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The tissues of origin of plasma DNA can be revealed by methylation patterns. However, the relative DNA contributions from megakaryocytes and erythroblasts into plasma appeared inconsistent among studies. To shed light into this phenomenon, we developed droplet digital PCR (ddPCR) assays for the differential detection of contributions from these cell types in plasma based on megakaryocyte-specific and erythroblast-specific methylation markers. Megakaryocytic DNA and erythroid DNA contributed a median of 44.2% and 6.2% in healthy individuals, respectively. Patients with idiopathic thrombocytopenic purpura had a significantly higher proportion of megakaryocytic DNA in plasma compared to healthy controls (median: 59.9% versus 44.2%; P = 0.03). Similarly, patients with ß-thalassemia were shown to have higher proportions of plasma erythroid DNA compared to healthy controls (median: 50.9% versus 6.2%) (P < 0.0001). Hence, the concurrent analysis of megakaryocytic and erythroid lineage-specific markers could facilitate the dissection of their relative contributions and provide information on patients with hematological disorders.
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Abscisic acid (ABA)-based chemically induced proximity (CIP) is primarily mediated by the interaction of the ABA receptor pyrabactin resistance 1-like 1 (PYL1) and the 2C-type protein phosphatase ABI1, which confers ABA-induced proximity to their fusion proteins, and offers precise temporal control of a wide array of biological processes. However, broad application of ABA-based CIP has been limited by ABA response intensity. In this study, we demonstrated that ABA-induced interaction between another ABA receptor pyrabactin resistance 1 (PYR1) and ABI1 exhibited higher ABA response intensity than that between PYL1 and ABI1 in HEK293T cells. We engineered PYR1-ABI1 and PYL1-ABI1 into ABA-induced transcriptional activation tools in mammalian cells by integration with CRISPR/dCas9 and found that the tool based on PYR1-ABI1 demonstrated better ABA response intensity than that based on PYL1-ABI1 for both exogenous and endogenous genes in mammalian cells. We further achieved ABA-induced RNA m6A modification installation and erasure by combining ABA-induced PYR1-ABI1 interaction with CRISPR/dCas13, successfully inhibiting tumor cell proliferation. We subsequently improved the interaction of PYR1-ABI1 through phage-assisted continuous evolution (PACE), successfully generating a PYR1 mutant (PYR1m) whose interaction with ABI1 exhibited a higher ABA response intensity than that of the wild-type. In addition, we tested the transcriptional activation tool based on PYRm-ABI1 and found that it also showed a higher ABA response intensity than that of the wild type. These results demonstrate that we have developed a novel ABA-based CIP and further improved upon it using PACE, providing a new approach for the modification of other CIP systems.
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Intraoperative hemorrhage is an important factor affecting intraoperative safety and postoperative patient recovery in percutaneous nephrolithotomy (PCNL). This study aimed to identify the factors that influence intraoperative hemorrhage during PCNL and develop a predictive nomogram model based on these factors.A total of 118 patients who underwent PCNL at the Department of Urology, The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University from January 2021 to September 2023 was included in this study. The patients were divided into a hemorrhage group (58 cases) and a control group (60 cases) based on the decrease in hemoglobin levels after surgery. The clinical data of all patients were collected, and both univariate analysis and multivariate logistic regression analysis were conducted to identify the independent risk factors for intraoperative hemorrhage during PCNL. The independent risk factors were used to construct a nomogram model using R software. Additionally, receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA) were utilized to evaluate the model.Multivariate logistic regression analysis revealed that diabetes, long operation time and low psoas muscle mass index (PMI) were independent risk factors for intraoperative hemorrhage during PCNL (P < 0.05). A nomogram model was developed incorporating these factors, and the areas under the ROC curve (AUCs) in the training set and validation set were 0.740 (95% CI: 0.637-0.843) and 0.742 (95% CI: 0.554-0.931), respectively. The calibration curve and Hosmer-Lemeshow test (P = 0.719) of the model proved that the model was well fitted and calibrated. The results of the DCA showed that the model had high value for clinical application.Diabetes, long operation time and low PMI were found to be independent risk factors for intraoperative hemorrhage during PCNL. The nomogram model based on these factors can be used to predict the risk of intraoperative hemorrhage, which is beneficial for perioperative intervention in high-risk groups to improve the safety of surgery and reduce the incidence of postoperative complications.
