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OBJECTIVES: This study aims to determine serum levels of human Krüppel-like factors (KLFs), sP-selectin and sE-selectin and establish correlations between them in patients with gestational diabetes mellitus (GDM). METHODS: Twenty-six GDM patients aged between 22 and 35 years and 25 healthy pregnant women aged between 23 and 34 years were recruited. Maternal serum levels of KLF2, KLF4, and their target proteins sP-selectin, sE-selectin were measured using enzyme-linked immunosorbent assays at 24-28 weeks of gestation. RESULTS: Women with GDM had significantly lower serum KLF2 than controls. However, the differences in levels of serum KLF4 between the control and GDM groups were not significant. Additionally, elevated serum sP-selectin and sE-selectin were found in the GDM group and not in the healthy group. Importantly, we also found that serum KLF2 levels were negatively correlated with indicators of glucose metabolism, including insulin, fasting blood glucose, 1-h oral glucose tolerance test, and glycated hemoglobin. CONCLUSION: We conclude that (i) serum KLF2 might be indicative of GDM risk, and (ii) sP-selectin and sE-selectin were increased in GDM patients.
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Diabetes Gestacional , Adulto , Femenino , Humanos , Embarazo , Adulto Joven , Glucemia/metabolismo , Prueba de Tolerancia a la Glucosa , Insulina , Factores de Transcripción de Tipo Kruppel , Selectinas , Selectina-PRESUMEN
Influenza virus RNA-dependent RNA polymerase consists of three viral protein subunits: PA, PB1, and PB2. Protein-protein interactions (PPIs) of these subunits play pivotal roles in assembling the functional polymerase complex, which is essential for the replication and transcription of influenza virus RNA. Here we developed a highly specific and robust bimolecular luminescence complementation (BiLC) reporter system to facilitate the investigation of influenza virus polymerase complex formation. Furthermore, by combining computational modeling and the BiLC reporter assay, we identified several novel small-molecule compounds that selectively inhibited PB1-PB2 interaction. Function of one such lead compound was confirmed by its activity in suppressing influenza virus replication. In addition, our studies also revealed that PA plays a critical role in enhancing interactions between PB1 and PB2, which could be important in targeting sites for anti-influenza intervention. Collectively, these findings not only aid the development of novel inhibitors targeting the formation of influenza virus polymerase complex but also present a new tool to investigate the exquisite mechanism of PPIs. IMPORTANCE Formation of the functional influenza virus polymerase involves complex protein-protein interactions (PPIs) of PA, PB1, and PB2 subunits. In this work, we developed a novel BiLC assay system which is sensitive and specific to quantify both strong and weak PPIs between influenza virus polymerase subunits. More importantly, by combining in silico modeling and our BiLC assay, we identified a small molecule that can suppress influenza virus replication by disrupting the polymerase assembly. Thus, we developed an innovative method to investigate PPIs of multisubunit complexes effectively and to identify new molecules inhibiting influenza virus polymerase assembly.
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Antivirales/farmacología , Virus de la Influenza A/enzimología , Proteínas no Estructurales Virales/metabolismo , Células A549 , Animales , Perros , Evaluación Preclínica de Medicamentos , Células HEK293 , Humanos , Virus de la Influenza A/efectos de los fármacos , Gripe Humana/tratamiento farmacológico , Gripe Humana/virología , Células de Riñón Canino Madin Darby , Mapeo de Interacción de Proteínas , Multimerización de Proteína/efectos de los fármacosRESUMEN
Self-referenced demodulating methods of fiber optic hydrogen sensors based on WO3-Pd2Pt-Pt composite film are studied in this paper. By employing the proper baseline intensity as sensing parameters, fluctuations of the sensing signal of the hydrogen sensor can be obviously depressed, and sensitivity can be greatly improved. Experimental results show that the resolution of the hydrogen sensor can reach 3 parts per million (ppm) when the hydrogen concentration is lower than 1000 ppm. Additionally, the hydrogen sensor shows better sensitivity toward lower concentrations of hydrogen, enabling a hydrogen threshold down to 10 ppm in air at room temperature. To the best of our knowledge, this is the lowest threshold reported for an optical hydrogen sensor operated at room temperature in air. Moreover, the sensor has good repeatability during hydrogen response. This work proposes a simple and novel method to improve the performance of fiber optic hydrogen sensors, which can greatly promote their potential application in various fields.
