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BACKGROUND: Tenecteplase is an effective thrombolytic agent for eligible patients with stroke who are treated within 4.5 hours after the onset of stroke. However, data regarding the effectiveness of tenecteplase beyond 4.5 hours are limited. METHODS: In a trial conducted in China, we randomly assigned patients with large-vessel occlusion of the middle cerebral artery or internal carotid artery who had salvageable brain tissue as identified on perfusion imaging and who did not have access to endovascular thrombectomy to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or standard medical treatment 4.5 to 24 hours after the time that the patient was last known to be well (including after stroke on awakening and unwitnessed stroke). The primary outcome was the absence of disability, which was defined as a score of 0 or 1 on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability), at day 90. The key safety outcomes were symptomatic intracranial hemorrhage and death. RESULTS: A total of 516 patients were enrolled; 264 were randomly assigned to receive tenecteplase and 252 to receive standard medical treatment. Less than 2% of the patients (4 in the tenecteplase group and 5 in the standard-treatment group) underwent rescue endovascular thrombectomy. Treatment with tenecteplase resulted in a higher percentage of patients with a modified Rankin scale score of 0 or 1 at 90 days than standard medical treatment (33.0% vs. 24.2%; relative rate, 1.37; 95% confidence interval, 1.04 to 1.81; P = 0.03). Mortality at 90 days was 13.3% with tenecteplase and 13.1% with standard medical treatment, and the incidence of symptomatic intracranial hemorrhage within 36 hours after treatment was 3.0% and 0.8%, respectively. CONCLUSIONS: In this trial involving Chinese patients with ischemic stroke due to large-vessel occlusion, most of whom did not undergo endovascular thrombectomy, treatment with tenecteplase administered 4.5 to 24 hours after stroke onset resulted in less disability and similar survival as compared with standard medical treatment, and the incidence of symptomatic intracranial hemorrhage appeared to be higher. (Funded by the National Natural Science Foundation of China and others; TRACE-III ClinicalTrials.gov number, NCT05141305.).
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Fibrinolíticos , AVC Isquêmico , Tenecteplase , Tempo para o Tratamento , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fibrinolíticos/uso terapêutico , Fibrinolíticos/efeitos adversos , Fibrinolíticos/administração & dosagem , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/cirurgia , Hemorragias Intracranianas/etiologia , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/etiologia , AVC Isquêmico/cirurgia , Tenecteplase/uso terapêutico , Tenecteplase/efeitos adversos , Trombectomia , Ativador de Plasminogênio Tecidual/administração & dosagem , Ativador de Plasminogênio Tecidual/efeitos adversos , Ativador de Plasminogênio Tecidual/uso terapêutico , ChinaRESUMO
BACKGROUND: Infections caused by linezolid-resistant enterococci (LRE) are clinically difficult to treat and threaten patient health. However, there is a lack of studies on long time-span LRE strains in China. For this reason, our study comprehensively revealed the resistance mechanisms of LRE strains collected in a Chinese tertiary care hospital from 2011 to 2022. METHODS: Enterococcal strains were screened and verified after retrospective analysis of microbial data. Subsequently, 65 LRE strains (61 Enterococcus faecalis and 4 Enterococcus faecium, MIC ≥ 8 µg/ml), 1 linezolid-intermediate Enterococcus faecium (MIC = 4 µg/ml) and 1 linezolid-susceptible Enterococcus faecium (MIC = 1.5 µg/ml) were submitted for whole-genome sequencing (WGS) analysis and bioinformatics analysis. RESULTS: The optrA gene was found to be the most common linezolid resistance mechanism in our study. We identified the wild-type OptrA and various OptrA variants in 98.5% of LRE strains (61 Enterococcus faecalis and 3 Enterococcus faecium). We also found one linezolid-resistant Enterococcus faecium strain carried both optrA and cfr(D) gene, while one linezolid-resistant Enterococcus faecium only harbored the poxtA gene. Most optrA genes (55/64) were located on plasmids, with impB-fexA-optrA, impB-fexA-optrA-erm(A), fexA-optrA-erm(A), and fexA-optrA segments. A minority of optrA genes (9/64) were found on chromosomes with the Tn6674-like platform. Besides, other possible linezolid resistance-associated mechanisms (mutations in the rplC and rplD genes) were also found in 26 enterococcal strains. CONCLUSIONS: Our study suggested that multiple mechanisms of linezolid resistance exist among clinical LRE strains in China.
