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A new series of thiophenpiperazine amide derivatives as potent dual ligands for the µ-opioid (MOR) and sigma-1 (σ1R) receptors are reported. Compound 23 exhibited good affinity to σ1R (Ki = 44.7 ± 7.05 nM) and high selectivity to σ2R. Furthermore, Compound 23 exerted MOR agonism and σ1R antagonism and potent analgesic activity in animal moldes (the abdominal constriction test (ED50 = 3.83 mg/kg) and carrageenan-induced inflammatory hyperalgesia model (ED50 = 5.23 mg/kg)). We obtained new dual ligands that might serve as starting points for preparing targeted tools. Furthermore, 23 may be a useful chemical probe for understanding more fully analgesic effects associated with MOR agonism and σ1R antagonism.
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Amidas , Receptores sigma , Animais , Amidas/farmacologia , Amidas/uso terapêutico , Dor/induzido quimicamente , Dor/tratamento farmacológico , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Analgésicos/química , Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Ligantes , Receptores Opioides muRESUMO
2D metal-organic frameworks-based (2D MOF-related) materials benefit from variable topological structures, plentiful open active sites, and high specific surface areas, demonstrating promising applications in gas storage, adsorption and separation, energy conversion, and other domains. In recent years, researchers have innovatively designed multiple strategies to avoid the adverse effects of conventional methods on the synthesis of high-quality 2D MOFs. This review focuses on the latest advances in creative synthesis techniques for 2D MOF-related materials from both the top-down and bottom-up perspectives. Subsequently, the strategies are categorized and summarized for synthesizing 2D MOF-related composites and their derivatives. Finally, the current challenges are highlighted faced by 2D MOF-related materials and some targeted recommendations are put forward to inspire researchers to investigate more effective synthesis methods.
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BACKGROUND: Sepsis is a severe systemic inflammatory disorder manifested by a dysregulated immune response to infection and multi-organ failure. Numerous studies have shown that elevated ferritin levels exist as an essential feature during sepsis and are able to suggest patients' prognoses. At the same time, the specific mechanism of ferritin-induced inflammatory injury remains unclear. METHODS: Hyper-ferritin state during inflammation was performed by injecting ferritin into a mouse model and demonstrated that injection of ferritin could induce a systemic inflammatory response and increase neutrophil extracellular trap (NET) formation.Padi4-/-, Elane-/- and Cybb-/- mice were used for the NETs formation experiment. Western blot, immunofluorescence, ELISA, and flow cytometry examined the changes in NETs, inflammation, and related signaling pathways. RESULTS: Ferritin induces NET formation in a peptidylarginine deiminase 4 (PAD4), neutrophil elastase (NE), and reactive oxygen species (ROS)-dependent manner, thereby exacerbating the inflammatory response. Mechanistically, ferritin induces the expression of neutrophil macrophage scavenger receptor (MSR), which promotes the formation of NETs. Clinically, high levels of ferritin in patients with severe sepsis correlate with NETs-mediated cytokines storm and are proportional to the severity of sepsis-induced lung injury. CONCLUSIONS: In conclusion, we demonstrated that hyper-ferritin can induce systemic inflammation and increase NET formation in an MSR-dependent manner. This process relies on PAD4, NE, and ROS, further aggravating acute lung injury. In the clinic, high serum ferritin levels are associated with elevated NETs and worse lung injury, which suggests a poor prognosis for patients with sepsis. Our study indicated that targeting NETs or MSR could be a potential treatment to alleviate lung damage and systemic inflammation during sepsis. Video Abstract.
