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BACKGROUND: Our primary objective was to assess the association between joint exposure to various air pollutants and the risk of ischemic stroke (IS) and the modification of the genetic susceptibility. METHODS: This observational cohort study included 307 304 British participants from the United Kingdom Biobank, who were stroke-free and possessed comprehensive baseline data on genetics, air pollutant exposure, alcohol consumption, and dietary habits. All participants were initially enrolled between 2006 and 2010 and were followed up until 2022. An air pollution score was calculated to assess joint exposure to 5 ambient air pollutants, namely particulate matter with diameters equal to or <2.5 µm, ranging from 2.5 to 10 µm, equal to or <10 µm, as well as nitrogen oxide and nitrogen dioxide. To evaluate individual genetic risk, a polygenic risk score for IS was calculated for each participant. We adjusted for demographic, social, economic, and health covariates. Cox regression models were utilized to estimate the associations between air pollution exposure, polygenic risk score, and the incidence of IS. RESULTS: Over a median follow-up duration of 13.67 years, a total of 2476 initial IS events were detected. The hazard ratios (95% CI) of IS for per 10 µg/m3 increase in particulate matter with diameters equal to or <2.5 µm, ranging from 2.5 to 10 µm, equal to or <10 µm, nitrogen dioxide, and nitrogen oxide were 1.73 (1.33-2.14), 1.24 (0.88-1.70), 1.13 (0.89-1.33), 1.03 (0.98-1.08), and 1.04 (1.02-1.07), respectively. Furthermore, individuals in the highest quintile of the air pollution score exhibited a 29% to 66% higher risk of IS compared with those in the lowest quintile. Notably, participants with both high polygenic risk score and air pollution score had a 131% (95% CI, 85%-189%) greater risk of IS than participants with low polygenic risk score and air pollution score. CONCLUSIONS: Our findings suggested that prolonged joint exposure to air pollutants may contribute to an increased risk of IS, particularly among individuals with elevated genetic susceptibility to IS.
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Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Ambientales , Accidente Cerebrovascular Isquémico , Humanos , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Dióxido de Nitrógeno/efectos adversos , Dióxido de Nitrógeno/análisis , Accidente Cerebrovascular Isquémico/inducido químicamente , Biobanco del Reino Unido , Bancos de Muestras Biológicas , Material Particulado/efectos adversos , Material Particulado/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Óxidos de Nitrógeno , Óxido Nítrico , Puntuación de Riesgo Genético , Exposición a Riesgos Ambientales/efectos adversosRESUMEN
Arenobufagin (ArBu) is a natural monomer extracted and isolated from the secretion of the Chinese toad, also known as toad venom. This compound exerts anti-tumor effects by promoting apoptosis in tumor cells, inhibiting tumor angiogenesis, and preventing the invasion and migration of tumor cells. However, their impact on ferroptosis in tumor cells has yet to be fully confirmed. In this study, we established a subcutaneous transplant tumor model in nude mice to investigate the inhibitory effect of ArBu on gastric cancer cells (MGC-803) and the safety of drug delivery. in vitro experiments, we screened the most sensitive cancer cell lines using the MTT method and determined the response of ArBu to cell death. Use flow cytometry to measure cytoplasmic and lipid reactive oxygen species (ROS) levels. Determine the expression levels of ferritin-related proteins through Western blot experiments. In addition, a MGC-803 cell model overexpressing Nrf2 was created using lentiviral transfection to investigate the role of ArBu in inducing ferroptosis in cancer cells. Our research findings indicate that ArBu inhibits the proliferation of MGC-803 cells and is linked to ferroptosis. In summary, our research findings indicate that ArBu is a potential anti-gastric cancer drug that can induce ferroptosis in human cancer cells through the Nrf2/SLC7A11/GPX4 pathway.
