memory B molecular units, follicular helper T molecular units, regulatory T molecular units, and M1 macrophages differed remarkably between the groups at high and low risk (P < 0.05). Adipocytokine signaling pathways, cancer pathways, and degradation of valine, leucine, and isoleucine vary between high- and low-risk populations. The findings of the GO enrichment revealed that the extracellular matrix and cellular structure were the two most enriched pathways. PTGIS, which is an important gene in fatty acid metabolism, was identified as the hub gene. This result was verified in ovarian cancer and ovarian tissues. The connection between the gene and survival was statistically remarkable (P = 0.015). The pRRophetic algorithm revealed that the low-risk group was more adaptable to cisplatin, doxorubicin, 5-fluorouracil, and etoposide (P < 0.001). Conclusion: PTGIS may be an indicator of prognosis and a possible therapeutic target for the therapy of ovarian cancer patients. The fatty acid metabolism of immune cells may be controlled, which has an indirect effect on cancer cell growth.
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Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/genética , Metabolismo dos Lipídeos , Cisplatino , Doxorrubicina , Ácidos Graxos , Sistema Enzimático do Citocromo P-450 , Dodecenoil-CoA IsomeraseRESUMO
Crystal monochromators are indispensable optical components for the majority of beamlines at synchrotron radiation facilities. Channel-cut monochromators are sometimes chosen to filter monochromatic X-ray beams by virtue of their ultrahigh angular stability. Nevertheless, high-accuracy polishing on the inner diffracting surfaces remains challenging, thus hampering their performance in preserving the coherence or wavefront of the photon beam. Herein, a magnetically controlled chemical-mechanical polishing (MC-CMP) approach has been successfully developed for fine polishing of the inner surfaces of channel-cut crystals. This MC-CMP process relieves the constraints of narrow working space dictated by small offset requirements and achieves near-perfect polishing on the surface of the crystals. Using this method, a high-quality surface with roughness of 0.614â nm (root mean square, r.m.s.) is obtained in a channel-cut crystal with 7â mm gap designed for beamlines at the High Energy Photon Source, a fourth-generation synchrotron radiation source under construction. On-line X-ray topography and rocking-curve measurements indicate that the stress residual layer on the crystal surface was removed. Firstly, the measured rocking-curve width is in good agreement with the theoretical value. Secondly, the peak reflectivity is very close to theoretical values. Thirdly, topographic images of the optics after polishing were uniform without any speckle or scratches. Only a nearly 2.5â nm-thick SiO2 layer was observed on the perfect crystalline matrix from high-resolution transmission electron microscopy photographs, indicating that the structure of the bulk material is defect- and dislocation-free. Future development of MC-CMP is promising for fabricating wavefront-preserving and ultra-stable channel-cut monochromators, which are crucial to exploit the merits of fourth-generation synchrotron radiation sources or hard X-ray free-electron lasers.
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The current effective method for the treatment of myocardial infarction is timely restoration of the blood supply to the ischemic area of the heart. Although reperfusion is essential for reestablishing oxygen and nutrient supplies, it often leads to additional myocardial damage, creating an important clinical dilemma. Reports from long-term studies have confirmed that mitochondrial damage is the critical mechanism in cardiac ischemia/reperfusion (I/R) injury. Mitochondria are dynamic and possess a quality control system that targets mitochondrial quantity and quality by modifying mitochondrial fusion, fission, mitophagy, and biogenesis and protein homeostasis to maintain a healthy mitochondrial network. The system of mitochondrial quality control involves complex molecular machinery that is highly interconnected and associated with pathological changes such as oxidative stress, calcium overload, and endoplasmic reticulum (ER) stress. Because of the critical role of the mitochondrial quality control systems, many reports have suggested that defects in this system are among the molecular mechanisms underlying myocardial reperfusion injury. In this review, we briefly summarize the important role of the mitochondrial quality control in cardiomyocyte function and focus on the current understanding of the regulatory mechanisms and molecular pathways involved in mitochondrial quality control in cardiac I/R damage.
