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Cell segmentation is a critical step for quantitative single-cell analysis in microscopy images. Existing cell segmentation methods are often tailored to specific modalities or require manual interventions to specify hyper-parameters in different experimental settings. Here, we present a multimodality cell segmentation benchmark, comprising more than 1,500 labeled images derived from more than 50 diverse biological experiments. The top participants developed a Transformer-based deep-learning algorithm that not only exceeds existing methods but can also be applied to diverse microscopy images across imaging platforms and tissue types without manual parameter adjustments. This benchmark and the improved algorithm offer promising avenues for more accurate and versatile cell analysis in microscopy imaging.
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Algoritmos , Aprendizado Profundo , Processamento de Imagem Assistida por Computador , Análise de Célula Única , Análise de Célula Única/métodos , Processamento de Imagem Assistida por Computador/métodos , Humanos , Microscopia/métodos , AnimaisRESUMO
Dual/multimodal imaging strategies are increasingly recognized for their potential to provide comprehensive diagnostic insights in cancer imaging by harnessing complementary data. This study presents an innovative probe that capitalizes on the synergistic benefits of afterglow luminescence and magnetic resonance imaging (MRI), effectively eliminating autofluorescence interference and delivering a superior signal-to-noise ratio. Additionally, it facilitates deep tissue penetration and enables noninvasive imaging. Despite the advantages, only a limited number of probes have demonstrated the capability to simultaneously enhance afterglow luminescence and achieve high-resolution MRI and afterglow imaging. Herein, we introduce a cutting-edge imaging platform based on semiconducting polymer nanoparticles (PFODBT) integrated with NaYF4@NaGdF4 (Y@Gd@PFO-SPNs), which can directly amplify afterglow luminescence and generate MRI and afterglow signals in tumor tissues. The proposed mechanism involves lanthanide nanoparticles producing singlet oxygen (1O2) upon white light irradiation, which subsequently oxidizes PFODBT, thereby intensifying afterglow luminescence. This innovative platform paves the way for the development of high signal-to-background ratio imaging modalities, promising noninvasive diagnostics for cancer.
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Elementos da Série dos Lantanídeos , Imageamento por Ressonância Magnética , Nanopartículas , Polímeros , Semicondutores , Imageamento por Ressonância Magnética/métodos , Animais , Elementos da Série dos Lantanídeos/química , Polímeros/química , Nanopartículas/química , Camundongos , Humanos , Gadolínio/química , Luminescência , Oxigênio Singlete/química , Ítrio/química , Fluoretos/química , Camundongos NusRESUMO
BACKGROUND: Hepatic encephalopathy (HE) is closely associated with inflammatory responses. However, as a crucial regulator of the immune and inflammatory responses, the role of leucine-rich repeat kinase 2 (LRRK2) in the pathogenesis of HE remains unraveled. Herein, we investigated this issue in thioacetamide (TAA)-induced HE following acute liver failure (ALF). METHODS: TAA-induced HE mouse models of LRRK2 wild type (WT), LRRK2 G2019S mutation (Lrrk2G2019S) and LRRK2 knockout (Lrrk2-/-) were established. A battery of neurobehavioral experiments was conducted. The biochemical indexes and pro-inflammatory cytokines were detected. The prefrontal cortex (PFC), striatum (STR), hippocampus (HIP), and liver were examined by pathology and electron microscopy. The changes of autophagy-lysosomal pathway and activity of critical Rab GTPases were analyzed. RESULTS: The Lrrk2-/--HE model reported a significantly lower survival rate than the other two models (24% vs. 48%, respectively, p < 0.05), with no difference found between the WT-HE and Lrrk2G2019S-HE groups. Compared with the other groups, after the TAA injection, the Lrrk2-/- group displayed a significant increase in ammonium and pro-inflammatory cytokines, aggravated hepatic inflammation/necrosis, decreased autophagy, and abnormal phosphorylation of lysosomal Rab10. All three models reported microglial activation, neuronal loss, disordered vesicle transmission, and damaged myelin structure. The Lrrk2-/--HE mice presented no severer neuronal injury than the other genotypes. CONCLUSIONS: LRRK2 deficiency may exacerbate TAA-induced ALF and HE in mice, in which inflammatory response is evident in the brain and aggravated in the liver. These novel findings indicate a need of sufficient clinical awareness of the adverse effects of LRRK2 inhibitors on the liver.