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Bufanólidos , Ferroptosis , Neoplasias Gástricas , Humanos , Animales , Ratones , Neoplasias Gástricas/tratamiento farmacológico , Factor 2 Relacionado con NF-E2/genética , Ratones Desnudos , Especies Reactivas de OxígenoRESUMEN
Background: Recent studies have indicated that heart failure (HF) with preserved ejection fraction (HFpEF) within different left ventricular ejection fraction (LVEF) ranges presents distinct morphological and pathophysiological characteristics, potentially leading to diverse prognoses. Methods: We included chronic HF patients hospitalized in the Department of Cardiology at Hebei General Hospital from January 2018 to June 2021. Patients were categorized into four groups based on LVEF: HF with reduced ejection fraction (HFrEF, LVEF ≤ 40%), HF with mildly reduced ejection fraction (HFmrEF, 41% ≤ LVEF ≤ 49%), low LVEF-HFpEF (50% ≤ LVEF ≤ 60%), and high LVEF-HFpEF (LVEF > 60%). KaplanâMeier curves were plotted to observe the occurrence rate of endpoint events (all-cause mortality and cardiovascular mortality) within a 2-year period. Cox proportional hazards regression models were employed to predict the risk factors for endpoint events. Sensitivity analyses were conducted using propensity score matching (PSM), and Fine-Gray tests were used to evaluate competitive risk. Results: A total of 483 chronic HF patients were ultimately included. KaplanâMeier curves indicated a lower risk of endpoint events in the high LVEF-HFpEF group than in the low LVEF-HFpEF group. After PSM, there were still statistically significant differences in endpoint events between the two groups (all-cause mortality p = 0.048, cardiovascular mortality p = 0.027). Body mass index (BMI), coronary artery disease, cerebrovascular disease, hyperlipidemia, hypoalbuminemia, and diuretic use were identified as independent risk factors for all-cause mortality in the low LVEF-HFpEF group (p < 0.05). Hyperlipidemia, the estimated glomerular filtration rate (eGFR), and ß -blocker use were independent risk factors for cardiovascular mortality (p < 0.05). In the high LVEF-HFpEF group, multivariate Cox regression analysis revealed that age, smoking history, hypoalbuminemia, and the eGFR were independent risk factors for all-cause mortality, while age, heart rate, blood potassium level, and the eGFR were independent risk factors for cardiovascular mortality (p < 0.05). After controlling for competitive risk, cardiovascular mortality risk remained higher in the low LVEF-HFpEF group than in the high LVEF-HFpEF group (Fine-Gray p < 0.01). Conclusions: Low LVEF-HFpEF and high LVEF-HFpEF represent two distinct phenotypes of HFpEF. Patients with high LVEF-HFpEF have lower risks of both all-cause mortality and cardiovascular mortality than those with low LVEF-HFpEF. The therapeutic reduction in blood volume may not be the best treatment option for patients with high LVEF-HFpEF.
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Compared to japonica, the lower genetic transformation efficiency of indica is a technical bottleneck for rice molecular breeding. Specifically, callus browning frequently occurs during the culture of the elite indica variety 93-11, leading to poor culturability and lower genetic transformation efficiency. Here, 67 QTLs related to culturability were detected using 97 introgression lines (designated as 9DILs) derived from Dongxiang common wild rice (DXCWR, Oryza rufipogon Griff.) with 93-11 genetic background, explaining 4% ~12% of the phenotypic variations. The QTL qCBT9 on chromosome 9 was a primary QTL for reducing callus browning derived from DXCWR. Five 9DILs with light callus browning and high differentiation were screened. We evaluated the callus browning index (CBI) of 100 F2 population crossed of 93-11 and 9DIL71 and the recombinant plants screened from 3270 individuals. The qCBT9 was delimited to a ~148kb region between the markers X16 and X23. RNA-seq analysis of DEGs between 9DIL71 and 93-11 showed three upregulated DEGs (Os09g0526500, Os09g0527900, Os09g0528200,) and three downregulated DEGs (Os09g0526700, Os09g0526800, Os09g0527700) were located in the candidate region of qCBT9. Furthermore, callus browning may be involved in cell senescence and death caused by oxidative stress. The differentiation of indica and japonica in this region suggested that qCBT9 was possibly a vital QTL contributed to better culturability of japonica. Our results laid a foundation for further cloning of the gene for reduced callus browning in O. rufipogon, and also provided a new genetic resource and material basis for improving the culturability and genetic transformation efficiency of cultivated rice. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01470-z.