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Lesão Pulmonar Aguda , Armadilhas Extracelulares , Sepse , Humanos , Camundongos , Animais , Armadilhas Extracelulares/metabolismo , Síndrome da Liberação de Citocina , Espécies Reativas de Oxigênio/metabolismo , Neutrófilos/metabolismo , Inflamação/metabolismo , Sepse/complicações , Sepse/metabolismo , Lesão Pulmonar Aguda/metabolismo , Receptores Depuradores/metabolismoRESUMO
The construction of doped molecular clusters is an intriguing way to perform bimetallic doping for electrocatalysts. However, efficiently harnessing the benefits of a doping strategy and alloy engineering to create a nanostructure for electrocatalytic application at the molecular level has consistently posed a challenge. Here we propose an in situ reconstruction strategy aimed at producing an alloy nanostructure through a pyrolysis process, originating from bowknot-like heterometallic clusters. The Schiff base, denoted as ligand L1 (o-vanillin ethylenediamine), was introduced as a precursor to coordinate Fe and Co metals, thereby yielding a heteronuclear metal cluster [(FeCo)(L1)2O]CH3CN. Subsequently, a comprehensive investigation of the in situ reconstruction process [(FeCo)(L1)2O](CH3CN) â [(FeCo)(L1)2O] â [M-O-M/M-O] [CH3+/CH3O+/H2CâN/C2H5+/C4H4+] â [FeCo/Fe3O4/Fe2O3/Co3O4][carbon layer] led to the formation of MOx/CoFe@NC-700 during the pyrolysis. This process reveals that the metals Fe and Co in the clusters undergo partly in situ evolution into FeCo alloys, resulting in the successful preparation of MOx/CoFe@NC (M = Fe, Co) nanomaterials that leverage the advantages of both doping strategies and alloy engineering. The synergistic interaction between alloy particles and metal oxides establishes active sites that contribute to the excellent oxygen evolution (OER) and hydrogen evolution (HER) catalytic behaviors. Notably, these materials exhibit outstanding OER and HER properties under alkaline conditions, with overpotentials of 191 and 88 mV for OER and HER, respectively, at 10 mA cm-2. Investigation of the in situ conversion of Schiff base bimetal clusters into alloy materials through pyrolysis offers a novel strategy for advancing electrocatalytic applications.
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OBJECTIVE: This exploratory study examined whether central auditory tests show differences between people living with HIV (PLWH) treated with two predominant antiretroviral drug therapy (ART) regimens. DESIGN: Cross-sectional. STUDY SAMPLE: 253 PLWH (mean age 39.8 years) from the Shanghai Public Health Clinical Centre, China. METHODS: The Hearing in Noise Test speech reception threshold (SRT) assessed central auditory function and the Montreal Cognitive Assessment (MoCA) assessed cognition. The relationship between ART regimen and SRT was evaluated with multivariable linear regression incorporating age, HIV duration, and peripheral hearing ability. Multivariable logistic regression was used to ascertain if SRT and ART regimen predicted MoCA impairment. RESULTS: The two predominant ART regimens differed by one drug (zidovudine or tenofovir). Participants taking the zidovudine-containing regimen had poorer SRT performance (p=.012) independent of age and hearing thresholds. MoCA scores did not differ between drug regimens, but a negative relationship was found between SRT and MoCA impairment (p=.048). CONCLUSIONS: ART regimens differed in their association with central auditory test performance likely reflecting neurocognitive changes in PLWH taking the zidovudine-containing regimen. Central auditory test performance also marginally predicted cognitive impairment, supporting further assessment of central auditory tests to detect neurocognitive deficits in PLWH.