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Antibacterianos , Farmacorresistência Bacteriana , Enterococcus faecalis , Enterococcus faecium , Infecções por Bactérias Gram-Positivas , Linezolida , Testes de Sensibilidade Microbiana , Sequenciamento Completo do Genoma , Linezolida/farmacologia , China/epidemiologia , Humanos , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Bactérias Gram-Positivas/epidemiologia , Enterococcus faecium/genética , Enterococcus faecium/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecalis/genética , Antibacterianos/farmacologia , Estudos Retrospectivos , Enterococcus/efeitos dos fármacos , Enterococcus/genética , Proteínas de Bactérias/genética , Genoma Bacteriano , Epidemiologia Molecular , Centros de Atenção Terciária , GenômicaRESUMO
Excessive exposure to light is a global issue. Artificial light pollution has been shown to disrupt the body's natural circadian rhythm. To investigate the impacts of light on metabolism, we studied Sprague-Dawley rats chronically exposed to red or blue light during daytime or nighttime. Rats in the experimental group were exposed to extended light for 4â¯hours during daytime or nighttime to simulate the effects of excessive light usage. Strikingly, we found systemic metabolic alterations only induced by blue light during daytime. Furthermore, we conducted metabolomic analyses of the cerebrospinal fluid, serum, heart, liver, spleen, adrenal, cerebellum, pituitary, prostate, spermatophore, hypothalamus and kidney from rats in the control and blue light exposure during daytime. Signiï¬cant changes in metabolites have been observed in cerebrospinal fluid, serum, hypothalamus and kidney of rats exposed to blue light during daytime. Metabolic alterations observed in rats encompassing pyruvate metabolism, glutathione metabolism homocysteine degradation, phosphatidylethanolamine biosynthesis, and phospholipid biosynthesis, exhibit analogous patterns to those inherent in specific physiological processes, notably neurodevelopment, cellular injury, oxidative stress, and autophagic pathways. Our study provides insights into tissue-specific metabolic changes in rats exposed to blue light during the daytime and may help explain potential mechanisms of photopathogenesis.
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Ritmo Circadiano , Luz , Ratos Sprague-Dawley , Animais , Masculino , Ratos , Metabolômica , Estresse Oxidativo/efeitos da radiação , Rim/metabolismo , Rim/efeitos da radiação , Luz AzulRESUMO
BACKGROUND: Ureaplasma species are common pathogens of the urogenital tract and can cause a range of diseases. Unfortunately, there is still a scarcity of large-scale and cross-sectional studies on the prevalence of Ureaplasma species in China to clarify their epidemic patterns. METHODS: This study retrospectively analyzed the data of 18667 patients who visited Peking Union Medical College Hospital for showing various symptoms of (suspected) Ureaplasma species infection during the period 2013-2022. The overall prevalence of Ureaplasma species was calculated, and subgroup analyses were conducted in view of gender, age, specimen types, and diagnosis in every year within the period studied. Furthermore, previous literature that reported on the prevalence of Ureaplasma species in various regions of China was searched and summarized. RESULTS: The overall positive rate of Ureaplasma species in this study reached 42.1% (7861/18667). Specifically, the prevalence of Ureaplasma species was significantly higher in female patients, while the highest detection rate was found in the 21-50 age group. From 2013 to 2022, there were no significant differences in positive rates of Ureaplasma species among years. However, the detection rate of Ureaplasma species was decreased in COVID-19 period (2020-2022) compared to pre-COVID-19 period (2017-2019). In view of the distribution of patients, outpatients predominated, but the detection rate was lower than inpatients. Urine was the most common specimen type, while cervical swabs had the highest detection rate of Ureaplasma species. When grouped by diagnosis, the highest positive rate of Ureaplasma species was seen in patients with adverse pregnancy outcomes and the lowest rate in patients with prostate disease. The previous literature, although heterogeneous, collectively suggested a high prevalence of Ureaplasma species in China. CONCLUSIONS: Our study has shown that Ureaplasma species have reached a significant prevalence in China and demands adequate attention.
