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SARS-CoV-2 is an enveloped virus responsible for the COVID-19 pandemic. Despite recent advances in the structural elucidation of SARS-CoV-2 proteins, the detailed architecture of the intact virus remains to be unveiled. Here we report the molecular assembly of the authentic SARS-CoV-2 virus using cryoelectron tomography (cryo-ET) and subtomogram averaging (STA). Native structures of the S proteins in pre- and postfusion conformations were determined to average resolutions of 8.7-11 Å. Compositions of the N-linked glycans from the native spikes were analyzed by mass spectrometry, which revealed overall processing states of the native glycans highly similar to that of the recombinant glycoprotein glycans. The native conformation of the ribonucleoproteins (RNPs) and their higher-order assemblies were revealed. Overall, these characterizations revealed the architecture of the SARS-CoV-2 virus in exceptional detail and shed light on how the virus packs its â¼30-kb-long single-segmented RNA in the â¼80-nm-diameter lumen.
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Betacoronavirus/fisiología , Betacoronavirus/ultraestructura , Ensamble de Virus , Animales , Chlorocebus aethiops , Microscopía por Crioelectrón , Humanos , Espectrometría de Masas , Modelos Moleculares , Conformación Proteica , SARS-CoV-2 , Células Vero , Proteínas Virales/química , Proteínas Virales/ultraestructura , Cultivo de VirusRESUMEN
The feeding mechanisms of animals constrain the spectrum of resources that they can exploit profitably. For floral nectar eaters, both corolla depth and nectar properties have marked influence on foraging choices. We report the multiple strategies used by honey bees to efficiently extract nectar at the range of sugar concentrations and corolla depths they face in nature. Honey bees can collect nectar by dipping their hairy tongues or capillary loading when lapping it, or they can attach the tongue to the wall of long corollas and directly suck the nectar along the tongue sides. The honey bee feeding apparatus is unveiled as a multifunctional tool that can switch between lapping and sucking nectar according to the instantaneous ingesting efficiency, which is determined by the interplay of nectar-mouth distance and sugar concentration. These versatile feeding mechanisms allow honey bees to extract nectar efficiently from a wider range of floral resources than previously appreciated and endow them with remarkable adaptability to diverse foraging environments.
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Boca , Néctar de las Plantas , Abejas , Animales , Lengua , Carbohidratos , AzúcaresRESUMEN
Early vascularization plays an essential role during the whole process in bone regeneration because of the function of secreting cytokines, transporting nutrients and metabolic wastes. As the preliminary basis of bone repair, angiogenesis is regulated by immune cells represented by macrophages to a great extent. However, with the discovery of the endolymphatic circulation system inside bone tissue, the role of vascularization became complicated and confusing. Herein, we developed a macrophage/lymphatic endothelial cells (LECs)/human umbilical vein endothelial cells (HUVECs) co-culture system to evaluate the effect of macrophage treated lymphatic endothelial cells on angiogenesis in vitro and in vivo. In this study, we collected the medium from macrophage (CM) for LECs culture. We found that CM2 could promote the expression of LECs markers and migration ability, which indicated the enhanced lymphogenesis. In addition, the medium from LECs was collected for culturing HUVECs. The CM2-treated LECs showed superior angiogenesis property including the migration capacity and expression of angiogenetic markers, which suggested the superior vascularization. Rat femoral condyle defect model was applied to confirm the hypothesis in vivo. Generally, M2-macrophage treated LECs showed prominent angiogenetic potential coupling with osteogenesis.
