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1.
Theor Appl Genet ; 137(6): 129, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740615

RESUMO

KEY MESSAGE: Through comprehensive genomic and transcriptomic analyses, we identified a set of 23 genes that act up- or downstream of erucic acid content (EAC) production in rapeseed seeds. We selected example genes to showcase the distribution of single nucleotide polymorphisms, haplotypes associated with EAC phenotypes, and the creation of molecular markers differentiating low EAC and high EAC genotypes. Erucic acid content (EAC) is a crucial trait in rapeseed, with low LEAC oil recognized for its health benefits and high EA oil holding industrial value. Despite its significance, the genomic consequences of intensive LEAC-cultivar selection and the genetic basis underlying EA regulation remain largely unexplored. To address this knowledge gap, we conducted selective signal analyses, genome-wide association studies (GWAS), and transcriptome analyses. Our investigation unveiled the genetic footprints resulting from LEAC selection in germplasm populations, drawing attention to specific loci that contribute to enriching diversity. By integrating GWAS and transcriptome analyses, we identified a set of 23 genes that play a significant role in determining EAC in seeds or are downstream consequences of EA-level alterations. These genes have emerged as promising candidates for elucidating the potential mechanisms governing EAC in rapeseed. To exemplify the findings, we selected specific genes to demonstrate the distribution of single nucleotide polymorphisms and haplotypes associated with different EAC phenotypes. Additionally, we showcased to develop molecular markers distinguishing between LEAC and high EAC genotypes.


Assuntos
Brassica napus , Ácidos Erúcicos , Polimorfismo de Nucleotídeo Único , Sementes , Sementes/genética , Sementes/crescimento & desenvolvimento , Brassica napus/genética , Ácidos Erúcicos/metabolismo , Fenótipo , Haplótipos , Transcriptoma , Estudo de Associação Genômica Ampla , Genótipo , Perfilação da Expressão Gênica , Genômica/métodos , Regulação da Expressão Gênica de Plantas , Locos de Características Quantitativas
2.
Fish Shellfish Immunol ; 149: 109614, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38710342

RESUMO

Chemokines are critical molecules involved in immune reaction and immune system homeostasis, and some chemokines play a role in antiviral immunity. It is not known if the C-C motif chemokine ligand 3 (CCL3), a member of the CC chemokine family, possesses antiviral properties in fish. In this study, a ccl3 was cloned from the mandarin fish (Siniperca chuatsi), and it has an open reading frame (ORF) of 276 base pairs, which are predicted to encode a 91-amino acid peptide. Mandarin fish CCL3 revealed conserved sequence features with four cysteine residues and closely relationships with the CCL3s from other vertebrates based on the sequence alignment and phylogenetic analysis. The transcripts of ccl3 were notably enriched in immune-related organs, such as spleen and gills in healthy mandarin fish, and the ccl3 was induced in the isolated mandarin fish brain (MFB) cells following infection with infectious spleen and kidney necrosis virus (ISKNV). Moreover, in MFB cells, overexpression of CCL3 induced immune factors, such as IL1ß, TNFα, MX, IRF1 and IFNh, and exhibited antiviral activity against ISKNV. This study sheds light on the immune role of CCL3 in immune response of mandarin fish, and its antiviral defense mechanism is of interest for further investigation.


Assuntos
Sequência de Aminoácidos , Infecções por Vírus de DNA , Doenças dos Peixes , Proteínas de Peixes , Imunidade Inata , Iridoviridae , Perciformes , Filogenia , Alinhamento de Sequência , Animais , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Proteínas de Peixes/química , Doenças dos Peixes/imunologia , Doenças dos Peixes/virologia , Perciformes/imunologia , Perciformes/genética , Infecções por Vírus de DNA/imunologia , Infecções por Vírus de DNA/veterinária , Iridoviridae/fisiologia , Alinhamento de Sequência/veterinária , Imunidade Inata/genética , Regulação da Expressão Gênica/imunologia , Quimiocina CCL3/genética , Quimiocina CCL3/imunologia , Clonagem Molecular , Perfilação da Expressão Gênica/veterinária , Sequência de Bases
3.
Front Immunol ; 15: 1374368, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38715616

