RESUMO
Herein is the first example of photocatalytic cross-coupling of alkenes with aldehydes by a single catalyst without an external photosensitizer and any additives. Irradiation of the aromatic aldehyde and cobaloxime catalyst results in the formation of an acyl radical, which undergoes radical addition with alkene or indole and subsequently ß-H elimination to afford alkenyl ketone. The reaction features cheap and readily available raw materials, a broad substrate scope, and mild conditions, even for late-stage derivatization of bioactive compounds.
RESUMO
Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors in the contemporary era, representing a significant global health concern. Early HCC patients have mild symptoms or are asymptomatic, which promotes the onset and progression of the disease. Moreover, advanced HCC is insensitive to chemotherapy, making traditional clinical treatment unable to block cancer development. Sorafenib (SFB) is a first-line targeted drug for advanced HCC patients with anti-angiogenesis and anti-tumor cell proliferation effects. However, the efficacy of SFB is constrained by its off-target distribution, rapid metabolism, and multi-drug resistance. In recent years, nanoparticles based on a variety of materials have been demonstrated to enhance the targeting and therapeutic efficacy of SFB against HCC. Concurrently, the advent of joint drug delivery systems has furnished crucial empirical evidence for reversing SFB resistance. This review will summarize the application of nanotechnology in the field of HCC treatment over the past five years. It will focus on the research progress of SFB delivery systems combined with multiple therapeutic modalities in HCC treatment.
Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Sistemas de Liberação de Medicamentos , Neoplasias Hepáticas , Sorafenibe , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Sorafenibe/administração & dosagem , Sorafenibe/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Animais , Nanopartículas , Resistencia a Medicamentos AntineoplásicosRESUMO
Over the past decade, significant progress has been made in the direct C-H acylation of naphthalenes, occurring at the α or ß-positions to yield valuable ketones through Friedel-Crafts acylation or transition-metal-catalysed carbonylative coupling reactions. Nevertheless, highly regioselective acylation of naphthalenes remains a formidable challenge. Herein, we developed a nickel-catalysed reductive ring-opening reaction of 7-oxabenzonorbornadienes with acyl chlorides as the electrophilic coupling partner, providing a new method for the exclusive preparation of ß-acyl naphthalenes.
RESUMO
The mitochondrial (mt) genome can provide data for phylogenetic analyses and evolutionary biology. Herein, we sequenced and annotated the complete mt genome of Ergasilus anchoratus. This mt genome was 13852 bp long and comprised 13 protein-coding genes (PCGs), 22 tRNAs and 2 rRNAs. All PCGs used the standard ATN start codons and complete TAA/TAG termination codons. A majority of tRNA genes exhibited standard cloverleaf secondary structures, with the exception of one tRNA that lacked the TψC arm (trnC), and three tRNAs that lacked the DHU arm (trnR, trnS1 and trnS2). Phylogenetic analyses conducted using Bayesian inference (BI) and maximum likelihood (ML) methods both supported Ergasilidae as a monophyletic family forming a sister group to Lernaea cyprinacea and Paracyclopina nana. It also supported the monophyly of orders Calanoida, Cyclopoida, and Siphonostomatoida; and the monophyly of families Harpacticidae, Ergasilidae, Diaptomidae, and Calanidae. The gene orders of E. anchoratus and Sinergasilus undulatus were identical, which represents the first instance of two identical gene orders in copepods. More mt genomes are needed to better understand the phylogenetic relationships within Copepoda in the future.