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COVID-19 , Infecções por Mycoplasma , Infecções por Ureaplasma , Masculino , Gravidez , Humanos , Feminino , Ureaplasma , Estudos Retrospectivos , Prevalência , Centros de Atenção Terciária , Estudos Transversais , Infecções por Mycoplasma/microbiologia , Mycoplasma hominis , Infecções por Ureaplasma/epidemiologia , Infecções por Ureaplasma/microbiologia , Ureaplasma urealyticumRESUMO
PURPOSE: To investigate the performance of novel intraocular lens calculation formulae (Barrett Universal II, Emmetropia Verifying Optical, and Kane) and conventional formulae (Haigis, Hoffer Q, Holladay 1, and Sanders-Retzlaff-Kraff/T [SRK/T]) in patients who underwent pars plana vitrectomy or silicone oil removal combined with cataract surgery. METHODS: In total, 301 eyes from 301 patients who underwent pars plana vitrectomy/silicone oil removal with concomitant cataract surgery were enrolled and divided into the following four groups according to preoperative diagnosis: silicone oil-filled eyes after pars plana vitrectomy, epiretinal membrane, primary retinal detachment, and macular hole. RESULTS: Barrett Universal II exhibited the smallest mean absolute error (0.65 diopters [D]) and median absolute error (0.39 D) in total. In patients with primary retinal detachment, each formula exhibited the worst refractive outcomes in diverse vitreoretinal pathologies ( P < 0.01), and no difference in accuracy between the seven formulas was observed ( P = 0.075). For long eyes, the second linear (Wang-Koch 2) version of the Wang-Koch adjustment significantly reduced the median absolute error for Holladay 1 and SRK/T ( P < 0.001 and P = 0.019). CONCLUSION: In combined surgery, both new and conventional formulas using the second linear version of the Wang-Koch 2 adjustment demonstrated satisfactory performance, with Barrett Universal II exhibiting the best overall performance. However, in patients with primary retinal detachment, all seven formulas showed less favorable performance.
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Catarata , Lentes Intraoculares , Facoemulsificação , Descolamento Retiniano , Humanos , Óleos de Silicone , Vitrectomia , Descolamento Retiniano/cirurgia , Implante de Lente Intraocular , Refração Ocular , Biometria , Estudos Retrospectivos , Óptica e Fotônica , Comprimento Axial do OlhoRESUMO
BACKGROUND AND PURPOSE: This study assessed the predictive factors for symptomatic intracranial hemorrhage (sICH) in patients with acute ischemic stroke (AIS) after receiving intravenous thrombolysis (IVT) within 6 h in northern China. METHODS: We retrospectively analyzed ischemic stroke patients who were treated with IVT between November 2016 and December 2018 in 19 hospitals in Shandong Province, China. Potential predictors of sICH were investigated using univariate and multivariate analyses. RESULTS: Of the 1293 enrolled patients (845 men, aged 62 ± 11 years), 33 (2.6%) developed sICH. The patients with sICH had increased coronary heart disease (36.4% vs. 13.7%, P = 0.001), more severe stroke (mean National Institutes of Health Stroke Scale [NIHSS] score on admission of 14 vs.7, P < 0.001), longer door-to-needle time [DNT] (66 min vs. 50 min, P < 0.001), higher blood glucose on admission, higher white blood cell counts (9000/mm3 vs. 7950/mm3, P = 0.004) and higher neutrophils ratios (73.4% vs. 67.2%, P = 0.006) et al. According to the results of multivariate analysis, the frequency of sICH was independently associated with the NIHSS score (OR = 3.38; 95%CI [1.50-7.63]; P = 0.003), DNT (OR = 4.52; 95%CI [1.69-12.12]; P = 0.003), and white blood cell count (OR = 3.59; 95%CI [1.50-8.61]; P = 0.004). When these three predictive factors were aggregated, compared with participants without any factors, the multi-adjusted odds ratios (95% confidence intervals) of sICH for persons concurrently having one, two or three of these factors were 2.28 (0.25-20.74), 15.37 (1.96-120.90) and 29.05 (3.13-270.11), respectively (P for linear trend < 0.001), compared with participants without any factors. CONCLUSION: NIHSS scores higher than 10 on admission, a DNT > 50 min, and a white blood cell count ≥9000/mm3 were independent risk factors for sICH in Chinese patients within 6 h after IVT for AIS.