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OBJECTIVE: To explore the relationship between ventilator efficiency of cardiopulmonary exercising test (the slope of the relation between ventilation and carbon dioxide production, VE/VCO(2)slope) and systolic pulmonary artery pressure (sPAP) measured by echocardiography in patients with chronic heart failure (HF). METHODS: Data from 86 HF patients who were treated in Fuwai Hospital between December 2012 and July 2014 and performed the symptom limited maximal cardiopulmonary exercise test (CPET) and echocardiography were retrospectively analyzed.H F patients were divided into 3 groups (mild, moderate and severe) according to the maximum oxygenconsumption (peakVO(2)). RESULTS: There is a significant linear correlation between VE/VCO(2)slope and sPAP (r=0.260, P=0.016). Using VE/VCO(2)slope>34.2 as a cutoff value to predict patients with sPAP>50 mmHg (1 mmHg=0.133 kPa) yielded a sensitivity of 70.0% and a specificity of 64.3%. The degree of the linear correlation between VE/VCO(2)slope and sPAP is stronger in mild HF patients (peakVO(2)>14 ml·kg(-1)·min(-1), r=0.686, P<0.001). Using VE/VCO(2) slope>34.2 as a cutoff value to predict sPAP>50 mmHg in mild HF patients, the sensitivity is 71.4% and the specificity is 93.8%. CONCLUSION: There is a significant linear correlation between VE/VCO(2)slope and sPAP in HF patients. VE/VCO(2)slope>34.2 is linked with a high possibility of sPAP>50 mmHg in HF patients, especially for patients with mild HF. Invasive hemodynamic examination and impact of special therapy are warranted in future studies to veryfy present results.
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Insuficiencia Cardíaca , Arteria Pulmonar , Dióxido de Carbono , Enfermedad Crónica , Ecocardiografía , Prueba de Esfuerzo , Hemodinámica , Humanos , Estudios RetrospectivosRESUMEN
BACKGROUND: A subset of neutrophils isolated from the peripheral blood mononuclear cells (PBMC) layer has recently been described in cancer patients. METHODS: Double-gradient centrifugation was used to separate the neutrophil subsets. Western blotting and immunohistochemical assays were performed to assess CCDC25 expression levels. RESULTS: In this study, we found that low-density neutrophils (LDNs) were more highly enriched in metastatic hepatocellular carcinoma (HCC) patients than in non-metastatic HCC patients. We then showed a CD61+ LDNs subset, which displayed distinct functions and gene expression, when compared with high-density neutrophils (HDNs) and CD61- LDNs. Transcriptomic analysis revealed that the CD61+ LDNs were predominantly enhanced in the transcription of glycolysis and angiogenesis associated gene, HMGB1 associated gene and granulation protein gene. These CD61+ LDNs displayed a prominent ability to trigger metastasis, compared with HDNs and CD61- LDNs. Specifically, CD61+ LDN-derived HMGB1 protein increased the invasion of HCC cells by upregulating CCDC25. Mechanistically, the CD61+ LDN-derived HMGB1 protein enhanced the invasiveness of HCC cells and triggered their metastatic potential, which was mediated by TLR9-NF-κB-CCDC25 signaling. Blocking this signaling pathway reversed the invasion of the CD61+ LDN-induced HCC cells. In vivo, we consistently showed that CD61+ LDN-derived HMGB1 enhances HCC metastasis to the lungs. CONCLUSIONS: Overall, our findings showed that a subset of CD61+ LDNs has pro-metastatic effects on HCC, and may be used to target HCC in the clinical setting.