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Infecções por HIV , Percepção da Fala , Adulto , Humanos , Zidovudina/uso terapêutico , Estudos Transversais , China , Testes Auditivos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologiaRESUMO
AIM AND OBJECTIVES: To investigate the prevalence of dysphagia in patients with COPD, identify the risk factors for dysphagia, develop a visual clinical prediction model and quantitatively predict the probability of developing dysphagia. BACKGROUND: Patients with COPD are at high risk of dysphagia, which is strongly linked to the acute exacerbation of their condition. The use of effective tools to predict its risk may contribute to the early identification and treatment of dysphagia in patients with COPD. DESIGN: A cross-sectional design. METHODS: From July 2021 to April 2023, we enrolled 405 patients with COPD for this study. The clinical prediction model was constructed according to the results of a univariate analysis and a logistic regression analysis, evaluated by discrimination, calibration and decision curve analysis and visualized by a nomogram. This study was reported using the TRIPOD checklist. RESULTS: In total, 405 patients with COPD experienced dysphagia with a prevalence of 59.01%. A visual prediction model was constructed based on age, whether combined with cerebrovascular disease, chronic pulmonary heart disease, acute exacerbation of COPD, home noninvasive positive pressure ventilation, dyspnoea level and xerostomia level. The model exhibited excellent discrimination at an AUC of .879. Calibration curve analysis indicated a good agreement between experimental and predicted values, and the decision curve analysis showed a high clinical utility. CONCLUSION: The model we devised may be used in clinical settings to predict the occurrence of dysphagia in patients with COPD at an early stage. RELEVANCE TO CLINICAL PRACTICE: The model can help nursing staff to calculate the risk probability of dysphagia in patients with COPD, formulate personalized preventive care measures for high-risk groups as soon as possible to achieve early prevention or delay of dysphagia and its related complications and improve the prognosis. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.
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Prussian blue analogues (PBAs) have been widely studied in aqueous zinc-ion batteries (AZIBs) due to the characteristics of large specific surface area, open aperture, and straightforward synthesis. In this work, vanadium-based PBA nanocubes were firstly prepared using a mild in-situ conversion strategy at room temperature without the protection of noble gas. Benefiting from the multiple-redox active sites of V3+/V4+, V4+/V5+ and Fe2+/Fe3+, the cathode exhibited an excellent discharge specific capacity of 200 mA h g-1 in AZIBs, which is much higher than those of other metal-based PBAs nanocubes. To further improve the long-term cycling stability of the V-PBA cathode, a high concentration water-in-salt electrolyte (4.5 M ZnSO4 + 3 M Zn(OTf)2), and a water-based eutectic electrolyte (5.55 M glucose + 3 M Zn(OTf)2) were designed to successfully inhibit the dissolution of vanadium and improve the deposition of Zn2+ onto the zinc anode. More importantly, the assembled AZIBs maintained 55% of their highest discharge specific capacity even after 10000 cycles at 10 A g-1 with superior rate capability. This study provides a new strategy for the preparation of pure PBA nanostructures and a new direction for enhancing the long-term cycling stability of PBA-based AZIBs at high current densities for industrialization prospects.
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Defect engineering can provide a feasible approach to achieving ambient molecular oxygen activation. However, conventional surface defects (e.g., oxygen vacancies, OVs), featured with the coordinatively unsaturated metal sites, often favor the reduction of O2 to â¢O2- rather than O22- via two-electron transfer, hindering the efficient pollutant removal with high electron utilization. Herein, we demonstrate that this bottleneck can be well discharged by modulating the electronic structure of OVs via phosphorization. As a proof of concept, TiO2 nanoparticles are adopted as a model material for NaH2PO2 (HP) modification, in which HP induces the formation of OVs via weakening the Ti-O bonds through the hydrogen bond interactions. Additionally, the formed Ti-O-P covalent bond refines the electronic structure of OVs, which enables rapid electron transfer for two-electron molecular oxygen activation. As exemplified by NO oxidation, HP-modified TiO2 with abundant OVs achieved complete NO removal with high selectivity for benign nitrate, superior to that of pristine TiO2. This study highlights a promising approach to regulate the O2 activation via an electronic structure modulation and provides fresh insights into the rational design of a photocatalyst for environmental remediation.