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BACKGROUND: Phenomenography emerged from pedagogy to examine the qualitatively different ways that individuals experience and perceive the same phenomenon. Despite its uniqueness, the uptake of phenomenography in nursing research is still limited. Potentially, this may be related to confusion regarding what the design is about, its philosophical underpinnings and how distinct it is from other qualitative designs. OBJECTIVES: To offer a better understanding of phenomenography by comparing it with other established qualitative research designs, examining its theoretical foundations, highlighting some studies that have employed the approach in nursing and offering methodological guidance to improve its uptake in nursing. DESIGN: Discussion paper. FINDINGS: Compared to the traditional qualitative designs employed in nursing, phenomenography has been utilized in fewer studies. The ontological, epistemological and methodological basis of phenomenography highlights it as a distinct design. The strength of phenomenography lies in its emphasis on understanding the collective variations between participants and presenting these holistically as an 'outcome space'. DISCUSSION: Phenomenography is a distinct qualitative research approach that presents a unique opportunity for nursing to further its use. Issues regarding bracketing, the inclusion of phenomenography studies in qualitative meta-synthesis and employing a hermeneutic approach to phenomenography are avenues for further work in nursing. PATIENT AND PUBLIC CONTRIBUTION: No patient or public contribution.
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Aprendizaje , Investigación en Enfermería , Humanos , Investigación Cualitativa , Hermenéutica , Proyectos de InvestigaciónRESUMEN
Gastrointestinal cancers are a major global health challenge, with high mortality rates. This study investigated the anti-cancer activities of 30 monomers extracted from Morus alba L. (mulberry) against gastrointestinal cancers. Toxicological assessments revealed that most of the compounds, particularly immunotoxicity, exhibit some level of toxicity, but it is generally not life-threatening under normal conditions. Among these components, Sanggenol L, Sanggenon C, Kuwanon H, 3'-Geranyl-3-prenyl-5,7,2',4'-tetrahydroxyflavone, Morusinol, Mulberrin, Moracin P, Kuwanon E, and Kuwanon A demonstrate significant anti-cancer properties against various gastrointestinal cancers, including colon, pancreatic, and gastric cancers. The anti-cancer mechanism of these chemical components was explored in gastric cancer cells, revealing that they inhibit cell cycle and DNA replication-related gene expression, leading to the effective suppression of tumor cell growth. Additionally, they induced unfolded protein response (UPR) and endoplasmic reticulum (ER) stress, potentially resulting in DNA damage, autophagy, and cell death. Moracin P, an active monomer characterized as a 2-arylbenzofuran, was found to induce ER stress and promote apoptosis in gastric cancer cells, confirming its potential to inhibit tumor cell growth in vitro and in vivo. These findings highlight the therapeutic potential of Morus alba L. monomers in gastrointestinal cancers, especially focusing on Moracin P as a potent inducer of ER stress and apoptosis.
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Neoplasias Gastrointestinales , Morus , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Estrés del Retículo Endoplásmico , Respuesta de Proteína Desplegada , Neoplasias Gastrointestinales/tratamiento farmacológicoRESUMEN
Domestication has shaped the population structure and agronomic traits of tea plants, yet the complexity of tea population structure and genetic variation that determines these traits remains unclear. We here investigated the resequencing data of 363 diverse tea accessions collected extensively from almost all tea distributions and found that the population structure of tea plants was divided into eight subgroups, which were basically consistent with their geographical distributions. The genetic diversity of tea plants in China decreased from southwest to east as latitude increased. Results also indicated that Camellia sinensis var. assamica (CSA) illustrated divergent selection signatures with Camellia sinensis var. sinensis (CSS). The domesticated genes of CSA were mainly involved in leaf development, flavonoid and alkaloid biosynthesis, while the domesticated genes in CSS mainly participated in amino acid metabolism, aroma compounds biosynthesis, and cold stress. Comparative population genomics further identified ~730 Mb novel sequences, generating 6,058 full-length protein-encoding genes, significantly expanding the gene pool of tea plants. We also discovered 217,376 large-scale structural variations and 56,583 presence and absence variations (PAVs) across diverse tea accessions, some of which were associated with tea quality and stress resistance. Functional experiments demonstrated that two PAV genes (CSS0049975 and CSS0006599) were likely to drive trait diversification in cold tolerance between CSA and CSS tea plants. The overall findings not only revealed the genetic diversity and domestication of tea plants, but also underscored the vital role of structural variations in the diversification of tea plant traits.