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Carcinoma Hepatocelular , Proteína HMGB1 , Neoplasias Hepáticas , Neutrófilos , Regulación hacia Arriba , Animales , Femenino , Humanos , Masculino , Ratones , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Proteína HMGB1/metabolismo , Proteína HMGB1/genética , Integrina beta3 , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundario , Metástasis de la Neoplasia , Neutrófilos/inmunología , Neutrófilos/metabolismoRESUMEN
Sodium-ion batteries (SIBs) have garnered significant attention as ideal candidates for large-scale energy storage due to their notable advantages in terms of resource availability and cost-effectiveness. However, there remains a substantial energy density gap between SIBs and commercially available lithium-ion batteries (LIBs), posing challenges to meeting the requirements of practical applications. The fabrication of high-energy cathodes has emerged as an efficient approach to enhancing the energy density of SIBs, which commonly requires cathodes operating in high-voltage regions. Layered oxide cathodes (LOCs), with low cost, facile synthesis, and high theoretical specific capacity, have emerged as one of the most promising candidates for commercial applications. However, LOCs encounter significant challenges when operated in high-voltage regions such as irreversible phase transitions, migration and dissolution of metal cations, loss of reactive oxygen, and the occurrence of serious interfacial parasitic reactions. These issues ultimately result in severe degradation in battery performance. This review aims to shed light on the key challenges and failure mechanisms encountered by LOCs when operated in high-voltage regions. Additionally, the corresponding strategies for improving the high-voltage stability of LOCs are comprehensively summarized. By providing fundamental insights and valuable perspectives, this review aims to contribute to the advancement of high-energy SIBs.
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SiCp/Al composite materials are widely used in various industries such as the aerospace and the electronics industries, primarily due to their excellent material properties. However, their machinability is significantly weakened due to their unique characteristics. Consequently, efficient and precise machining technology for SiCp/Al composite materials has become a crucial research area. By conducting a comprehensive analysis of the relevant research literature from both domestic and international sources, this study examines the processing mechanism, as well as the turning, milling, drilling, grinding, special machining, and hybrid machining characteristics, of SiCp/Al composite materials. Moreover, it summarizes the latest research progress in composite material processing while identifying the existing problems and shortcomings in this area. The aim of this review is to enhance the machinability of SiCp/Al composite materials and promote high-quality and efficient processing methods.
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China has been continuously improving its monitoring methods and strategies to address key infectious diseases (KIDs). After the severe acute respiratory syndrome epidemic in 2003, China established a comprehensive reporting system for infectious diseases (IDs) and public health emergencies. The relatively lagging warning thresholds, limited warning information, and outdated warning technology are insufficient to meet the needs of comprehensive monitoring for modern KIDs. Strengthening early monitoring and warning capabilities to enhance the public health system has become a top priority, with increasing demand for early warning thresholds, information, and techniques, thanks to constant innovation and development in molecular biology, bioinformatics, artificial intelligence, and other identification and analysis technologies. A panel of 31 experts has recommended a fourth-generation comprehensive surveillance system targeting KIDs (41 notifiable diseases and emerging IDs). The aim of this surveillance system is to systematically monitor the epidemiology and causal pathogens of KIDs in hosts such as humans, animals, and vectors, along with associated environmental pathogens. By integrating factors influencing epidemic spread and risk assessment, the surveillance system can serve to detect, predict, and provide early warnings for the occurrence, development, variation, and spread of known or novel KIDs. Moreover, we recommend comprehensive ID monitoring based on the fourth-generation surveillance system, along with a data-integrated monitoring and early warning platform and a consortium pathogen detection technology system. This series of considerations is based on systematic and comprehensive monitoring across multiple sectors, dimensions, factors, and pathogens that is supported by data integration and connectivity. This expert consensus will provides an opportunity for collaboration in various fields and relies on interdisciplinary application to enhance comprehensive monitoring, prediction, and early warning capabilities for the next generation of ID surveillance. This expert consensus will serve as a reference for ID prevention and control as well as other related activities.
