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1.
Comput Biol Med ; 180: 108867, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39089114

RESUMO

Non-coding RNAs (ncRNAs), as key regulators involving in intercellular biological processes, are more prominent in many malignancies, especially for hepatocellular carcinoma (HCC). Herein, we conduct a comprehensive review to summarize diverse ncRNAs roles in HCC metastatic mechanism. We focus on four signaling pathways that predominate in HCC metastatic process, including Wnt/ß-catenin, HIF-1α, IL-6, and TGF-ß pathways. MicroRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) employed different mechanisms to participate in the regulation of the key genes in these pathways, typical as interaction with DNA to control transcription, with RNA to control translation, and with protein to control stability. Therefore, ncRNAs may become potential biomarkers and therapeutic targets for HCC metastasis.

2.
Nat Commun ; 15(1): 6486, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39090088

RESUMO

Recent research in multi-principal element alloys (MPEAs) has increasingly focused on the role of short-range order (SRO) on material performance. However, the mechanisms of SRO formation and its precise control remain elusive, limiting the progress of SRO engineering. Here, leveraging advanced additive manufacturing techniques that produce samples with a wide range of cooling rates (up to 107 K s-1) and an enhanced semi-quantitative electron microscopy method, we characterize SRO in three CoCrNi-based face-centered-cubic (FCC) MPEAs. Surprisingly, irrespective of the processing and thermal treatment history, all samples exhibit similar levels of SRO. Atomistic simulations reveal that during solidification, prevalent local chemical order arises in the liquid-solid interface (solidification front) even under the extreme cooling rate of 1011 K s-1. This phenomenon stems from the swift atomic diffusion in the supercooled liquid, which matches or even surpasses the rate of solidification. Therefore, SRO is an inherent characteristic of most FCC MPEAs, insensitive to variations in cooling rates and even annealing treatments typically available in experiments.

3.
J Anim Sci Biotechnol ; 15(1): 102, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39090689

RESUMO

Understanding biological mechanisms is fundamental for improving animal production and health to meet the growing demand for high-quality protein. As an emerging biotechnology, single-cell transcriptomics has been gradually applied in diverse aspects of animal research, offering an effective method to study the gene expression of high-throughput single cells of different tissues/organs in animals. In an unprecedented manner, researchers have identified cell types/subtypes and their marker genes, inferred cellular fate trajectories, and revealed cell‒cell interactions in animals using single-cell transcriptomics. In this paper, we introduce the development of single-cell technology and review the processes, advancements, and applications of single-cell transcriptomics in animal research. We summarize recent efforts using single-cell transcriptomics to obtain a more profound understanding of animal nutrition and health, reproductive performance, genetics, and disease models in different livestock species. Moreover, the practical experience accumulated based on a large number of cases is highlighted to provide a reference for determining key factors (e.g., sample size, cell clustering, and cell type annotation) in single-cell transcriptomics analysis. We also discuss the limitations and outlook of single-cell transcriptomics in the current stage. This paper describes the comprehensive progress of single-cell transcriptomics in animal research, offering novel insights and sustainable advancements in agricultural productivity and animal health.