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BACKGROUND: Genetic transformation of indica rice (Oryza sativa ssp. indica) is limited by callus browning, which results in poor in vitro tissue culturability. Elucidating the genes in common wild rice (Oryza rufipogon Griff.) that control callus browning is fundamental for improving the tissue culturability of indica rice varieties. METHODS AND RESULTS: We used a population of 129 O. rufipogon (Dongxiang common wild rice; DXCWR) introgression lines in the elite cultivar GC2 (Oryza sativa ssp. indica) background and 159 simple sequence repeat (SSR) markers to identify quantitative trait loci (QTLs) associated with callus browning. We evaluated callus browning based on the indices of callus browning rate (CBR), callus browning index (CBI), and standard callus browning index (SCBI). CONCLUSIONS: We detected 30 QTLs associated with callus browning across all lines, mapping to chromosomes 1, 2, 3, 4, 8, 9, and 12. These genomic regions were repeatedly associated with differences in CBR, CBI, and SCBI. The alleles from DXCWR showed additive effects in reducing callus browning. We identified new QTLs near the markers RM247 and RM7003 on chromosome 12, indicating that these QTLs are unique to DXCWR. Furthermore, we identified six introgression lines with significantly lower callus browning. These lines will be useful germplasms for genetic transformation and fine-mapping of the culturability trait.
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Oryza , Sitios de Carácter Cuantitativo , Sitios de Carácter Cuantitativo/genética , Oryza/genética , Cromosomas de las Plantas/genética , Fenotipo , AlelosRESUMEN
MnO2 is an oxide with many crystalline phases and is often used as a cathode material for aqueous zinc-ion batteries. However, its poor electrical conductivity and structural instability limit its further application. In the present work, Mo-doped MnO2 microflowers are successfully prepared by a facile hydrothermal method. Interestingly, it is found that the doping of Mo inhibits the phase transition from δ-MnO2 to α-MnO2, which may be related to the low crystallinity of Mo doped MnO2. Compared with undoped MnO2, Mo-doped MnO2 maintains two-dimensional morphology with a large specific surface area and mesoporous structure. In addition, the electronic conductivity and reversibility of Zn2+ insertion/extraction are improved in Mo doped MnO2. Therefore, Mo-doped MnO2 exhibits high reversible capacity and long cycling stability. For example, a high reversible capacity of 72.6 mA h g-1 can be achieved at a current density of 2000 mA g-1 after 2500 cycles.
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Long non-coding RNAs (lncRNAs) can not only regulate gene transcription and translation, but also participate in the development of central nervous system diseases as epigenetic modification factors. However, their functional significance in atherosclerosis-induced ischemic stroke (AIIS) is unclear. The study aimed to screen out differentially expressed lncRNAs (delncRNAs), and to elucidate their potential regulatory mechanisms in the pathophysiology of AIIS. Based on the clinicopathological features and clinical images, we screened out 10 patients with AIIS and recruited 10 healthy volunteers. Then we used microarray to detect the whole blood RNA of subjects, and explored the biological functions of delncRNAs by GO and KEGG analysis. After further analyzing the delncRNAs of THP-1 stimulated with ox-LDL, selective lncRNAs were screened and a corresponding lncRNA-mRNA interaction network was constructed through co-expression analysis. We yielded 180 delncRNAs (44 up-regulated and 136 down-regulated) and 218 demRNAs (45 up-regulated and 173 down-regulated). Lnc-SCARNA8 and lnc-SNRPN-2 are the most significant elevated and decreased lncRNA in AIIS, respectively. The delncRNAs may play a significant role in ubiquitination-mediated protein degradation signaling pathways. According to lncRNA-mRNA network, the expression of vacuolar protein sorting 13 homolog B (VPS13B) and biliverdin reductase B (BLVRB) were significantly regulated. Our findings suggest that the ubiquitinated proteasome pathway, VPS13B and BLVRB may play a fundamental role in the pathological process of AIIS.