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Augmentation of endogenous double-stranded RNA (dsRNA) has become a promising strategy for activating anti-tumor immunity through induction of type I interferon (IFN) in the treatment of ovarian carcinoma. However, the underlying regulatory mechanisms of dsRNA in ovarian carcinoma remain elusive. From The Cancer Genome Atlas (TCGA), we downloaded RNA expression profiles and clinical data of patients with ovarian carcinoma. Using the consensus clustering method, patients can be classified by their expression level of core interferon-stimulated genes (ISGs): IFN signatures high and IFN signatures low. The IFN signatures high group had a good prognosis. Gene set enrichment analysis (GSEA) showed that differentially expressed genes (DEGs) were primarily associated with anti-foreign immune responses. Based on results from protein-protein interaction (PPI) networks and survival analysis, ISG20 was identified as a key gene involved in host anti-tumor immune response. Further, elevated ISG20 expression in ovarian cancer cells led to increased IFN-ß production. The elevated interferon improved the immunogenicity of tumor cells and generated chemokines that attract immune cells to infiltrate the area. Upon overexpression of ISG20, endogenous dsRNA accumulated in the cell and stimulated IFN-ß production through the Retinoic acid-inducible gene I (RIG-I)-mediated dsRNA sense pathway. The accumulation of dsRNA was associated with the ribonuclease activity of ISG20. This study suggests that targeting ISG20 is a potential immune therapeutic approach to treat ovarian cancer.
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Interferón Tipo I , Neoplasias Ováricas , Humanos , Femenino , ARN Bicatenario , Interferón Tipo I/metabolismo , Neoplasias Ováricas/genética , Exorribonucleasas/genéticaRESUMEN
The eXTP (enhanced X-ray Timing and Polarization) satellite is a prominent X-ray astronomy satellite designed primarily for conducting deep space X-ray astronomical observations. The satellite's scientific payload consists of X-ray focusing mirrors. In order to fulfill the requirements of weight reduction and enhanced effective area, the thickness of mirrors is reduced to the sub-millimeter range and a multi-layer nested structure is employed. Manufacturing mirrors poses a significant challenge to both their quality and efficiency. The present research investigates the optimal replication process for mandrel ultraprecision machining, polishing, coating, electroforming nickel, and demolding. It analyzes the factors contributing to the challenging separation and the inability to release the mirror shells. Additionally, an automatic demolding device is developed, and the X-ray performance of the replication mirrors is verified. The fabrication process flow of the mirrors was initially introduced. To ensure the easy release of the mirror shells from the mandrels, a layer of diamond-like carbon (DLC) was applied as a release layer between the Au and NiP alloy. The adhesion strength of Au-C was found to be significantly lower than that of Au-NiP, as demonstrated by both molecular dynamic simulation and tensile testing. The development of an automatic demolding device with force feedback has been successfully completed. The reduction in the half-power diameter (HPD) of the mirror from 48 inches to 25 inches is an improvement that surpasses the production target.
