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BACKGROUND: Dual antiplatelet treatment has been shown to lower the risk of recurrent stroke as compared with aspirin alone when treatment is initiated early (≤24 hours) after an acute mild stroke. The effect of clopidogrel plus aspirin as compared with aspirin alone administered within 72 hours after the onset of acute cerebral ischemia from atherosclerosis has not been well studied. METHODS: In 222 hospitals in China, we conducted a double-blind, randomized, placebo-controlled, two-by-two factorial trial involving patients with mild ischemic stroke or high-risk transient ischemic attack (TIA) of presumed atherosclerotic cause who had not undergone thrombolysis or thrombectomy. Patients were randomly assigned, in a 1:1 ratio, within 72 hours after symptom onset to receive clopidogrel (300 mg on day 1 and 75 mg daily on days 2 to 90) plus aspirin (100 to 300 mg on day 1 and 100 mg daily on days 2 to 21) or matching clopidogrel placebo plus aspirin (100 to 300 mg on day 1 and 100 mg daily on days 2 to 90). There was no interaction between this component of the factorial trial design and a second part that compared immediate with delayed statin treatment (not reported here). The primary efficacy outcome was new stroke, and the primary safety outcome was moderate-to-severe bleeding - both assessed within 90 days. RESULTS: A total of 6100 patients were enrolled, with 3050 assigned to each trial group. TIA was the qualifying event for enrollment in 13.1% of the patients. A total of 12.8% of the patients were assigned to a treatment group no more than 24 hours after stroke onset, and 87.2% were assigned after 24 hours and no more than 72 hours after stroke onset. A new stroke occurred in 222 patients (7.3%) in the clopidogrel-aspirin group and in 279 (9.2%) in the aspirin group (hazard ratio, 0.79; 95% confidence interval [CI], 0.66 to 0.94; P = 0.008). Moderate-to-severe bleeding occurred in 27 patients (0.9%) in the clopidogrel-aspirin group and in 13 (0.4%) in the aspirin group (hazard ratio, 2.08; 95% CI, 1.07 to 4.04; P = 0.03). CONCLUSIONS: Among patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause, combined clopidogrel-aspirin therapy initiated within 72 hours after stroke onset led to a lower risk of new stroke at 90 days than aspirin therapy alone but was associated with a low but higher risk of moderate-to-severe bleeding. (Funded by the National Natural Science Foundation of China and others; INSPIRES ClinicalTrials.gov number, NCT03635749.).
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Aspirina , Clopidogrel , Accidente Cerebrovascular Isquémico , Inhibidores de Agregación Plaquetaria , Humanos , Aspirina/administración & dosificación , Aspirina/efectos adversos , Aspirina/uso terapéutico , Aterosclerosis/complicaciones , Aterosclerosis/tratamiento farmacológico , Clopidogrel/administración & dosificación , Clopidogrel/efectos adversos , Clopidogrel/uso terapéutico , Método Doble Ciego , Quimioterapia Combinada , Hemorragia/inducido químicamente , Ataque Isquémico Transitorio/tratamiento farmacológico , Ataque Isquémico Transitorio/etiología , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/etiología , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Prevención Secundaria , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/etiología , Resultado del TratamientoRESUMEN
The coronavirus disease-2019 pandemic reflects the underdevelopment of point-of-care diagnostic technology. Nuclei acid (NA) detection is the "gold standard" method for the early diagnosis of the B.1.1.529 (Omicron) variant of severe acute respiratory syndrome-coronavirus disease-2. Polymerase chain reaction is the main method for NA detection but requires considerable manpower and sample processing taking ≥ 3 h. To simplify the operation processes and reduce the detection time, exonuclease III (Exo III)-aided MoS2 /AIE nanoprobes were developed for rapid and sensitive detection of the oligonucleotides of Omicron. Molybdenum disulfide (MoS2 ) nanosheets with excellent optical absorbance and distinguishable affinity to single-strand and duplex DNAs were applied as quenchers, and aggregation-induced emission (AIE) molecules with high luminous efficiency were designed as donor in fluorescence resonance energy transfer-based nanoprobes. Exo III with catalytic capability was used for signal amplification to increase the sensitivity of detection. The composite nanoprobes detected the mutated nucleocapsid (N)-gene and spike (S)-gene oligonucleotides of Omicron within 40 min with a limit of detection of 4.7 pM, and showed great potential for application in community medicine.