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Encefalopatia Hepática , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Falência Hepática Aguda , Camundongos Knockout , Tioacetamida , Animais , Camundongos , Encefalopatia Hepática/patologia , Encefalopatia Hepática/genética , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/metabolismo , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/patologia , Falência Hepática Aguda/genética , Camundongos Endogâmicos C57BL , Tioacetamida/toxicidadeRESUMO
Developing well-crystallized light-absorbing layers remains a formidable challenge in the progression of kesterite Cu2ZnSn(S,Se)4 (CZTSSe) solar cells. A critical aspect of optimizing CZTSSe lies in accurately governing the high-temperature selenization reaction. This process is intricate and demanding, with underlying mechanisms requiring further comprehension. This study introduces a precursor microstructure-guided hetero-nucleation regulation strategy for high-quality CZTSSe absorbers and well-performing solar cells. The alcoholysis of 2-methoxyethanol (MOE) and the generation of high gas-producing micelles by adding hydrogen chloride (HCl) as a proton additive into the precursor solution are successfully suppressed. This tailored modification of solution components reduces the emission of volatiles during baking, yielding a compact and dense precursor microstructure. The reduced-roughness surface nurtures the formation of larger CZTSSe nuclei, accelerating the ensuing Ostwald ripening process. Ultimately, CZTSSe absorbers with enhanced crystallinity and diminished defects are fabricated, attaining an impressive 14.01% active-area power conversion efficiency. The findings elucidate the influence of precursor microstructure on the selenization reaction process, paving a route for fabricating high-quality kesterite CZTSSe films and high-efficiency solar cells.
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Bile acids are bioactive metabolites that are biotransformed into secondary bile acids by the gut microbiota, a vast consortium of microbes that inhabit the intestines. The first step in intestinal secondary bile acid metabolism is carried out by a critical enzyme, bile salt hydrolase (BSH), that catalyzes the gateway reaction that precedes all subsequent microbial metabolism of these important metabolites. As gut microbial metabolic activity is difficult to probe due to the complex nature of the gut microbiome, approaches are needed to profile gut microbiota-associated enzymes such as BSH. Here, we develop a panel of BSH activity-based probes (ABPs) to determine how changes in diurnal rhythmicity of gut microbiota-associated metabolism affects BSH activity and substrate preference. This panel of covalent probes enables determination of BSH activity and substrate specificity from multiple gut anerobic bacteria derived from the human and mouse gut microbiome. We found that both gut microbiota-associated BSH activity and substrate preference is rhythmic, likely due to feeding patterns of the mice. These results indicate that this ABP-based approach can be used to profile changes in BSH activity in physiological and disease states that are regulated by circadian rhythms.
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Amidoidrolases , Ácidos e Sais Biliares , Microbioma Gastrointestinal , Animais , Camundongos , Humanos , Amidoidrolases/metabolismo , Ácidos e Sais Biliares/metabolismo , Ácidos e Sais Biliares/química , Especificidade por Substrato , Camundongos Endogâmicos C57BL , Bactérias/metabolismo , Bactérias/enzimologia , Ritmo Circadiano , Sondas Moleculares/química , Sondas Moleculares/metabolismoRESUMO
OBJECTIVE: In the knee, synovial fibrosis after ligamentous injury is linked to progressive joint pain and stiffness. The objective of this study was to evaluate changes in synovial architecture, mechanical properties, and transcriptional profiles following naturally occurring cruciate ligament injury in canines and to test potential therapeutics that target drivers of synovial inflammation and fibrosis. DESIGN: Synovia from canines with spontaneous cruciate ligament tears and from healthy knees were assessed via histology (n = 10/group) and micromechanical testing (n = 5/group) to identify changes in tissue architecture and stiffness. Additional samples (n = 5/group) were subjected to RNA-sequencing to define the transcriptional response to injury. Finally, synovial tissue samples from injured animals (n = 6 (IL1) or n = 8 (IL6)/group) were assessed in vitro for response to therapeutic molecules directed against interleukin (IL) signaling (IL1 or IL6). RESULTS: Cruciate injury resulted in increased synovial fibrosis, vascularity, inflammatory cell infiltration, and intimal hyperplasia. Additionally, the stiffness of both the intima and subintima regions were higher in diseased compared to healthy tissue. Differential gene expression analysis showed that diseased synovium had an upregulation of immune response and cell adhesion pathways and a downregulation of Rho protein transduction pathways. In vitro application of small molecule therapeutics targeting IL1 (anakinra) or IL6 (tocilizumab) dampened expression of inflammatory and matrix deposition mediators. CONCLUSION: Spontaneous cruciate ligament injury in canines is associated with synovial inflammation and fibrosis in a relevant model for testing emerging intra-articular treatments. Small molecule therapeutics targeting IL pathways may be ideal interventions for delivery to the joint space after injury.