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Natural killer(NK) cells comprise one subset of the innate lymphoid cells family. Despite reported anti-tumor activity of NK cells, their tangible contribution to tumor control remains controversial. This is due to the incomplete understanding of NK alterations within tumor microenvironment(TME). Here we showed, using murine hepatocellular carcinoma(HCC) model, that early NK cells deletion markedly attenuated tumor growth in a CD8+T cells dependent manner. This effect was accompanied by an enhanced CD8+T cells effector function in tumor rather than circulating blood. Then, we demonstrated that abundant NKp46+ NK subset, but not NKp46- NK, were recruited towards tumor microenvironment during tumor progression. Frequency of intratumor NKP46+ NK cells were inversely related to CD8+T cells activation, and positively correlated with tumor growth. Intratumor NKp46+ NK cells exhibited dysfunction and increased expression of inhibitory receptors, when compared with NKp46- NK cells. Blockade of NK cells-associated NKp46 effectively attenuated HCC growth. Infusion of tumor-derived NKp46+ NK cells markedly enhanced HCC growth in vivo, in contrast to tumor cells inoculation alone. The further mechanistic investigations unveiled that NK cells boosted tumor growth by NKp46-mediated impairment of CD8+T cells effector function. Overall, this work supported a previously unappreciated regulatory property of tumor-associated NK cells in HCC, and NKp46 as a potential target against HCC in clinical setting.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Animales , Ratones , Carcinoma Hepatocelular/metabolismo , Linfocitos T CD8-positivos/metabolismo , Inmunidad Innata , Células Asesinas Naturales/metabolismo , Neoplasias Hepáticas/metabolismo , Receptor 1 Gatillante de la Citotoxidad Natural/metabolismo , Microambiente TumoralRESUMEN
Streptococcus suis (S. suis) is an important food-borne zoonotic pathogen that causes swine streptococcosis, which threatens human health and brings economic loss to the swine industry. Three-quarters of human S. suis infections are caused by serotype 2. A retrospective analysis of human S. suis cases in Shenzhen, a megacity in China, with high pork consumption, between 2005 and 2021 was conducted to understand its genomic epidemiology, pathogen virulence, and drug resistance characteristics. The epidemiological investigation showed that human cases of S. suis in Shenzhen were mainly associated with people who had been in close contact with raw pork or other swine products. Whole-genome sequence analysis showed that 33 human isolates in Shenzhen were dominated by serotype 2 (75.76%), followed by serotype 14 (24.24%), and the most prevalent sequence types (STs) were ST7 (48.48%) and ST1 (39.40%). ST242 (9.09%) and ST25 (3.03%), which were rarely reported, were also found. Phylogenetic analysis showed that the Shenzhen human isolates had close genetic relatedness to isolates from Guangxi (China), Sichuan (China), and Vietnam. We found a new 82 KB pathogenicity island (PAI) in the serotype 2 isolate that may play a role in sepsis. Similarly, a serotype 14 isolate, containing 78 KB PAI, was isolated from a patient presenting with streptococcal toxic shock syndrome (STSLS) who subsequently died. Multi-drug resistance (MDR) was high in human isolates of S. suis from Shenzhen. Most human isolates were resistant to tetracycline, streptomycin, erythromycin, and clindamycin, and 13 isolates had intermediate resistance to penicillin. In conclusion, swine importation from Guangxi, Sichuan, and Vietnam should be more closely monitored, and the use of antibiotics limited to reduce the potential for antimicrobial resistance (AMR).
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Background: Chlamydia psittaci is a small bacterium often found in birds, including poultry, and domesticated mammals, which causes psittacosis (or parrot fever) in humans. Different strains of C. psittaci respond variably to antibiotics, suggesting a possible risk of antibiotic resistance. In general, different genotypes of C. psittaci have relatively stable hosts and different pathogenicity. Methods: Macrogenomic sequencing was performed using nucleic acids extracted from psittacosis patients' alveolar lavage fluid samples and analyzed for genetic variability and antibiotic resistance genes. Nucleic acid amplification sequences specific to the core coding region of the C. psittaci ompA gene were used, and a phylogenetic tree was constructed with C. psittaci genotypic sequences from other sources, including Chinese published sources. The C. psittaci found in each patient were genotyped by comparing ompA gene sequences. In addition, to better illustrate the relationship between genotype and host of C. psittaci, 60 bird fecal samples were collected from bird-selling stores for screening and C. psittaci typing. Results: Macrogenomic sequence alignment revealed the presence of resistance genes in varying abundance in samples from all three patients, including C. psittaci resistance gene sequences from two patients that matched those previously published on NCBI. Based on ompA genotyping, two patients were infected with C. psittaci genotype A and one patient was infected with genotype B. All five C. psittaci-positive samples obtained from bird-selling stores were genotype A. Both genotypes are reported to be infectious to humans. The host origin of the samples and the previously reported main sources of each genotype suggested that all but one of the C. psittaci genotype A in this study were derived from parrots, while genotype B was probably derived from chickens. Conclusion: The presence of bacterial resistance genes in psittacosis patients may affect the efficacy of clinical antibiotic therapy. Focusing on the developmental progression of bacterial resistance genes and differences in the therapeutic efficacy may facilitate effective treatment of clinical bacterial infections. Pathogenicity genotypes (e.g., genotype A and genotype B) are not limited to one animal host, suggesting that monitoring the development and changes of C. psittaci may help prevent transmission to humans.