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Pérdida de Sangre Quirúrgica , Nefrolitotomía Percutánea , Nomogramas , Humanos , Nefrolitotomía Percutánea/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Factores de Riesgo , Adulto , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Cálculos Renales/cirugía , Tempo Operativo , Estudios Retrospectivos , Curva ROC , Complicaciones Intraoperatorias/etiología , Complicaciones Intraoperatorias/epidemiología , AncianoRESUMEN
Ferroptosis is a specific type of programmed cell death characterized by iron-dependent lipid peroxidation. Understanding the involvement of ferroptosis in calcium oxalate (CaOx) stone formation may reveal potential targets for this condition. The publicly available dataset GSE73680 was used to identify 61 differentially expressed ferroptosis-related genes (DEFERGs) between normal kidney tissues and Randall's plaques (RPs) from patients with nephrolithiasis through employing weighted gene co-expression network analysis (WGCNA). The findings were validated through in vitro and in vivo experiments using CaOx nephrolithiasis rat models induced by 1% ethylene glycol administration and HK-2 cell models treated with 1 mM oxalate. Through WGCNA and the machine learning algorithm, we identified LAMP2 and MDM4 as the hub DEFERGs. Subsequently, nephrolithiasis samples were classified into cluster 1 and cluster 2 based on the expression of the hub DEFERGs. Validation experiments demonstrated decreased expression of LAMP2 and MDM4 in CaOx nephrolithiasis animal models and cells. Treatment with ferrostatin-1 (Fer-1), a ferroptosis inhibitor, partially reversed oxidative stress and lipid peroxidation in CaOx nephrolithiasis models. Moreover, Fer-1 also reversed the expression changes of LAMP2 and MDM4 in CaOx nephrolithiasis models. Our findings suggest that ferroptosis may be involved in the formation of CaOx kidney stones through the regulation of LAMP2 and MDM4.
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Biomarcadores , Ferroptosis , Nefrolitiasis , Ferroptosis/efectos de los fármacos , Animales , Nefrolitiasis/metabolismo , Nefrolitiasis/genética , Nefrolitiasis/patología , Ratas , Biomarcadores/metabolismo , Humanos , Masculino , Oxalato de Calcio/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Cálculos Renales/metabolismo , Cálculos Renales/genética , Cálculos Renales/patología , Ciclohexilaminas/farmacología , Fenilendiaminas/farmacología , Modelos Animales de Enfermedad , Ratas Sprague-Dawley , Línea CelularRESUMEN
BACKGROUND: The relationship between placental pathology and the maternal syndrome of preeclampsia is incompletely characterized. Mismatch between placental nutrient supply and fetal demands induces stress in the syncytiotrophoblast, the layer of placenta in direct contact with maternal blood. Such stress alters the content and increases the release of syncytiotrophoblast extracellular vesicles (STB-EVs) into the maternal circulation. We have previously shown 5'-tRNA fragments (5'-tRFs) constitute the majority of small RNA in STB-EVs in healthy pregnancy. 5'-tRFs are produced in response to stress. We hypothesized STB-EV 5'-tRF release might change in preeclampsia. METHODS: We perfused placentas from 8 women with early-onset preeclampsia and 6 controls, comparing small RNA expression in STB-EVs. We used membrane-affinity columns to isolate maternal plasma vesicles and investigate placental 5'-tRFs in vivo. We quantified 5'-tRFs from circulating STB-EVs using a placental alkaline phosphatase immunoassay. 5'-tRFs and scrambled RNA controls were added to monocyte, macrophage and endothelial cells in culture to investigate transcriptional responses. RESULTS: 5'-tRFs constitute the majority of small RNA in STB-EVs from both preeclampsia and normal pregnancies. More than 900 small RNA fragments are differentially expressed in preeclampsia STB-EVs. Preeclampsia-dysregulated 5'-tRFs are detectable in maternal plasma, where we identified a placentally derived load. 5'-tRF-Glu-CTC, the most abundant preeclampsia-upregulated 5'-tRF in perfusion STB-EVs, is also increased in preeclampsia STB-EVs from maternal plasma. 5'-tRF-Glu-CTC induced inflammation in macrophages but not monocytes. The conditioned media from 5'-tRF-Glu-CTC-activated macrophages reduced eNOS (endothelial NO synthase) expression in endothelial cells. CONCLUSIONS: Increased release of syncytiotrophoblast-derived vesicle-bound 5'-tRF-Glu-CTC contributes to preeclampsia pathophysiology.