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/epidemiologia , China/epidemiologia , Fibrinolíticos/uso terapêutico , Humanos , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/epidemiologia , Masculino , Estudos Retrospectivos , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Terapia Trombolítica/efeitos adversos , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Venous thromboembolism (VTE) is a life-threatening cardiovascular syndrome that characterized by the imbalance of hemostasis and thrombosis and the formation of thrombi in the blood vessels. The aim of this study was to elucidate the clinical impact of the PAI-1 4G/5G polymorphism in Chinese patients with VTE. METHODS: A total of 169 subjects (89 VTE, 10 hyperbilirubinemia, 10 hyperlipidemia and 60 healthy controls) were recruited at Peking Union Medical College Hospital. The accuracy of the TaqMan-MGB RT-PCR method for detecting F5 G1691A (FVL) and PAI-1 4G/5G polymorphisms was evaluated by using sequencing method as the gold standard. Besides, the association of the PAI-1 4G/5G polymorphism with susceptibility, treatment efficacy and recurrence status of VTE in Chinese population were explored. Eventually, the plasma PAI-1 antigen levels and PAI-1 4G/5G polymorphisms were determined on additional 64 subjects (32 VTE and 32 healthy controls) simultaneously. RESULTS: The TaqMan-MGB RT-PCR method was proven to be highly accurate in determining the FVL and PAI-1 4G/5G polymorphisms without interference from bilirubin and lipids in the samples. No obvious correlation of the PAI-1 4G/5G polymorphism with VTE was observed in our study by using five genetic models (allele, genotype, dominant, recessive and additive). Additionally, we also observed that individuals with the 4G/5G genotype had lower neutrophil counts and neutrophil-to-lymphocyte ratio (NLR) than the 5G/5G genotype. Furthermore, we found that the patients with the 5G/5G genotype were more likely to achieve complete recanalization compared to the 4G/4G genotype. In addition, individuals carrying the 5G/5G genotype were more likely to develop a recurrence-free status as compared to individuals with the 4G/4G or 4G/5G genotypes. PAI-1 antigen levels in the VTE group were significantly higher than those in the HC group. However, there was no significant difference in the antigen levels of PAI-1 among subjects carrying various genotypes in the VTE group or HC group. CONCLUSION: The PAI-1 4G/5G polymorphism has potential value in assessing the prognosis of Chinese patients with VTE. Our study has laid the foundation for the application of PAI-1 4G/5G polymorphism in the personalized management and monitoring of patients with VTE.
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Tomato spotted wilt virus (TSWV) poses a serious threat to tomato (Solanum lycopersicum) production. In this study, tomato inbred line YNAU335 was developed without the Sw-5 locus, which confers resistance or immunity to TSWV (absence of infection). Genetic analysis demonstrated that immunity to TSWV was controlled by a dominant nuclear gene. The candidate genes were mapped into a 20-kb region in the terminal of the long arm of chromosome 9 using bulk segregant analysis and linkage analysis. In this candidate region, a chalcone synthase-encoding gene (SlCHS3) was identified as a strong candidate gene for TSWV resistance. Silencing SlCHS3 reduced flavonoid synthesis, and SlCHS3 overexpression increased flavonoid content. The increase in flavonoids improved TSWV resistance in tomato. These findings indicate that SlCHS3 is indeed involved in the regulation of flavonoid synthesis and plays a significant role in TSWV resistance of YNAU335. This could provide new insights and lay the foundation for analyzing TSWV resistance mechanisms. Supplementary information: The online version contains supplementary material available at 10.1007/s11032-022-01325-5.
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BACKGROUND: Bagging can improve the appearance of fruits and increase the food safety and commodification, it also has effects on intrinsic quality of the fruits, which was commonly reported negative changes. Fig can be regarded as a new model fruit with its relatively small genome size and long fruit season. RESULTS: In this study, widely targeted metabolomics based on HPLC MS/MS and RNA-seq of the fruit tissue of the 'Zibao' fig before and after bagging were analyzed to reveal the metabolites changes of the edible part of figs and the underneath gene expression network changes. A total of 771 metabolites were identified in the metabolome analysis using fig female flower tissue. Of these, 88 metabolites (including one carbohydrate, eight organic acids, seven amino acids, and two vitamins) showed significant differences in fruit tissue before and after bagging. Changes in 16 structural genes, 13 MYB transcription factors, and endogenous hormone (ABA, IAA, and GA) metabolism and signal transduction-related genes in the biosynthesis pathway of flavonoids after bagging were analyzed by transcriptome analysis. KEGG enrichment analysis also determined significant differences in flavonoid biosynthesis pathways in female flower tissue before and after bagging. CONCLUSIONS: This work provided comprehensive information on the composition and abundance of metabolites in the female flower tissue of fig. The results showed that the differences in flavor components of the fruit before and after bagging could be explained by changes in the composition and abundance of carbohydrates, organic acids, amino acids, and phenolic compounds. This study provides new insights into the effects of bagging on changes in the intrinsic and appearance quality of fruits.