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Spontaneous infrared radiation dissipation is a critical factor in facilitating object cooling, which influences the thermal stability and stealth efficacy of infrared stealth devices. Furthermore, the compatibility between efficient visible, infrared, and radar stealth is challenging due to different camouflage principles in different bands. This Letter presents a five-layer etched film structure to achieve multispectral stealth, and the utilization of the high-quality ultrathin silver films enables highly efficient infrared selective emission. This etched film structure with few layers demonstrates potential applications in diverse domains, including multi-band anti-detection and multispectral manipulation.
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BACKGROUND: Studies on potential disruptions in rich club structure in nursing staff with occupational burnout are lacking. Moreover, existing studies on nurses with burnout are limited by their cross-sectional design. PURPOSE: To investigate rich club reorganization in nursing staff before and after the onset of burnout and the underlying impact of anatomical distance on such reconfiguration. STUDY TYPE: Prospective, longitudinal. POPULATION: Thirty-nine hospital nurses ( 23.67 ± 1.03 $$ 23.67\pm 1.03 $$ years old at baseline, 24.67 ± 1.03 $$ 24.67\pm 1.03 $$ years old at a follow-up within 1.5 years, 38 female). FIELD STRENGTH/SEQUENCE: Magnetization-prepared rapid gradient-echo and gradient-echo echo-planar imaging sequences at 3.0 T. ASSESSMENT: The Maslach Burnout Inventory and Symptom Check-List 90 testing were acquired at each MRI scan. Rich club structure was assessed at baseline and follow-up to determine whether longitudinal changes were related to burnout and to changes in connectivities with different anatomical distances (short-, mid-, and long range). STATISTICAL TESTS: Chi-square, paired-samples t, two-sample t, Mann-Whitney U tests, network-based statistic, Spearman correlation analysis, and partial least squares regression analysis. Significance level: Bonferroni-corrected P < 0.05 $$ P<0.05 $$ . RESULTS: In nurses who developed burnout: 1) Strengths of rich club, feeder, local, short-, mid-, and long-range connectivities were significantly decreased at follow-up compared with baseline. 2) At follow-up, strengths of above connectivities and that between A5m.R and dlPu.L were significantly correlated with emotional exhaustion (r ranges from -0.57 to -0.73) and anxiety scores (r = -0.56), respectively. 3) Longitudinal change (follow-up minus baseline) in connectivity strength between A5m.R and dlPu.L reflected change in emotional exhaustion score (r = 0.87). Longitudinal changes in strength of connectivities mainly involving parietal lobe were significantly decreased in nurses who developed burnout compared with those who did not. DATA CONCLUSION: In nurses after the onset of burnout, rich club reorganization corresponded to significant reductions in strength of connectivities with different anatomical distances. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.