4.
Curr Neuropharmacol ; 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39092642

RESUMO

BACKGROUND: The link between Alzheimer's disease and depression has been confirmed by clinical and epidemiological research. Therefore, our study examined the literary landscape and prevalent themes in depression-related research works on Alzheimer's disease through bibliometric analysis. METHODS: Relevant literature was identified from the Web of Science core collection. Bibliometric parameters were extracted, and the major contributors were defined in terms of countries, institutions, authors, and articles using Microsoft Excel 2019 and VOSviewer. VOSviewer and CiteSpace were employed to visualize the scientific networks and seminal topics. RESULTS: The analysis of literature utilised 10,553 articles published from 1991 until 2023. The three countries or regions with the most publications were spread across the United States, China, and England. The University of Toronto and the University of Pittsburgh were the major contributors to the institutions. Lyketsos, Constantine G., Cummings, JL were found to make outstanding contributions. Journal of Alzheimer's Disease was identified as the most productive journal. Furthermore, "Alzheimer's", "depression", "dementia", and "mild cognitive decline" were the main topics of discussion during this period. LIMITATIONS: Data were searched from a single database to become compatible with VOSviewer and CiteSpace, leading to a selection bias. Manuscripts in English were considered, leading to a language bias. CONCLUSION: Articles on "Alzheimer's" and "depression" displayed an upward trend. The prevalent themes addressed were the mechanisms of depression-associated Alzheimer's disease, the identification of depression and cognitive decline in the early stages of Alzheimer's, alleviating depression and improving life quality in Alzheimer's patients and their caregivers, and diagnosing and treating neuropsychiatric symptoms in Alzheimer. Future research on these hot topics would promote understanding in this field.

5.
Sensors (Basel) ; 24(13)2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-39001137

RESUMO

Low-light imaging capabilities are in urgent demand in many fields, such as security surveillance, night-time autonomous driving, wilderness rescue, and environmental monitoring. The excellent performance of SPAD devices gives them significant potential for applications in low-light imaging. This article presents a 64 (rows) × 128 (columns) SPAD image sensor designed for low-light imaging. The chip utilizes a three-dimensional stacking architecture and microlens technology, combined with compact gated pixel circuits designed with thick-gate MOS transistors, which further enhance the SPAD's photosensitivity. The configurable digital control circuit allows for the adjustment of exposure time, enabling the sensor to adapt to different lighting conditions. The chip exhibits very low dark noise levels, with an average DCR of 41.5 cps at 2.4 V excess bias voltage. Additionally, it employs a denoising algorithm specifically developed for the SPAD image sensor, achieving two-dimensional grayscale imaging under 6 × 10-4 lux illumination conditions, demonstrating excellent low-light imaging capabilities. The chip designed in this paper fully leverages the performance advantages of SPAD image sensors and holds promise for applications in various fields requiring low-light imaging capabilities.

6.
Cancers (Basel) ; 16(13)2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-39001468

RESUMO

Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous disorder caused by loss-of-function variants in the NF1 gene. As of 20 November 2023, over 5000 distinct pathogenic or likely pathogenic variants have been reported in public databases. However, only a few NF1 genotype-phenotype correlations have been established so far. In this study, we present findings on 40 individuals with NF1, comprising 26 unrelated probands and 14 affected relatives, who carry one of nine NF1 heterozygous pathogenic splicing variants, all of which result in the in-frame skipping of exon 24 [19a] (NM_000267.3:r.3114_3197del, p.Asn1039_Arg1066del). These variants include c.3114-2A>G, c.3114-1G>A, c.3196A>G, c.3197G>A, c.3197G>T, c.3197+1G>A, c.3197+1G>T, c.3197+2T>C, and c.3197+3A>T. Among individuals with these variants, none exhibit externally visible plexiform neurofibromas, histopathologically confirmed cutaneous or subcutaneous neurofibromas, symptomatic spinal neurofibromas, or symptomatic optic pathway gliomas. The most prevalent, and sometimes sole, clinical feature observed in this cohort is multiple café-au-lait macules, with or without skinfold freckles: 85% and 60.5% of the individuals display six or more café-au-lait macules and freckles, respectively. In comparison to established NF1 genotype-phenotype correlations, these patients demonstrate highly similar clinical presentations to those associated with the NF1 pathogenic variant c.2970_2972del (p.Met992del), known for resulting in the mildest clinical features. Despite the generally mild phenotype, cognitive impairment, developmental delay, and/or learning difficulties are still observed in 33.3% of these patients, suggesting that learning challenges remain a prominent aspect of the phenotypic presentation in these individuals and necessitate specialized care. This newly established genotype-phenotype correlation will assist clinicians in improving the management of patients harboring NF1 exon 24 [19a] skipping variants and provide a new therapeutic target for NF1 treatment.