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Técnicas de Cocultivo , Células Endoteliales de la Vena Umbilical Humana , Macrófagos , Neovascularización Fisiológica , Osteogénesis , Humanos , Animales , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Macrófagos/metabolismo , Ratas , Células Endoteliales/metabolismo , Movimiento Celular , Ratas Sprague-Dawley , Regeneración Ósea/fisiología , Ratones , Células Cultivadas , Masculino , AngiogénesisRESUMEN
BACKGROUND: Floating bamboo (Hygroryza aristata) is an endangered species with a narrow native distribution and is renowned for its unique aesthetic qualities, which holds significant ecological and ornamental value. However, the lack of genetic information research, with only one complete plastome available, significantly hampers conservation efforts and further research for this species. RESULTS: In this research, we sequenced and assembled the organelle genomes of floating bamboo, including the mitogenome (587,847 bp) and plastome (135,675 bp). The mitogenome can recombine into various configurations, which are mediated by 25 repeat pairs (13 SRs, 6 MRs, 1 LR, and 5 CRs). LR1 and SR5 are particularly notable as they have the ability to combine with other contigs, forming complex repeat units that facilitate further homologous recombination. The rate of homologous recombination varies significantly among species, yet there is still a pronounced positive correlation observed between the length of these repeat pairs and the rate of recombination they mediate. The mitogenome integrates seven intact protein-coding genes from the chloroplast. The codon usage patterns in both organelles are similar, with a noticeable bias towards C and T on the third codon. The gene map of Poales shows the entire loss of rpl6, succinate dehydrogenase subunits (sdh3 and sdh4). Additionally, the BOP clade retained more variable genes compared to the PACMAD clade. CONCLUSIONS: We provided a high-quality and well-annotated mitogenome for floating bamboo and demonstrated the presence of diverse configurations. Our study has revealed the correlation between repeat length and their corresponding recombination rate despite variations among species. Although the mitogenome can potentially exist in the form of a unicircular in vivo, this occurrence is rare and may not be stable.
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Genoma Mitocondrial , Poaceae , Poaceae/genética , Recombinación Genética , Secuencias Repetitivas de Ácidos Nucleicos/genética , Genoma de PlantaRESUMEN
Sulfur (S) is an essential bioelement with vital roles in serving regulatory and catalytic functions and tightly coupled with N and P in plants. However, globally stoichiometric patterns of leaf S and its relationships to leaf N and P are less well studied. We compiled 31 939 records of leaf-based data for 2600 plant species across 6652 sites worldwide. All plant species were divided into different phylogenetic taxa and growth forms. Standard major axis analysis was employed to fit the bivariate element relationships. A phylogenetic linear mixed-effect model and a multiple-regression model were used to partition the variations of bioelements into phylogeny and environments, and then to estimate the importance of environmental variables. Global geometric mean leaf S, N and P concentrations were 1.44, 15.70 and 1.27 mg g-1, respectively, with significant differences among plant groups. Leaf S-N-P positively correlated with each other, ignoring plant groups. The scaling exponents of LN-LS, LP-LS and LN-LP were 0.64, 0.76 and 0.79, respectively, for all species, but differed among plant groups. Both phylogeny and environments regulated the bioelements. The variability, rather than mean temperature, controlled the bioelements. Phylogeny explained more for the concentrations of all the three bioelements than environments, of which S was the one most affected by phylogenetic taxa.
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Nitrógeno , Fósforo , Filogenia , Hojas de la Planta , Azufre , Fósforo/metabolismo , Azufre/metabolismo , Nitrógeno/metabolismo , Plantas , AmbienteRESUMEN
Plant JASMONATE ZIM-DOMAIN (JAZ) genes play crucial roles in regulating the biosynthesis of specialized metabolites and stressful responses. However, understanding of JAZs controlling these biological processes lags due to numerous JAZ copies. Here, we found that two leaf-specific CwJAZ4/9 genes from Curcuma wenyujin are strongly induced by methyl-jasmonate (MeJA) and negatively correlated with terpenoid biosynthesis. Yeast two-hybrid, luciferase complementation imaging and in vitro pull-down assays confirmed that CwJAZ4/9 proteins interact with CwMYC2 to form the CwJAZ4/9-CwMYC2 regulatory cascade. Furthermore, transgenic hairy roots showed that CwJAZ4/9 acts as repressors of MeJA-induced terpenoid biosynthesis by inhibiting the terpenoid pathway and jasmonate response, thus reducing terpenoid accumulation. In addition, we revealed that CwJAZ4/9 decreases salt sensitivity and sustains the growth of hairy roots under salt stress by suppressing the salt-mediated jasmonate responses. Transcriptome analysis for MeJA-mediated transgenic hairy root lines further confirmed that CwJAZ4/9 negatively regulates the terpenoid pathway genes and massively alters the expression of genes related to salt stress signaling and responses, and crosstalks of multiple phytohormones. Altogether, our results establish a genetic framework to understand how CwJAZ4/9 inhibits terpenoid biosynthesis and confers salt tolerance, which provides a potential strategy for producing high-value pharmaceutical terpenoids and improving resistant C. wenyujin varieties by a genetic approach.