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Elétrons , Oxigênio , Ligação de Hidrogênio , OxirreduçãoRESUMO
Recurrent lumbar disc herniation (rLDH) is one of the most serious complications and major causes of surgical failure and paralysis following percutaneous endoscopic lumbar discectomy (PELD). There are reports in the literature on the identification of risk factors associated with rLDH; however, the results are controversial. Therefore, we conducted a meta-analysis to identify risk factors for rLDH among patients following spinal surgery. PubMed, EMBASE, and the Cochrane Library were searched without language restrictions from inception to April 2018 for studies reporting risk factors for LDH recurrence after PELD. MOOSE guidelines were followed in this meta-analysis. We used a random effects model to aggregate odds ratios (ORs) with 95% confidence intervals (CIs). The evidence of observational studies was classified into high quality (class I), medium quality (class II/III), and low quality (class IV) based on the P value of the total sample size and heterogeneity between studies. Fifty-eight studies were identified with a mean follow-up of 38.8 months. Studies with high-quality (class I) evidence showed that postoperative LDH recurrence after PELD was significantly correlated with diabetes (OR, 1.64; 95% CI, 1.14 to 2.31), the protrusion type LDH (OR, 1.62; 95% CI, 1.02 to 2.61), and less experienced surgeons (OR, 1.54; 95% CI, 1.10 to 2.16). Studies with medium-quality (class II or III) evidence showed that postoperative LDH recurrence was significantly correlated with advanced age (OR, 1.11; 95% CI, 1.05 to 1.19), Modic changes (OR, 2.23; 95% CI, 1.53 to 2.29), smoking (OR, 1.31; 95% CI, 1.00 to 1.71), no college education (OR, 1.56; 95% CI, 1.05 to 2.31), obesity (BMI ≥ 25 kg/m2) (OR, 1.66; 95% CI, 1.11 to 2.47), and inappropriate manual labor (OR, 2.18; 95% CI, 1.33 to 3.59). Based on the current literature, eight patient-related and one surgery-related risk factor are predictors of postoperative LDH recurrence after PELD. These findings may help clinicians raise awareness of early intervention for patients at high risk of LDH recurrence after PELD.
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Discotomia Percutânea , Deslocamento do Disco Intervertebral , Humanos , Deslocamento do Disco Intervertebral/cirurgia , Vértebras Lombares/cirurgia , Discotomia , Fatores de Risco , Estudos de CoortesRESUMO
OBJECTIVE: To synthesize the best available evidence in exploring the experiences and perceptions of loneliness among older adults with chronic conditions aging at home. METHODS: Web of Science, PubMed, Embase, CINAHL and other databases were searched, and qualitative research on the loneliness experience of older adults with chronic conditions aging at home was collected. The included studies were appraised independently by two reviewers using The JBI Critical Appraisal Checklist for Qualitative Research. RESULTS: 6 studies were included and 4 themes were summarized, including: (a) negative emotions and unmet social needs of loneliness, (b) self-perceived influences of chronic conditions on loneliness, (c) self-strategy to deal with loneliness, and (d) social support to alleviate loneliness. CONCLUSION: Older adults aging at home were suffering from negative emotions and unmet social needs of loneliness, which were influenced by their chronic conditions, and they adopted self-strategies and social supports to cope with their loneliness.
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Envelhecimento , Solidão , Humanos , Idoso , Pesquisa Qualitativa , Doença CrônicaRESUMO
Ferroptosis is a form of regulated cell death characterized by the accumulation of lipid peroxides in an iron-dependent manner. Ferroptotic cell death is modulated by many metabolic pathways, such as pathways governing the metabolism of sugars, lipids, amino acids, and iron, as well as mitochondrial activity and redox homeostasis. Tumor metastasis and therapy resistance are the main obstacles to curing cancers. Because tumor cells usually exhibit higher iron dependence than normal cells, they may be more susceptible to ferroptosis despite being resistant to other forms of cell death. Moreover, recent evidence has suggested that ferroptosis is involved in tumor-host interactions, modulates the tumor microenvironment, and serves as an antimetastatic mechanism. Thus, inducing ferroptosis in tumor cells has the potential to improve cancer treatment. Here, we review ferroptosis-regulating mechanisms and the roles of ferroptosis in malignant progression, including the tumor-host interactions, metastasis, and cancer therapy response.