7.
J Dig Dis ; 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39004929

RESUMO

OBJECTIVES: Pancreatic serous cystic neoplasm (SCN) is a benign cystic neoplasm that is likely to be surgically resected due to preoperative misdiagnosis or tentative diagnosis even using endoscopic ultrasonography (EUS). We aimed to analyze EUS findings of SCN associated with misdiagnosis. METHODS: Between January 2012 and September 2023, histologically confirmed pancreatic SCN were included and EUS features were reviewed. RESULTS: Overall, 294 patients with 300 surgically resected SCNs were included. The median age of the patients was 51 years and 75.9% were females. The lesions were predominantly located in the body/neck/tail of the pancreas (63.0%). The overall preoperative diagnostic rate of SCN was 36.3%, with the most common misdiagnosis being intraductal papillary mucinous neoplasm (IPMN) (31.3%), while 16.3% remained undefined. The preoperative diagnostic rate of SCN varied across different endosonographic morphologies, with oligocystic, macrocystic, microcystic, and solid patterns yielding rates of 12.8%, 37.9%, 76.5%, and 19.2%, respectively. Notably, the presence of central scar and vascularity improved the diagnostic accuracy and correctly identified 41.4% and 52.3% of the lesions. While mucus or pancreatic duct (PD) communication significantly increased the likelihood of misdiagnosis, particularly as IPMN. Multivariate analysis revealed a morphological pattern, mucin-producing signs, wall thickening, vascularity, and PD communication were independent factors related to preoperative misdiagnosis, with an overall accuracy of 82.3%. CONCLUSIONS: Preoperative diagnosis of SCN remains challenging. The microcystic pattern emerged as a reliable feature, while mucin-producing signs, including mural nodules, mucus, and PD communication, pose diagnostic pitfalls despite the presence of typical central scar or vascularity commonly in SCN.

8.
Shanghai Kou Qiang Yi Xue ; 33(2): 164-169, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-39005093

RESUMO

PURPOSE: The characteristics of saliva and intestinal microbial community in children with high caries and no caries were analyzed by 16S rDNA high-throughput sequencing. METHODS: Among 431 children aged 3-5 years old in Zunyi City who were investigated previously by our team, 25 children in the high caries group and the same in the caries-free group were selected for fecal and saliva samples. 16S rDNA high-throughput sequencing was used to analyze the bacterial flora structure of the samples and identify the species with different relative abundance at the species level. SPSS 18.0 software package was used for data analysis. RESULTS: The diversity of intestinal flora in the high caries group was higher than that in the caries-free group, and the difference was statistically significant(P<0.05). The diversity of salivary flora in the high caries group was more than that in the caries-free group, with no significant difference(P>0.05). At phylum level,there was no significant difference in intestinal and salivary flora between children with high caries and children without caries. At gene level, Blautia, [Eubacterium] hallii group and [Eubacterium] eligens group in the intestine of caries-free group were significantly higher than those of high caries group(P<0.05), while Parasutterella and Christensenellaceae R-7 group were significantly lower than those of high caries group(P<0.05). At gene level, Peptostreptococcus in saliva of caries-free group was significantly higher than that in high caries group(P<0.05). Dialister, Kingella, Escherichia-Shigella and Treponema in saliva of caries-free group were significantly lower than those in high caries group(P<0.05). CONCLUSIONS: There are significant differences in species composition of intestinal flora but no in salivary flora between children with high caries and children without caries.