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Acetatos , Curcuma , Ciclopentanos , Regulación de la Expresión Génica de las Plantas , Oxilipinas , Proteínas de Plantas , Tolerancia a la Sal , Terpenos , Oxilipinas/metabolismo , Ciclopentanos/metabolismo , Tolerancia a la Sal/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Terpenos/metabolismo , Acetatos/farmacología , Acetatos/metabolismo , Curcuma/metabolismo , Curcuma/genética , Plantas Modificadas Genéticamente , Reguladores del Crecimiento de las Plantas/metabolismo , Raíces de Plantas/metabolismo , Raíces de Plantas/genética , Raíces de Plantas/efectos de los fármacosRESUMEN
BACKGROUND: The atherogenic index of plasma (AIP) and cardiovascular disease (CVD) in participants with abnormal glucose metabolism have been linked in previous studies. However, it was unclear whether AIP control level affects the further CVD incidence among with diabetes and pre-diabetes. Therefore, our study aimed to investigate the association between AIP control level with risk of CVD in individuals with abnormal glucose metabolism. METHODS: Participants with abnormal glucose metabolism were included from the China Health and Retirement Longitudinal Study. CVD was defined as self-reporting heart disease and/or stroke. Using k-means clustering analysis, AIP control level, which was the log-transformed ratio of triglyceride to high-density lipoprotein cholesterol in molar concentration, was divided into five classes. The association between AIP control level and incident CVD among individuals with abnormal glucose metabolism was investigated multivariable logistic regression analysis and application of restricted cubic spline analysis. RESULTS: 398 (14.97%) of 2,659 participants eventually progressed to CVD within 3 years. After adjusting for various confounding factors, comparing to class 1 with the best control of the AIP, the OR for class 2 with good control was 1.31 (95% CI, 0.90-1.90), the OR for class 3 with moderate control was 1.38 (95% CI, 0.99-1.93), the OR for class 4 with worse control was 1.46 (95% CI, 1.01-2.10), and the OR for class 5 with consistently high levels was 1.56 (95% CI, 1.03-2.37). In restricted cubic spline regression, the relationship between cumulative AIP index and CVD is linear. Further subgroup analysis demonstrated that the similar results were observed in the individuals with agricultural Hukou, history of smoking, diastolic blood pressure ≥ 80mmHg, and normal body mass index. In addition, there was no interaction between the AIP control level and the subgroup variables. CONCLUSIONS: In middle-aged and elderly participants with abnormal glucose metabolism, constant higher AIP with worst control may have a higher incidence of CVD. Monitoring long-term AIP change will contribute to early identification of high risk of CVD among individuals with abnormal glucose metabolism.
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Enfermedades Cardiovasculares , Persona de Mediana Edad , Anciano , Humanos , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Glucosa , Factores de Riesgo , Estudios Longitudinales , Triglicéridos , China/epidemiologíaRESUMEN
Motivated by recent surprising experimental findings, we develop a strong-coupling theory for Bose-Fermi mixtures capable of treating resonant interspecies interactions while satisfying the compressibility sum rule. We show that the mixture can be stable at large interaction strengths close to resonance, in agreement with the experiment, but at odds with the widely used perturbation theory. We also calculate the sound velocity of the Bose gas in the ^{133}Cs-^{6}Li mixture, again finding good agreement with the experimental observations both at weak and strong interactions. A central ingredient of our theory is the generalization of a fermion mediated interaction to strong Bose-Fermi scatterings and to finite frequencies. This further leads to a predicted hybridization of the sound modes of the Bose and Fermi gases, which can be directly observed using Bragg spectroscopy.