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Técnicas Biosensibles , COVID-19 , Exodesoxirribonucleasas , Humanos , Oligonucleótidos , SARS-CoV-2/genética , Molibdeno , Técnicas Biosensibles/métodos , COVID-19/diagnósticoRESUMEN
The fabrication of a multimodal phototheranostic platform on the basis of single-component theranostic agent to afford both imaging and therapy simultaneously, is attractive yet full of challenges. The emergence of aggregation-induced emission luminogens (AIEgens), particularly those emit fluorescence in the second near-infrared window (NIR-II), provides a powerful tool for cancer treatment by virtue of adjustable pathway for radiative/non-radiative energy consumption, deeper penetration depth and aggregation-enhanced theranostic performance. Although bulky thiophene π-bridges such as ortho-alkylated thiophene, 3,4-ethoxylene dioxythiophene and benzo[c]thiophene are commonly adopted to construct NIR-II AIEgens, the subtle differentiation on their theranostic behaviours has yet to be comprehensively investigated. In this work, systematical investigations discovered that AIEgen BT-NS bearing benzo[c]thiophene possesses acceptable NIR-II fluorescence emission intensity, efficient reactive oxygen species generation, and high photothermal conversion efficiency. Eventually, by using of BT-NS nanoparticles, unprecedented performance on NIR-II fluorescence/photoacoustic/photothermal imaging-guided synergistic photodynamic/photothermal elimination of tumors was demonstrated. This study thus offers useful insights into developing versatile phototheranostic systems for clinical trials.
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Nanopartículas , Neoplasias , Humanos , Fototerapia/métodos , Nanomedicina Teranóstica/métodos , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Nanopartículas/uso terapéutico , Medicina de Precisión , Línea Celular TumoralRESUMEN
BACKGROUND: Plums are one of the most important economic crops of the Rosaceae family and are produced all over the world. China has many local varieties, but the genomic information is limited for genetic studies. Here, we first sequenced, assembled, and analyzed the plastomes of twelve plum cultivars and developed molecular markers to distinguish them. RESULTS: The twelve plastomes of plum cultivars have a circular structure of 157,863-157,952 bp containing a large single-copy region (LSC) of 86,109-86,287 bp, a small copy region (SSC) of 18,927-19,031 bp, and two inverted repeats (IR) of 26,353-26,387 bp each. The plastomes of plum cultivars encode 131 genes, including 86 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. We detected 50, 54, 54, 53, 53, 50, 54, 54, 54, 49, 50, 54 SSRs in the twelve analyzed varieties, respectively. For repeat sequences, we identified 553 tandem repeats, 204 direct repeats, and 270 palindromic repeats. We also analyzed the expansion/contraction of IR regions. The genes rpl22, rps19, rpl2, ycf1, ndhF, and the trnH span on or near the boundary of IR and single-copy regions. Phylogenetic analysis showed that the twelve cultivars were clustered with the P. salicina and P. domestica. We developed eight markers LZ01 to LZ08 based on whole plastomes and nuclear genes and validated them successfully with six repetitions. CONCLUSIONS: The results obtained here could fill in the blanks of the plastomes of these twelve plum cultivars and provide a wider perspective based on the basis of the plastomes of Prunus to the molecular identification and phylogenetic construction accurately. The analysis from this study provides an important and valuable resource for studying the genetic basis for agronomic and adaptive differentiation of the Prunus species.
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Prunus domestica , Prunus , Rosaceae , Filogenia , Prunus domestica/genética , Prunus/genética , Rosaceae/genética , Secuencia de BasesRESUMEN
Rotavirus A (RVA) is a major diarrhoea-causing pathogen in young animals and children. The zoonotic potential of RVA has received extensive attention in recent years. In May 2018, an outbreak of diarrhoea among piglets occurred on a swine farm in Sichuan province, PR China. RVA was detected in 95.7â% (22/23) of piglet samples, 60â% (9/15) of sow samples and 100â% (3/3) of pig-breeder faecal samples. The predominant RVA genotype on this swine farm was G3P[13], and G3P[13] RVA was also detected in the three breeder faecal samples. Three G3P[13] RVA strains were isolated from a piglet faecal sample, a sow faecal sample and a pig-breeder faecal sample, and were named SCLS-X1, SCLS-3 and SCLS-R3, respectively. The complete sequences of 11 gene segments of these three isolates were derived. Phylogenetic analysis showed that ten gene segments (VP7, VP4, VP1-VP3 and NSP1-NSP5) of pig-breeder isolate SCLS-R3 were closely related to pig isolates SCLS-X1 and SCLS-3 from this farm. Only the VP6 gene shared higher homology with human RVA strain I321. Therefore, a G3P[13] porcine RVA strain most likely infected pig breeders. These results provided the first complete epidemiological link demonstrating interspecies transmission of G3P[13] RVA from pigs to human. Our data contribute to an improved understanding of the genetic evolution and interspecies transmission of RVA.