RESUMO

NOD1 and NOD2 as two representative members of nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family play important roles in antimicrobial immunity. However, transcription mechanism of nod1 and nod2 and their signal circle are less understood in teleost fish. In this study, with the cloning of card9 and ripk2 in Chinese perch, the interaction between NOD1, NOD2, and CARD9 and RIPK2 were revealed through coimmunoprecipitation and immunofluorescence assays. The overexpression of NOD1, NOD2, RIPK2 and CARD9 induced significantly the promoter activity of NF-κB, IFNh and IFNc. Furthermore, it was found that nod1 and nod2 were induced by poly(I:C), type I IFNs, RLR and even NOD1/NOD2 themselves through the ISRE site of their proximal promoters. It is thus indicated that nod1 and nod2 can be classified also as ISGs due to the presence of ISRE in their proximal promoter, and their expression can be mechanistically controlled through PRR pathway as well as through IFN signaling in antiviral immune response.


Assuntos
Proteínas de Peixes , Proteína Adaptadora de Sinalização NOD1 , Proteína Adaptadora de Sinalização NOD2 , Proteína Serina-Treonina Quinase 2 de Interação com Receptor , Transdução de Sinais , Animais , Proteína Adaptadora de Sinalização NOD1/genética , Proteína Adaptadora de Sinalização NOD1/metabolismo , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/metabolismo , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/genética , Proteína Adaptadora de Sinalização NOD2/genética , Proteína Adaptadora de Sinalização NOD2/metabolismo , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Proteínas de Peixes/imunologia , Percas/genética , Percas/imunologia , Percas/metabolismo , Interferons/metabolismo , Interferons/genética , Regiões Promotoras Genéticas , Transcrição Gênica , Imunidade Inata/genética , Ligação Proteica
4.
BMC Pediatr ; 24(1): 298, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702673

RESUMO

BACKGROUND: A large number of psychological consequences including sleep health emerged during the 2019 Coronavirus disease (COVID-19) pandemic. Sleep patterns in toddlers are vulnerable to negative environmental exposures, however, very few studies on this topic have been published so far. OBJECTIVES: In this paper, we aimed to investigate the sleep patterns and associated factors in toddlers from China confined at home in the context of COVID-19 pandemic. METHODS: From April to November 2021, a convenience sample of 493 parents of young children aged (12-35 months) were surveyed from Fuzhou, Sanming, Quanzhou, Nanping, and Longyan cities in the Fujian Province, China. A cross-sectional survey was conducted via Electronic questionnaires to collect parent and child social-demographic characteristics. The Brief Infant Sleep Questionnaire (BISQ) was used to collect data on sleep practices, sleep duration and patterns, as well as the number of nocturnal awaking . RESULTS: The mean age of toddlers was 2.11 years old, and 52.54% (259/493) were males. Among the 493 toddlers' sleep patterns, 331(67.1%) initiated sleep accompanied by parents, 67(13.6%) slept independently, 59 (12.0%) were breast fed/bottle fed to initiate sleep, 27 (5.5%) were held and 9 (1.8%) rocked. The clear longitudinal association between the duration of night-time sleep, the frequency of nighttime awakenings, and various sleep patterns remains clear (p < 0.05). Multiple linear regression analysis indicated that sleep initiation with bottle-feeding/breast-feeding and rocked significantly increased the frequency of nighttime awakenings and reduced the duration of nighttime sleep (p < 0.05), as held was dramatically only for increasing the number of nighttime awakenings (p < 0.05). Multi-variate logistic regression analysis demonstrated that toddlers with severe sleep difficulties had a higher probability of being rocked to initiate sleep (p < 0.05). Conversely, young children with minor sleep problems were more apt to be in bed alone to initiate sleep (p < 0.05). CONCLUSIONS: During the COVID-19 pandemic, most infants and toddlers initiated sleep accompanied by parents and tend to have electronic media exposure before bedtime. Increased waking at night may be associated with sleep initiation with breast-feeding/bottle-feeding. Therefore, pediatric practitioners in primary community hospitals should pay attention to the education and promotion of sleep hygiene and parenting knowledge of young children to avoid the formation of poor sleep hygiene habits.