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OBJECTIVE: The optimal timing for surgery following neoadjuvant immunochemotherapy for lung squamous cell carcinoma appears to be a topic of limited data. Many clinical studies lack stringent guidelines regarding this timing. The objective of this study is to explore the effect of the interval between neoadjuvant immunochemotherapy and surgery on survival outcomes in patients with lung squamous cell carcinoma. METHODS: This study conducted a retrospective analysis of patients with lung squamous cell carcinoma who underwent neoadjuvant immunochemotherapy between January 2019 and October 2022 at The First Affiliated Hospital, Zhejiang University School of Medicine. Patients were divided into two groups based on the treatment interval: ≤33 days and > 33 days. The primary observational endpoints of the study were Disease-Free Survival (DFS) and Overall Survival (OS). Secondary observational endpoints included Objective response rate (ORR), Major Pathological Response (MPR), and Pathological Complete Remission (pCR). RESULTS: Using the Kaplan-Meier methods, the ≤ 33d group demonstrated a superior DFS curve compared to the > 33d group (p = 0.0015). The median DFS for the two groups was 952 days and 590 days, respectively. There was no statistical difference in the OS curves between the groups (p = 0.66), and the median OS was not reached for either group. The treatment interval did not influence the pathologic response of the tumor or lymph nodes. CONCLUSIONS: The study observed that shorter treatment intervals were associated with improved DFS, without influencing OS, pathologic response, or surgical safety. Patients should avoid having a prolonged treatment interval between neoadjuvant immunochemotherapy and surgery.
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Carcinoma de Células Escamosas , Neoplasias Pulmonares , Terapia Neoadyuvante , Humanos , Masculino , Terapia Neoadyuvante/métodos , Femenino , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Supervivencia sin Enfermedad , Neumonectomía , Tiempo de Tratamiento , Adulto , Resultado del TratamientoRESUMEN
BACKGROUND: Cardiac diffusion-weighted imaging (DWI) using second-order motion-compensated spin echo (M2C) can provide noninvasive in-vivo microstructural assessment, but limited by relatively low signal-to-noise ratio (SNR). Echo-planar imaging (EPI) with compressed sensitivity encoding (EPICS) could address these issues. PURPOSE: To combine M2C DWI and EPCIS (M2C EPICS DWI), and compare image quality for M2C DWI. STUDY TYPE: Prospective. POPULATION: Ten ex-vivo hearts, 10 healthy volunteers (females, 5 [50%]; mean ± SD of age, 25 ± 4 years), and 12 patients with diseased hearts (female, 1 [8.3%]; mean ± SD of age, 44 ± 16 years; including coronary artery heart disease, congenital heart disease, dilated cardiomyopathy, amyloidosis, and myocarditis). FIELD STRENGTH/SEQUENCE: 3-T, M2C EPICS DWI, and M2C DWI. ASSESSMENT: The apparent SNR (aSNR) and the rating scores were used to evaluate and compared image quality of all three groups. The aSNR was calculated using aSNR = Mean intensity myocardium / Standard deviation myocardium $$ \mathrm{aSNR}={\mathrm{Mean}\ \mathrm{intensity}}_{\mathrm{myocardium}}/{\mathrm{Standard}\ \mathrm{deviation}}_{\mathrm{myocardium}} $$ , and the myocardium was segmented manually. Three observers independently rated subjective image quality using a 5-point Likert scale. STATISTICAL TESTS: Bland-Altman analysis and paired t-tests. The threshold for statistical significance was set at P < 0.05. RESULTS: In healthy volunteers, the aSNR with a b-value of 450 s/mm2 acquired by M2C EPICS DWI was significantly higher than M2C DWI at in-plane resolutions of 3.0 × 3.0, 2.5 × 2.5, and 2.0 × 2.0 mm2. In patients with diseased hearts, the aSNR ofM2C EPICS DWI was also significantly higher than that for M2C DWI (bias of M2C EPICS-M2C = 1.999, 95% limits of agreement, 0.362 to 3.636; mean ± SD, 7.80 ± 1.37 vs. 5.80 ± 0.81). The ADC values of M2C EPICS was significantly higher than M2C DWI in in-vivo hearts. Over 80% of the images with rating scores for M2C EPICS DWI were higher than M2C DWI in in-vivo hearts. DATA CONCLUSION: Cardiac imaging by M2C EPICS DWI may demonstrate better overall image quality and higher aSNR than M2C DWI. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.