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Vesículas Extracelulares , Preeclampsia , Embarazo , Femenino , Humanos , Placenta/metabolismo , Células Endoteliales/metabolismo , Trofoblastos/metabolismo , Vesículas Extracelulares/metabolismo , ARN de Transferencia/metabolismo , Macrófagos/metabolismo , Inflamación/metabolismoRESUMEN
BACKGROUND: The suboptimal uptake of COVID-19 and influenza vaccines among those with non-communicable chronic diseases is a public health concern, because it poses a higher risk of severe illness for individuals with underlying health conditions, emphasizing the need to address barriers to vaccination and ensure adequate protection for this vulnerable population. In the present study, we aimed to identify whether people with chronic illnesses are more likely to get vaccinated against COVID-19 and influenza in the European Union. METHODS: Cross-sectional data on 49,253 men (n = 20,569) and women (n = 28,684) were obtained from the ninth round of the Survey of Health, Ageing and Retirement in Europe (June - August, 2021). The outcome variables were self-reported COVID-19 and influenza vaccine uptake status. The association between the uptake of the vaccines and six preexisting conditions including high blood pressure, high blood cholesterol, chronic lung disease, diabetes, chronic bronchitis, and asthma was estimated using binary logistic regression methods. RESULTS: The vaccination coverage for COVID-19 ranged from close to 100% in Denmark (98.2%) and Malta (98.2%) to less than 50% in Bulgaria (19.1%) and Romania (32.7%). The countries with the highest percentage of participants with the influenza vaccine included Malta (66.7%), Spain (63.7%) and the Netherlands (62.5%), and those with the lowest percentage included Bulgaria (3.7%), Slovakia (5.8%) and Poland (9.2%). Participants with high blood pressure were 3% less likely [Risk difference (RD) = -0.03, 95% CI = -0.04, -0.03] to report taking COVID-19 and influenza [RD = -0.03, 95% CI= -0.04, -0.01] vaccine. Those with chronic lung disease were 4% less likely [RD = -0.04, 95% CI= -0.06, -0.03] to report taking COVID-19 and 2% less likely [RD= -0.02, 95% CI = -0.04, -0.01] to report taking influenza vaccine. Men and women with high blood pressure were 3% less likely to have reported taking both of the vaccines. CONCLUSIONS: Current findings indicate a suboptimal uptake of COVID-19 and influenza vaccines among adult men and women in the EU countries. Those with preexisting conditions, including high blood pressure and chronic lung disease are less likely to take the vaccines.