Assuntos
COVID-19 , Qualidade do Sono , Humanos , Masculino , Feminino , China/epidemiologia , Lactente , Estudos Transversais , Pré-Escolar , COVID-19/epidemiologia , Sono , Inquéritos e Questionários , Pais , Aleitamento Materno/estatística & dados numéricos
5.
IBRO Neurosci Rep ; 16: 535-541, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38706972

RESUMO

Background: Ischaemic stroke can lead to many complications, but treatment options are limited. Icariin is a traditional Chinese medicine with reported neuroprotective effects against ischaemic cerebral injury; however, the underlying mechanisms by which icariin ameliorates cell apoptosis require further study. Purpose: This study aimed to investigate the therapeutic potential of icariin after ischaemic stroke and the underlying molecular mechanisms. Methods: N2a neuronal cells were used to create an in vitro oxygen-glucose deprivation (OGD) model. The effects of icariin on OGD cells were assessed using the CCK-8 kit to detect the survival of cells and based on the concentration, apoptosis markers, inflammation markers, and M2 pyruvate kinase isoenzyme (PKM2) expression were detected using western blotting, RT-qPCR, and flow cytometry. To investigate the underlying molecular mechanisms, we used the PKM2 agonist TEPP-46 and detected apoptosis-related proteins. Results: We demonstrated that icariin alleviated OGD-induced apoptosis in vitro. The expression levels of the apoptosis marker proteins caspase-3 and Bax were upregulated and Bcl-2 was downregulated. Furthermore, icariin reduced inflammation and downregulated the expression of PKM2. Moreover, activation of the PKM2 by pretreatment with the PKM2 agonist TEPP-46 enhanced the effects on OGD induced cell apoptosis in vitro. Conclusion: This study elucidated the underlying mechanism of PKM2 in OGD-induced cell apoptosis and highlighted the potential of icariin in the treatment of ischaemic stroke.

6.
PLoS One ; 19(5): e0293517, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38743798

RESUMO

As a UNESCO World Cultural Heritage, the aesthetic value of bronze artifacts from the Shang and Chow Dynasties has had a profound influence on Chinese traditional culture and art. To facilitate the digital preservation and protection of these Shang and Chow bronze artifacts (SCB), it becomes imperative to categorize their decorative patterns. Therefore, a SCB pattern classification method of differential evolution called Shang and Chow Bronze Convolutional Neural Network (SCB-CNN) is proposed. Firstly, the original bronze decorative patterns of Shang and Chow dynasties are collected, and the samples are expanded through image augmentation technology to form a training dataset. Secondly, based on the classical convolutional neural network structure, the recognition and classification of bronze patterns are implemented by adjusting the network parameters. Then, the initial parameters of the convolutional neural network are optimized by differential evolution algorithm, and the optimized SCB-CNN is simulated. Finally, comparative experiments were conducted between the optimized SCB-CNN, the unoptimized model, VGG-Net, and GoogleNet. The experimental results indicate that the optimized SCB-CNN significantly reduces training time while maintaining fast prediction speed, convergence speed, and high accuracy. This study provides new insights for the inheritance and innovation research of SCB patterns.


Assuntos
Algoritmos , Redes Neurais de Computação , Humanos , China , Arqueologia/métodos , História Antiga
7.
Artigo em Inglês | MEDLINE | ID: mdl-38619196