Assuntos
Copépodes , Genoma Mitocondrial , Filogenia , Animais , Genoma Mitocondrial/genética , Copépodes/genética , Copépodes/classificaçãoRESUMO
OBJECTIVE: A flat superciliary arch is relatively common in East Asian women. Superciliary arch augmentation aims to increase the facial three-dimensionality of the upper face. However, there are few reports in the literature specifically introducing the surgery. In this study, the authors present the clinical outcomes after a series of superciliary arch augmentation with silicone implants. METHODS: From May 2020 to December 2022, 54 patients underwent superciliary arch augmentation with silicone implants. Silicone implants generally have a length of 50 to 60 mm, a width of 13 to 14 mm, and an arc of 170 degrees. The thickness was 2 to 7 mm. The implant was placed subperiosteal at the lower edges of the eyebrows through a 7 mm incision below the brow tail. All patients evaluated the outcome according to the Global Esthetic Improvement Scale. Four plastic surgeons evaluated postsurgery results with a 5-point Likert Scale (5 = excellent, 4 = good, 3 = fair, 2 = no change, and 1 = worse). RESULTS: Fifty-four patients were successfully enrolled. The mean follow-up period was 12.02 ± 3.38 months. The mean thickness was 4.55 ± 0.67 mm for the thickest part of the implant. The minor complication rate was 44.44%. They all subsided within 1 month without treatment. Patients' outcome ratings were 4.45 ± 0.55 (3 mo), 4.51 ± 0.48 (6 mo), and 4.51 ± 0.45 (1 y). The surgeons' outcome scoring was 4.49 ± 0.31. CONCLUSIONS: Superciliary arch augmentation with silicone implants is a quite simple, effective, inexpensive, and safe strategy to improve the three-dimensionality and contour of the upper face in East Asians.
RESUMO
BACKGROUND: Observational studies have suggested a link between panic disorder (PD) and Alzheimer disease (AD). This study aimed to identify the underlying association of PD with the risk of AD using Mendelian randomization. METHODS: Genetic instrumental variables (IVs) were retrieved in the genome-wide association study between PD and AD. Then, five different models, namely inverse variance weighting (IVW), weighted median, weighted mode, MR-Egger and MR-robust adjusted profile scores (MR-RAPS), were used for MR Analysis. Finally, the heterogeneity and pleiotropy of identified IVs were verified by multiple sensitivity tests. RESULTS: The Cochran's Q test based on MR Egger and IVW showed that no evidence of heterogeneity was found in the effects of instrumental variables, so a fixed-effect model was used. IVW analysis (OR 1.000479, 95% CI [1.000147056, 1.000811539], p = 0.005) indicated that PD was associated with an increased risk of AD, and a causal association existed between them. Meanwhile, weighted median (OR 1.000513373, 95% CI [1.000052145, 1.000974814], p = 0.029) and MR-RAPS (OR 1.000510118, 95% CI [1.000148046, 1.00087232], p = 0.006) also showed the similar findings. In addition, extensive sensitivity analyses confirmed the robustness and accuracy of these results. CONCLUSION: This investigation provides evidence of a potential causal relationship between PD and the increased risk of AD. Based on our MR results, when diagnosing and treating patients with PD, clinicians should pay more attention to their AD-related symptoms to choose therapeutic measures or minimize comorbidities. Furthermore, the development of drugs that improve both PD and AD may better treat patients with these comorbidities.
Assuntos
Doença de Alzheimer , Transtorno de Pânico , Humanos , Análise da Randomização Mendeliana , Transtorno de Pânico/genética , Doença de Alzheimer/genética , Estudo de Associação Genômica Ampla , Análise de VariânciaRESUMO
Current research has found the amorphous/crystal interface has some unexpected electrochemical behaviors. This work designed a surface modification strategy using NaBH4 to induce in situ conversion of the surface structure of Ni-rich LiNi0.8Co0.1Mn0.1O2 (NCM811) into TM-B-O amorphous interface layer. Oxidizing the surface from transition metals (TM) with high valence and reductive BH4- in a weak polar medium of ethanol results in an easy redox reacton. A TM-B-O amorphous structure is formed on NCM811 surface. The action of reactive wetting ensures a complete and uniform structure evolution of the surface crystals. The complete coverage protects the outer crystal and the heterogeneous interface impedance between the modified layer and bulk is reduced. More importantly, this amorphous interface layer through in situ conversion enhances the heterogeneous link at interface and its own structural stability. The modified NCM811 (TB2@NCM) treated with 1 wt % NaBH4 shows excellent electrochemical performance, especially cyclic stability. At a high cutoff voltage of 4.5 V, the capacity retention was 72.5% at 1 C after 500 cycles. The electrode achieves 173.7 mAh·g-1 at 10 C. This work creates a modifying strategy with potential application prospect due to simple technology with low-cost raw material under mild operating conditions.