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Diarrea/etiología , Infecciones por Rotavirus/transmisión , Infecciones por Rotavirus/virología , Rotavirus/genética , Enfermedades de los Porcinos/virología , Adulto , Animales , Brotes de Enfermedades , Granjas , Heces/virología , Femenino , Genoma Viral , Humanos , Masculino , Filogenia , Rotavirus/aislamiento & purificación , Porcinos , Proteínas no Estructurales Virales/genéticaRESUMEN
Yak is an iconic species of the Qinghai-Tibet Plateau, which is the world's highest plateau. Here, a total of 541 yak diarrhoeic samples were collected from 69 farms in four provinces in the Qinghai-Tibet Plateau from April 2015 to June 2018, and 73.6â% of samples were detected as Bovine Rotavirus A (BRVA) positive by RT-PCR assay. Two G genotypes (G6, G10) and two P genotypes (P[1], P[11]) were determined, in which G6P[1] BRVA was the predominant strain. Moreover, VP7 and VP4 of these G6P[1] strains showed unique amino acid mutations, such that they clustered into an independent branch in the phylogenetic tree. A strain of BRVA designated as RVA/Yak-tc/CHN/QH-1/2015/G6P[1] was isolated successfully using MA104 cells, and the virus titre was determined as 105.84 TCID50 ml-1. The genome of strain QH-1 had a G6-P[1]-I2-R2-C2-M2-A3-N3-T6-E2-H3 genotype constellation. QH-1 was identified as a reassortment strain of BRVA, human RVA and ovine RVA based on the nucleotide identity and phylogenetic tree of 11 gene segments, indicating its public health significance. To the best of our knowledge, this is the first report on the molecular prevalence and genome characteristics of BRVA in yak, contributing to further understanding of the epidemic and genetic evolution of BRVA.
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Enfermedades de los Bovinos/epidemiología , Enfermedades de los Bovinos/virología , Genoma Viral , Genómica , Infecciones por Rotavirus/veterinaria , Rotavirus/genética , Animales , Bovinos , China/epidemiología , Genómica/métodos , Genotipo , Geografía Médica , Filogenia , Prevalencia , ARN Viral , Rotavirus/clasificación , Rotavirus/aislamiento & purificación , Proteínas Virales/genéticaRESUMEN
Outer membrane protein P2 (OmpP2) of the virulent Haemophilus (Glaesserella) parasuis has been shown to induce the release of proinflammatory cytokines. The OmpP2 protein is composed of eight or nine surface-exposed loops, but it is unclear which of them participates in the OmpP2-induced inflammatory response. In this study, we synthesized linear peptides corresponding to surface-exposed loops L1-L8 of OmpP2 from the virulent H. parasuis SC096 strain to stimulate porcine alveolar macrophages (PAMs) in vitro. We found that both L7 and L8 significantly upregulated the mRNA expression of interleukin (IL)-1α, IL-1ß, IL-6, IL-8, IL-17, and IL-23 and the chemokines CCL-4 and CCL-5 in a time- and dose-dependent manner. Additionally, we constructed ompP2ΔLoop7 and ompP2ΔLoop8 mutant SC096 strains and extracted their native OmpP2 proteins to stimulate PAMs. These mutant proteins induced significantly less mRNA expression of inflammatory cytokines than SC096 OmpP2. Next, the amino acid sequences of L7 and L8 from 15 serovars of H. parasuis OmpP2 were aligned. These sequences were relatively conserved among the most virulent reference strains, suggesting that L7 and L8 are the most active peptides of the OmpP2 protein. Furthermore, L7 and L8 significantly upregulated the NF-κB and AP-1 activity levels based on luciferase reporter assays in a dose-dependent manner. Therefore, our results demonstrated that both surface-exposed loops L7 and L8 of H. parasuis OmpP2 induced the expression of proinflammatory cytokines possibly by activating the NF-κB and MAPK signalling pathways in cells infected by H. parasuis.