RESUMO

BRCA1-associated RING domain protein 1 (BARD1) gene polymorphisms may be associated with neuroblastoma (NB) susceptibility. However, the results remain controversial. Relevant studies were identified by searching PubMed, Web of Science, Embase, China National Knowledge Infrastructure databases up to March 5, 2023. The strength of the association between BARD1 polymorphisms and susceptibility of NB was assessed by calculating odds ratios (ORs) and 95% confidence intervals (95% CIs) through the fixed- or random-effects model. Eight articles involving 12 studies were finally included. We found that rs6435862 T > G, rs3768716 A > G, rs17487792 C > T and rs7587476 C > T variant increase the risk of NB in allelic, dominant, recessive, homozygous and heterozygous genetic models, while rs7585356 G > A variant appeared protective against NB. When stratified by ethnicity, subgroup analysis indicated that the above association remained significant in Caucasian populations in all genetic models, except for rs7585356G > A polymorphism in Asians. In Asian populations, we found the similar results in the allelic and dominant model of rs6435862 T > G, rs3768716 A > G, rs17487792 C > T and rs7587476 C > T as in Caucasians, while there lacked a significant association in the other three model. In addition, rs7585356 G > A was not associated with an increased risk of NB in the Asian population. After Bonferroni correction, significant associations for rs7585356 G > A disappeared in both Asian and Caucasian populations, with no significant association found for rs7587476 in the allelic and dominant models among Asians. BARD1 polymorphisms might be significantly associated with NB susceptibility. It is crucial that these finding should be further confirmed through extensive and well-planned studies.

9.
J Stroke Cerebrovasc Dis ; : 107731, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38657831

RESUMO

BACKGROUND: Several studies report that radiomics provides additional information for predicting hematoma expansion in intracerebral hemorrhage (ICH). However, the comparison of diagnostic performance of radiomics for predicting revised hematoma expansion (RHE) remains unclear. METHODS: The cohort comprised 312 consecutive patients with ICH. A total of 1106 radiomics features from seven categories were extracted using Python software. Support vector machines achieved the best performance in both the training and validation datasets. Clinical factors models were constructed to predict RHE. Receiver operating characteristic curve analysis was used to assess the abilities of non-contrast computed tomography (NCCT) signs, radiomics features, and combined models to predict RHE. RESULTS: We finally selected the top 21 features for predicting RHE. After univariate analysis, 4 clinical factors and 5 NCCT signs were selected for inclusion in the prediction models. In the training and validation dataset, radiomics features had a higher predictive value for RHE (AUC = 0.83) than a single NCCT sign and expansion-prone hematoma. The combined prediction model including radiomics features, clinical factors, and NCCT signs achieved higher predictive performances for RHE (AUC = 0.88) than other combined models. CONCLUSIONS: NCCT radiomics features have a good degree of discrimination for predicting RHE in ICH patients. Combined prediction models that include quantitative imaging significantly improve the prediction of RHE, which may assist in the risk stratification of ICH patients for anti-expansion treatments.

10.
Nat Commun ; 15(1): 2951, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580660

RESUMO

Hepatitis B virus is a globally distributed pathogen and the history of HBV infection in humans predates 10000 years. However, long-term evolutionary history of HBV in Eastern Eurasia remains elusive. We present 34 ancient HBV genomes dating between approximately 5000 to 400 years ago sourced from 17 sites across Eastern Eurasia. Ten sequences have full coverage, and only two sequences have less than 50% coverage. Our results suggest a potential origin of genotypes B and D in Eastern Asia. We observed a higher level of HBV diversity within Eastern Eurasia compared to Western Eurasia between 5000 and 3000 years ago, characterized by the presence of five different genotypes (A, B, C, D, WENBA), underscoring the significance of human migrations and interactions in the spread of HBV. Our results suggest the possibility of a transition from non-recombinant subgenotypes (B1, B5) to recombinant subgenotypes (B2 - B4). This suggests a shift in epidemiological dynamics within Eastern Eurasia over time. Here, our study elucidates the regional origins of prevalent genotypes and shifts in viral subgenotypes over centuries.


Assuntos
Vírus da Hepatite B , Migração Humana , Humanos , Vírus da Hepatite B/genética , Filogenia , Genótipo , Evolução Biológica , DNA Viral/genética
11.
medRxiv ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38585973