Assuntos
Cárie Dentária , Microbioma Gastrointestinal , Sequenciamento de Nucleotídeos em Larga Escala , RNA Ribossômico 16S , Saliva , Humanos , Saliva/microbiologia , Cárie Dentária/microbiologia , Pré-Escolar , Sequenciamento de Nucleotídeos em Larga Escala/métodos , RNA Ribossômico 16S/genética , Microbioma Gastrointestinal/genética , Fezes/microbiologia , Eubacterium/genética , DNA Bacteriano/genética , DNA Ribossômico/genética
9.
J Cardiovasc Nurs ; 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39010267

RESUMO

BACKGROUND: Older patients with chronic heart failure (CHF) are prone to insomnia. Studies have shown that insomnia affects the onset of cognitive frailty and is also strongly associated with depressive symptoms and social support. However, information on how these factors interact to influence cognitive frailty remains underexplored. OBJECTIVE: Our aim in this study was to explore the multiple mediating roles of depressive symptoms and social support in the relationship between insomnia and cognitive frailty. METHODS: We recruited 300 hospitalized older patients with CHF to participate in this study. The participants completed the Athens Insomnia Scale, Geriatric Depression Scale, Montreal Cognitive Assessment, FRAIL Scale, and Social Support Rating Scale. The mediation hypothesis was tested using a multiple mediation model and bootstrapping method. RESULTS: In this study, 44% of the patients experienced insomnia, and 51.3% were in a state of cognitive frailty. Our main findings suggest that insomnia has an indirect effect on cognitive frailty through 2 pathways: the multiple mediating effects of depressive symptoms and social support, and a single mediating effect of depressive symptoms. The direct effect of insomnia on cognitive frailty is also significant. CONCLUSIONS: Older patients with CHF who experience insomnia tend to have more severe depressive symptoms, cognitive frailty, and poor social support. Thus, interventions to recognize insomnia early, improve depressive symptoms, and provide social support may reduce cognitive frailty in older patients with CHF. Longitudinal studies are necessary to further refine our findings and address the limitations of the current study.

10.
Int J Biol Macromol ; : 133814, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38996888

RESUMO

The incidence of esophageal cancer continues to increase worldwide. Current therapeutic approaches have limited efficacy, so in order to search for better markers of the disease, it is necessary to further elucidate its molecular pathogenesis. Regulation of gene expression by long non-coding Rnas plays a role in many diseases, however the role in esophageal cancer is unclear. The aim of this study was to elucidate the role and regulatory mechanism of long non-coding RNA NRSN2-AS1 in the progression of esophageal cancer. By real-time quantitative PCR, immunohistochemistry, RNA interference, western blotting, and double luciferase reporter gene analysis, we found that NRSN2-AS1 was up-regulated in esophageal cancer tissues and cell lines, and was closely related to disease stage and prognosis. Functional studies have shown that the silencing of NRSN2-AS1 inhibits the proliferation of esophageal cancer cells, induces apoptosis, and prevents cell migration and invasion. In mouse models, NRSN2-AS1 also promoted tumor growth. The transcription factor TCFL5 upregulates the transcription of NRSN2-AS1, which acts as a sponge for microRNA(miR)-874-5p, thereby upregulating the expression of the oncogene RELT. Activation of the NRSN2-AS1/miR-874-5p/RELT regulatory axis was validated in vivo.