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Proteínas de la Membrana Bacteriana Externa/genética , Citocinas/genética , Expresión Génica , Infecciones por Haemophilus/veterinaria , Haemophilus parasuis/genética , Porinas/genética , Enfermedades de los Porcinos/inmunología , Animales , Proteínas de la Membrana Bacteriana Externa/metabolismo , Citocinas/inmunología , Infecciones por Haemophilus/inmunología , Infecciones por Haemophilus/microbiología , Macrófagos Alveolares/inmunología , Porinas/metabolismo , Sus scrofa , Porcinos , Enfermedades de los Porcinos/microbiologíaRESUMEN
BACKGROUND The aim of this study was to investigate the incidence and related risk factors of new silent cerebral infarction in patients with acute non-cerebral amyloid angiopathy (non-CAA) intracerebral hemorrhage (ICH) and to explore clinical cerebrovascular event recurrence within 1 year. MATERIAL AND METHODS This prospective study observed 152 patients with non-CAA ICH diagnosed by computed tomography within 3 days after onset. All patients underwent magnetic resonance imaging on day 14 to identify silent cerebral infarction, and their subsequent clinical cerebrovascular events were followed up regularly within 1 year. RESULTS Of the 152 patients, 46 (30.26%) had silent cerebral infarctions. Multiple logistic regression analysis revealed that the white blood cell (WBC) count, cerebral microbleeds (CMBs), and leukoaraiosis were silent cerebral infarction risk factors. At 1-year follow-up, 34 (22.37%) had clinical cerebrovascular events, with 8 (23.53%) having vascular-related deaths. Multiple logistic regression analysis showed that silent cerebral infarction was the only independent predictor of future clinical cerebrovascular events. CONCLUSIONS Silent cerebral infarction is common during acute non-CAA ICH and is independently related to WBC counts, CMBs, and leukoaraiosis. The risk of clinical cerebrovascular events in non-CAA ICH patients with silent cerebral infarction increases in the following year; thus, silent cerebral infarction may be a useful predictor of recurrent cerebrovascular events.
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Angiopatía Amiloide Cerebral/patología , Hemorragia Cerebral/patología , Infarto Cerebral/patología , Anciano , Anciano de 80 o más Años , Encéfalo/patología , China , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recurrencia , Factores de Riesgo , Accidente Cerebrovascular , Tomografía Computarizada por Rayos XRESUMEN
Despite their impressive optical properties, lead halide perovskite quantum dots (PQDs) have not realized their potential, especially in bioimaging applications, as they suffer from poor moisture and thermal stability, solvent incompatibility, and significant toxicity. Here, a spray-assisted coil-globule transition method for encapsulating CsPbBr3 (CPB) PQDs into poly(methyl methacrylate) (PMMA) polymer nanospheres is reported. Polyvinylpyrrolidone-capped CPB PQDs are synthesized via the ligand assisted reprecipitation method in dichloromethane. After dissolving PMMA, the above precursor solution is sprayed into petroleum ether under high pressure N2 . High-pressure nebulization restricts the interactions between PMMA polymer chains, resulting in the formation of ≈112 nm nanoscale composite spheres after a coil-globule transition. The CPB@PMMA nanospheres not only possess 73% quantum yields but retain 81% of fluorescence intensity after the exposure to water for over 80 days. Due to their confined size and biocompatible encapsulation, they are readily available for cellular uptake and exhibit no toxicity on live HeLa cells. Furthermore, the PMMA surface allows for functional surface modification, carrying the possibility of targeting specific biological species and processes.