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Aterosclerosis , Accidente Cerebrovascular Isquémico , ARN Largo no Codificante , Aterosclerosis/complicaciones , Aterosclerosis/genética , Redes Reguladoras de Genes , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Transcriptoma/genéticaRESUMEN
BACKGROUND: To determine the optimal delivery time for women with diet-controlled gestational diabetes mellitus by comparing differences in adverse maternal-fetal outcome and cesarean section rates. METHODS: This real-world retrospective study included 1,050 patients with diet-controlled gestational diabetes mellitus who delivered at 35-42 weeks' gestation. Data on patient characteristics, maternal-fetal outcomes, and cesarean section rate based on fetal gestational age were collected and analyzed. Differences between deliveries with and without iatrogenic intervention were also analyzed. RESULTS: The cesarean section rate at ≥ 41 weeks' gestation was significantly higher than that at 39-39 + 6 weeks (56% vs. 39%, p = 0.031). There were no significant differences in multiple adverse maternal or neonatal outcomes at delivery before and after 39 weeks. Vaginal delivery rates were increased significantly at 39-39 + 6 weeks due to iatrogenic intervention (p = 0.005) and 40-40 + 6 weeks (p = 0.003) in patients without and with spontaneous uterine contractions, respectively. CONCLUSIONS: It's recommended that optimal delivery time for patients with diet-controlled gestational diabetes mellitus should be between 39- and 40 + 6 weeks' gestation. Patients who have Bishop scores higher than 4 can undergo iatrogenic intervention at 39-39 + 6 weeks. However iatrogenic interventions are not recommended for patients with low Bishop scores.
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Cesárea , Diabetes Gestacional , Dieta , Femenino , Edad Gestacional , Humanos , Enfermedad Iatrogénica , Recién Nacido , Embarazo , Estudios RetrospectivosRESUMEN
DEK protein is critical to the formation of neutrophil extracellular traps (NETs) in rheumatoid arthritis (RA). Blocking DEK using the aptamer DTA via articular injection has been shown to have robust anti-inflammatory efficacy in a previous study. However, DTA is prone to nuclease degradation and renal clearance in vivo. RA is a systemic disease that involves multiple joints, and local injection is impractical in clinical settings. In this study, DTA was modified with methoxy groups on all deoxyribose sugar units and inverted deoxythymidine on the 3' end (DTA4) to enhance its stability against nuclease. DTA4 is stable for 72 h in 90% mouse serum and maintains a high binding affinity to DEK. DTA4 effectively inhibits the formation of NETs and the migration of HUVECs in vitro. DTA4 was then modified with cholesterol on its 5' end to form DTA6. DTA6 dramatically reduces DEK expression in inflammatory RAW264.7 cells. A hydrogel microneedle (hMN) was then fabricated for the transdermal delivery of DTA6. The hMN maintains morphological integrity after absorbing the aptamer solution, effectively pierces the skin, and rapidly releases DTA6 into the dermis. The DTA6-loaded hMN significantly attenuates inflammation and protects joints from cartilage/bone erosion in collagen-induced arthritis (CIA) mice.
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Aptámeros de Nucleótidos/administración & dosificación , Artritis Experimental/inducido químicamente , Artritis Experimental/tratamiento farmacológico , Colágeno/farmacología , Proteínas de Unión al ADN/metabolismo , Hidrogeles/administración & dosificación , Proteínas Oncogénicas/metabolismo , Proteínas de Unión a Poli-ADP-Ribosa/metabolismo , Animales , Antiinflamatorios/administración & dosificación , Artritis Experimental/metabolismo , Artritis Reumatoide/inducido químicamente , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/metabolismo , Cartílago/efectos de los fármacos , Cartílago/metabolismo , Línea Celular , Trampas Extracelulares/efectos de los fármacos , Trampas Extracelulares/metabolismo , Células Endoteliales de la Vena Umbilical Humana , Humanos , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Ratones , Sustancias Protectoras/administración & dosificación , Células RAW 264.7RESUMEN
Brusatol is a butyrolactone compound isolated from traditional Chinese medicine Brucea javanica. It has been reported to possess strong cytotoxicity against various cancer cells, thus showing its potential as an anticancer drug. Besides, lipopolysaccharide (LPS) plays a central role in the tumor microenvironment, while epithelial-mesenchymal transformation (EMT), a biological process by which epithelial cells are transformed into mesenchymal phenotypic cells through specific procedures, participates in chronic inflammation and tumor metastasis. This study aimed to investigate the inhibition of LPS-induced tumor cell invasion and metastasis and the molecular mechanism of apoptosis induced by brusatol in human gastric cancer SGC-7901 cells. Cell viability, cell migration and invasion ability, inflammatory factor release, and protein expression were detected using methyl thiazolyl tetrazolium assays, transwell assays, ELISA kit, and Western blot analysis, respectively. The change of EMT marker protein vimentin was assessed using immunofluorescence, while the apoptosis rate was measured using flow cytometry. In summary, brusatol inhibited LPS-induced EMT via the deactivation of the PI3K/Akt/NF-кB signaling pathway. This provides a useful new theoretical basis for the treatment of gastric cancer in the future.