11.
J Transl Med ; 22(1): 652, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-38997719

RESUMO

BACKGROUND: The incidence of early-stage lung adenocarcinoma (ES-LUAD) is steadily increasing among non-smokers. Previous research has identified dysbiosis in the gut microbiota of patients with lung cancer. However, the local microbial profile of non-smokers with ES-LUAD remains largely unknown. In this study, we systematically characterized the local microbial community and its associated features to enable early intervention. METHODS: A prospective collection of ES-LUAD samples (46 cases) and their corresponding normal tissues adjacent to the tumor (41 cases), along with normal lung tissue samples adjacent to pulmonary bullae in patients with spontaneous pneumothorax (42 cases), were subjected to ultra-deep metagenomic sequencing, host transcriptomic sequencing, and proteomic sequencing. The obtained omics data were subjected to both individual and integrated analysis using Spearman correlation coefficients. RESULTS: We concurrently detected the presence of bacteria, fungi, and viruses in the lung tissues. The microbial profile of ES-LUAD exhibited similarities to NAT but demonstrated significant differences from the healthy controls (HCs), characterized by an overall reduction in species diversity. Patients with ES-LUAD exhibited local microbial dysbiosis, suggesting the potential pathogenicity of certain microbial species. Through multi-omics correlations, intricate local crosstalk between the host and local microbial communities was observed. Additionally, we identified a significant positive correlation (rho > 0.6) between Methyloversatilis discipulorum and GOLM1 at both the transcriptional and protein levels using multi-omics data. This correlated axis may be associated with prognosis. Finally, a diagnostic model composed of six bacterial markers successfully achieved precise differentiation between patients with ES-LUAD and HCs. CONCLUSIONS: Our study depicts the microbial spectrum in patients with ES-LUAD and provides evidence of alterations in lung microbiota and their interplay with the host, enhancing comprehension of the pathogenic mechanisms that underlie ES-LUAD. The specific model incorporating lung microbiota can serve as a potential diagnostic tool for distinguishing between ES-LUAD and HCs.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Metagenômica , Microbiota , Proteômica , Transcriptoma , Humanos , Adenocarcinoma de Pulmão/microbiologia , Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/microbiologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Metagenômica/métodos , Masculino , Feminino , Transcriptoma/genética , Microbiota/genética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Disbiose/microbiologia , Perfilação da Expressão Gênica , Interações entre Hospedeiro e Microrganismos/genética , Idoso
12.
Plants (Basel) ; 13(13)2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38999577

RESUMO

Fungi as heterotrophs are key participants in the decomposition of organic materials and the transformation of nutrients in agroecosystems. Ditch-buried straw return as a novel conservation management strategy can improve soil fertility and alter hydrothermal processes. However, how ditch-buried straw return strategies affect the soil fungal community is still unclear. Herein, a 7-year field trial was conducted to test the influences of burial depth (0, 10, 20, 30, and 40 cm) and the amount of ditch-buried straw (half, full, double) on the diversity, composition, and predicted functions of a soil fungal community, as well as the activities of carbon-degraded enzymes. Under the full amount of straw burial, the abundance of phylum Ascomycota was 7.5% higher as compared to other burial amount treatments. This further increased the activity of cellobiohydrolase by 32%, as revealed by the positive correlation between Ascomycota and cellobiohydrolase. With deeper straw burial, however, the abundance of Ascomycota and ß-D-glucopyranoside activity decreased. Moreover, genus Alternaria and Fusarium increased while Mortierella decreased with straw burial amount and depth. FUNgild prediction showed that plant fungal pathogens were 1- to 2-fold higher, whilst arbuscular mycorrhizal fungi were 64% lower under straw buried with double the amount and at a depth of 40 cm. Collectively, these findings suggest that ditch-buried straw return with a full amount and buried at a depth less than 30 cm could improve soil nutrient cycles and health and may be beneficial to subsequent crop production.

13.
Int J Mol Sci ; 25(13)2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-39000320

RESUMO

The toxic metal cadmium (Cd) poses a serious threat to plant growth and human health. Populus euphratica calcium-dependent protein kinase 21 (CPK21) has previously been shown to attenuate Cd toxicity by reducing Cd accumulation, enhancing antioxidant defense and improving water balance in transgenic Arabidopsis. Here, we confirmed a protein-protein interaction between PeCPK21 and Arabidopsis nuclear transcription factor YC3 (AtNF-YC3) by yeast two-hybrid and bimolecular fluorescence complementation assays. AtNF-YC3 was induced by Cd and strongly expressed in PeCPK21-overexpressed plants. Overexpression of AtNF-YC3 in Arabidopsis reduced the Cd inhibition of root length, fresh weight and membrane stability under Cd stress conditions (100 µM, 7 d), suggesting that AtNF-YC3 appears to contribute to the improvement of Cd stress tolerance. AtNF-YC3 improved Cd tolerance by limiting Cd uptake and accumulation, activating antioxidant enzymes and reducing hydrogen peroxide (H2O2) production under Cd stress. We conclude that PeCPK21 interacts with AtNF-YC3 to limit Cd accumulation and enhance the reactive oxygen species (ROS) scavenging system and thereby positively regulate plant adaptation to Cd environments. This study highlights the interaction between PeCPK21 and AtNF-YC3 under Cd stress conditions, which can be utilized to improve Cd tolerance in higher plants.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Cádmio , Regulação da Expressão Gênica de Plantas , Plantas Geneticamente Modificadas , Populus , Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/efeitos dos fármacos , Cádmio/toxicidade , Cádmio/metabolismo , Populus/genética , Populus/metabolismo , Populus/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Estresse Fisiológico/efeitos dos fármacos , Proteínas Quinases/metabolismo , Proteínas Quinases/genética , Espécies Reativas de Oxigênio/metabolismo , Peróxido de Hidrogênio/metabolismo , Raízes de Plantas/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Ligação Proteica
14.
Commun Biol ; 7(1): 838, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982182