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Puntos Cuánticos , Agua/química , Compuestos de Calcio/química , Células HeLa , Humanos , Nanosferas/química , Óxidos/química , Polímeros/química , Polimetil Metacrilato/química , Titanio/químicaRESUMEN
We fabricate high-mobility p-type few-layer WSe_{2} field-effect transistors and surprisingly observe a series of quantum Hall (QH) states following an unconventional sequence predominated by odd-integer states under a moderate strength magnetic field. By tilting the magnetic field, we discover Landau level crossing effects at ultralow coincident angles, revealing that the Zeeman energy is about 3 times as large as the cyclotron energy near the valence band top at the Γ valley. This result implies the significant roles played by the exchange interactions in p-type few-layer WSe_{2}, in which itinerant or QH ferromagnetism likely occurs. Evidently, the Γ valley of few-layer WSe_{2} offers a unique platform with unusually heavy hole carriers and a substantially enhanced g factor for exploring strongly correlated phenomena.
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Chemical analysis of Chinese black ink on xuan paper is useful for the authentication of Asian artwork. The analysis has to be nondestructive and has to accommodate artworks of all sizes. We apply three analytical techniques, ArF laser-induced plume fluorescence, Fourier transform infrared (FTIR) spectroscopy, and portable X-ray fluorescence (pXRF) to analyze five commercial Chinese black inks on two kinds of xuan paper. The FTIR signal is found to be interfered by the substrate which is inevitable because the pigments diffuse extensively into the xuan fiber network. The XRF signal is shown to be feeble and no signal can be registered until the samples are stacked and when the analytes are present at tens of percent. In contrast, the plume fluorescence technique can detect the minor and trace signature elements. The method is based on a two-laser-pulse scheme performed on a high precision optical setup: the first 355 nm laser pulse ablates a thin layer of the ink to create a plume; the second 193 nm laser pulse induces multi analytes in the plume to fluoresce. Partial-least-squares discriminant analysis of the fluorescence spectra unambiguously sorts the ink-xuan combinations while the sampled area is not visibly damaged even under the microscope. The laser probe can handle samples of arbitrary size and shape, is air compatible, and no sample pretreatment is necessary.
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Cold-inducible RNA-binding protein (Cirp), the first cold-shock protein identified in mammals, is a sensor protein whose expression increases in response to stress. Recent reports have shown that Cirp is involved in cell proliferation, development, circadian modulation under physiological conditions, and tumor formation and progression. However, the molecular mechanisms underlying the activities of Cirp in the mammalian kidney cells remain unclear. In this study, we constructed BHK-21cells overexpressing Cirp (Cirp + BHK-21) knockdown BHK-21 cells (Cirp - BHK-21) to investigate the function of Cirp in cell proliferation. We analyzed the gene expression of Cirp - BHK-21 cells using genome-wide expression microarrays to explore the molecular mechanism of Cirp action. We found that (1) Cirp overexpression significantly enhanced cell proliferation, whereas Cirp knockdown dramatically reduced cell proliferation, suggesting that Cirp is a positive regulator of BHK-21 cell proliferation. (2) Differentially expressed genes in Cirp - BHK-21 and control cells were shown to be involved in many biological processes. (3) Pathway analysis showed that five enriched pathways, namely, Focal adhesion, Mapk, Wnt, Apoptosis, and Cancer-related signaling pathways, were identified as central pathway networks regulated by Cirp. These results can provide new insights into the molecular mechanisms of Cirp function.
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Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Proteínas de Unión al ARN/metabolismo , Animales , Línea Celular , Proliferación Celular , Mapeo Cromosómico , Cricetinae , Ontología de Genes , Ratones , Proteínas de Unión al ARN/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reproducibilidad de los ResultadosRESUMEN
Brain biological age, which measures the aging process in the brain using neuroimaging data, has been used to assess advanced brain aging in neurodegenerative diseases, including Parkinson disease (PD). However, assuming that whole brain degeneration is uniform may not be sufficient for assessing the complex neurodegenerative processes in PD. In this study we constructed a multiscale brain age prediction models based on structural MRI of 1240 healthy participants. To assess the brain aging patterns using the brain age prediction model, 93 PD patients and 91 healthy controls matching for sex and age were included. We found increased global and regional brain age in PD patients. The advanced aging regions were predominantly noted in the frontal and temporal cortices, limbic system, basal ganglia, thalamus, and cerebellum. Furthermore, region-level rather than global brain age in PD patients was associated with disease severity. Our multiscale brain age prediction model could aid in the development of objective image-based biomarkers to detect advanced brain aging in neurodegenerative diseases.