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Evolutionarily conserved microRNAs (miRNAs) usually have high copy numbers in the genome. The redundant and specific roles of each member of a multimember miRNA gene family are poorly understood. Previous studies have shown that the miR156-SPL-miR172 axis constitutes a signaling cascade in regulating plant developmental transitions. Here, we report the feasibility and utility of CRISPR-Cas9 technology to investigate the functions of all 5 MIR172 family members in Arabidopsis. We show that an Arabidopsis plant devoid of miR172 is viable, although it displays pleiotropic morphological defects. MIR172 family members exhibit distinct expression pattern and exert functional specificity in regulating meristem size, trichome initiation, stem elongation, shoot branching, and floral competence. In particular, we find that the miR156-SPL-miR172 cascade is bifurcated into specific flowering responses by matching pairs of coexpressed SPL and MIR172 genes in different tissues. Our results thus highlight the spatiotemporal changes in gene expression that underlie evolutionary novelties of a miRNA gene family in nature. The expansion of MIR172 genes in the Arabidopsis genome provides molecular substrates for the integration of diverse floral inductive cues, which ensures that plants flower at the optimal time to maximize seed yields.
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Arabidopsis/crescimento & desenvolvimento , Arabidopsis/genética , MicroRNAs/genética , Arabidopsis/metabolismo , Sistemas CRISPR-Cas , Flores/genética , Flores/crescimento & desenvolvimento , Edição de Genes , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Desenvolvimento Vegetal/genéticaRESUMO
BACKGROUND AND AIMS: The use of corticosteroids in chronic drug-induced liver injury (DILI) is an important issue. Our previous randomized controlled trial showed that patients with chronic DILI benefited from a 48-week steroid stepwise reduction (SSR) regimen. However, it remains unclear whether a shorter course of therapy can achieve similar efficacy. In this study, we aimed to assess whether a 36-week SSR can achieve efficacy similar to that of 48-week SSR. METHODS: A randomized open-label trial was performed. Eligible patients were randomly assigned to the 36- or 48-week (1:1) SSR group. Liver biopsies were performed at baseline and at the end of treatment. The primary outcome was the proportion of patients with relapse rate (RR). The secondary outcomes were improvement in liver histology and safety. RESULTS: Of the 90 participants enrolled, 84 (87.5%) completed the trial, and 62 patients (68.9%) were women. Hepatocellular damage was observed in 53.4% of the cohort. The RR was 7.1% in the 36-week SSR group but 4.8% in the 48-week SSR group, as determined by per-protocol set analysis (p = 1.000). Significant histological improvements in histological activity (93.1% vs. 92.9%, p = 1.000) and fibrosis (41.4% vs. 46.4%, p = .701) were observed in both the groups. Biochemical normalization time did not differ between the two groups. No severe adverse events were observed. CONCLUSIONS: Both the 36- and 48-week SSR regimens demonstrated similar biochemical response and histological improvements with good safety, supporting 36-week SSR as a preferable therapeutic choice (ClinicalTrials.gov, NCT03266146).
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Fígado , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto , Fígado/patologia , Fígado/efeitos dos fármacos , Doença Hepática Crônica Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Crônica Induzida por Substâncias e Drogas/etiologia , Resultado do Tratamento , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Recidiva , Idoso , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Esquema de MedicaçãoRESUMO
Three Gram-stain-negative, rod-shaped, non-spore-forming bacteria were isolated from activated sludge samples. The results of phylogenetic analysis based on the 16S rRNA gene sequences indicated that the three strains, designated HXWNR29T, HXWNR69T and HXWNR70T, had the highest sequence similarity to the type strains Flavobacterium cheniae NJ-26T, Flavobacterium channae KSM-R2A30T and Flavobacterium amniphilum KYPY10T with similarities of 97.66â%, 98.66 and 98.14â%, respectively. The draft genomes of these three strains were 2.93 Mbp (HXWNR29T), 2.69 Mbp (HXWNR69T) and 2.65 Mbp (HXWNR70T) long with DNA G+C contents of 31.84â%, 32.83â% and 34.66â%, respectively. These genomes contained many genes responsible for carbohydrate degradation and antibiotic resistance. The major fatty acids (>5â%) included iso-C15â:â0, iso-C15â:â0 3-OH and iso-C17â:â0 3-OH. The major menaquinone was MK-6 for all the three strains. The average nucleotide identity (ANI; 72.7-88.5â%) and digital DNA-DNA hybridization (dDDH; 19.6-35.3â%) results further indicated that these three strains represented three novel species within the genus Flavobacterium, for which the names Flavobacterium odoriferum sp. nov. (type strain HXWNR29T = KCTC 92446T = CGMCC 1.61821T), Flavobacterium fragile sp. nov. (type strain HXWNR69T = KCTC 92468T = CGMCC 1.61442T) and Flavobacterium luminosum sp. nov. (type strain HXWNR70T = KCTC 92447T = CGMCC 1.61443T) are proposed.