RESUMO

Natural Language Processing (NLP) is a study of automated processing of text data. Application of NLP in the clinical domain is important due to the rich unstructured information implanted in clinical documents, which often remains inaccessible in structured data. Empowered by the recent advance of language models (LMs), there is a growing interest in their application within the clinical domain. When applying NLP methods to a certain domain, the role of benchmark datasets are crucial as benchmark datasets not only guide the selection of best-performing models but also enable assessing of the reliability of the generated outputs. Despite the recent availability of LMs capable of longer context, benchmark datasets targeting long clinical document classification tasks are absent. To address this issue, we propose LCD benchmark, a benchmark for the task of predicting 30-day out-of-hospital mortality using discharge notes of MIMIC-IV and statewide death data. Our notes have a median word count of 1687 and an interquartile range of 1308 to 2169. We evaluated this benchmark dataset using baseline models, from bag-of-words and CNN to Hierarchical Transformer and an open-source instruction-tuned large language model. Additionally, we provide a comprehensive analysis of the model outputs, including manual review and visualization of model weights, to offer insights into their predictive capabilities and limitations. We expect LCD benchmarks to become a resource for the development of advanced supervised models, prompting methods, or the foundation models themselves, tailored for clinical text. The benchmark dataset is available at https://github.com/Machine-Learning-for-Medical-Language/long-clinical-doc.

12.
Behav Sci (Basel) ; 14(4)2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38667062

RESUMO

Physical exercise is crucial to the development of students' physical and mental health. This study explored the relationship between live sports learning and college students' exercise behaviors, and the mediating roles of exercise motivation and exercise commitment, aiming to provide theoretical bases for the future that explain the mechanism of live sports learning in exercise behaviors, as well as practical guidance for the promotion of positive physical exercise behaviors in college students. In total, 1189 college students from China volunteered to complete questionnaires. The results showed that live sports learning positively predicted college students' exercise behavior and that live sports learning was able to affect exercise behavior through the mediating roles of exercise motivation and exercise commitment, with specific mediating paths including the two independent mediating paths and a serial mediating path of exercise motivation and exercise commitment. This study confirmed, for the first time, on live sports learning in the process of promoting exercise behavior. It is suggested that educators instruct college students to regulate their participation in live sports learning and to cultivate healthy exercise motivation and exercise commitment, which is an effective way to facilitate college students' practice of physical activity.

13.
Poult Sci ; 103(6): 103673, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38564837

RESUMO

Type IV interferon (IFN) has been shown to be a cytokine with antiviral activity in fish and amphibian. But, it has not been cloned and characterized functionally in avian species. In this study, type IV IFN, IFN-υ, and its 2 possible receptors, IFN-υR1 and IL10RB, were identified from an avian species, the mallard (Anas platyrhynchos). Mallard IFN-υ has a 531 bp open reading frame (ORF), encoding 176 amino acids (aa), and has highly conserved features as reported in different species, with an N-terminal signal peptide and a predicted multi-helix structure. The IFN-υR1 and IL10RB contain 528 and 343 aa, respectively, with IFN-υR1 protein containing JAK1 and STAT binding sites, and IL10RB containing TYK2 binding site. These 2 receptor subunits also possess 3 domains, the N-terminal extracellular domain, the transmembrane domain, and the C-terminal intracellular domain. Expression analysis indicated that IFN-υ, IFN-υR1 and IL10RB were widely expressed in examined organs/tissues, with the highest level observed in pancreas, blood, and kidney, respectively. The expression of IFN-υ, IFN-υR1 and IL10RB in liver, spleen or kidney was significantly upregulated after stimulation with polyI:C. Furthermore, recombinant IFN-υ protein induced the expression of ISGs, and the receptor of IFN-υ was verified as IFN-υR1 and IL10RB using a chimeric receptor approach in HEK293 cells. Taken together, these results indicate that IFN-υ is involved in the host innate immune response in mallard.