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Ficus/genética , Ficus/metabolismo , Flavonoides/análise , Flavonoides/biossíntese , Flavonoides/genética , Frutas/genética , Frutas/metabolismo , China , Produtos Agrícolas/genética , Produtos Agrícolas/metabolismo , Flores/genética , Flores/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Variação Genética , Genótipo , MetabolomaRESUMO
Abnormal elevated levels of cytokines such as interferon (IFN), interleukin (IL), and tumor necrosis factor (TNF), are considered as one of the prognosis biomarkers for indicating the progression to severe or critical COVID-19. Hence, it is of great significance to develop devices for monitoring their levels in COVID-19 patients, and thus enabling detecting COVID-19 patients that are worsening and to treat them before they become critically ill. Here, an intelligent aptameric dual channel graphene-TWEEN 80 field effect transistor (DGTFET) biosensing device for on-site detection of IFN-γ, TNF-α, and IL-6 within 7 min with limits of detection (LODs) of 476 × 10-15 , 608 × 10-15 , or 611 × 10-15 m respectively in biofluids is presented. Using the customized Android App together with this intelligent device, asymptomatic or mild COVID-19 patients can have a preliminary self-detection of cytokines and get a warning reminder while the condition starts to deteriorate. Also, the device can be fabricated on flexible substrates toward wearable applications for moderate or even critical COVID-19 cases for consistently monitoring cytokines under different deformations. Hence, the intelligent aptameric DGTFET biosensing device is promising to be used for point-of-care applications for monitoring conditions of COVID-19 patients who are in different situations.
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COVID-19 , Grafite , Biomarcadores , Síndrome da Liberação de Citocina , Citocinas , Humanos , Interleucina-6 , SARS-CoV-2RESUMO
BACKGROUND: C5aR has been extensively studied in recent years as an essential component of the complement system. However, the role of C5aR in tumors has not been sufficiently investigated and summarized. The aim of this meta-analysis was to investigate the prognostic value of C5aR in solid tumors as well as the correlation between C5aR and clinicopathological features. METHODS: Relevant study collection was performed in PubMed, Embase, Web of Science, BIOSIS Previews, Cochrane Library until July 10, 2021. Pooled hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Sensitivity analyses were performed to assess the robustness of this study, while publication bias was tested by Begg's and Egger's tests. RESULTS: A total of 11 studies involving 1577 patients were included in the study. Our results suggest that the high-level C5aR expression in tumor tissue predicted unsatisfactory overall survival (OS) (HR = 1.92, 95% CI:1.47-2.50, P < 0.001) and recurrence-free survival (RFS) (HR = 2.19, 95% CI:1.47-3.27, P < 0.001). Besides, a higher level of C5aR expression was associated with larger tumor size (OR = 1.58, 95% CI: 1.18-2.10, P = 0.002) and the occurrence of metastases in lymph nodes (OR = 1.99, 95% CI: 1.46-2.72, P<0.001), whereas it was independent of tumor stage, vascular invasion and tumor differentiation. CONCLUSION: In conclusion, C5aR may be a potential biomarker for evaluating tumor prognosis and treatment.
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Biomarcadores Tumorais/metabolismo , Receptor da Anafilatoxina C5a/metabolismo , Humanos , PrognósticoRESUMO
Counting the number of work cycles per unit of time of earthmoving excavators is essential in order to calculate their productivity in earthmoving projects. The existing methods based on computer vision (CV) find it difficult to recognize the work cycles of earthmoving excavators effectively in long video sequences. Even the most advanced sequential pattern-based approach finds recognition difficult because it has to discern many atomic actions with a similar visual appearance. In this paper, we combine atomic actions with a similar visual appearance to build a stretching-bending sequential pattern (SBSP) containing only "Stretching" and "Bending" atomic actions. These two atomic actions are recognized using a deep learning-based single-shot detector (SSD). The intersection over union (IOU) is used to associate atomic actions to recognize the work cycle. In addition, we consider the impact of reality factors (such as driver misoperation) on work cycle recognition, which has been neglected in existing studies. We propose to use the time required to transform "Stretching" to "Bending" in the work cycle to filter out abnormal work cycles caused by driver misoperation. A case study is used to evaluate the proposed method. The results show that SBSP can effectively recognize the work cycles of earthmoving excavators in real time in long video sequences and has the ability to calculate the productivity of earthmoving excavators accurately.