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Lipopolisacáridos/farmacología , FN-kappa B/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Cuassinas/farmacología , Neoplasias Gástricas/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Biomarcadores de Tumor/biosíntesis , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Citocinas/metabolismo , Interacciones Farmacológicas , Transición Epitelial-Mesenquimal/efectos de los fármacos , Humanos , Lipopolisacáridos/antagonistas & inhibidores , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologíaRESUMEN
OBJECTIVE: We used National Cancer Institute's Surveillance, Epidemiology and End Result database to assess the role of salvage radiotherapy for women with unanticipated cervical cancer after simple hysterectomy. METHODS: Patients with non-metastatic cervical cancer and meeting inclusion criteria were divided into three groups based on treatment strategy: simple hysterectomy, salvage radiotherapy after hysterectomy and radical surgery. Parallel propensity score-matched datasets were established for salvage radiotherapy group vs. simple hysterectomy group (matching ratio 1: 1), and salvage radiotherapy group vs. radical surgery group (matching ratio 1:2). The primary endpoint was the overall survival advantage of salvage radiotherapy over simple hysterectomy or radical surgery within the propensity score-matched datasets. RESULTS: In total, 2682 patients were recruited: 647 in the simple hysterectomy group, 564 in the salvage radiotherapy group and 1471 in the radical surgery group. Age, race, histology, grade, FIGO stage, insured and marital status and chemotherapy were comprised in propensity score-matched. Matching resulted in two comparison groups with neglectable differences in most variables, except for black race, FIGO stage III and chemotherapy in first matching. In the matched analysis for salvage radiotherapy vs. simple hysterectomy, the median follow-up time was 39 versus 32 months. In the matched analysis for salvage radiotherapy vs. radical surgery, the median follow-up time was 39 and 41 months, respectively. Salvage radiotherapy (HR 0.53, P = 0.046) significantly improved overall survival compared with simple hysterectomy, while salvage radiotherapy cannot achieve similar overall survival to radical surgery (HR 1.317, P = 0.045). CONCLUSIONS: This is the largest study of the effect of salvage radiotherapy on overall survival in patients with unanticipated cervical cancer. Salvage radiotherapy can improve overall survival compared with hysterectomy alone, while cannot achieve comparable survival to radical surgery.
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Bases de Datos como Asunto , Histerectomía , Oncología Médica , Puntaje de Propensión , Terapia Recuperativa , Neoplasias del Cuello Uterino/radioterapia , Neoplasias del Cuello Uterino/cirugía , Adulto , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Estadificación de Neoplasias , Oportunidad Relativa , Neoplasias del Cuello Uterino/patologíaRESUMEN
Many researchers from scientific and industrial fields have devoted their efforts to the laser interferometer, aiming to improve the measurement accuracy and extend the practical applications. Here, we present a modified homodyne laser interferometer based on phase modulation for simultaneously measuring displacement and angle. The active sawtooth wave phase modulation enhances immunity of this interferometer to the environmental fluctuations and laser power drift. Based on polarized optic theory and the sinusoidal measurement retro-reflector, a modified Michelson-type interferometer configuration is designed to simultaneously measure displacement and angle. Phase difference between the reference and measurement interference signals can be obtained using the sawtooth wave phase modulation and zero crossing detection technique, where the real-time displacement and angle values can be derived directly. Experimental results demonstrate our proposed interferometer has good static and dynamic performance.