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Ferroptose , Neoplasias , Morte Celular , Humanos , Ferro/metabolismo , Mitocôndrias/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Microambiente TumoralRESUMO
OBJECTIVE: To develop and evaluate a radiomics signature based on magnetic resonance imaging (MRI) from multicenter datasets for identification of invisible basal cisterns changes in tuberculous meningitis (TBM) patients. METHODS: Our retrospective study enrolled 184 TBM patients and 187 non-TBM controls from 3 Chinese hospitals (training dataset, 158 TBM patients and 159 non-TBM controls; testing dataset, 26 TBM patients and 28 non-TBM controls). nnU-Net was used to segment basal cisterns in fluid-attenuated inversion recovery (FLAIR) images. Subsequently, radiomics features were extracted from segmented basal cisterns in FLAIR and T2-weighted (T2W) images. Feature selection was carried out in three steps. Support vector machine (SVM) and logistic regression (LR) classifiers were applied to construct the radiomics signature to directly identify basal cisterns changes in TBM patients. Finally, the diagnostic performance was evaluated by the receiver operating characteristic (ROC) curve analysis, calibration curve, and decision curve analysis (DCA). RESULTS: The segmentation model achieved the mean Dice coefficients of 0.920 and 0.727 in the training and testing datasets, respectively. The SVM model with 7 T2WI-based radiomics features achieved best discrimination capability for basal cisterns changes with an AUC of 0.796 (95% CI, 0.744-0.847) in the training dataset, and an AUC of 0.751 (95% CI, 0.617-0.886) with good calibration in the testing dataset. DCA confirmed its clinical usefulness. CONCLUSION: The T2WI-based radiomics signature combined with deep learning segmentation could provide a fully automatic, non-invasive tool to identify invisible changes of basal cisterns, which has the potential to assist in the diagnosis of TBM. KEY POINTS: ⢠The T2WI-based radiomics signature was useful for identifying invisible basal cistern changes in TBM. ⢠The nnU-Net model achieved acceptable results for the auto-segmentation of basal cisterns. ⢠Combining radiomics and deep learning segmentation provided an automatic, non-invasive approach to assist in the diagnosis of TBM.
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Tuberculose Meníngea , Humanos , Tuberculose Meníngea/diagnóstico por imagem , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Curva ROC , Máquina de Vetores de SuporteRESUMO
OBJECTIVE: HIV positive (HIV+) individuals with otherwise normal hearing ability show central auditory processing deficits as evidenced by worse performance in speech-in-noise perception compared with HIV negative (HIV-) controls. HIV infection and treatment are also associated with lower neurocognitive screening test scores, suggesting underlying central nervous system damage. To determine how central auditory processing deficits in HIV+ individuals relate to brain alterations in the cortex involved with auditory processing, we compared auditory network (AN) functional connectivity between HIV+ adults with or without speech-in-noise perception difficulties and age-matched HIV- controls using resting-state fMRI. DESIGN: Based on the speech recognition threshold of the hearing-in-noise test, twenty-seven HIV+ individuals were divided into a group with speech-in-noise perception abnormalities (HIV+SPabnl, 38.2 ± 6.8 years; 11 males and 2 females) and one without (HIV+SPnl 34.4 ± 8.8 years; 14 males). An HIV- group with normal speech-in-noise perception (HIV-, 31.3 ± 5.2 years; 9 males and 3 females) was also enrolled. All of these younger and middle-aged adults had normal peripheral hearing determined by audiometry. Participants were studied using resting-state fMRI. Independent component analysis was applied to identify the AN. Group differences in the AN were identified using statistical parametric mapping. RESULTS: Both HIV+ groups had increased functional connectivity (FC) in parts of the AN including the superior temporal gyrus, middle temporal gyrus, supramarginal gyrus, and Rolandic operculum compared to the HIV- group. Compared with the HIV+SPnl group, the HIV+SPabnl group showed greater FC in parts of the AN including the middle frontal and inferior frontal gyri. CONCLUSIONS: The classical auditory areas in the temporal lobe are affected by HIV regardless of speech perception ability. Increased temporal FC in HIV+ individuals might reflect functional compensation to achieve normal primary auditory perception. Furthermore, increased frontal FC in the HIV+SPabnl group compared with the HIV+SPnl group suggest that speech-in-noise perception difficulties in HIV-infected adults also affect areas involved in higher-level cognition, providing imaging evidence consistent with the hypothesis that HIV-related neurocognitive deficits can include central auditory processing deficits.