RESUMO

Aberrant RNA editing has emerged as a pivotal factor in the pathogenesis of hepatocellular carcinoma (HCC), but the impact of RNA co-editing within HCC remains underexplored. We used a multi-step algorithm to construct an RNA co-editing network in HCC, and found that HCC-related RNA editings are predominantly centralized within the network. Furthermore, five pairs of risk RNA co-editing events were significantly correlated with the overall survival in HCC. Based on presence of risk RNA co-editings resulted in the categorization of HCC patients into high-risk and low-risk groups. Disparities in immune cell infiltrations were observed between the two groups, with the high-risk group exhibiting a greater abundance of exhausted T cells. Additionally, seven genes associated with risk RNA co-editing pairs were identified, whose expression effectively differentiates HCC tumor samples from normal ones. Our research offers an innovative perspective on the etiology and potential therapeutics for HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Edição de RNA , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/mortalidade , Humanos , Regulação Neoplásica da Expressão Gênica , Prognóstico , Biomarcadores Tumorais/genética
15.
Expert Opin Investig Drugs ; : 1-10, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38988285

RESUMO

BACKGROUND: Considering the rise of new SARS-CoV-2 variants that have reduced the efficacy of COVID-19 vaccines, the development of new antiviral medications for the disease has become increasingly necessary. In this study, ASC10, a novel antiviral prodrug, was studied in a phase 1 trial in healthy Chinese participants. RESEARCH DESIGN AND METHODS: Part 1 involved 60 participants, receiving 50-800 mg ASC10 or placebo twice daily for 5.5 days. Part 2, with 12 participants, explored ASC10 dosing in the fed/fasting states. RESULTS: ASC10-A, the main pharmacologically active metabolite, rapidly appeared in plasma (Tmax: 1.00-2.00 h) and decreased (t1/2: 1.10-3.04 h) without accumulation. The Cmax and area under the plasma concentration - time curve (AUC) of ASC10-A increased dose-dependently (50-800 mg BID) over 5.5 days, with no accumulation. The Tmax was slightly delayed in the fed state; however, the Cmax and AUC were similar between the fed and fasting states. Adverse events (AEs) were comparable (ASC10/placebo, 66.7%) and mostly mild (95%). CONCLUSION: ASC10 was demonstrated to be safe and well tolerated and exhibited dose-proportional exposure and minimal food effects. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT05523141.

16.
Chem Sci ; 15(26): 10232-10236, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38966351

RESUMO

Despite the long-standing exploration of the catalytic asymmetric Tsuji-Trost allylation reaction since the mid-20th century, most reported instances have adhered to a two-component approach. Here, we present a remarkably efficient three-component asymmetric allylation reaction enabled by the collaborative action of chiral aldehyde and palladium. A diverse array of NH2-unprotected amino acid esters, aryl or alkenyl iodides, and allyl alcohol esters exhibit robust participation in this reaction, resulting in the synthesis of structurally diverse non-proteinogenic α-amino acid esters with favorable experimental outcomes. Mechanistic investigations reveal the dominance of the allylation/Heck coupling cascade in reactions involving electron-rich aryl iodides, while the Heck coupling/allylation cascade emerges as the dominant pathway in reactions involving electron-deficient aryl iodides. This chiral aldehyde/palladium combining catalytic system precisely governs the chemoselectivity of C-allylation and N-allylation, the regioselectivity of linear and branched allylation, and the enantioselectivity of C-allylation products.