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Ácidos Graxos , Flavobacterium , Ácidos Graxos/química , Esgotos , Filogenia , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , Composição de Bases , Análise de Sequência de DNA , Técnicas de Tipagem Bacteriana , Vitamina K 2RESUMO
The use of upconversion luminescent materials to broaden the utilization range of the solar spectrum to enhance the efficiency of photovoltaic cells offers a promising and sustainable approach. However, the low luminescence intensity and easy quenching of upconversion luminescent materials bring serious challenges to the practical application. Herein, a novel method using Co2+ ion doping to regulate the luminescence properties of NaYF4:Yb/Er/Tm is proposed. NaYF4:Yb/Er/Tm microcrystals doped with different proportions of Co2+ ions are prepared and used as coatings on the surface of photovoltaic cells. Co2+ ions regulate the crystallinity and size of the NaYF4:Yb/Er/Tm microcrystals and reduce the crystal field symmetry of the activator (Er3+ and Tm3+) ions. The results show that the emission intensity of green and red light is 18.19% and 83.24% times higher than that of undoped Co2+ ion materials, respectively. Besides, the efficiency of photovoltaic cells after coating Co2+ ion doped NaYF4:Yb/Er/Tm is 2.08% higher than that of the uncoated one. This work underscores the importance of Co2+ ion doping to improve and enhance the luminescence properties of NaYF4:Yb/Er/Tm, to further enhance the efficiency of photovoltaic cells.
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OBJECTIVE: Calcific aortic valve disease (CAVD) is the leading cause of angina, heart failure, and death from aortic stenosis. However, the molecular mechanisms of its progression, especially the complex disease-related transcriptional regulatory mechanisms, remain to be further elucidated. METHODS: This study used porcine valvular interstitial cells (PVIC) as a model. We used osteogenic induced medium (OIM) to induce calcium deposition in PVICs to calcify them, followed by basic fibroblast growth factor (bFGF) treatment to inhibit calcium deposition. Transcriptome sequencing was used to study the mRNA expression profile of PVICs and its related transcriptional regulation. We used DaPars to further examine alternative polyadenylation (APA) between different treatment groups. RESULTS: We successfully induced calcium deposition of PVICs through OIM. Subsequently, mRNA-seq was used to identify differentially expressed mRNAs for three different treatments: control, OIM-induced and OIM-induced bFGF treatment. Global APA events were identified in the OIM and bFGF treatment groups by bioinformatics analysis. Finally, it was discovered and proven that catalase (CAT) is one of the potential targets of bFGF-induced APA regulation. CONCLUSION: We described a global APA change in a calcium deposition model related to CAVD. We revealed that transcriptional regulation of the CAT gene may contribute to bFGF-induced calcium deposition inhibition.
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Estenose da Valva Aórtica , Valva Aórtica/patologia , Calcinose , Suínos , Animais , Estenose da Valva Aórtica/metabolismo , Valva Aórtica/metabolismo , Cálcio/metabolismo , Fator 2 de Crescimento de Fibroblastos/genética , Fator 2 de Crescimento de Fibroblastos/farmacologia , Poliadenilação , Células Cultivadas , Calcinose/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
BACKGROUND: Ultrasound three-dimensional visualization, a cutting-edge technology in medical imaging, enhances diagnostic accuracy by providing a more comprehensive and readable portrayal of anatomical structures compared to traditional two-dimensional ultrasound. Crucial to this visualization is the segmentation of multiple targets. However, challenges like noise interference, inaccurate boundaries, and difficulties in segmenting small structures exist in the multi-target segmentation of ultrasound images. This study, using neck ultrasound images, concentrates on researching multi-target segmentation methods for the thyroid and surrounding tissues. METHOD: We improved the Unet++ to propose PA-Unet++ to enhance the multi-target segmentation accuracy of the thyroid and its surrounding tissues by addressing ultrasound noise interference. This involves integrating multi-scale feature information using a pyramid pooling module to facilitate segmentation of structures of various sizes. Additionally, an attention gate mechanism is applied to each decoding layer to progressively highlight target tissues and suppress the impact of background pixels. RESULTS: Video data obtained from 2D ultrasound thyroid serial scans served as the dataset for this paper.4600 images containing 23,000 annotated regions were divided into training and test sets at a ratio of 9:1, the results showed that: compared with the results of U-net++, the Dice of our model increased from 78.78% to 81.88% (+ 3.10%), the mIOU increased from 73.44% to 80.35% (+ 6.91%), and the PA index increased from 92.95% to 94.79% (+ 1.84%). CONCLUSIONS: Accurate segmentation is fundamental for various clinical applications, including disease diagnosis, treatment planning, and monitoring. This study will have a positive impact on the improvement of 3D visualization capabilities and clinical decision-making and research in the context of ultrasound image.