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Cold stress is one of the main abiotic stresses that affects rice growth and production worldwide. Dissection of the genetic basis is important for genetic improvement of cold tolerance in rice. In this study, a new source of cold-tolerant accession from the Yunnan plateau, Lijiangxiaoheigu, was used as the donor parent and crossed with a cold-sensitive cultivar, Deyou17, to develop recombinant inbred lines (RILs) for quantitative trait locus (QTL) analysis for cold tolerance at the early seedling and booting stages in rice. In total, three QTLs for cold tolerance at the early seedling stage on chromosomes 2 and 7, and four QTLs at the booting stage on chromosomes 1, 3, 5, and 7, were identified. Haplotype and linear regression analyses showed that QTL pyramiding based on the additive effect of these favorable loci has good potential for cold tolerance breeding. Effect assessment in the RIL and BC3F3 populations demonstrated that qCTB1 had a stable effect on cold tolerance at the booting stage in the genetic segregation populations. Under different cold stress conditions, qCTB1 was fine-mapped to a 341-kb interval between markers M3 and M4. Through the combination of parental sequence comparison, candidate gene-based association analysis, and tissue and cold-induced expression analyses, eight important candidate genes for qCTB1 were identified. This study will provide genetic resources for molecular breeding and gene cloning to improve cold tolerance in rice. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01488-3.
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OBJECTIVES: Older people are more likely to have digital exclusion, which is associated with poor health. This study investigated the relationship between digital exclusion and cognitive impairment in older adults from 23 countries across five longitudinal surveys. DESIGN AND MEASUREMENTS: Digital exclusion is defined as self-reported non-use of the Internet. We assessed cognitive impairment on three dimensions: orientation, memory, and executive function. We used generalized estimation equations fitting binary logistic regression with exchangeable correlations to study the relationship between digital exclusion and cognitive impairment, and apply the minimum sufficiently adjusted set of causally directed acyclic graphs as the adjusted variable. SETTING AND PARTICIPANTS: We pooled a nationally representative sample of older adults from five longitudinal studies, including the China Health and Retirement Longitudinal study (CHARLS), the English Longitudinal Study of Ageing (ELSA), the Health and Retirement Study (HRS), the Mexican Health and Ageing Study (MHAS) and the Survey of Health, Ageing and Retirement in European (SHARE). RESULTS: We included 62,413 participants from five longitudinal studies. Digital exclusion varied by country, ranging from 21.69% (SHARE) in Denmark to 97.15% (CHARLS) in China. In the original model, digital exclusion was significantly associated with cognitive impairment in all five studies. In the adjusted model, these associations remained statistically significant: CHARLS (Odds ratio [OR] = 2.81, 95% confidence interval [CI] 1.84-4.28, ELSA (1.92 [1.70-2.18]), HRS(2.48[2.28-2.71), MHAS (1.92 [1.74-2.12]), and SHARE (2.60 [2.34-2.88]). CONCLUSION: Our research shows that a significant proportion of older people suffer from digital exclusion, especially in China. Digital exclusion was positively correlated with cognitive impairment. These findings suggest that digital inclusion could be an important strategy to improve cognitive function and reduce the risk of cognitive impairment in older adults.