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COVID-19 , Hipertensión , Vacunas contra la Influenza , Gripe Humana , Masculino , Humanos , Femenino , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Estudios Transversales , Cobertura de Afecciones Preexistentes , COVID-19/epidemiología , COVID-19/prevención & control , Europa (Continente)/epidemiología , Vacunación , Enfermedad CrónicaRESUMEN
OBJECTIVE: Develop a mesh model to define a new "index amount of stone" to evaluate calculus and predict lithotripsy time. METHODS: The stones were divided into target units with diameter of 5 mm by the mesh from x, y and z directions, and the cross-sectional areas between units were calculated as amount of stone as a new index to evaluate calculus. Design a prospective study with 112 cases of percutaneous nephrolithotomy to verify the reliability of this index, and to compare the accuracy of the quantity, volume and maximum diameter of stones in predicting the time of lithotripsy. RESULTS: Amount of stone (Q) is reliable. The lithotripsy time was significantly correlated with the amount of stone, volume and maximum diameter of the stone (p < 0.01). The three regression equations were valid. The linear fit in the amount group was larger than that in the volume group, and further larger than that in the maximum diameter group, with R2 values of 0.716, 0.661 and 0.471, respectively. CONCLUSIONS: It is more accurate and convenient to use amount of stone to evaluate calculus, which can be used to predict the lithotripsy time.
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Cálculos Renales , Litotricia , Nefrostomía Percutánea , Humanos , Cálculos Renales/terapia , Estudios Prospectivos , Reproducibilidad de los Resultados , Mallas Quirúrgicas , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
Cervical cancer is a widely distributed disease that is preventable and controllable through early intervention. The World Health Organization has identified three key measures, coverage populations and coverage targets to eliminate cervical cancer. The WHO and several countries have conducted model predictions to determine the optimal strategy and timing of cervical cancer elimination. However, specific implementation strategies need to be developed in the context of local conditions. China has a relatively high disease burden of cervical cancer but a low human papillomavirus vaccination rate and cervical cancer screening population coverage. The purpose of this paper is to review interventions and prediction studies for the elimination of cervical cancer and to analyze the problems, challenges and strategies for the elimination of cervical cancer in China.
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Objective: To implement and evaluate a large-scale online cervical cancer screening programme in Hubei Province, China, supported by artificial intelligence and delivered by trained health workers. Methods: The screening programme, which started in 2017, used four types of health worker: sampling health workers, slide preparation technicians, diagnostic health workers and cytopathologists. Sampling health workers took samples from the women on site; slide preparation technicians prepared slides for liquid-based cytology; diagnostic health workers identified negative samples and classified positive samples based on the Bethesda System after cytological assessment using online artificial intelligence; and cytopathologists reviewed positive samples and signed reports of the results online. The programme used fully automated scanners, online artificial intelligence, an online screening management platform, and mobile telephone devices to provide screening services. We evaluated the sustainability, performance and cost of the programme. Results: From 2017 to 2021, 1â¯518â¯972 women in 16 cities in Hubei Province participated in the programme, of whom 1â¯474â¯788 (97.09%) had valid samples for the screening. Of the 86â¯648 women whose samples were positive, 30â¯486 required a biopsy but only 19â¯495 had one. The biopsy showed that 2785 women had precancerous lesions and 191 had invasive cancers. The cost of screening was 6.31 United States dollars (US$) per woman for the public payer: US$ 1.03 administrative costs and US$â¯5.28 online screening costs. Conclusion: Cervical cancer screening using artificial intelligence in Hubei Province provided a low-cost, accessible and effective service, which will contribute to achieving universal cervical cancer screening coverage in China.