RESUMO
Developing efficient organic solar cells (OSCs) with thick active layers is crucial for roll-to-roll printing. However, thicker layers often result in lower efficiency. This study tackles this challenge using a polymer adsorption strategy combined with a layer-by-layer approach. Incorporating insulator polystyrene (PS) into the PM6:L8-BO system creates PM6+PS:L8-BO blends, effectively suppressing trap states and extending exciton diffusion length in the mixed donor domain. Adding insulating polymers with benzene rings to the donor enhances π-π stacking of donors, boosting intermolecular interactions and electron wave function overlap. This results in more orderly molecular stacking, longer exciton lifetimes, and higher diffusion lengths. The promoted long-range exciton diffusion leads to high power conversion efficiencies of 19.05% and 18.15% for PM6+PS:L8-BO blend films with 100 and 300 nm thickness, respectively, as well as a respectable 16.00% for 500 nm. These insights guide material selection for better exciton diffusion, and offer a method for thick-film OSC fabrication, promoting a prosperous future for practical OSC mass production.
RESUMO
BACKGROUND: Reduction malarplasty presents challenges in terms of postoperative complications, particularly limited mouth opening. Excessive inward displacement of the zygomatic complex can impinge on the coronoid process resulting in restricted mouth opening. This study aimed to assess the spatial relationship between the coronoid process and the zygomatic complex after reduction malarplasty. METHODS: A retrospective study was conducted, including consecutive patients underwent reduction malarplasty. Radiological measurements were performed before surgery and during the final follow-up, including the coronoid-condylar index, distance between the coronoid process and zygomatic complex, and thickness and density of the temporal and masseter muscles. Clinical and radiographic data were recorded and analyzed. RESULTS: A total of 159 female patients were included with an average age of 28.1 years and a mean follow-up of 6.7 months. The mean coronoid-condylar index was 1:1.4, ranging from 1:0.6 to 1:2.6. Following surgery, the distances between the coronoid process and the anterior zygoma decreased by approximately 1 mm. Additionally, the postoperative distance between the highest point of the coronoid process and the zygomatic arch decreased by around 4 mm horizontally and changed approximately 1 mm vertically. No significant changes were observed in the thickness and density of the temporal and masseter muscles after surgery. CONCLUSIONS: Reduction malarplasty led to a slight decrease in the distance between the coronoid process and the zygoma. The operation generally resulted in proximity between the highest point of the coronoid process and the zygomatic arch. However, we believe that common reduction malarplasty rarely leads to osseous impingement. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
Assuntos
Zigoma , Humanos , Zigoma/cirurgia , Zigoma/diagnóstico por imagem , Feminino , Estudos Retrospectivos , Adulto , Adulto Jovem , Pessoa de Meia-Idade , Adolescente , Procedimentos de Cirurgia Plástica/métodos , Estudos de Coortes , Resultado do Tratamento , Estética , Medição de RiscoRESUMO
Herein we reported a directing-group assisted strategy for nickel-catalysed reductive defluorinative sulfenylation of trifluoropropionic acid derivatives with disulfides in the presence of Zn, involving triple C-F bond cleavage. This process yielded a diverse array of carbonyl-sulfide di-substituted alkenes in moderate to good yields with good functional group tolerance. Specifically, the reactions exhibited high E-selectivity with E/Z ratio up to >99 : 1.