14.
JAMA Netw Open ; 7(4): e247919, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38683612

RESUMO

Importance: Bipolar mania is a common disabling illness. Electroconvulsive therapy (ECT) is an effective treatment for patients with severe mania, though it is limited by the risk of cognitive adverse effects. Magnetic seizure therapy (MST) as an alternative treatment to ECT for bipolar mania has not yet been reported. Objective: To compare the effectiveness and cognitive adverse effects of MST and ECT in bipolar mania. Design, Setting, and Participants: This randomized clinical trial was conducted at the Shanghai Mental Health Center from July 1, 2017, through April 26, 2021. Forty-eight patients with bipolar mania were recruited and randomly allocated to receive MST or ECT. The data analysis was performed from June 5, 2021, through August 30, 2023. Interventions: Patients completed 2 or 3 sessions of MST or ECT per week for a total of 8 to 10 sessions. The MST was delivered at 100% device output with a frequency of 75 Hz over the vertex. Main Outcomes and Measures: The primary outcomes were reduction of total Young Manic Rating Scale (YMRS) score and response rate (more than 50% reduction of the total YMRS score compared with baseline). An intention-to-treat (ITT) analysis and repeated-measures analyses of variance were conducted for the primary outcomes. Results: Twenty patients in the ECT group (mean [SD] age, 31.6 [8.6] years; 12 male [60.0%]) and 22 patients in the MST group (mean [SD] age, 34.8 [9.8] years; 15 male [68.2%]) were included in the ITT analysis. The response rates were 95.0% (95% CI, 85.4%-100%) in the ECT group and 86.4% (95% CI, 72.1%-100%) in the MST group. The YMRS reduction rate (z = -0.82; 95% CI, -0.05 to 0.10; P = .41) and response rate (χ2 = 0.18; 95% CI, -0.13 to 0.31; P = .67) were not significantly different between the groups. The time-by-group interaction was significant for the language domain (F1,24 = 7.17; P = .01), which was well preserved in patients receiving MST but worsened in patients receiving ECT. No serious adverse effects were reported in either group. Conclusions and Relevance: These findings suggest that MST is associated with a high response rate and fewer cognitive impairments in bipolar mania and that it might be an alternative therapy for the treatment of bipolar mania. Trial Registration: ClinicalTrials.gov Identifier: NCT03160664.


Assuntos
Transtorno Bipolar , Eletroconvulsoterapia , Humanos , Masculino , Feminino , Eletroconvulsoterapia/métodos , Eletroconvulsoterapia/efeitos adversos , Transtorno Bipolar/terapia , Transtorno Bipolar/psicologia , Adulto , Resultado do Tratamento , Pessoa de Meia-Idade , Convulsões , China
15.
Brain Inj ; 38(7): 524-530, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38433503

RESUMO

BACKGROUND: Autophagy is recognized as a promising therapeutic target for traumatic brain injury (TBI). Crocetin is an aglycone of crocin naturally occurring in saffron and has been found to alleviate brain injury diseases. However, whether crocetin affects autophagy after TBI remains unknown. Therefore, we explore crocetin roles in autophagy after TBI. METHODS: We used a weight-dropped model to induce TBI in C57BL/6J mice. Neurological severity scoring (NSS) and grip tests were used to evaluate the neurological level of injury. Brain edema, neuronal apoptosis, neuroinflammation and autophagy were detected by measurements of brain water content, TUNEL staining, ELISA kits and western blotting. RESULTS: Crocetin ameliorated neurological dysfunctions and brain edema after TBI. Crocetin reduced neuronal apoptosis and neuroinflammation and enhanced autophagy after TBI. CONCLUSION: Crocetin alleviates TBI by inhibiting neuronal apoptosis and neuroinflammation and activating autophagy.


Assuntos
Apoptose , Autofagia , Lesões Encefálicas Traumáticas , Carotenoides , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores , Vitamina A , Animais , Carotenoides/farmacologia , Carotenoides/uso terapêutico , Vitamina A/análogos & derivados , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/patologia , Autofagia/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Camundongos , Masculino , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Edema Encefálico/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Neurônios/efeitos dos fármacos , Neurônios/patologia
16.
bioRxiv ; 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38464060