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Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/prevención & control , Displasia del Cuello del Útero/diagnóstico , Frotis Vaginal/métodos , Detección Precoz del Cáncer , Inteligencia Artificial , China , Tamizaje Masivo/métodosRESUMEN
The effect of pachymic acid (PA) on pulmonary fibrosis in rats was expected to be investigated in this study. Firstly, bleomycin (BLM) was used to establish pulmonary fibrosis rat model, then PA (10, 20, or 40 mg/kg) was intragastrically administered to the rats for 14 days. Subsequently, a variety of tests was performed to observe changes in sample tissues after different treatments. Briefly, the degree of pulmonary edema in rats was assessed through dry/wet weight ratio. Hematoxylin and eosin (H&E) staining and Masson's trichrome staining were used to observe the pathological injury and fibrosis of lung tissue. Biochemical kits were applied to measure the levels of hydroxyproline (Hyp), transforming growth factor beta-1 (TGFß-1), malondialdehyde (MDA), reactive oxygen species (ROS), and adenosine triphosphate (ATP) and the activities of superoxide dismutase (SOD) and catalase (CAT) in rat lung tissues of each group. The mitochondrial DNA (mtDNA) copy number in rat lung tissue was tested using qRT-PCR. Additionally, the western blot was employed to detect the expression levels of pulmonary fibrosis-related proteins and endoplasmic reticulum (ER) stress-related proteins in each group of rat lung tissue. By virtue of experimental verification above, PA was discovered to alleviate BLM-induced pulmonary edema, pulmonary fibrosis and histopathological damage. On the one hand, PA treatment decreased Hyp and TGF-ß1 levels and down-regulated pulmonary fibrosis-related protein expression [collagen I, α-smooth muscle actin (α-SMA), and fibronectin] in the lung tissue of BLM rats. On the other hand, it significantly increased the levels of SOD, CAT and ATP while decreased the activities of MDA and ROS in BLM rat lung tissues. In addition, the expression levels of ER stress-related proteins [glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), Caspase 9, and activating transcription factor 4 (ATF4)] were significantly down-regulated in the lung tissue of BLM rats after PA treatment. Collectively, PA may ameliorate BLM-induced pulmonary fibrosis and histopathological damage in rats through inhibiting ER stress and improving mitochondrial function.
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In recent years, due to the contribution to elucidating the functional mechanisms of miRNAs and lncRNAs, the research on miRNA-lncRNA interaction prediction has increased exponentially. However, the prediction research is challenging in bioinformatics domain. It is expensive and time-consuming to verify the interactions by biological experiments. The existing prediction models have some limitations, such as the need to manually extract features, the potential loss of features from pre-treatment approaches, long-distance dependency to be solved, and so on. Additionally, most of the current models prefer to the animal data. However, the establishment of an efficient and accurate plant miRNA-lncRNA interaction prediction model is necessary. In this work, a new deep learning model called PmlIPM is presented to infer plant miRNA-lncRNA associations. PmlIPM is a four-step framework including Input Embedding, Positional Encoding, Multi-Head Attention and Max Pooling. PmlIPM accepts separately input of miRNA and lncRNA to extract sequence features, avoiding information loss caused by direct splicing the two sequences as model inputs. The attention mechanisms give the model the ability to capture long distance features. PmlIPM is compared with the existing models on 2 benchmark datasets. The results show that our model performs better than other methods and obtains AUC scores of 0.8412, 0.8587, 0.9666 and 0.9225 in the four independent test sets of Arabidopsis lyrata (A.ly), Solanum lycopersicum (S.ly), Brachypodium distachyon (B.di) and Solanum tuberosum (S.tu), respectively.
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Arabidopsis , Aprendizaje Profundo , MicroARNs , ARN Largo no Codificante , Animales , MicroARNs/genética , ARN Largo no Codificante/genética , Biología Computacional/métodos , Arabidopsis/genéticaRESUMEN
Although radiotherapy (RT) is the preferred treatment for elderly patients with brain tumors, certain negative effects can't be ignored. Fortunately, platelet-rich plasma (PRP) presents with a promising potential for the treatment of neurological diseases. Therefore, this study aimed to explore the effect of PRP on neuroinflammation, emotional disorder and cognitive dysfunction induced by RT in aged rats. Firstly, whole brain RT (WBRT) model was established by whole brain irradiation with 10 Gy of 6-MeV electron beam in rats. Next, twenty 20-month-old female SD rats were divided into four groups (sham group, PRP group, WBRT group, and WBRT + PRP group) according different treatments. After that, the cognitive dysfunction and depression-like behavior of rats were examined by novel object recognition test (NORT), Morris water maze test (MWM), open field test (OFT) and elevated plus maze test (EPM). Besides, immunohistochemistry was used to detect the expression of microglial marker protein Iba-1 in rat hippocampus; enzyme linked immunosorbent assay (ELISA) to examine the levels of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1 beta (IL-1ß), IL-18, and monocyte chemoattractant protein 1 (MCP-1) in rat hippocampus; real-time quantitative reverse transcription PCR (qRT-PCR) and western blot to measure the levels of neurotrophic factors brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B receptor (TrkB), and nerve growth factor (NGF) in rat hippocampus; and western blot also to observe the protein expression levels of NOD-like receptor protein 3 (NLRP3), caspase-1, apoptosis-associated speck-like protein containing a CARD (ASC), and IL-1ß in rat hippocampus. After experiments, some results obtained were shown as follows. PRP could significantly improve learning and memory ability and depression-like behavior, increase the level of neurotrophic factors, inhibit the activation of microglia and decrease the level of pro-inflammatory factors in WBRT rats. In addition, PRP significantly inhibited the activation of NLRP3 inflammasomes. To sum up, PRP can ameliorate neuroinflammation, emotional disorder and cognitive dysfunction induced by RT in aged rats, and the mechanism may be related to its inhibitory effect on NLRP3 inflammasome activation.