RESUMO
BACKGROUND: The current pandemic and future public health emergencies highlight the importance of evaluating a telehealth care model. Previous studies have reached mixed conclusions about the effectiveness of remote monitoring on glycemic control and maternal and infant outcomes in women with gestational diabetes mellitus (GDM). OBJECTIVES: This meta-analysis aimed to evaluate the effectiveness of remote blood glucose monitoring for women with gestational diabetes mellitus and to provide evidence-based guidance on the management of women with gestational diabetes mellitus for policymakers and healthcare providers during situations such as pandemics or natural disasters. METHODS: The Cochrane Library, PubMed, Web of Science, EBSCO, Embase, Medline, CINAHL databases, and ClinicalTrials.gov were systematically searched from their inception to July 10, 2021. Randomized controlled trials (RCTs) published in English with respect to remote blood glucose monitoring in women with GDM were included in the meta-analysis. Two independent reviewers performed data extraction and assessed the quality of the studies. Risk ratios, mean differences, 95% confidence intervals, and heterogeneity were calculated. RESULTS: A total of 1265 participants were included in the 11 RCTs. There were no significant differences in glycemic control and maternal-fetal outcomes between the remote monitoring group and a standard care group, which included glycosylated hemoglobin (HbA1c), fasting blood glucose, mean 2-h postprandial blood glucose, caesarean birth, gestational weight gain, shoulder dystocia, neonatal hypoglycemia, and other outcomes. CONCLUSION: This meta-analysis reveals that it is unclear if remote glucose monitoring is preferable to standard of care glucose monitoring. To improve glycemic control and maternal-fetal outcomes during the current epidemic or other natural disasters, the implementation of double-blind RCTs in the context of simulating similar disasters remains to be studied in the future.
Assuntos
Diabetes Gestacional , Telemedicina , Gravidez , Recém-Nascido , Lactente , Feminino , Humanos , Diabetes Gestacional/terapia , Glicemia/análise , Controle Glicêmico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Meal supervision for post-stroke dysphagia patients significantly improves prognosis during rehabilitation. Aspiration often occurs during meals, which may further incur aspiration pneumonia. Therefore, it's necessary to know the patient's swallowing ability as well as the occurrence of cough. Recently, some researchers have detected swallowing or coughing with audio signals and have made remarkable achievements. However, the users need to stay in quiet environments or wear uncomfortable cervical auscultation devices because the signals generated by swallowing are weak. In this work, we present MealCoach, a system that utilizes a contact microphone to collect high-quality signals to identify the events during meals. We take advantage of the insensitivity of contact microphones to ambient noise for free-living environment supervision. After balancing the wearing experience and identification accuracy, we elaborately select the optimal site to leverage the unique characteristics of cricoid cartilage movement during meals to accurately identify swallowing, coughing, speaking, and other events during meals. We collected data from thirty PSD patients in the hospital and evaluated our system, and the results demonstrate that MealCoach achieves a mean classification accuracy of 95.4%.
Assuntos
Transtornos de Deglutição , Acidente Vascular Cerebral , Humanos , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/etiologia , Deglutição , Acidente Vascular Cerebral/complicações , Pescoço , Tosse/etiologiaRESUMO
Objective: To preliminarily verify the effectiveness of self-designed artificial condyle-mandibular distraction (AC-MD) complex in the treatment of Pruzansky type â ¡B and â ¢ hemifacial microsomia (HFM) through model test. Methods: Five children with Pruzansky type â ¡B and â ¢ HFM who were treated with mandibular distraction osteogenesis (MDO) between December 2016 and December 2021 were selected as the subjects. There were 3 boys and 2 girls wih an average age of 8.4 years (range, 6-10 years). Virtual surgery and model test of AC-MD complex were performed according to preoperative skull CT of children. The model was obtained by three-dimensional (3D) printing according to the children's CT data at a ratio of 1â¶1. The occlusal guide plate was designed and 3D printed according to the children's toothpaste model. The results of the model test and the virtual surgery were matched in three dimensions to calculate the error of the residual condyle on the affected side, and the model test was matched with the actual skull CT after MDO to measure and compare the inclination rotation of the mandible, the distance between the condylar of the healthy side and the residual condyle of the affected side, and the lengthening length of the mandible. Results: The error of residual condyle was (1.07±0.78) mm. The inclination rotation of the mandible, the distance between the condylar of the healthy side and the residual condyle of the affected side, and the lengthening length of the mandible after 3D printing model test were significantly larger than those after MDO ( P<0.05). Conclusion: In the model test, the implantation of AC-MD complex can immediately rotate the mandible to the horizontal position and improve facial symmetry, and the residual condyle segment can be guided close to the articular fossa or the preset pseudoarticular position of the skull base after operation.