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Córtex Auditivo , Infecções por HIV , Percepção da Fala , Adulto , Audiometria , Limiar Auditivo/fisiologia , Feminino , Infecções por HIV/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Ruído , Percepção da Fala/fisiologiaRESUMO
Sanguinarine, a plant-derived phytoalexin, displays various biological activities, such as insecticidal, antimicrobial, anti-inflammatory, anti-angiogenesis and antitumor effects. But its potential neurotoxicity and the underlying mechanisms has rarely been investigated. Therefore, we aimed to assess the neurotoxicity of sanguinarine using zebrafish model and PC12 cells in this study. The results showed that sanguinarine induced the reduction of the length of dopamine neurons and inhibited the blood vessel in the head area of the zebrafish. Further studies demonstrated that the behavioral phenotype of the larval zebrafish was changed by sanguinarine. In addition, there were more apoptotic cells in the larval zebrafish head area. The mRNA expression levels of ß-syn, th, pink1 and parkin, closely related to the nervous function, were changed after sanguinarine treatment. The in vitro studies show that notably increases of ROS and apoptosis levels in PC12 cells were observed after sanguinarine treatment. Moreover, the protein expression of Caspase3, Parp, Bax, Bcl2, α-Syn, Th, PINK1 and Parkin were also altered by sanguinarine. Our data indicated that the inhibition of mitophagy, ROS elevation and apoptosis were involved in the neurotoxicity of sanguinarine. These findings will be useful to understand the toxicity induced by sanguinarine.
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Mitofagia , Peixe-Zebra , Animais , Ratos , Células PC12 , Espécies Reativas de Oxigênio , Apoptose , Ubiquitina-Proteína Ligases , Larva , Proteínas QuinasesRESUMO
Carbon quantum dots (CQDs) have developed into prospective nanomaterials for next-generation lighting and displays due to their intrinsic advantages of high stability, low cost, and environmental friendliness. However, confined by the spin-forbidden nature of triplet state transitions, the highest theoretical value of external quantum efficiency (EQE) of fluorescent CQDs is merely 5%, which fundamentally limits their further application in electroluminescent light-emitting diodes (LEDs). Soluble phosphorescent CQDs offer a means of breaking the shackle to achieve efficient monochromatic electroluminescence, especially red emission, which is a pivotal constituent in full-color displays. Here, the synthesis of red (625 nm) phosphorescent carbon quantum dot organic frameworks (CDOFs) with a quantum yield of up to 42.3% and realization of high-efficiency red phosphorescent electroluminescent LEDs are reported. The LEDs based on the CDOFs exhibited a red emission with a maximum luminance of 1818 cd m-2 and an EQE of 5.6%. This work explores the possibility of a new perspective for developing high-performance CQD-based electroluminescent LEDs.