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We analyzed variations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome during a flight-related cluster outbreak of coronavirus disease 2019 (COVID-19) in Shenzhen, China, to explore the characteristics of SARS-CoV-2 transmission and intra-host single nucleotide variations (iSNVs) in a confined space. Thirty-three patients with COVID-19 were sampled, and 14 were resampled 3-31 days later. All 47 nasopharyngeal swabs were deep-sequenced. iSNVs and similarities in the consensus genome sequence were analyzed. Three SARS-CoV-2 variants of concern, Delta (n = 31), Beta (n = 1), and C.1.2 (n = 1), were detected among the 33 patients. The viral genome sequences from 30 Delta-positive patients had similar SNVs; 14 of these patients provided two successive samples. Overall, the 47 sequenced genomes contained 164 iSNVs. Of the 14 paired (successive) samples, the second samples (T2) contained more iSNVs (median: 3; 95% confidence interval [95% CI]: 2.77-10.22) than did the first samples (T1; median: 2; 95% CI: 1.63-3.74; Wilcoxon test, P = 0.021). 38 iSNVs were detected in T1 samples, and only seven were also detectable in T2 samples. Notably, T2 samples from two of the 14 paired samples had additional mutations than the T1 samples. The iSNVs of the SARS-CoV-2 genome exhibited rapid dynamic changes during a flight-related cluster outbreak event. Intra-host diversity increased gradually with time, and new site mutations occurred in vivo without a population transmission bottleneck. Therefore, we could not determine the generational relationship from the mutation site changes alone.
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Importance: Assessment of additional protection of a booster dose with an inactivated SARS-CoV-2 vaccine is key to developing vaccination strategies for billions of people worldwide who have received the primary 2-dose regimen. Objective: To estimate the relative effectiveness of a booster dose of an inactivated SARS-CoV-2 vaccine against Omicron infection. Design, Setting, and Participants: This cohort study was conducted among primary close contacts without previous SARS-CoV-2 infection identified in Shenzhen, China, between February and October 2022. Multiple strict nucleic acid testing and symptom surveillance for SARS-CoV-2 infection were regularly conducted during the 7-day centralized plus 7-day home-based quarantine. Exposure: A booster with an inactivated SARS-CoV-2 vaccine vs no booster after receipt of the primary 2-dose inactivated SARS-CoV-2 vaccine regimen. Main Outcomes and Measures: The primary outcomes were overall, symptomatic, and asymptomatic infections. Secondary outcomes were length of incubation and level of cycle threshold values. All the outcomes were assessed during the quarantine period. Results: Among 119â¯438 eligible participants (mean [SD] age, 37.6 [12.0] years; 66â¯201 men [55.4%]), 86â¯251 (72.2%) received a booster dose of an inactivated SARS-CoV-2 vaccine and 33â¯187 (27.8%) did not. A total of 671 cases infected with Omicron BA.2 were confirmed (464 symptomatic and 207 asymptomatic), and no severe infection or death events were observed. At a median (IQR) duration of 111 (75 to 134) days after booster vaccination, the relative effectiveness of a booster was 32.2% (95% CI, 11.3% to 48.2%) for overall infection, 23.8% (95% CI, -8.2% to 46.4%) for symptomatic infection, and 43.3% (95% CI, 12.3% to 63.3%) for asymptomatic infection. The effectiveness against overall infection changed nonlinearly over time following booster vaccination: 44.9% (95% CI, 4.9% to 68.1%) within 60 days, 50.4% (95% CI, 23.7% to 67.7%) at 61 to 120 days, 29.1% (95% CI, -4.8% to 52.1%) at 121 to 180 days, and 19.4% (95% CI, -14.4% to 43.2%) after 180 days (nonlinear P = .03). The effectiveness did not vary significantly according to the interval between booster vaccination and completion of primary vaccination. There was no association of booster vaccination with incubation or cycle threshold values. Conclusions and Relevance: In this cohort study, a booster dose of an inactivated SARS-CoV-2 vaccine provided additional moderate protection against mild infection for 120 days after receipt, but more research is needed to determine the optimal timing of a booster and its effectiveness in preventing severe infection for a longer duration.