Assuntos
Síndrome de Goldenhar , Osteogênese por Distração , Masculino , Criança , Feminino , Humanos , Síndrome de Goldenhar/cirurgia , Mandíbula/cirurgia , Osteogênese por Distração/métodos , Impressão Tridimensional , Assimetria Facial/cirurgiaRESUMO
Objectives: This study aimed to evaluate the effect of manual lymphatic drainage (MLD) combined with targeted rehabilitation therapies on the recovery of upper limb function in patients with breast cancer after modified radical mastectomy. Patients and methods: In the randomized controlled study conducted between October 2019 and June 2020, 104 eligible breast cancer patients who underwent modified radical mastectomy were randomly divided into two groups. The routine functional exercise group (Group RF) received regular functional exercise guidance. In addition, the MLD combined with targeted rehabilitation therapies group (Group MLDT) received MLD, targeted rehabilitation therapies, and regular functional exercise guidance. The primary endpoints were shoulder range of motion, arm circumference and the incidence of axillary web syndrome (AWS). The secondary endpoints included the duration of axillary drainage, the duration of chest wall drainage, and complications. Results: One hundred participants (mean age: 51.9±8.0 years; range, 28 to 72 years) were included in the final analysis as four patients could not complete the study. A significant improvement in shoulder range of motion was observed in Group MLDT compared to Group RF (p<0.05). Additionally, in Group MLDT, the duration of chest wall drainage was reduced (p=0.037). The frequency of AWS in Group RF was twice that in Group MLDT (p=0.061), but there was no significant difference in arm circumference (p>0.05) or the duration of axillary drainage (p=0.519). Regarding complications, there was one case of necrosis in the MLDT group and four cases in the RF group, including wound infection and seroma. Conclusion: Manual lymphatic drainage combined with targeted rehabilitation therapies is an effective strategy to improve shoulder function, shorten the duration of chest wall drainage, reduce complications, and partly lower the incidence of AWS.
RESUMO
The quality of moxa is an important factor affecting moxibustion therapy, and traditionally, 3-year moxa is considered optimal, although scientific data are lacking. This study focused on 1-year and 3-year moxa from Artemisia stolonifera and A. argyi(leaf-to-moxa ratio of 10â¶1) as research objects. Scanning electron microscopy(SEM), Van Soest method, and simultaneous thermal analysis were used to investigate the differences in the combustion heat quality of 1-year and 3-year moxa and their influencing factors. The results showed that the combustion of A. stolonifera moxa exhibited a balanced heat release pattern. The 3-year moxa released a concentrated heat of 9 998.84 mJ·mg~(-1)(accounting for 54% of the total heat release) in the temperature range of 140-302 â, with a heat production efficiency of 122 mW·mg~(-1). It further released 7 512.51 mJ·mg~(-1)(accounting for 41% of the total heat release) in the temperature range of 302-519 â. The combustion of A. argyi moxa showed a rapid heat release pattern. The 3-year moxa released a heat of 16 695.28 mJ·mg~(-1)(accounting for 70% of the total heat release) in the temperature range of 140-311 â, with an instantaneous power output of 218 mW·mg~(-1). It further released 5 996.95 mJ·mg~(-1)(accounting for 25% of the total heat release) in the temperature range of 311-483 â. Combustion parameters such as-R_p,-R_v, D_i, C, and D_b indicated that the combustion heat quality of 3-year moxa was superior to that of 1-year moxa. It exhibited greater combustion heat, heat production efficiency, flammability, mild and sustained burning, and higher instantaneous combustion efficiency. This study utilized scientific data to demonstrate that A. stolonifera could be used as excellent moxa, and the quality of 3-year moxa surpassed that of 1-year moxa. The research results provide a scientific basis for the in-depth development of A. stolonifera moxa and the improvement of moxa quality standards.