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Imageamento Tridimensional , Glândula Tireoide , Glândula Tireoide/diagnóstico por imagem , Projetos de Pesquisa , Tecnologia , Processamento de Imagem Assistida por ComputadorRESUMO
Cells of most eukaryotic species contain mitochondria, which play a role in physiological processes such as cellular senescence, metabolism, and autophagy. Viscosity is considered a key marker for many illnesses and is involved in several crucial physiological processes. Cyanide (CN-) can target cytochrome-c oxidase, disrupting the mitochondrial electron transport chain and causing cell death through asphyxiation. In this study, a fluorescent probe named HL-1, which targets mitochondria and measures viscosity and CN- levels, was designed and synthesized. HL-1 is viscosity-sensitive, with a linear correlation coefficient of up to 0.992. In addition, HL-1 was found to change color substantially during a nucleophilic addition reaction with CN-, which has a low detection limit of 47 nM. HL-1 not only detects viscosity and exogenous CN- in SKOV-3 cells and zebrafish but also monitors viscosity changes during mitochondrial autophagy in real time. Furthermore, HL-1 has been used successfully to monitor changes in mitochondrial membrane potential during apoptosis. Endogenous CN- in plant samples was quantified. HL-1 provides new ideas for studying viscosity and CN-.
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Corantes Fluorescentes , Peixe-Zebra , Animais , Humanos , Corantes Fluorescentes/metabolismo , Viscosidade , Cianetos , Mitocôndrias/metabolismo , Células HeLa , Carbazóis/metabolismoRESUMO
BACKGROUND: Migraine and severe headaches are extremely prevalent neurological disorders that plague humans and society. Prior research has revealed that DII may affect the occurrence of migraines, but there are too few relevant studies and more are required. This study aimed to determine the association between severe headache or migraine and the Dietary Inflammatory Index (DII), with particular attention to age and gender differences. METHODS: Using data from the National Health and Nutrition Examination Survey (NHANES), we performed a cross-sectional study. In addition, we investigated the association between DII and severe headache or migraine using weighted multivariate logistic regression models, and restricted cubic splines models were plotted to explore their linear correlation. RESULTS: There were a total of 13,439 people participating in the study, and of those, 2745 experienced a severe headache or migraine within the previous three months. The DII was linearly and positively correlated with severe headache or migraine (odds ratio [OR] = 1.05, 95% confidence interval [CI] = 1.01-1.08, p = 0.0051). Stratified analysis showed that this relationship persisted among women and those aged < 60 years, with ORs of 1.08 (95% CI = 1.04-1.13, p = 0.0004) and 1.05 (95% CI = 1.01-1.09, p = 0.0071), respectively. CONCLUSIONS: We found that greater levels of DII were significantly related to an increased likelihood of migraine onset, especially among women and young and middle-aged populations. Further research is required to validate and expand upon our results.