RESUMO

Vascular inflammation critically regulates endothelial cell (EC) pathophenotypes, particularly in pulmonary arterial hypertension (PAH). Dysregulation of lysosomal activity and cholesterol metabolism have known inflammatory roles in disease, but their relevance to PAH is unclear. In human pulmonary arterial ECs and in PAH, we found that inflammatory cytokine induction of the nuclear receptor coactivator 7 (NCOA7) both preserved lysosomal acidification and served as a homeostatic brake to constrain EC immunoactivation. Conversely, NCOA7 deficiency promoted lysosomal dysfunction and proinflammatory oxysterol/bile acid generation that, in turn, contributed to EC pathophenotypes. In vivo, mice deficient for Ncoa7 or exposed to the inflammatory bile acid 7α-hydroxy-3-oxo-4-cholestenoic acid (7HOCA) displayed worsened PAH. Emphasizing this mechanism in human PAH, an unbiased, metabolome-wide association study (N=2,756) identified a plasma signature of the same NCOA7-dependent oxysterols/bile acids associated with PAH mortality (P<1.1x10-6). Supporting a genetic predisposition to NCOA7 deficiency, in genome-edited, stem cell-derived ECs, the common variant intronic SNP rs11154337 in NCOA7 regulated NCOA7 expression, lysosomal activity, oxysterol/bile acid production, and EC immunoactivation. Correspondingly, SNP rs11154337 was associated with PAH severity via six-minute walk distance and mortality in discovery (N=93, P=0.0250; HR=0.44, 95% CI [0.21-0.90]) and validation (N=630, P=2x10-4; HR=0.49, 95% CI [0.34-0.71]) cohorts. Finally, utilizing computational modeling of small molecule binding to NCOA7, we predicted and synthesized a novel activator of NCOA7 that prevented EC immunoactivation and reversed indices of rodent PAH. In summary, we have established a genetic and metabolic paradigm and a novel therapeutic agent that links lysosomal biology as well as oxysterol and bile acid processes to EC inflammation and PAH pathobiology. This paradigm carries broad implications for diagnostic and therapeutic development in PAH and in other conditions dependent upon acquired and innate immune regulation of vascular disease.

17.
Appl Opt ; 63(6): 1457-1470, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38437357

RESUMO

Most near-eye displays with one fixed focal plane suffer from the vergence-accommodation conflict and cause visual discomfort to users. In contrast, light field displays can provide natural and comfortable 3D visual sensation to users without the conflict. This paper presents a near-eye light field display consisting of a geometric lightguide and a light field generator, along with a collimator to ensure the light rays propagating in the lightguide are collimated. Unlike most lightguides, which reduce thickness by employing total internal reflection that can easily generate stray light, our lightguide directly propagates light rays without total internal reflection. The partially reflective mirrors of the lightguide expand the exit pupil to achieve an eyebox of 13m m(h o r i z o n t a l)×6.5m m(v e r t i c a l) with an eye relief of 18 mm. The collimator and the light field generator, both having effective focal lengths different in the horizontal and vertical directions, are designed to provide a 40-deg diagonal field of view. The working range of the light field generator, which is 30 cm to infinity, is verified qualitatively and quantitatively by experiments. We optimize the illuminance uniformity and analyze the illuminance variation across the eyebox. Further, we minimize the ghost artifact (referring to the split-up of light fields replicated by the partially reflective mirrors) by orienting the partially reflective mirrors at slightly different angles to enhance the image quality for short-range applications such as medical surgery.

18.
Sci Rep ; 14(1): 5444, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443671

RESUMO

With the development of distributed power sources in the distribution network, the algorithm of distribution network reconfiguration is gaining attention from experts and scholars. Its goal is to reduce the power loss during power transmission, so as to reduce the power grid loss during power transmission. And weaken the electric heating effect in the process of electric energy transmission, thus maintaining the safety of the surrounding residents. Due to the wire impedance effect, a lot of electric energy of the circuit is lost to electric heating, which is easy to cause local overheating and lead to fire. This will not only cause power loss, but also endanger the safety of surrounding residents. To address the issue, experiments on distribution grid reconstruction are performed using the enhanced particle swarm-fish swarm algorithm with the Elecgrid self-constructed dataset. Initially, low-voltage distributed power sources in parallel are connected to the circuit, thereby decreasing internal resistance and electrical heat. Then, by controlling the circuit in the system, the double separation relay adjusts the inductance and capacitance of the conductor, thus reducing the reactance length. Additionally, particle swarm particles are mutated to enable them to jump out of the local optimum, and elite fish approach is used to expand the search area. Finally, the proposed fusion algorithm is applied to the self-built data set of Elecgrid and compared with the other three algorithms. The fusion algorithm serves as the standard test system for this comparison. The active power loss of the hybrid algorithm is 63 kW at an operating voltage of 0.74 V. The loss work of the other three algorithms is 74 kW, 97 kW and 109 kW respectively. The mixed algorithm has the lowest loss among the four algorithms. The experiments are repeated for six times, and the linear fitting degrees of the four algorithms are 0.9804, 0.9527, 0.9612 and 0.9503, respectively. The experimental results show that the application of this algorithm can effectively reduce the active loss in the process of distribution network reconfiguration, thus reducing energy consumption; At the same time, it can reduce the electric heating in the process of electric energy transmission, and then prevent the occurrence of fire. There are three main contributions of this study. Firstly, the resistance in the transmission path is reduced by using this algorithm, so that the power transmission efficiency can be analyzed more accurately. Secondly, the new algorithm enriches the power safety maintenance method; Finally, the fire caused by local overheating of the line is reduced by fusion algorithm.