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Disfunción Cognitiva , Humanos , Anciano , Estudios Longitudinales , Masculino , Femenino , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/psicología , Persona de Mediana Edad , Anciano de 80 o más Años , China/epidemiología , Uso de Internet/estadística & datos numéricosRESUMEN
PURPOSE: The impact of air pollution on semen quality has been confirmed, yet the joint effect remains unclear. We evaluate the individual and joint associations of particulate (PM2.5 and PM10) and gaseous pollutants (NO2, SO2, O3 and CO) with semen quality. METHODS: We included 5,114 men in this study from 2014 to 2022. The individual and joint associations were measured by multiple linear regression models. RESULTS: Sperm motility and semen volume were inversely associated with pollutant concentrations during every stage of sperm development, especially at lag days 0-9 and 10-14 (all P < 0.05). Stratified analyses showed that the study pollutants (except CO) had a positive effect on semen concentration during the stage of sperm development, especially in spring and autumn, while a decreased total sperm number was associated with CO (all P < 0.05). However, joint associations of particulate and gaseous pollutants with semen quality parameters were not statistically significant (all P > 0.05). CONCLUSIONS: During all stages of sperm development, particulate and gaseous pollutants had individual negative impacts on sperm motility and semen volume, and these impacts were less pronounced in spring and autumn. Our findings highlight the importance and necessity of reducing the exposure to pollutants especially in the critical stage of sperm development to improve semen quality.
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On-orbit servicing using a space robot is gaining popularity among the space community for both economic and safety aspects. In particular, the estimation of the relative motion of a noncooperative target is a challenging problem. This study presents a relative motion estimation scheme based on stereovision for noncooperative targets considering multiple solutions of rotational parameters. Specifically, the mass distribution of the target is identified based on the least-square method and the principle of conservation of angular momentum. Then, the determination of a unique principal axis coordinate frame of the target is employed to resolve the multiple-solution problem. In addition, an EKF (extended Kalman filter)-based filter with global observability is designed to estimate the full motion states and inertia parameters of the target. The convergence performance of the proposed method is verified by numerical simulation. The results also demonstrate that the method is robust to occlusion.
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Site-specific protein decaging by light has become an effective approach for in situ manipulation of protein activities in a gain-of-function fashion. Although successful decaging of amino acid side chains of Lys, Tyr, Cys, and Glu has been demonstrated, this strategy has not been extended to aspartic acid (Asp), an essential amino acid residue with a range of protein functions and protein-protein interactions. We herein reported a genetically encoded photocaged Asp and applied it to the photocontrolled manipulation of a panel of proteins including firefly luciferase, kinases (e.g., BRAF), and GTPase (e.g., KRAS) as well as mimicking the in situ phosphorylation event on kinases. As a new member of the increasingly expanded amino acid-decaging toolbox, photocaged Asp may find broad applications for gain-of-function study of diverse proteins as well as biological processes in living cells.
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Fotoquímica , Ácido Aspártico/química , Ácido Aspártico/genética , Fotoquímica/métodos , Fosforilación , Proteínas/química , Proteínas/genética , Modelos Moleculares , Estructura Terciaria de Proteína , Secuencias de AminoácidosRESUMEN
PURPOSE: This work introduces and validates a deep-learning-based fitting method, which can rapidly provide accurate and robust estimation of cytological features of brain tumor based on the IMPULSED (imaging microstructural parameters using limited spectrally edited diffusion) model fitting with diffusion-weighted MRI data. METHODS: The U-Net was applied to rapidly quantify extracellular diffusion coefficient (Dex ), cell size (d), and intracellular volume fraction (vin ) of brain tumor. At the training stage, the image-based training data, synthesized by randomizing quantifiable microstructural parameters within specific ranges, was used to train U-Net. At the test stage, the pre-trained U-Net was applied to estimate the microstructural parameters from simulated data and the in vivo data acquired on patients at 3T. The U-Net was compared with conventional non-linear least-squares (NLLS) fitting in simulations in terms of estimation accuracy and precision. RESULTS: Our results confirm that the proposed method yields better fidelity in simulations and is more robust to noise than the NLLS fitting. For in vivo data, the U-Net yields obvious quality improvement in parameter maps, and the estimations of all parameters are in good agreement with the NLLS fitting. Moreover, our method is several orders of magnitude faster than the NLLS fitting (from about 5 min to <1 s). CONCLUSION: The image-based training scheme proposed herein helps to improve the quality of the estimated parameters. Our deep-learning-based fitting method can estimate the cell microstructural parameters fast and accurately.