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BACKGROUND: Cumulative CT radiation damage was positively correlated with increased tumor risks. Although it has recently been known that non-radiation MRI is alternative for pulmonary imaging. There is little known about the value of MRI T1-mapping in the diagnosis of pulmonary nodules. This article aimed to investigate the value of native T1-mapping-based radiomics features in differential diagnosis of pulmonary lesions. METHODS: 73 patients underwent 3 T-MRI examination in this prospective study. The 99 pulmonary lesions on native T1-mapping images were segmented twice by one radiologist at indicated time points utilizing the in-house semi-automated software, followed by extraction of radiomics features. The inter-class correlation coefficient (ICC) was used for analyzing intra-observer's agreement. Dimensionality reduction and feature selection were performed via univariate analysis, and least absolute shrinkage and selection operator (LASSO) analysis. Then, the binary logical regression (LR), support vector machine (SVM) and decision tree classifiers with the input of optimal features were selected for differentiating malignant from benign lesions. The receiver operative characteristics (ROC) curve, area under the curve (AUC), sensitivity, specificity and accuracy were calculated. Z-test was used to compare differences among AUCs. RESULTS: 107 features were obtained, of them, 19.5% (n = 21) had relatively good reliability (ICC ≥ 0.6). The remained 5 features (3 GLCM, 1 GLSZM and 1 shape features) by dimensionality reduction were useful. The AUC of LR was 0.82(95%CI: 0.67-0.98), with sensitivity, specificity and accuracy of 70%, 85% and 80%. The AUC of SVM was 0.82(95%CI: 0.67-0.98), with sensitivity, specificity and accuracy of 70, 85 and 80%. The AUC of decision tree was 0.69(95%CI: 0.49-0.87), with sensitivity, specificity and accuracy of 50, 85 and 73.3%. CONCLUSIONS: The LR and SVM models using native T1-mapping-based radiomics features can differentiate pulmonary malignant from benign lesions, especially for uncertain nodules requiring long-term follow-ups.
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KEY MESSAGE: Association analysis for ionomic concentrations of 20 elements identified independent genetic factors underlying the root and shoot ionomes of rice, providing a platform for selecting and dissecting causal genetic variants. Understanding the genetic basis of mineral nutrient acquisition is key to fully describing how terrestrial organisms interact with the non-living environment. Rice (Oryza sativa L.) serves both as a model organism for genetic studies and as an important component of the global food system. Studies in rice ionomics have primarily focused on above ground tissues evaluated from field-grown plants. Here, we describe a comprehensive study of the genetic basis of the rice ionome in both roots and shoots of 6-week-old rice plants for 20 elements using a controlled hydroponics growth system. Building on the wealth of publicly available rice genomic resources, including a panel of 373 diverse rice lines, 4.8 M genome-wide single-nucleotide polymorphisms, single- and multi-marker analysis pipelines, an extensive tome of 321 candidate genes and legacy QTLs from across 15 years of rice genetics literature, we used genome-wide association analysis and biparental QTL analysis to identify 114 genomic regions associated with ionomic variation. The genetic basis for root and shoot ionomes was highly distinct; 78 loci were associated with roots and 36 loci with shoots, with no overlapping genomic regions for the same element across tissues. We further describe the distribution of phenotypic variation across haplotypes and identify candidate genes within highly significant regions associated with sulfur, manganese, cadmium, and molybdenum. Our analysis provides critical insight into the genetic basis of natural phenotypic variation for both root and shoot ionomes in rice and provides a comprehensive resource for dissecting and testing causal genetic variants.
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Mapeamento Cromossômico/métodos , Cromossomos de Plantas/genética , Regulação da Expressão Gênica de Plantas , Oryza/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/genética , Brotos de Planta/genética , Estudo de Associação Genômica Ampla , Oryza/crescimento & desenvolvimento , Fenótipo , Proteínas de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Brotos de Planta/crescimento & desenvolvimento , Locos de Características QuantitativasRESUMO
BACKGROUND: To explore the long-term trajectories considering pneumonia volumes and lymphocyte counts with individual data in COVID-19. METHODS: A cohort of 257 convalescent COVID-19 patients (131 male and 126 females) were included. Group-based multi-trajectory modelling was applied to identify different trajectories in terms of pneumonia lesion percentage and lymphocyte counts covering the time from onset to post-discharge follow-ups. We studied the basic characteristics and disease severity associated with the trajectories. RESULTS: We characterised four distinct trajectory subgroups. (1) Group 1 (13.9%), pneumonia increased until a peak lesion percentage of 1.9% (IQR 0.7-4.4) before absorption. The slightly decreased lymphocyte rapidly recovered to the top half of the normal range. (2) Group 2 (44.7%), the peak lesion percentage was 7.2% (IQR 3.2-12.7). The abnormal lymphocyte count restored to normal soon. (3) Group 3 (26.0%), the peak lesion percentage reached 14.2% (IQR 8.5-19.8). The lymphocytes continuously dropped to 0.75 × 109/L after one day post-onset before slowly recovering. (4) Group 4 (15.4%), the peak lesion percentage reached 41.4% (IQR 34.8-47.9), much higher than other groups. Lymphopenia was aggravated until the lymphocytes declined to 0.80 × 109/L on the fourth day and slowly recovered later. Patients in the higher order groups were older and more likely to have hypertension and diabetes (all P values < 0.05), and have more severe disease. CONCLUSIONS: Our findings provide new insights to understand the heterogeneous natural courses of COVID-19 patients and the associations of distinct trajectories with disease severity, which is essential to improve the early risk assessment, patient monitoring, and follow-up schedule.