19.
Fa Yi Xue Za Zhi ; 40(1): 30-36, 2024 Feb 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38500458

RESUMO

OBJECTIVES: To establish a rapid screening method for 34 emerging contaminants in surface water by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q-TOF-MS). METHODS: The pretreatment conditions of solid phase extraction (SPE) were optimized by orthogonal experimental design and the surface water samples were concentrated and extracted by Oasis® HLB and Oasis® MCX SPE columns in series. The extracts were separated by Kinetex® EVO C18 column, with gradient elution of 0.1% formic acid aqueous solution and 0.1% formic acid methanol solution. Q-TOF-MS 'fullscan' and 'targeted MS/MS' modes were used to detect 34 emerging contaminants and to establish a database with 34 emerging contaminants precursor ion, product ion and retention times. RESULTS: The 34 emerging contaminants exhibited good linearity in the concentration range respectively and the correlation coefficients (r) were higher than 0.97. The limit of detection was 0.2-10 ng/L and the recoveries were 81.2%-119.2%. The intra-day precision was 0.78%-18.70%. The method was applied to analyze multiple surface water samples and 6 emerging contaminants were detected, with a concentration range of 1.93-157.71 ng/L. CONCLUSIONS: The method is simple and rapid for screening various emerging contaminants at the trace level in surface water.


Assuntos
Espectrometria de Massas em Tandem , Água , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Formiatos , Extração em Fase Sólida/métodos
20.
J Pain Symptom Manage ; 67(6): 544-553, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38479538

RESUMO

CONTEXT: Despite making do-not-resuscitate or comfort care decisions during advance care planning, terminally ill patients sometimes receive life-sustaining treatments as they approach end of life. OBJECTIVES: To examine factors contributing to nonconcordance between end-of-life care and advance care planning. METHODS: In this longitudinal retrospective cohort study, terminally ill patients with a life expectancy shorter than six months, who had previously expressed a preference for do-not-resuscitate or comfort care, were followed up after palliative shared care intervention. An instrument with eight items contributing to non-concordant care, developed through literature review and experts' consensus, was employed. An expert panel reviewed electronic medical records to determine factors associated with non-concordant care for each patient. Statistical analysis, including descriptive statistics and the chi-square test, examines demographic characteristics, and associations. RESULTS: Among the enrolled 7871 patients, 97 (1.2%) received non-concordant care. The most prevalent factor was "families being too distressed about the patient's deteriorating condition and therefore being unable to let go" (84.5%) followed by "limited understanding of medical interventions among patients and surrogates" (38.1%), and "lack of patient participation in the decision-making process" (25.8%). CONCLUSIONS: This study reveals that factors related to relational autonomy, emotional support, and health literacy may contribute to non-concordance between advance care planning and end-of-life care. In the future, developing an advance care planning model emphasizes respecting relational autonomy, providing emotional support, and enhancing health literacy could help patients receiving a goal concordant and holistic end-of-life care.


Assuntos
Planejamento Antecipado de Cuidados , Assistência Terminal , Humanos , Masculino , Feminino , Idoso , Estudos Retrospectivos , Estudos Longitudinais , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Ordens quanto à Conduta (Ética Médica) , Preferência do Paciente , Doente Terminal , Cuidados Paliativos
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