Assuntos
Artemisia , Moxibustão , Temperatura Alta , Folhas de PlantaRESUMO
OBJECTIVE: This study aims to examine the characteristics of dysphagia in stroke patients with different lesion sites and explore the factors that impact the duration of nasogastric tube after post-stroke dysphagia (PSD). METHODS: Patients with PSD were screened for analysis. Stroke types and lesion sites were confirmed using MRI or CT scans. Included patients were categorized into two groups: supratentorial stroke group (including lobar and deep intracerebral stroke subgroups) and infratentorial stroke group (including brainstem and cerebellar stroke subgroups). Fiberoptic endoscopic evaluation of swallowing (FEES), Penetration-aspiration scale (PAS), Yale pharyngeal residue (PR) severity rating scale, Functional oral intake scale (FOIS), Murray secretion severity rating scale (MSS), laryngopharyngeal sensation, and vocal fold mobility were investigated to assess the swallowing function. RESULTS: A total of 94 patients were included in the final analysis. Significant differences were found in PR scores (p < .001), PAS scores (p < .05), MSS scores (p < .05), and vocal fold mobility (p < .001) between infratentorial and supratentorial stroke groups. Moreover, lobar stroke showed significantly higher PR scores compared to the deep intracerebral stroke group (p < .05). Kaplan-Meier survival analysis indicated significant differences in the duration of nasogastric tube placement among the following groups: infratentorial versus supratentorial stroke, PAS ≤ 5 versus PAS > 5, PR ≥ 3 versus PR < 3, and normal vocal fold mobility versus vocal fold motion impairment group (p < .05). CONCLUSIONS: The infratentorial stroke may lead to worse swallowing function as compared to a supratentorial stroke. Additionally, patients with infratentorial stroke, PAS > 5, PR ≥ 3, or vocal fold motion impairment may contribute to a longer duration of nasogastric tube placement.
Assuntos
Transtornos de Deglutição , Acidente Vascular Cerebral , Humanos , Transtornos de Deglutição/etiologia , Acidente Vascular Cerebral/complicações , Índice de Gravidade de Doença , Estudos Retrospectivos , Intubação Gastrointestinal , Fluoroscopia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Reabilitação do Acidente Vascular Cerebral , Esôfago/diagnóstico por imagemRESUMO
Objective: Most methods to detect copy number variation (CNV) have high false positive rates, especially for small CNVs and in real-life samples from clinical studies. In this study, we explored a novel scatterplot-based method to detect CNVs in microarray samples. Methods: Illumina SNP microarray data from 13,254 individuals were analyzed with scatterplots and by PennCNV. The data were analyzed without the prior exclusion of low-quality samples. For CNV scatterplot visualization, the median signal intensity of all SNPs located within a CNV region was plotted against the median signal intensity of the flanking genomic region. Since CNV causes loss or gain of signal intensities, carriers of different CNV alleles pop up in clusters. Moreover, SNPs within a deletion are not heterozygous, whereas heterozygous SNPs within a duplication show typical 1:2 signal distribution between the alleles. Scatterplot-based CNV calls were compared with standard results of PennCNV analysis. All discordant calls as well as a random selection of 100 concordant calls were individually analyzed by visual inspection after noise-reduction. Results: An algorithm for the automated scatterplot visualization of CNVs was developed and used to analyze six known CNV regions. Use of scatterplots and PennCNV yielded 1019 concordant and 108 discordant CNV calls. All concordant calls were evaluated as true CNV-findings. Among the 108 discordant calls, 7 were false positive findings by the scatterplot method, 80 were PennCNV false positives, and 21 were true CNVs detected by the scatterplot method, but missed by PennCNV (i.e., false negative findings). Conclusion: CNV visualization by scatterplots allows for a reliable and rapid detection of CNVs in large studies. This novel method may thus be used both to confirm the results of genome-wide CNV detection software and to identify known CNVs in hitherto untyped samples.