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COVID-19 , Convalescença , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Adulto , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
The dramatic reorganization of chromatin during mitosis is perhaps one of the most fundamental of all cell processes. It remains unclear how epigenetic histone modifications, despite their crucial roles in regulating chromatin architectures, are dynamically coordinated with chromatin reorganization in controlling this process. We have developed and characterized biosensors with high sensitivity and specificity based on fluorescence resonance energy transfer (FRET). These biosensors were incorporated into nucleosomes to visualize histone H3 Lys-9 trimethylation (H3K9me3) and histone H3 Ser-10 phosphorylation (H3S10p) simultaneously in the same live cell. We observed an anticorrelated coupling in time between H3K9me3 and H3S10p in a single live cell during mitosis. A transient increase of H3S10p during mitosis is accompanied by a decrease of H3K9me3 that recovers before the restoration of H3S10p upon mitotic exit. We further showed that H3S10p is causatively critical for the decrease of H3K9me3 and the consequent reduction of heterochromatin structure, leading to the subsequent global chromatin reorganization and nuclear envelope dissolution as a cell enters mitosis. These results suggest a tight coupling of H3S10p and H3K9me3 dynamics in the regulation of heterochromatin dissolution before a global chromatin reorganization during mitosis.
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Técnicas Biossensoriais/métodos , Montagem e Desmontagem da Cromatina , Código das Histonas , Proteínas de Bactérias , Montagem e Desmontagem da Cromatina/genética , Transferência Ressonante de Energia de Fluorescência/métodos , Proteínas de Fluorescência Verde , Células HEK293 , Heterocromatina/genética , Heterocromatina/metabolismo , Código das Histonas/genética , Histonas/química , Histonas/genética , Histonas/metabolismo , Humanos , Proteínas Luminescentes , Mitose , Modelos Biológicos , Análise de Célula Única/métodosRESUMO
This paper aims to develop an automatic method to segment pulmonary parenchyma in chest CT images and analyze texture features from the segmented pulmonary parenchyma regions to assist radiologists in COVID-19 diagnosis. A new segmentation method, which integrates a three-dimensional (3D) V-Net with a shape deformation module implemented using a spatial transform network (STN), was proposed to segment pulmonary parenchyma in chest CT images. The 3D V-Net was adopted to perform an end-to-end lung extraction while the deformation module was utilized to refine the V-Net output according to the prior shape knowledge. The proposed segmentation method was validated against the manual annotation generated by experienced operators. The radiomic features measured from our segmentation results were further analyzed by sophisticated statistical models with high interpretability to discover significant independent features and detect COVID-19 infection. Experimental results demonstrated that compared with the manual annotation, the proposed segmentation method achieved a Dice similarity coefficient of 0.9796, a sensitivity of 0.9840, a specificity of 0.9954, and a mean surface distance error of 0.0318 mm. Furthermore, our COVID-19 classification model achieved an area under curve (AUC) of 0.9470, a sensitivity of 0.9670, and a specificity of 0.9270 when discriminating lung infection with COVID-19 from community-acquired pneumonia and healthy controls using statistically significant radiomic features. The significant features measured from our segmentation results agreed well with those from the manual annotation. Our approach has great promise for clinical use in facilitating automatic diagnosis of COVID-19 infection on chest CT images.