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Disfunción Cognitiva , Plasma Rico en Plaquetas , Ratas , Femenino , Animales , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteínas NLR , Enfermedades Neuroinflamatorias , Ratas Sprague-Dawley , Disfunción Cognitiva/terapia , Factores de Crecimiento Nervioso , Plasma Rico en Plaquetas/metabolismoRESUMEN
Objectives: To identify differences in healthcare use between older migrant workers (OMWs) and older migrants (OMs) and explore associated factors and paths of healthcare use. Methods: The data came from the 2015 China Migrant Dynamic Monitoring Survey (CMDMS). CMDMS used a multi-stage stratified probability proportionate to size method as the sampling technique and conducted a desk review. The samples include OMWs, OMs for caring offspring (N = 4,439), and OMs for receiving care from family (N = 4,184). We built logistic regression and path analysis models to analyze the data. Results: Social health insurance (SHI) in current place of residence is associated with less expenditure among all subgroups. OMWs and OMs for receiving care from family with SHI in current place of residence are more likely to use healthcare. Conclusion: OMWs are particularly vulnerable in healthcare use and socioeconomic status. Having SHI registered in current place of residence helps decrease expenditure among OMs. We urge policymakers to consider a united health financing scheme across OMWs and other urban employees and streamline policies for migrants to enroll in SHI in current place of residence.
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Migrantes , Humanos , Servicios de Salud , Encuestas y Cuestionarios , Clase Social , Accesibilidad a los Servicios de Salud , ChinaRESUMEN
Background: There are many reconstruction methods after sternal tumor resection, but the method that LARS mesh combines with bone-cement has not been reported. Case report: A 54-year-old female patient and a 55-year-old male patient admitted to our department all presented with sternum masses, but neither presented with respiratory disorders. In women with limited manubrium sternum lesions, we resected the manubrium sternum completely. In men with sternal lesions, we removed part of the sternum and part of the sternocostal joint. The patients recovered well after surgery, and there were no respiratory complications and no tumor recurrence during the 1-year follow-up respectively. Conclusion: We report two cases of sternal defect repair using LARS mesh combined with bone cement. This method is safe and stable, and can achieve satisfactory results.