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Investigated in this paper is the defocusing nonlinear Schrödinger (NLS) equation, which is used for describing the wave-packet dynamics in certain weakly nonlinear media. With the physics-informed neural networks (PINNs), we modify the corresponding loss function in the existing literature and obtain two types of dark solitons, type-I and type-II solitons. It is demonstrated that the modified loss function presents higher-precision wave-packet behaviors based on fewer initial and boundary data. Taking type-I solitons into consideration, we find that when only a small fraction of initial and boundary data are given, the prediction accuracy of the wave packets will be increased one or two orders of magnitude at least if the modification term of the loss function is introduced. Furthermore, for the inverse problem, the modified loss function provides a better estimate of the nonlinear coefficient of the NLS equation based on fewer observed data of the wave packets. For type-II solitons, we compare the required data and predicted results of the PINNs with those of the conventional time-splitting finite difference (TSFD) method and reveal that achieving the same precision of the wave-packet behavior, the PINNs with the modified loss functions require only one tenth of the amount of the initial and boundary data of the TSFD method. Besides, both unmodified and modified loss functions are exploited for predicting the behaviors of Gaussian wave packets, and it is observed that the predicted result of the modified loss function agrees with the high-precision solution of the time-splitting Fourier pseudospectral method, whereas the unmodified loss function fails.
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To probe the function of miR-518a-5p/Granzyme B (GZMB) in hypoxia/reoxygenation (H/R) -induced vascular endothelial cell injury.The key genes of myocardial infarction were screened by bioinformatic methods. The upstream micro RNAs (miRNAs) of GZMB were predicted by TargetScan. The binding of miR-518a-5p to GZMB was verified with luciferase reporter assay. The H/R model was constructed with human vascular endothelial cell (HUVEC) in vitro. Cell Counting Kit-8 (CCK8) assay was performed to detect cell proliferation. Western blot was utilized to evaluate the levels of indicated proteins.GZMB was up-regulated in patients with myocardial infarction and identified as the key gene by the bioinformatics analysis. Then the prediction from TargetScan indicated that miR-518a-5p, which is down-regulated in myocardial infarction patients, might be the potential upstream miRNA for GZMB. The following experiments verified that miR-518a-5p could bind to the 3'UTR of GZMB and negatively modulates GZMB expression. More importantly, the miR-518a-5p mimic enhanced cell proliferation and repressed apoptosis of H/R-injured HUVEC cells by inhibiting GZMB expression.We proved that miR-518a-5p could partly attenuate H/R-induced HUVEC cell injury by targeting GZMB, and perhaps the miR-518a-5p/GZMB axis could be potential therapeutic targets for myocardial infarction.
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Células Endoteliales/metabolismo , Granzimas/metabolismo , MicroARNs/metabolismo , Daño por Reperfusión Miocárdica/metabolismo , Células Endoteliales de la Vena Umbilical Humana , Humanos , Hipoxia/metabolismoRESUMEN
Cervical cancer is one of the leading female health-killers among all types of malignancies globally. Human papillomavirus infection combined with genetic and epigenetic alterations have been indicated to be closely associated with the pathogenesis, progression, and malignant transformation of cervical cancer. Notably, during the complex tumorigenesis process, a series of DNA methylations occurs early and is the most frequent molecular behavior. In this study, to exploit the specific DNA methylation sites influencing the prognosis of patients with cervical cancer, 275 samples were downloaded from The Cancer Genome Atlas database and further analyzed. As a result, 1253 CpGs were found to have a significant correlation with patient prognosis and were further selected for the consistent clustering of samples into six subgroups. Specifically, the samples in every subgroup were different regarding the following: race, age, tumor stage, receptor status, histological type, metastasis status, and patient prognosis. In addition, we calculated the levels of methylation sites in all subgroups, with 79 methylation sites (corresponding to 81 genes) screened as the intrasubgroup-specific methylation sites. Moreover, signaling pathway enrichment analysis was conducted on the genes of the corresponding promoter regions of the above-described specific methylation sites, revealing that these genes were enriched in biological pathways closely associated with tumors, such as the cyclic guanosine monophosphate-dependent protein kinase and focal adhesion signaling pathways. Finally, the least absolute shrinkage and selection operator algorithm was employed to establish a prognostic prediction model for cervical cancer patients, with training and test sets used for testing and validation, respectively. In summary, the specific DNA methylation site-based classification is able to reflect the heterogeneity of cervical cancer tissue, contributing to the development of personalized therapy and the accurate prediction of patient prognosis.