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Vacunas contra la COVID-19 , COVID-19 , Masculino , Humanos , Adulto , Vacunas contra la COVID-19/uso terapéutico , COVID-19/prevención & control , Estudios de Cohortes , Cuarentena , SARS-CoV-2 , Infecciones AsintomáticasRESUMEN
Ovarian cancer (OC) is one of the most common cancer in women worldwide. A recent study reported that long noncoding RNA (lncRNA) Ubiquitin like modifier activating enzyme 6 antisense RNA 1 (UBA6-AS1) is significantly correlated with the prognosis of patients with OC and also involved in N6-methyladenosine (m6A) regulation. However, its influence on OC progression and the underlying mechanism is still not well demonstrated. Here, we found that UBA6-AS1 directly associated with UBA6 mRNA and inhibited its decay. Further mechanism investigation revealed that UBA6-AS1 increased the m6A methylation of UBA6 mRNA via recruiting RNA binding motif protein 15 (RBM15). Insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) was identified as the m6A reader protein of UBA6-AS1-RBM15-mediated m6A modification of UBA6 mRNA, which enhanced the stability of UBA6 mRNA. Functionally, UBA6-AS1 suppressed the proliferation, migration and invasion of OC cells via UBA6. Moreover, UBA6-AS1 positively correlated with UBA6 expression in OC tissues. Downregulation of UBA6-AS1 or UBA6 expression indicated poor. Collectively, we have identified a tumor-suppressive lncRNA that regulates its target mRNA via a m6A mechanism, highlighting the role that lncRNAs can play in OC progression.
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Neoplasias Ováricas/genética , ARN Largo no Codificante/genética , ARN Mensajero/metabolismo , Proteínas de Unión al ARN/metabolismo , Enzimas Activadoras de Ubiquitina/genética , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Ováricas/metabolismo , Pronóstico , Estabilidad del ARN , Regulación hacia ArribaRESUMEN
Objective: To understand the related influencing factors of outpatient hypertension detection and control and self-test control compliance rate. Methods: A total of 637 hypertensive patients who visited the outpatient clinic of our hospital from January 2021 to December 2021 were selected for investigation and research, and the relevant information such as blood pressure, treatment detection, and other related information of the patients were counted, and the detection and control of outpatient hypertension were explored through regression analysis and the related factors of the self-test control compliance rate. Results: There was no statistically significant difference in the number of patients who met the standard or not under the gender difference (P > 0.05), and it can be found that there was no statistically significant difference in the age of patients who met the standard and those who did not (P > 0.05). The proportion of patients with self-test hypertension control at home was 64.68%, and the compliance rate of self-test blood pressure was 42.54%. The compliance rate of blood pressure control in outpatient testing was 61.85%. Heart rate, exercise, smoking, medication compliance, and other factors are important factors affecting the control of hypertension. Knowing hypertension-related knowledge, regular follow-up, office blood pressure compliance, smoking, excessive salt intake, and hypertension complications are important factors affecting the self-test control of hypertension in the family. Conclusion: By urging patients to do daily physical exercise, admonishing patients to quit smoking, and improving patients' medication compliance, the control rate of hypertension in outpatient clinics can be effectively improved. Understanding the knowledge of hypertension, controlling the salt content in the diet, and receiving regular follow-up surveys from doctors can effectively improve the effect of self-measurement and control of blood pressure at home and further improve the control rate of hypertension.