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Cytoplasmic male sterility (CMS) is a maternally inherited trait that derives from the inability to produce functional pollen in higher plants. CMS results from recombination of the mitochondrial genome. However, understanding of the molecular mechanism of CMS in pepper is limited. In this study, comparative transcriptomic analyses were performed using a near-isogenic CMS line 14A (CMS-14A) and a maintainer line 14B (ML-14B) as experimental materials. A total of 17,349 differentially expressed genes were detected between CMS-14A and ML-14B at the PMC meiosis stage. Among them, six unigenes associated with CMS and 108 unigenes involved in energy metabolism were identified. The gene orf165 was found in CMS-14A. When orf165 was introduced into ML-14B, almost 30% of transgenic plants were CMS. In addition, orf165 expression in transgenic CMS plants resulted in abnormal function of some genes involved in energy metabolism. When orf165 in transgenic CMS plant was silenced, the resulted orf165-silenced plant was male fertile and the expression patterns of some genes associated with energy metabolism were similar to ML-14B. Thus, we confirmed that orf165 influenced CMS in pepper.
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Non-small-cell lung cancer (NSCLC) accounts for nearly 85% of lung cancer cases. LukS-PV, one of the two components of Panton-Valentine leucocidin (PVL), is produced by Staphylococcus aureus. The present study showed that LukS-PV can induce apoptosis in human acute myeloid leukemia (AML) lines (THP-1 and HL-60). However, the role of LukS-PV in NSCLC is unclear. In this study, we treated NSCLC cell lines A549 and H460 and a normal lung cell line, 16HBE, with LukS-PV and investigated the biological roles of LukS-PV in NSCLC. Cells were treated with varying concentrations of LukS-PV and cell viability was evaluated by CCK8 and EdU assay. Flow cytometry was used to detect cell apoptosis and analyze the cell cycle, and the expression of apoptosis and cell cycle-associated proteins and genes were identified by western blotting analysis and qRT-polymerase chain reaction, respectively. We found that LukS-PV inhibited the proliferation of NSCLC cells but had little cytotoxicity in normal lung cells. LukS-PV induced NSCLC cell apoptosis and increased the BAX/BCL-2 ratio, triggering S-phase arrest in A549 and H460â¯cells while increasing P21 expression and decreasing CDK2, cyclin D1, and cyclin A2 expression. We also observed increased P-p38 and P-ERK in NSCLC cells treated with LukS-PV. Treatment of NSCLC with LukS-PV combined with p38 and ERK inhibitors reversed the pro-apoptotic and pro-cell cycle arrest effects of LukS-PV. Overall, these findings indicate that LukS-PV has anti-tumor effects in NSCLC and may contribute to the development of anti-cancer agents.
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Toxinas Bacterianas/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Exotoxinas/farmacologia , Leucocidinas/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Proteínas de Bactérias/farmacologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Neoplasias Pulmonares/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Hepatocellular carcinoma (HCC) is a complicated and poor prognosis cancer, necessitating the development of a potential treatment strategy. In this study, we initially revealed that LukS-PV belonged to leukocidin family performs an anti-HCC action. Then, we used liquid chromatography-mass spectrometry (LC/MS) to compare protein expression profiles of the LukS-PV-treated human HCC cell lines HepG2 and the control cells. GO annotations and Kyoto Encyclopedia of Genes and Genomes pathway analysis were carried out of differential expression followed by protein-protein interactome, to explore the underlying cancer suppressor mechanisms of LukS-PV for human HCC. A total of 88 upregulated proteins and 46 downregulated proteins were identified. The top 10 proteins identified by the MCC method are FN1, APP, TIMP1, nucleobindin-1, GOLM1, APLP2, CYR61, CD63, ENG, and CD9. Our observation on protein expression indicated that LukS-PV produces a signature affecting central carbon metabolism in cancer, galactose metabolism, and fructose and mannose metabolism pathways. The results give a functional effects and molecular mechanism insight, following LukS-PV treatment.