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Biomarcadores de Tumor/genética , Metilación de ADN , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Neoplasias del Cuello Uterino/clasificación , Neoplasias del Cuello Uterino/patología , Progresión de la Enfermedad , Femenino , Perfilación de la Expresión Génica , Humanos , Pronóstico , Regiones Promotoras Genéticas , Tasa de Supervivencia , Neoplasias del Cuello Uterino/genéticaRESUMEN
Melanoma is characterized by high malignancy and early onset of metastasis. Epithelial-to-mesenchymal transition (EMT) is an early event during tumor metastasis. Tumor cells that develop EMT can escape apoptosis, but they are vulnerable to ferroptosis inducers. Gambogenic acid (GNA), a xanthone found in Gamboge, has cytotoxic effects in highly invasive melanoma cells. This study investigated the anti-melanoma effect and mechanism of action of GNA in TGF-ß1-induced EMT melanoma cells. We found that GNA significantly inhibited the invasion, migration and EMT in melanoma cells, and these cells exhibited small mitochondrial wrinkling (an important feature of ferroptosis). An iron chelator, but not an apoptosis inhibitor or a necrosis inhibitor, abolished the inhibitory effects of GNA on proliferation, invasion and migration of TGF-ß1-stimulated melanoma cells. GNA upregulated the expression of p53, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in the model cells, contributing to the mechanisms underlying GNA-induced ferroptosis. Collectively, our findings suggest that GNA induces ferroptosis in TGF-ß1-stimulated melanoma cells via the p53/SLC7A11/GPX4 signaling pathway.
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Medicamentos Herbarios Chinos/toxicidad , Transición Epitelial-Mesenquimal/efectos de los fármacos , Ferroptosis/efectos de los fármacos , Melanoma/metabolismo , Neoplasias Cutáneas/metabolismo , Xantenos/toxicidad , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Medicamentos Herbarios Chinos/uso terapéutico , Transición Epitelial-Mesenquimal/fisiología , Ferroptosis/fisiología , Humanos , Melanoma/tratamiento farmacológico , Melanoma/patología , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Xantenos/uso terapéuticoRESUMEN
Ferroptosis is a form of necrosis caused by iron-induced accumulation of lipid hydroperoxide, involving several molecular events, and has been implicated in Parkinson's disease. Gastrodin is a component of Gastrodia elata Blume with strong antioxidant activity. We examined whether gastrodin can prevent H2O2-induced cytotoxicity in rat glioma cell line C6. For this purpose, C6 cells were pretreated with gastrodin (1, 5, 25 µM) and then exposed to 100 µM H2O2. Results showed that pretreatment of C6 cells with gastrodin decreased H2O2-induced lactate dehydrogenase (LDH) release and cell death. Moreover, gastrodin decreased intracellular malondialdehyde (MDA) level, whereas increased glutathione peroxidase (GPX) activity and glutathione (GSH) level after H2O2 treatment. In addition, treatment of deferoxamine (DFO), ferrostatin-1, and liproxstatin-1 abolished ferroptosis induced by H2O2 or erastin pretreatment. Treatment with gastrodin attenuated H2O2-induced ferroptosis and decreased lipid reactive oxygen species (ROS) (C11-BODIPY) production in C6 cells. Moreover, gastrodin increased the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), GPX4, ferroportin-1 (FPN1), and heme oxygenase-1 (HO-1) in C6 cells treated with H2O2. RSL3, a GPX4 inhibitor, inhibited GPX4 protein level in cells co-treated with gastrodin and 100 µM H2O2. These findings indicate that gastrodin can inhibit H2O2-induced ferroptosis through its antioxidative effect in C6 cells.