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Envejecimiento , Encéfalo , Imagen por Resonancia Magnética , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/fisiopatología , Masculino , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Femenino , Envejecimiento/patología , Persona de Mediana Edad , AncianoRESUMEN
OJECTIVES: Low-grade glioma (LGG) is associated with increased mortality owing to recrudescence and the tendency for malignant transformation. Therefore, it is imperative to discover novel prognostic biomarkers as existing traditional prognostic biomarkers of glioma, including clinicopathological features and imaging examinations, are unable to meet the clinical demand for precision medicine. Accordingly, we aimed to evaluate the prognostic value of cyclin D1 (CCND1) expression levels and construct radiomic models to predict these levels in patients with LGG MATERIALS AND METHODS: A total of 412 LGG cases from The Cancer Genome Atlas (TCGA) were used for gene-based prognostic analysis. Using magnetic resonance imaging (MRI) images stored in The Cancer Imaging Archive with genomic data from TCGA, 149 cases were selected for radiomics feature extraction and model construction. After feature extraction, the radiomic signature was constructed using logistic regression (LR) and support vector machine (SVM) analyses. RESULTS: CCND1 was identified as a prognosis-related gene with differential expression in tumor and normal samples and plays a role in regulating both the cell cycle and immune response. Landmark analysis revealed that high-expression levels of CCND1 were beneficial for survival (P < 0.05) in advanced LGG. Four optimal radiomics features were selected to construct radiomics models. The performance of LR and SVM achieved areas under the curve of 0.703 and 0.705, as well as 0.724 and 0.726 in the training and validation sets, respectively. CONCLUSION: Elevated levels of CCND1 expression could impact the prognosis of patients with LGG. MRI-based radiomics, especially the AUC values, can serve as a novel tool for predicting CCND1 expression and understanding the correlation between elevated CCND1 expression and prognosis. AVAILABILITY OF DATA AND MATERIALS: The datasets analyzed during the current study are available in the TCGA, TCIA, UCSC XENA and GTEx repository, https://portal.gdc.cancer.gov/, https://www.cancerimagingarchive.net/, https://xenabrowser.net/datapages/, https://www.gtexportal.org/home/.
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Runoff and evapotranspiration (ET) are pivotal constituents of the water, energy, and carbon cycles. This research presents a 5-km monthly gridded runoff and ET dataset for 1998-2017, encompassing seven headwaters of Tibetan Plateau rivers (Yellow, Yangtze, Mekong, Salween, Brahmaputra, Ganges, and Indus) (hereinafter TPRED). The dataset was generated using the advanced cryosphere-hydrology model WEB-DHM, yielding a Nash coefficient ranging from 0.77 to 0.93 when compared to the observed discharges. The findings indicate that TPRED's monthly runoff notably outperforms existing datasets in capturing hydrological patterns, as evidenced by robust metrics such as the correlation coefficient (CC) (0.944-0.995), Bias (-0.68-0.53), and Root Mean Square Error (5.50-15.59 mm). Additionally, TPRED's monthly ET estimates closely align with expected seasonal fluctuations, as reflected by a CC ranging from 0.94 to 0.98 when contrasted with alternative ET products. Furthermore, TPRED's annual values exhibit commendable concordance with operational products across multiple dimensions. Ultimately, the TPRED will have great application on hydrometeorology, carbon transport, water management, hydrological modeling, and sustainable development of water resources.