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Environmental heterogeneity can not only increase species diversity to some extent but also affect the stability of terrestrial communities. However, how environmental heterogeneity affects species diversity of epilithic diatom communities in aquatic ecosystems is rarely reported. In this study, therefore, epilithic diatoms and their roles in driving species diversity were explored by quantifying and comparing the environmental heterogeneity in Xiangxi River, a tributary of the Three Gorges Reservoir Area (TGR), on a time scale. The results showed that environmental heterogeneity, taxonomic ß-diversity, and functional ß-diversity in non-impoundment periods were significantly higher than those in impoundment periods. Moreover, the turnover components in the two hydrological periods showed the highest contribution to ß-diversity. However, the taxonomic α-diversity in impoundment periods was significantly higher than that in non-impoundment periods. In addition, functional richness in functional α-diversity was significantly higher in non-impoundment periods than that in impoundment periods, whereas there was no significant difference in other functional α-diversity, i.e., functional dispersion and functional evenness, found between the two periods. Multiple regression on (dis)similarity matrices (MRM) analysis indicated that ammonium nitrogen (NH4+-N) and silicate (SiO32--Si) were the key environmental heterogeneous factors affecting the epilithic diatom community in Xiangxi River during the non-impoundment periods, whereas the key heterogeneous factors were ammonium nitrogen (NH4+-N), silicate (SiO32--Si), and total phosphorus (TP) during the impoundment periods. These results suggested that the environmental heterogeneity during different hydrological periods in TGR can significantly affect the community structure of epilithic diatoms, resulting in the differentiation of species within the community and even affecting the stability of aquatic ecosystems.
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Diatomeas , Ríos , Ecosistema , Monitoreo del Ambiente/métodos , Nitrógeno/análisisRESUMEN
Cell-free DNA (cfDNA) fragmentation is nonrandom, at least partially mediated by various DNA nucleases, forming characteristic cfDNA end motifs. However, there is a paucity of tools for deciphering the relative contributions of cfDNA cleavage patterns related to underlying fragmentation factors. In this study, through non-negative matrix factorization algorithm, we used 256 5' 4-mer end motifs to identify distinct types of cfDNA cleavage patterns, referred to as "founder" end-motif profiles (F-profiles). F-profiles were associated with different DNA nucleases based on whether such patterns were disrupted in nuclease-knockout mouse models. Contributions of individual F-profiles in a cfDNA sample could be determined by deconvolutional analysis. We analyzed 93 murine cfDNA samples of different nuclease-deficient mice and identified six types of F-profiles. F-profiles I, II, and III were linked to deoxyribonuclease 1 like 3 (DNASE1L3), deoxyribonuclease 1 (DNASE1), and DNA fragmentation factor subunit beta (DFFB), respectively. We revealed that 42.9% of plasma cfDNA molecules were attributed to DNASE1L3-mediated fragmentation, whereas 43.4% of urinary cfDNA molecules involved DNASE1-mediated fragmentation. We further demonstrated that the relative contributions of F-profiles were useful to inform pathological states, such as autoimmune disorders and cancer. Among the six F-profiles, the use of F-profile I could inform the human patients with systemic lupus erythematosus. F-profile VI could be used to detect individuals with hepatocellular carcinoma, with an area under the receiver operating characteristic curve of 0.97. F-profile VI was more prominent in patients with nasopharyngeal carcinoma undergoing chemoradiotherapy. We proposed that this profile might be related to oxidative stress.
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Ácidos Nucleicos Libres de Células , Humanos , Ratones , Animales , Ácidos Nucleicos Libres de Células/genética , Desoxirribonucleasas/genética , Ratones Noqueados , Endonucleasas/genética , Fragmentación del ADN , Endodesoxirribonucleasas/genéticaRESUMEN
Background: The COVID-19 pandemic has spread rapidly and heavily hit the globe, and the mutation and transmission speed of the coronavirus have accelerated so that the world is still in danger. Thus, this study aims to investigate the participants' risk perception and explore the associations of risk perception of COVID-19 with negative emotions, information value perception and other related dimensions. Methods: A cross-sectional, population-based online survey was conducted from April 4 to 15, 2020, in China. A total of 3,552 participants were included in this study. A descriptive measure of demographic information was used in this study. Multiple regression models and moderating effect analysis were used to estimate the effect of potential associations of risk perceptions. Results: Those who showed negative emotions (depressed, helplessness, loneliness) and perceived video information in social media to be useful were positively correlated with risk perception, whereas individuals who perceived experts' advice to be useful, shared risk information with friends and thought that their community made adequate emergency preparation reported lower risk perception. The moderating effect of information perceived value (ß = 0.020, p < 0.001) on the relationship between negative emotion and perception of risk was significant. Conclusions: Individual differences in risk cognition during the COVID-19 pandemic were observed in subgroups of age level. Furthermore, the role of negative emotional states, the perceived usefulness of risk information and the sense of security also contributed to improving the public's risk perception. It is crucial for authorities to focus on residents' negative emotions and to clarify misinformation in accessible and effective ways in a timely manner.