RESUMO
Objective: This study aims to establish a real-time dynamic monitoring system for silent aspiration (SA) to provide evidence for the early diagnosis of and precise intervention for SA after stroke. Methods: Multisource signals, including sound, nasal airflow, electromyographic, pressure and acceleration signals, will be obtained by multisource sensors during swallowing events. The extracted signals will be labeled according to videofluoroscopic swallowing studies (VFSSs) and input into a special dataset. Then, a real-time dynamic monitoring model for SA will be built and trained based on semisupervised deep learning. Model optimization will be performed based on the mapping relationship between multisource signals and insula-centered cerebral cortex-brainstem functional connectivity through resting-state functional magnetic resonance imaging. Finally, a real-time dynamic monitoring system for SA will be established, of which the sensitivity and specificity will be improved by clinical application. Results: Multisource signals will be stably extracted by multisource sensors. Data from a total of 3200 swallows will be obtained from patients with SA, including 1200 labeled swallows from the nonaspiration category from VFSSs and 2000 unlabeled swallows. A significant difference in the multisource signals is expected to be found between the SA and nonaspiration groups. The features of labeled and pseudolabeled multisource signals will be extracted through semisupervised deep learning to establish a dynamic monitoring model for SA. Moreover, strong correlations are expected to be found between the Granger causality analysis (GCA) value (from the left middle frontal gyrus to the right anterior insula) and the laryngeal rise time (LRT). Finally, a dynamic monitoring system will be established based on the former model, by which SA can be identified precisely. Conclusion: The study will establish a real-time dynamic monitoring system for SA with high sensitivity, specificity, accuracy and F1 score.
RESUMO
BACKGROUND: Genome-wide association studies (GWAS) are an effective way to explore genotype-phenotype associations in humans, animals, and plants. Various GWAS methods have been developed based on different genetic or statistical assumptions. However, no single method is optimal for all traits and, for many traits, the putative single nucleotide polymorphisms (SNPs) that are detected by the different methods do not entirely overlap due to the diversity of the genetic architecture of complex traits. Therefore, multi-tool-based GWAS strategies that combine different methods have been increasingly employed. To take this one step further, we propose an ensemble-like GWAS strategy (E-GWAS) that statistically integrates GWAS results from different single GWAS methods. RESULTS: E-GWAS was compared with various single GWAS methods using simulated phenotype traits with different genetic architectures. E-GWAS performed stably across traits with different genetic architectures and effectively controlled the number of false positive genetic variants detected without decreasing the number of true positive variants. In addition, its performance could be further improved by using a bin-merged strategy and the addition of more distinct single GWAS methods. Our results show that the numbers of true and false positive SNPs detected by the E-GWAS strategy slightly increased and decreased, respectively, with increasing bin size and when the number and the diversity of individual GWAS methods that were integrated in E-GWAS increased, the latter being more effective than the bin-merged strategy. The E-GWAS strategy was also applied to a real dataset to study backfat thickness in a pig population, and 10 candidate genes related to this trait and expressed in adipose-associated tissues were identified. CONCLUSIONS: Using both simulated and real datasets, we show that E-GWAS is a reliable and robust strategy that effectively integrates the GWAS results of different methods and reduces the number of false positive SNPs without decreasing that of true positive SNPs.