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Hipertensión , Autoevaluación (Psicología) , Humanos , Cloruro de Sodio Dietético/uso terapéutico , Hipertensión/diagnóstico , Hipertensión/tratamiento farmacológico , Cooperación del Paciente , Instituciones de Atención AmbulatoriaRESUMEN
In view of the fact that the noise in the same frequency band as the useful signal in the MEMS acceleration sensor observation data cannot be effectively removed by traditional filtering methods, a denoising method for strong earthquake signals based on the theory of sparse representation and compressive sensing is proposed in this paper. This skillfully realized the separation of strong earthquake signals from noise by adopting a fixed dictionary and utilizing sparse characteristics. Furthermore, considering the weakness of the sparse denoising method based on the fixed dictionary in the high signal-to-noise ratio, a spare denoising method based on learning an over-complete dictionary is proposed. Through the initial given seismic data, the ideal over-complete dictionary is trained to achieve seismic data denoising. In addition, for the interference waves of non-seismic events, this paper proposes an idea based on sparse representation classification to remove such non-seismic interference directly. Combining the ideas of noise reduction and non-seismic event elimination, we can obtain a standard sparse anti-interference denoising model for earthquake early warning. It's innovative that this model implements the sparse theory into the field of earthquake early warning. According to the experimental results, in the case of heavy noise, the denoising model based on sparse representation can reach average SNR of 8.73 and an average MSE of 29.53, and the denoising model based on compression perception can reach average SNR of 7.29 and an average MSE 41.34, and the denoising model based on learning dictionary can reach average SNR 11.07 and average MSE 17.32. The performance of these models is better than the traditional FIR filtering method (average SNR -0.73 and average MSE 260.37) or IIR filtering method (average SNR 4.73 and average MSE 73.95). On the other hand, the anti-interference method of the sparse classification proposed in this paper can accurately distinguish non-seismic interference events from natural earthquakes. The classification accuracy of the method based on the noise category of the selected test data set reaches 100% and achieves good results.
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Long non-coding RNAs are essential to hepatocellular carcinoma (HCC) development, progression, and incidence of drug resistance. However, the biological significance of long non-coding RNA muskelin 1 antisense RNA (MKLN1-AS) remains poorly characterized. In this study, we observed noticeable increased levels of MKLN1-AS in HCC tissues. This upregulation of MKLN1-AS was clinically associated with vascular invasion and decreased disease-free survival and overall survival of patients with HCC. Functionally, MKLN1-AS-knockdown dramatically suppressed the metastasis and growth of HCC cells in vitro and in vivo. Additionally, the knockdown of MKLN1-AS augmented the pro-apoptosis effect of lenvatinib. Taken together, our findings indicate that MKLN1-AS may be exploited as a potential prognostic predictor and therapeutic target for HCC treatment.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , ARN sin Sentido , ARN Largo no Codificante , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , MicroARNs/genética , Compuestos de Fenilurea/farmacología , Quinolinas/farmacología , ARN sin Sentido/genética , ARN sin Sentido/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismoRESUMEN
As the largest water conservancy and hydropower project in China, the Three Gorges Reservoir is a weak seismic activity area before impoundment, but the frequency of earthquakes increases significantly after impoundment. The spatial density scanning method was used to obtain the characteristics of spatio-temporal earthquake distribution in the reservoir area during loading and unloading processes. The results show that the frequencies of earthquakes during the loading and unloading processes were higher than that during the low-water-level operation period, which is well explained by the acoustic emission test results. The seismic b-value, fractal dimension D, and spatial correlation length SCL can be used together to indicate stress criticality. To analyze the impacts of reservoir water loading and unloading on seismicity in the reservoir area, time-scan analyses were performed on the b-value, D-value, and SCL of earthquakes near the Zigui segment and the Badong segment. Previous studies argued that the time-varying characteristics of b-values do not hold predictive significance for earthquakes in the M4.0-6.2 range. However, our study found that the time-varying characteristics of b-values are of predictive significance for earthquakes around M4.0. These seismic parameters decrease significantly before moderate earthquakes but at different rates in different regions.