Assuntos
Infarto do Miocárdio , Traumatismo por Reperfusão Miocárdica , Humanos , Mitocôndrias/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Infarto do Miocárdio/patologiaRESUMO
OBJECTIVE: Ovarian cancer has the highest mortality rate among gynecological malignant tumors, and it preferentially metastasizes to omental tissue, leading to intestinal obstruction and death. scRNA-seq is a powerful technique to reveal tumor heterogeneity. Analyzing omentum metastasis of ovarian cancer at the single-cell level may be more conducive to exploring and understanding omentum metastasis and prognosis of ovarian cancer at the cellular function and genetic levels. METHODS: The omentum metastasis site scRNA-seq data of GSE147082 were acquired from the GEO (Gene Expression Omnibus) database, and single cells were clustered by the Seruat package and annotated by the SingleR package. Cell differentiation trajectories were reconstructed through the monocle package. The ovarian cancer microarray data of GSE132342 were downloaded from GEO and were clustered by using the ConsensusClusterPlus package into omentum metastasis-associated clusters according to the marker genes gained from single-cell differentiation trajectory analysis. The tumor microenvironment (TME) and immune infiltration differences between clusters were analyzed by the estimate and CIBERSORT packages. The expression matrix of genes used to cluster GSE132342 patients was extracted from bulk RNA-seq data of TCGA-OV (The Cancer Genome Atlas ovarian cancer), and least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression were performed to establish an omentum metastasis-associated gene (OMAG) signature. The signature was then tested by GSE132342 data. Finally, the clinicopathological characteristics of TCGA-OV were screened by univariate and multivariate Cox regression analysis to draw the nomogram. RESULTS: A total of 9885 cells from 6 patients were clustered into 18 cell clusters and annotated into 14 cell types. Reconstruction of differentiation trajectories divided the cells into 5 branches, and a total of 781 cell trajectory-related characteristic genes were obtained. A total of 3769 patients in GSE132342 were subtyped into 3 clusters by 74 cell trajectory-related characteristic genes. Kaplan-Meier (K-M) survival analysis showed that the prognosis of cluster 2 was the worst, P < 0.001. The TME analysis showed that the ESTIMATE score and stromal score in cluster 2 were significantly higher than those in the other two clusters, P < 0.001. The immune infiltration analysis showed differences in the fraction of 8 immune cells among the 3 clusters, P < 0.05. The expression data of 74 genes used for GEO clustering were extracted from 379 patients in TCGA-OV, and combined with survival information, 10 candidates for OMAGs were filtered by LASSO. By using multivariate Cox regression, the 6-OMAGs signature was established as RiskScore = 0.307*TIMP3 + 3.516*FBN1-0.109*IGKC + 0.209*RPL21 + 0.870*UCHL1 + 0.365*RARRES1. Taking TCGA-OV as the training set and GSE132342 as the test set, receiver operating characteristic (ROC) curves were drawn to verify the prognostic value of 6-OMAGs. Screened by univariate and multivariate Cox regression analysis, 3 (age, cancer status, primary therapy outcome) of 5 clinicopathological characteristics were used to construct the nomogram combined with risk score. CONCLUSION: We constructed an ovarian cancer prognostic model related to omentum metastasis composed of 6-OMAGs and 3 clinicopathological features and analyzed the potential mechanism of these 6-OMAGs in ovarian cancer omental metastasis.
Assuntos
Neoplasias Ovarianas , Análise de Célula Única , Humanos , Feminino , Prognóstico , RNA-Seq , Omento , Carcinoma Epitelial do Ovário , Neoplasias Ovarianas/genética , Microambiente Tumoral/genética , Proteínas de MembranaRESUMO
RATIONALE: Surgery for abdominal aortic aneurysm (AAA) and concomitant severe coronary artery disease (CAD) is usually managed in a staged procedure. The anesthesia for concurrent surgery is rare and complex. In this report, we present an unusual case of undergoing simultaneous open abdominal aortic aneurysm (AAA) repair and coronary artery bypass grafting (CABG). PATIENT CONCERNS: A 70-year-old male AAA patient with concurrent triple-vessel CAD underwent a simultaneous surgery. DIAGNOSIS: The patient underwent computed tomography angiography (CTA) and coronary angiography. He was diagnosed with AAA and triple-vessel CAD. INTERVENTIONS: The patient underwent simultaneous surgery. OUTCOMES: The patient underwent anesthesia and surgery smoothly and was discharged on the 13th postoperative day. LESSONS: The anesthetic management of simultaneous open abdominal aortic aneurysm repair and coronary artery bypass grafting is rare and complicated. Reasonable operation and anesthesia protocols, close monitoring and management of hemodynamic changes, and appropriate cell salvage and hemostasis measures are of great significance to increase perioperative safety and reduce the risk of postoperative complications.