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Neoplasias Encefálicas , Imagen de Difusión por Resonancia Magnética , Humanos , Imagen de Difusión por Resonancia Magnética/métodos , Análisis de los Mínimos Cuadrados , Neoplasias Encefálicas/diagnóstico por imagen , Procesamiento de Imagen Asistido por ComputadorRESUMEN
The coronavirus disease 2019 (COVID-19) pandemic caused extensive loss of life worldwide. Further, the COVID-19 and influenza mix-infection had caused great distress to the diagnosis of the disease. To control illness progression and limit viral spread within the population, a real-time reverse-transcription PCR (RT-PCR) assay for early diagnosis of COVID-19 was developed, but detection was time-consuming (4-6 h). To improve the diagnosis of COVID-19 and influenza, we herein developed a recombinase polymerase amplification (RPA) method for simple and rapid amplification of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19 and Influenza A (H1N1, H3N2) and B (influenza B). Genes encoding the matrix protein (M) for H1N1, and the hemagglutinin (HA) for H3N2, and the polymerase A (PA) for Influenza B, and the nucleocapsid protein (N), the RNA-dependent-RNA polymerase (RdRP) in the open reading frame 1ab (ORF1ab) region, and the envelope protein (E) for SARS-CoV-2 were selected, and specific primers were designed. We validated our method using SARS-CoV-2, H1N1, H3N2 and influenza B plasmid standards and RNA samples extracted from COVID-19 and Influenza A/B (RT-PCR-verified) positive patients. The method could detect SARS-CoV-2 plasmid standard DNA quantitatively between 102 and 105 copies/ml with a log linearity of 0.99 in 22 min. And this method also be very effective in simultaneous detection of H1N1, H3N2 and influenza B. Clinical validation of 100 cases revealed a sensitivity of 100% for differentiating COVID-19 patients from healthy controls when the specificity was set at 90%. These results demonstrate that this nucleic acid testing method is advantageous compared with traditional PCR and other isothermal nucleic acid amplification methods in terms of time and portability. This method could potentially be used for detection of SARS-CoV-2, H1N1, H3N2 and influenza B, and adapted for point-of-care (POC) detection of a broad range of infectious pathogens in resource-limited settings.
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COVID-19 , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana , Ácidos Nucleicos , Humanos , COVID-19/diagnóstico , Gripe Humana/diagnóstico , SARS-CoV-2/genética , Recombinasas , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H3N2 del Virus de la Influenza A/genética , Sensibilidad y Especificidad , Nucleotidiltransferasas , ARN , Técnicas de Amplificación de Ácido Nucleico/métodos , ARN Viral/genéticaRESUMEN
Clinical medicine has experienced a rapid development in recent decades, during which therapies targeting specific cellular signaling pathways, or specific cell surface receptors, have been increasingly adopted. While these developments in clinical medicine call for improved precision in diagnosis and treatment monitoring, modern medical imaging methods are restricted mainly to anatomical imaging, lagging behind the requirements of precision medicine. Although positron emission tomography and single photon emission computed tomography have been used clinically for studies of metabolism, their applications have been limited by the exposure risk to ionizing radiation, the subsequent limitation in repeated and longitudinal studies, and the incapability in assessing downstream metabolism. Magnetic resonance spectroscopy (MRS) or spectroscopic imaging (MRSI) are, in theory, capable of assessing molecular activities in vivo, although they are often limited by sensitivity. Here, we review some recent developments in MRS and MRSI of multiple nuclei that have potential as molecular imaging tools in the clinic.