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COVID-19 , Humanos , COVID-19/epidemiología , Estudios Transversales , Pandemias , Emociones , PercepciónRESUMEN
In order to investigate the relationship between phytoplankton community functional group compositions and resource use efficiency in important tributaries of the Three Gorges Reservoir, phytoplankton and environment parameters were sampled from five tributaries, the Xiangxi River, Daning River, Meixi River, Pengxi River, and Huangjin River, in August and November, 2020. There were 119 species (variants) belonging to 62 genera and 7 phyla identified in summer, whereas 118 species (variants) belonging to 7 divisions of 58 genera were found in winter. According to Padisak's theory, all phytoplankton were divided into 25 functional groups, of which there were six important functional groups in both summer and winter:L0, H1, D, Y, MP, and P in summer and L0, H1, A, M, MP, and Y in winter. The α-diversity of the phytoplankton functional group in summer was higher than that in winter. Moreover, a higher α-diversity was also found in downstream samples relative to that in upstream samples, indicating that the community structure was more complex, and the community stability was relatively better in downstream regions of the rivers. Redundancy analysis (RDA) showed that the environment factors, i.e., ν, pH, permanganate index, WT, and RUETN, significantly affected phytoplankton functional groups (P<0.05). Variance partitioning analysis (VPA) indicated that environmental factors had a higher explanatory degree for the change in functional group composition in summer (45.23%); on the contrary, resource use efficiency had a higher explanatory degree in winter (42.33%). The linear fitted model showed that functional groups L0, H1, D, and Y showed a significant positive correlation relationship with RUETN and RUETP in summer, whereas only four functional groups (M, MP, Y, and A) had a linear relationship with RUETP, and all function groups had a good linear relationship with RUETN in winter. These results indicated that the functional groups belonging to cyanobacteria, dinoflagellates, and cryptophyta were more efficient at using limited resources in summer, whereas the diatoms had a good linear relationship with resource use efficiency and formed a dominant group in the low temperature environment of winter. These results suggest that the impounding of the Three Gorges Reservoir area can significantly change the resource use efficiency of phytoplankton, resulting in changes in the phytoplankton functional group composition and community structure.
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Cianobacterias , Diatomeas , Fitoplancton , Monitoreo del Ambiente/métodos , Fósforo/análisis , Estaciones del Año , ChinaRESUMEN
Current treatments for chronic pain are unsatisfactory, therefore, new therapeutics are urgently needed. Our previous study indicated that KATP channel openers have analgesic effects, but the underlying mechanism has not been elucidated. We speculated that KATP channel openers might increase suppressor of cytokine signaling (SOCS)-3 expression to induce inflammatory tolerance and attenuate chronic pain. Postoperative pain was induced by plantar incision to establish a chronic pain model. Growth arrest-specific 6 (Gas6)-/- and Axl-/- mice were used for signaling studies. The microglia cell line BV-2 was cultured for the in vitro experiments. The KATP channel opener significantly attenuated incision-induced mechanical allodynia in mice associated with the upregulated expression of SOCS3. Opening KATP channels induced the expression of SOCS3 in the Gas6/Axl signaling pathway in microglia, inhibited incision-induced mechanical allodynia by activating the Gas6/Axl-SOCS3 signaling pathway, and induced inflammatory tolerance to relieve neuroinflammation and postoperative pain. We demonstrated that opening of the KATP channel opening activated Gas6/Axl/SOCS3 signaling to induce inflammatory tolerance and relieve chronic pain. We explored a new target for anti-inflammatory and analgesic effects by regulating the innate immune system and provided a theoretical basis for clinical preemptive analgesia.