Assuntos
Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Humanos , Animais , Suínos , Estudo de Associação Genômica Ampla/métodos , Estudos de Associação Genética , FenótipoRESUMO
On the basis of establishing the prescription of Xinjianqu and clarifying the increase of the lipid-lowering active ingredients of Xinjianqu by fermentation, this paper further compared the differences in the lipid-lowering effects of Xinjianqu before and after fermentation, and studied the mechanism of Xinjianqu in the treatment of hyperlipidemia. Seventy SD rats were randomly divided into seven groups, including normal group, model group, positive drug simvastatin group(0.02 g·kg~(-1)), and low-dose and high-dose Xinjianqu groups before and after fermentation(1.6 g·kg~(-1) and 8 g·kg~(-1)), with ten rats in each group. Rats in each group were given high-fat diet continuously for six weeks to establish the model of hyperlipidemia(HLP). After successful modeling, the rats were given high-fat diet and gavaged by the corresponding drugs for six weeks, once a day, to compare the effects of Xinjianqu on the body mass, liver coefficient, and small intestine propulsion rate of rats with HLP before and after fermentation. The effects of Xinjianqu before and after fermentation on total cholesterol(TC), triacylglyceride(TG), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), alanine aminotransferase(ALT), aspartate aminotransferase(AST), blood urea nitrogen(BUN), creatinine(Cr), motilin(MTL), gastrin(GAS), and the Na~+-K~+-ATPase levels were determined by enzyme-linked immunosorbent assay(ELISA). The effects of Xinjianqu on liver morphology of rats with HLP were investigated by hematoxylin-eosin(HE) staining and oil red O fat staining. The effects of Xinjianqu on the protein expression of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK), phosphorylated AMPK(p-AMPK), liver kinase B1(LKB1), and 3-hydroxy-3-methylglutarate monoacyl coenzyme A reductase(HMGCR) in liver tissues were investigated by immunohistochemistry. The effects of Xinjianqu on the regulation of intestinal flora structure of rats with HLP were studied based on 16S rDNA high-throughput sequencing technology. The results showed that compared with those in the normal group, rats in the model group had significantly higher body mass and liver coefficient(P<0.01), significantly lower small intestine propulsion rate(P<0.01), significantly higher serum levels of TC, TG, LDL-C, ALT, AST, BUN, Cr, and AQP2(P<0.01), and significantly lower serum levels of HDL-C, MTL, GAS, Na~+-K~+-ATP levels(P<0.01). The protein expression of AMPK, p-AMPK, and LKB1 in the livers of rats in the model group was significantly decreased(P<0.01), and that of HMGCR was significantly increased(P<0.01). In addition, the observed_otus, Shannon, and Chao1 indices were significantly decreased(P<0.05 or P<0.01) in rat fecal flora in the model group. Besides, in the model group, the relative abundance of Firmicutes was reduced, while that of Verrucomicrobia and Proteobacteria was increased, and the relative abundance of beneficial genera such as Ligilactobacillus and Lachnospiraceae_NK4A136_group was reduced. Compared with the model group, all Xinjianqu groups regulated the body mass, liver coefficient, and small intestine index of rats with HLP(P<0.05 or P<0.01), reduced the serum levels of TC, TG, LDL-C, ALT, AST, BUN, Cr, and AQP2, increased the serum levels of HDL-C, MTL, GAS, and Na~+-K~+-ATP, improved the liver morphology, and increased the protein expression gray value of AMPK, p-AMPK, and LKB1 in the liver of rats with HLP and decreased that of LKB1. Xinjianqu groups could regulate the intestinal flora structure of rats with HLP, increased observed_otus, Shannon, Chao1 indices, and increased the relative abundance of Firmicutes, Ligilactobacillus(genus), Lachnospiraceae_NK4A136_group(genus). Besides, the high-dose Xinjianqu-fermented group had significant effects on body mass, liver coefficient, small intestine propulsion rate, and serum index levels of rats with HLP(P<0.01), and the effects were better than those of Xinjianqu groups before fermentation. The above results show that Xinjianqu can improve the blood lipid level, liver and kidney function, and gastrointestinal motility of rats with HLP, and the improvement effect of Xinjianqu on hyperlipidemia is significantly enhanced by fermentation. The mechanism may be related to AMPK, p-AMPK, LKB1, and HMGCR protein in the LKB1-AMPK pathway and the regulation of intestinal flora structure.