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Antineoplásicos/farmacologia , Proteínas de Bactérias/farmacologia , Toxinas Bacterianas/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Exotoxinas/farmacologia , Leucocidinas/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Proteômica/métodos , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/metabolismo , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Redes e Vias Metabólicas/efeitos dos fármacos , Invasividade Neoplásica , Mapas de Interação de Proteínas , Reação em Cadeia da Polimerase em Tempo RealRESUMO
A Gram-staining-positive, motile, rod-shaped, aerobic bacterial strain FJAT-25496 T was isolated from a forest soil sample collected from Dafu County, Chengdu City, Sichuan Province, China. Strain FJAT-25496 T grew at 15-50 °C (optimum 35 °C), pH 6.0-10.0 (optimum 8.0), and NaCl tolerance of 0-4.0% (w/v) (optimum 0%). The strain contained iso-C15:0 and anteiso-C15:0 as the predominant cellular fatty acids as well as MK-7 as the only menaquinone. The major polar lipids were diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), and phosphatidyl glycerol (PG). Phylogenetic analyses based on 16S rRNA gene sequences showed that strain FJAT-25496 T was a member of the genus Bacillus, and most closely related to Bacillus solani FJAT-18043 T (97.8%), Bacillus praedii FJAT-25547 T (97.8%), Bacillus depressus BZ1T (97.7%), Bacillus oceanisediminis H2T (97.7%), and Bacillus ciccensis 5L6T (97.6%). Based on complete genome comparisons between strain FJAT-25496 T and the type strains of its closely related species, the average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values were 73.4-76.3% and 21.7-23.2%, respectively. The genomic DNA G + C content of strain FJAT-25496 T was 36.9%. On the basis of phenotypic, phylogenetic, chemotaxonomic, and genomic features, strain FJAT-25496 T is considered to represent a novel species of the genus Bacillus, for which the name Bacillus dafuensis sp. nov. is proposed. The type strain is FJAT-25496 T (= CCTCC AB 2019182 T = KCTC 43120 T).
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Bacillus , Microbiologia do Solo , Bacillus/genética , Técnicas de Tipagem Bacteriana , Parede Celular , China , DNA Bacteriano/genética , Ácido Diaminopimélico , Florestas , Peptidoglicano , Fosfolipídeos , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , SoloRESUMO
Target Tracking (TT) is a fundamental application of wireless sensor networks. TT based on received signal strength indication (RSSI) is by far the cheapest and simplest approach, but suffers from a low stability and precision owing to multiple paths, occlusions, and decalibration effects. To address this problem, we propose an innovative TT algorithm, known as the SVM+KF method, which combines the support vector machine (SVM) and an improved Kalman filter (KF). We first use the SVM to obtain an initial estimate of the target's position based on the RSSI. This enhances the ability of our algorithm to process nonlinear data. We then apply an improved KF to modify this estimated position. Our improved KF adds the threshold value of the innovation update in the traditional KF. This value changes dynamically according to the target speed and network parameters to ensure the stability of the results. Simulations and real experiments in different scenarios demonstrate that our algorithm provides a superior tracking accuracy and stability compared to similar algorithms.
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BACKGROUND: Color directly affects fruit quality and consumer preference. In fig syconia, the female flower tissue is contained in a receptacle. Anthocyanin pigmentation of this tissue and the peel differs temporally and spatially. A transcriptome study was carried out to elucidate key genes and transcription factors regulating differences in fig coloring. RESULTS: Anthocyanins in the female flower tissue were identified mainly as pelargonidin-3-glucoside and cyanidin-3-rutinoside; in the peel, the major anthocyanins were cyanidin 3-O-glucoside and cyanidin-3-rutinoside. Anthocyanin content was significantly higher in the female flower tissue vs. peel before fig ripening, whereas at ripening, the anthocyanin content in the peel was 5.39 times higher than that in the female flower tissue. Light-deprivation treatment strongly inhibited peel, but not female flower tissue, anthocyanin pigmentation. RNA-Seq revealed 522 differentially expressed genes (recruited with criteria log2 ≥ 2 and P < 0.05) at fig ripening, with 50 upregulated and 472 downregulated genes in the female flower tissue. Light deprivation upregulated 1180 and downregulated 856 genes in the peel, and upregulated 909 and downregulated 817 genes in the female flower tissue. KEGG enrichment revealed significantly changed expression in the phenylpropanoid-biosynthesis and flavonoid-biosynthesis pathways in the peel, but not in the female flower tissue, with significant repression of FcCHS, FcCHI, FcF3H, FcF3'H, FcDFR and FcUFGT transcripts. Light deprivation led to differential expression of 71 and 80 transcription factor genes in the peel and female flower tissue, respectively. Yeast one-hybrid screen revealed that FcHY5 and FcMYB114 bind the promoter regions of FcCHS and FcDFR, respectively in the flavonoid-biosynthesis pathway. CONCLUSIONS: Phenylpropanoid- and flavonoid-biosynthesis pathways were differentially expressed spatially and temporally in the peel and female flower tissue of fig syconia; pathway expression in the peel was strongly regulated by light signal. Differentially expressed transcription factors were recruited as candidates to screen important expression regulators in the light-dependent and light-independent anthocyanin-synthesis pathway. Our study lays the groundwork for further elucidation of crucial players in fig pigmentation.