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Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética/métodos , Imagen MolecularRESUMEN
BACKGROUND: T1ρ mapping is a new quantitative MRI technique in recent years. In order to use T1ρ mapping as a noncontrast method to assess myocardial fibrosis, it is necessary to establish a range of normal values. PURPOSE: To establish a potential normal range of cardiac T1ρ values in healthy adults and to explore the influence of slice location and gender on T1ρ values. STUDY TYPE: Prospective. POPULATION: A total of 57 healthy volunteers without cardiovascular risk factors (age 26.7 ± 11.8 years; 29 males). FIELD STRENGTH/SEQUENCE: 1.5 T; modified Look-Locker inversion recovery (MOLLI) (T1 mapping), multiecho gradient-spin-echo (GraSE) (T2 mapping) and T1ρ -prepared steady-state free precession (T1ρ mapping) sequences. ASSESSMENT: Basal, mid, and apical short-axis left ventricular T1 , T2 , and T1ρ maps were acquired. T1ρ maps at spin-locking frequencies of 5 and 400 Hz were subtracted to create myocardial fibrosis index (mFI) maps. Slice-average and global average T1 , T2 , T1ρ , and mFI values were determined. STATISTICAL TESTS: Shapiro-Wilk test, Independent t-test, ANOVA test, Pearson correlation coefficient (r). SIGNIFICANCE: P value < 0.05. RESULTS: The global average values of T1 , T2 , T1ρ, and mFI were 1053 ± 34 msec, 51.9 ± 2.3 msec, 47.9 ± 2.8 msec, and 4.4 ± 1.6 msec. T1ρ values showed a significant gradual increase from the basal slice to the apical slice of the heart (basal 46.5 ± 2.7 msec, mid 48.0 ± 2.9 msec, apical 49.2 ± 3.3 msec). The T1ρ and mFI values of females (49.7 ± 2.4 msec and 5.1 ± 1.2 msec, respectively) were significantly higher than those of males (46.2 ± 1.9 msec and 3.7 ± 1.7 msec, respectively). In addition, there was a moderate positive correlation between global T1ρ values and global T1 values (r = 0.44, P < 0.05) and a moderate positive correlation between global T1ρ values and global T2 values (r = 0.42, P < 0.05). DATA CONCLUSION: In this study, the global T1ρ values of healthy adults' hearts were 47.9 ± 2.8 msec. This study found that gender and slice location of myocardium can affect the T1ρ values. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 1.
Asunto(s)
Corazón , Imagen por Resonancia Magnética , Masculino , Femenino , Humanos , Adulto , Adolescente , Adulto Joven , Valores de Referencia , Estudios Prospectivos , Imagen por Resonancia Magnética/métodos , Corazón/diagnóstico por imagen , Espectroscopía de Resonancia Magnética , Fibrosis , Reproducibilidad de los ResultadosRESUMEN
Multiple variables determine the success of an escape response of an animal, and the rapidity of the escape manoeuvre is often the most important. Fan worms (Annelida: Sabellidae) can rapidly withdraw their tentacles, which are covered in heavily ciliated ramifications called pinnules, into their tubes to protect them from approaching threats. Here, we explore the dynamic and mechanistic features behind this escape manoeuvre. The escape responses of fan worms were recorded by high-speed videography and quantified by computerized motion analysis, showing an ultrahigh retraction speed of 272±135â mmâ s-1 (8±4 body lengths s-1). We found that fan worms possess powerful muscle-driven systems, which can generate contractive forces up to 36 times their body weight. In order to achieve these rapid, forceful movements through seawater without damaging their tentacles, fan worms have developed functional morphological adaptations to reduce fluidic drag, including the flattening of their radiolar pinnules and the deformation of bodily segmental ridges. Our hydrodynamic models indicate that these mechanical processes can decrease fluidic drag by 47%, trapped mass by 75% and friction coefficient by 89%. These strategies allow fan worms to execute rapid escape responses and could inspire the design of fast in-pipe robots.