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Transtornos de Enxaqueca , Caracteres Sexuais , Pessoa de Meia-Idade , Humanos , Feminino , Masculino , Estudos Transversais , Inquéritos Nutricionais , Fatores Sexuais , Transtornos de Enxaqueca/epidemiologia , Transtornos de Enxaqueca/diagnóstico , Cefaleia/epidemiologiaRESUMO
Transaminase (TA) is a crucial biocatalyst for enantioselective production of the herbicide L-phosphinothricin (L-PPT). The use of enzymatic cascades has been shown to effectively overcome the unfavorable thermodynamic equilibrium of TA-catalyzed transamination reaction, also increasing demand for TA stability. In this work, a novel thermostable transaminase (PtTA) from Pseudomonas thermotolerans was mined and characterized. The PtTA showed a high specific activity (28.63 U/mg) towards 2-oxo-4-[(hydroxy)(methyl)phosphinoyl]butyric acid (PPO), with excellent thermostability and substrate tolerance. Two cascade systems driven by PtTA were developed for L-PPT biosynthesis, including asymmetric synthesis of L-PPT from PPO and deracemization of D, L-PPT. For the asymmetric synthesis of L-PPT from PPO, a three-enzyme cascade was constructed as a recombinant Escherichia coli (E. coli G), by co-expressing PtTA, glutamate dehydrogenase (GluDH) and D-glucose dehydrogenase (GDH). Complete conversion of 400 mM PPO was achieved using only 40 mM amino donor L-glutamate. Furthermore, by coupling D-amino acid aminotransferase (Ym DAAT) from Bacillus sp. YM-1 and PtTA, a two-transaminase cascade was developed for the one-pot deracemization of D, L-PPT. Under the highest reported substrate concentration (800 mM D, L-PPT), a 90.43% L-PPT yield was realized. The superior catalytic performance of the PtTA-driven cascade demonstrated that the thermodynamic limitation was overcome, highlighting its application prospect for L-PPT biosynthesis. KEY POINTS: ⢠A novel thermostable transaminase was mined for L-phosphinothricin biosynthesis. ⢠The asymmetric synthesis of L-phosphinothricin was achieved via a three-enzyme cascade. ⢠Development of a two-transaminase cascade for D, L-phosphinothricin deracemization.
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Aminobutiratos , Escherichia coli , Transaminases , Transaminases/genética , Escherichia coli/genética , Ácido Butírico , Glucose 1-Desidrogenase , Ácido GlutâmicoRESUMO
BACKGROUND: Due to the increasing incidence of ischaemic cerebrovascular diseases, the accurate assessment of internal carotid artery (ICA) stenosis is crucial for the development of treatment plans. This systematic review and meta-analysis aimed to evaluate the diagnostic value of computed tomography angiography (CTA) for severe ICAstenosis, thereby providing support for clinical decision-making and promoting diagnostic updates. METHODS: The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database for Chinese Technical Periodicals (VIP), and Chinese Biomedical Literature (CBM) electronic databases were searched from inception to March 21, 2024, to identify publicly available research literature on the use of CTA to diagnose severe ICA stenosis. Literature screening, data extraction, and quality assessment were conducted based on the inclusion and exclusion criteria as well as the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) standards. Data analysis was performed using Stata 17.0 and Meta-Disc 1.4 software. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of the included studies were calculated using Stata 17.0 software, and forest plots and summary receiver operating characteristic (SROC) curves were generated. The area under the curve (AUC) was calculated, and funnel plots were constructed to assess publication bias. RESULTS: A total of 16 studies with 2368 vascular segments were included. The meta-analysis revealed that the combined sensitivity and specificity of CTA for severe ICA stenosis were 0.93 (95% CI: 0.88 ~ 0.96) and 0.99 (95% CI: 0.96 ~ 1.00), respectively. The combined positive likelihood ratio and negative likelihood ratio were 92.0 (95% CI: 24.2 ~ 349.6) and 0.07 (95% CI: 0.04 ~ 0.13), respectively. The diagnostic odds ratio was 1302 (95% CI: 257 ~ 6606), and the AUC of the SROC curve was 0.98. The Deeks funnel plot suggested no publication bias among the included studies. CONCLUSION: CTA demonstrated high sensitivity and specificity for diagnosing severe ICA stenosis. Therefore, this study provided important evidence for the accurate diagnosis and treatment of severe ICA stenosis. However, there was considerable heterogeneity among the included studies, thus indicating the need for additional high-quality prospective studies to confirm the clinical applicability of CTA.