Assuntos
Ficus/fisiologia , Pigmentação , Transcriptoma , Ficus/genética , Ficus/crescimento & desenvolvimento , Ficus/efeitos da radiação , Flores/genética , Flores/crescimento & desenvolvimento , Flores/fisiologia , Flores/efeitos da radiação , Frutas/genética , Frutas/crescimento & desenvolvimento , Frutas/fisiologia , Frutas/efeitos da radiação , Pigmentação/efeitos da radiação , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Transcriptoma/efeitos da radiaçãoRESUMO
BACKGROUND: Fig fruit are highly perishable at the tree-ripe (TR) stage. Commercial-ripe (CR) fruit, which are harvested before the TR stage for their postharvest transportability and shelf-life advantage, are inferior to TR fruit in size, color and sugar content. The succulent urn-shaped receptacle, serving as the protective structure and edible part of the fruit, determines fruit quality. Quantitative iTRAQ and RNA-Seq were performed to reveal the differential proteomic and transcriptomic traits of the receptacle at the two harvest stages. RESULTS: We identified 1226 proteins, of which 84 differentially abundant proteins (DAPs) were recruited by criteria of abundance fold-change (FC) ≥1.3 and p < 0.05 in the TR/CR receptacle proteomic analysis. In addition, 2087 differentially expressed genes (DEGs) were screened by ≥2-fold expression change: 1274 were upregulated and 813 were downregulated in the TR vs. CR transcriptomic analysis. Ficin was the most abundant soluble protein in the fig receptacle. Sucrose synthase, sucrose-phosphate synthase and hexokinase were all actively upregulated at both the protein and transcriptional levels. Endoglucanase, expansin, beta-galactosidase, pectin esterase and aquaporins were upregulated from the CR to TR stage at the protein level. In hormonal synthesis and signaling pathways, high protein and transcriptional levels of aminocyclopropane-1-carboxylate oxidase were identified, together with a few diversely expressed ethylene-response factors, indicating the potential leading role of ethylene in the ripening process of fig receptacle, which has been recently reported as a non-climacteric tissue. CONCLUSIONS: We present the first delineation of intra- and inter-omic changes in the expression of specific proteins and genes of TR vs. CR fig receptacle, providing valuable candidates for further study of fruit-quality formation control and fig cultivar innovation to accommodate market demand.
Assuntos
Ficus/genética , Perfilação da Expressão Gênica , Proteoma/metabolismo , Árvores/genética , Vias Biossintéticas , Etilenos/biossíntese , Frutas/anatomia & histologia , Frutas/genética , Regulação da Expressão Gênica de Plantas , Marcação por Isótopo , Látex , Reguladores de Crescimento de Plantas/metabolismo , Proteínas de Plantas/metabolismo , Biossíntese de Proteínas , Metabolismo Secundário , Estresse Fisiológico , Açúcares/metabolismo , Transcriptoma/genéticaRESUMO
An ultraflexible and stretchable field-effect transistor nanosensor is presented that uses aptamer-functionalized monolayer graphene as the conducting channel. Specific binding of the aptamer with the target biomarker induces a change in the carrier concentration of the graphene, which is measured to determine the biomarker concentration. Based on a Mylar substrate that is only 2.5-µm thick, the nanosensor is capable of conforming to underlying surfaces (e.g., those of human tissue or skin) that undergo large bending, twisting, and stretching deformations. In experimental testing, the device is rolled on cylindrical surfaces with radii down to 40 µm, twisted by angles ranging from -180° to 180°, or stretched by extensions up to 125%. With these large deformations applied either cyclically or non-recurrently, the device is shown to incur no visible mechanical damage, maintain consistent electrical properties, and allow detection of TNF-α, an inflammatory cytokine biomarker, with consistently high selectivity and low limit of detection (down to 5 × 10-12M). The nanosensor can thus potentially enable consistent and reliable detection of liquid-borne biomarkers on human skin or tissue surfaces that undergo large mechanical deformations.