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Importance: Comparisons are limited for immediate-intensive and delayed-intensive statin for secondary stroke prevention and neuroprotection in patients with acute mild ischemic stroke or transient ischemic attack (TIA) from atherosclerosis. Objective: To estimate whether immediate-intensive statin therapy is safe and can lower the risk of recurrent stroke compared with delayed-intensive statin in patients with acute mild ischemic stroke or high-risk TIA from atherosclerosis. Design, Setting, and Participants: The Intensive Statin and Antiplatelet Therapy for High-Risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial, a double-blind, placebo-controlled, 2 × 2 factorial, randomized clinical trial enrolled patients from September 2018 to October 2022. The trial was conducted at 222 hospitals in China. Patients aged 35 to 80 years with mild ischemic stroke or high-risk TIA of presumed atherosclerosis within 72 hours of symptom onset were assessed. Interventions: Patients were randomly assigned to receive immediate-intensive atorvastatin (80 mg daily on days 1-21; 40 mg daily on days 22-90) or 3-day delayed treatment (placebo for days 1-3, followed by placebo and atorvastatin, 40 mg daily on days 4-21, and then atorvastatin, 40 mg daily on days 22-90). Main Outcomes and Measures: The primary efficacy outcome was new stroke within 90 days, and a secondary efficacy outcome was poor functional outcome. Moderate to severe bleeding was the primary safety outcome. Results: A total of 11â¯431 patients were assessed for eligibility, and 6100 patients (median [IQR] age, 65 [57-71] years; 3915 men [64.2%]) were enrolled, with 3050 assigned to each treatment group. Within 90 days, new stroke occurred in 245 patients (8.1%) in the immediate-intensive statin group and 256 patients (8.4%) in the delayed group (hazard ratio, 0.95; 95% CI, 0.80-1.13). Poor functional outcome occurred in 299 patients (9.8%) and 348 patients (11.4%) in the immediate-intensive and delayed-intensive statin groups, respectively (odds ratio, 0.83; 95% CI, 0.71-0.98). Moderate to severe bleeding occurred in 23 of 3050 patients (0.8%) and 17 of 3050 patients (0.6%), in the immediate-intensive and delayed-intensive statin groups, respectively. Conclusions and Relevance: Immediate-intensive statin initiated within 72 hours did not reduce the risk of stroke within 90 days and may be associated with improved functional outcomes without significant difference in moderate to severe bleeding, compared with 3-day delayed-intensive statin in Chinese patients with acute mild ischemic stroke or TIA from atherosclerosis. Trial Registration: ClinicalTrials.gov Identifier: NCT03635749.
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Atorvastatina , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Humanos , Masculino , Persona de Mediana Edad , Femenino , Anciano , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Método Doble Ciego , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/prevención & control , Atorvastatina/uso terapéutico , Atorvastatina/administración & dosificación , Ataque Isquémico Transitorio/tratamiento farmacológico , Adulto , Isquemia Encefálica/tratamiento farmacológico , Anciano de 80 o más Años , Prevención Secundaria/métodos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificaciónRESUMEN
OBJECTIVE: Previous studies linking Triglyceride Glucose (TyG) Index to carotid plaque have yielded inconsistent results. Moreover, related studies on the population of Japan are rare. This study aims to provide further results. DESIGN: A hospital-based cross-sectional study. SETTING: The Shin Takeo Hospital. PARTICIPANTS: We assessed 1904 Japanese participants (988 men and 916 women) whose mean age was 57±11.9 years, and those participants underwent health check-ups at Shinbuf Hospital at Shin Takeo Hospital from 1 April 2016 to 31 October 2017. METHODOLOGY: Carotid plaque, triglyceride and fasting glucose and other relevant indicators were collected. We used ultrasonography to evaluate carotid plaque. A multivariable logistic regression model and generalised additive model were used to evaluate the association between the TyG Index and carotid plaque. Subgroup and interaction analyses were validated for the consistency of these correlations. RESULTS: Following the adjustment of traditional carotid plaque risk factors, the non-linear relationship between the TyG Index and carotid plaque was investigated. Using a two-piecewise regression model, we calculated the inflection point to be 9.06. The OR and 95% CIs for the inflection points on the left and right sides were 1.70 (1.27 to 2.29) and 0.88 (0.52 to 1.47), respectively. According to the variables tested, the interactions between the TyG Index and all subgroup factors were analysed and significant interactions were not observed. CONCLUSION: In individuals who underwent a comprehensive check-up in Japan, the relationship between the TyG Index and carotid plaque is non-linear. When the TyG Index is less than 9.06, it is associated with carotid plaque.