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Artéria Carótida Interna , Estenose das Carótidas , Angiografia por Tomografia Computadorizada , Sensibilidade e Especificidade , Humanos , Estenose das Carótidas/diagnóstico por imagem , Angiografia por Tomografia Computadorizada/métodos , Artéria Carótida Interna/diagnóstico por imagem , Curva ROC , Índice de Gravidade de DoençaRESUMO
PURPOSE: Determine the prevalence and influencing factors of patient delay in stroke patients and explore variation in prevalence by country and delayed time. METHODS: PubMed, The Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Database (CBM), Weipu database, and Wanfang database were comprehensively searched for observational studies from inception to April, 2023. The pooled prevalence, odds ratio (OR), and 95% confidence intervals (CI) were calculated with Stata 16.0 software. RESULTS: In total, 2721 articles were screened and data from 70 studies involving 85,468 subjects were used in meta-analysis. The pooled prevalence of patient delay in stroke patients was 59% (95% CI, 0.54-0.64). The estimates of pooled prevalence calculated for African, Asian, and European patient delay in stroke patients were 55% (0.29-0.81), 61% (0.56-0.66), and 49% (0.34-0.64).According to the patient delay time, the prevalence of 6 h, 5 h, 4.5 h, 3.5 h, 3 h and 2 h were 54% (0.47-0.61), 73% (0.61-0.86), 60% (0.49-0.71), 81% (0.68-0.93), 52% (0.42-0.62), 63% (0.19-1.07). Distance from the place of onset to the hospital > 10 km [OR=2.49, 95%CI (1.92, 3.24)], having medical insurance [OR = 0.45, 95%CI (0.26,0.80)], lack of stroke-related knowledge [OR = 1.56, 95%CI (1.08,2.26)], education level below junior high school [OR = 1.69, 95%CI (1.22,2.36)], non-emergency medical services (Non-EMS) [OR = 2.10, 95%CI (1.49,2.97)], living in rural areas [OR = 1.54, 95%CI (1.15,2.07)], disturbance of consciousness [OR = 0.60, 95%CI (0.39,0.93)], history of atrial fibrillation [OR = 0.53, 95%CI (0.47,0.59)], age ≥ 65 years [OR = 1.18, 95%CI (1.02,1.37)], National institutes of health stroke scale (NIHSS) ≤ 4 points [OR= 2.26, 95%CI (1.06,4.79)]were factors for patient delay in stroke patients. CONCLUSIONS: The prevalence of patient delay in stroke patients is high, we should pay attention to the influencing factors of patient delay in stroke patients and provide a theoretical basis for shortening the treatment time of stroke patients.
Assuntos
Acidente Vascular Cerebral , Tempo para o Tratamento , Humanos , Acidente Vascular Cerebral/epidemiologia , Prevalência , Fatores de TempoRESUMO
Biological systems have a remarkable capability of synthesizing multifunctional materials that are adapted for specific physiological and ecological needs. When exploring structure-function relationships related to multifunctionality in nature, it can be a challenging task to address performance synergies, trade-offs, and the relative importance of different functions in biological materials, which, in turn, can hinder our ability to successfully develop their synthetic bioinspired counterparts. Here, we investigate such relationships between the mechanical and optical properties in a multifunctional biological material found in the highly protective yet conspicuously colored exoskeleton of the flower beetle, Torynorrhina flammea Combining experimental, computational, and theoretical approaches, we demonstrate that a micropillar-reinforced photonic multilayer in the beetle's exoskeleton simultaneously enhances mechanical robustness and optical appearance, giving rise to optical damage tolerance. Compared with plain multilayer structures, stiffer vertical micropillars increase stiffness and elastic recovery, restrain the formation of shear bands, and enhance delamination resistance. The micropillars also scatter the reflected light at larger polar angles, enhancing the first optical diffraction order, which makes the reflected color visible from a wider range of viewing angles. The synergistic effect of the improved angular reflectivity and damage localization capability contributes to the optical damage tolerance. Our systematic structural analysis of T. flammea's different color polymorphs and parametric optical and mechanical modeling further suggest that the beetle's microarchitecture is optimized toward maximizing the first-order optical diffraction rather than its mechanical stiffness. These findings shed light on material-level design strategies utilized in biological systems for achieving multifunctionality and could thus inform bioinspired material innovations.