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Glucemia , Enfermedades de las Arterias Carótidas , Placa Aterosclerótica , Triglicéridos , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Biomarcadores/sangre , Glucemia/análisis , Estudios Transversales , Pueblos del Este de Asia , Glucosa , Resistencia a la Insulina , Placa Aterosclerótica/sangre , Placa Aterosclerótica/diagnóstico por imagen , Factores de Riesgo , Triglicéridos/sangre , Enfermedades de las Arterias Carótidas/sangre , Enfermedades de las Arterias Carótidas/diagnóstico por imagenRESUMEN
Background: Alzheimer's disease (AD), a neurodegenerative disorder with progressive symptoms, seriously endangers human health worldwide. AD diagnosis and treatment are challenging, but molecular biomarkers show diagnostic potential. This study aimed to investigate AD biomarkers in the peripheral blood. Method: Utilizing three microarray datasets, we systematically analyzed the differences in expression and predictive value of mitophagy-related hub genes (MRHGs) in the peripheral blood mononuclear cells of patients with AD to identify potential diagnostic biomarkers. Subsequently, a protein-protein interaction network was constructed to identify hub genes, and functional enrichment analyses were performed. Using consistent clustering analysis, AD subtypes with significant differences were determined. Finally, infiltration patterns of immune cells in AD subtypes and the relationship between MRHGs and immune cells were investigated by two algorithms, CIBERSORT and single-sample gene set enrichment analysis (ssGSEA). Results: Our study identified 53 AD- and mitophagy-related differentially expressed genes and six MRHGs, which may be potential biomarkers for diagnosing AD. Functional analysis revealed that six MRHGs significantly affected biologically relevant functions and signaling pathways such as IL-4 Signaling Pathway, RUNX3 Regulates Notch Signaling Pathway, IL-1 and Megakaryocytes in Obesity Pathway, and Overview of Leukocyteintrinsic Hippo Pathway. Furthermore, CIBERSORT and ssGSEA algorithms were used for all AD samples to analyze the abundance of infiltrating immune cells in the two disease subtypes. The results showed that these subtypes were significantly related to immune cell types such as activated mast cells, regulatory T cells, M0 macrophages, and neutrophils. Moreover, specific MRHGs were significantly correlated with immune cell levels. Conclusion: Our findings suggest that MRHGs may contribute to the development and prognosis of AD. The six identified MRHGs could be used as valuable diagnostic biomarkers for further research on AD. This study may provide new promising diagnostic and therapeutic targets in the peripheral blood of patients with AD.
RESUMEN
On the alpine areas such as Tianshan Mountains, snow and glaciers are widely distributed, which are sensitive to temperature changes. However, due to high altitude and scarcity of observed stations, the temperature changes and their causes in Tianshan are unclear. To address this issue, this study integrated Thiel-Sen trend test, Pearson correlation, and wavelet analysis methods to analyze the driving factors of temperature changes in Tianshan. We draw the following conclusions: (1) In the past 40 years, Tianshan warmed at a rate of 0.30 °C/decade. Seasonally, the temperature increased the most in spring and summer; spatially, the east Tianshan experienced the most warming. (2) Climate change has affected significant warming in the Tianshan. (3) The large-scale climate teleconnections found to be associated with warming in the Tianshan include North Pacific pattern, Atlantic Multidecadal Variability (AMV), North Atlantic Oscillation, and Western Hemisphere Warm Pool (WHWP). During the study period, the temperature changes lagged AMV and WHWP by 1.5 months, North Tropical Atlantic Index and Tropical Northern Atlantic Index by 3 months, and Arctic Oscillation by 4 months. This research contributes to understanding the response of dry mountains to global warming and atmospheric circulation changes.
Asunto(s)
Calentamiento Global , Cubierta de Hielo , Temperatura , Cambio Climático , Estaciones del AñoRESUMEN
Aggregation-induced emission luminogens (AIEgens) have recently been developed at a tremendous pace in the area of organic luminescent materials by virtue of their superior properties. However, the practical applications of AIEgens still face the challenge of transforming AIEgens from molecules into materials. Till now, many AIEgens have been integrated into fiber, endowing the fiber with prominent fluorescence and/or photosensitizing capacities. AIEgens and fiber complement each other for making progress in flexible smart materials, in which the utilization of AIEgens creates new application possibilities for fiber, and the fiber provides an excellent carrier for AIEgens towards realizing the conversion from molecule to materials and an ideal platform to research the aggregate state of AIEgens in mesoscale and macroscale. This review begins with a brief summary of the recent advances related to some typical AIEgens with various functions and the technology for the fabrication of AIEgen-functionalized fiber. The most representative applications are then highlighted by focusing on energy conversion, personal protective equipment, biomedical, sensor, and fluorescence-related fields. Finally, the challenges, opportunities, and tendencies in future development are discussed in detail. This review hopes to inspire innovation in AIEgens and fiber from the view of mesoscale and macroscale.