17.
Acad Radiol ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38964984

RESUMO

RATIONALE AND OBJECTIVES: The aim of this study was to develop and validate a nomogram for predicting emergent conversion to general anaesthesia (GA) in stroke patients during thrombectomy. METHODS: In this retrospective study, 458 patients (320 and 138 were randomised into the training and validation cohorts) were enroled. Univariable and multivariable logistic regression analyses were employed to identify risk factors for emergent conversion to GA. Subsequently, a nomogram was constructed based on the identified risk factors. The discriminative ability, calibration, and clinical utility of the nomogram were assessed in both the training and validation cohorts using receiver operating characteristic (ROC) curve analysis, Hosmer-Lemeshow test, and decision curve analysis (DCA). RESULTS: The emergent conversion to GA occurred in 56 cases (12.2%). In the training cohort, four independent predictors of emergent conversion to GA were identified and incorporated into the nomogram: core infarct volume > 70 mL, severe aphasia, severe cerebral vessel tortuosity, and vertebrobasilar occlusion. The ROC curves illustrated area under curve values of 0.931 (95% CI: 0.863-0.998) and 0.893 (95% CI: 0.852-0.935) for the training and validation cohorts, respectively. Hosmer-Lemeshow testing resulted in average absolute errors of 0.028 and 0.031 for the two cohorts. DCA demonstrated the nomogram's exceptional utility and accuracy across a majority of threshold probabilities. CONCLUSION: The constructed nomogram displayed promising predictive accuracy for emergent conversion to GA in stroke patients during thrombectomy, thereby providing potential assistance for clinical decision-making.

19.
Nanomaterials (Basel) ; 14(14)2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39057876

RESUMO

Electrospinning is an effective method to prepare nanofibers at present. Aiming at problems such as low spinnable viscosity and the low productivity of the traditional multi-needle, a radial nozzle was proposed in this paper. In order to solve the problem of end effects in multi-nozzle electrospinning, COMSOL Multiphysics 6.0 software was used to simulate the electric field in electrospinning with seven radial nozzles. And the influence on the electric field intensity and distribution of the structural parameters of the radial nozzle, including the number, length, tip-shape, and tip-pointing direction of the vanes, were studied. Then, the electric field intensity of any point on the central axis of a radial nozzle was obtained based on the principle of electric field superposition, and then the rotation angle of the vanes corresponding to the minimum Coulomb repulsion force on the target point was deduced. At last, the method of electric field homogenization of a rotating vane arrangement was obtained. In the simulation, the strength and homogenization of the electric field were taken as the research objective, and the optimum structure parameters of the radial nozzle were obtained; the uniform theory of the electric field based on the orientation of the vanes was verified. Then, electrospinning with seven radial nozzles was performed, and it was found that each radial nozzle can produce multiple jets during electrospinning, and the prepared electrospun membranes have even thickness and high porosity. What is more, the fibers are relatively finer and more uniform.

20.
Medicine (Baltimore) ; 103(30): e38747, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39058887

RESUMO

This study aims to develop and validate a machine learning (ML) predictive model for assessing mortality in patients with malignant tumors and hyperkalemia (MTH). We extracted data on patients with MTH from the Medical Information Mart for Intensive Care-IV, version 2.2 (MIMIC-IV v2.2) database. The dataset was split into a training set (75%) and a validation set (25%). We used the Least Absolute Shrinkage and Selection Operator (LASSO) regression to identify potential predictors, which included clinical laboratory indicators and vital signs. Pearson correlation analysis tested the correlation between predictors. In-hospital death was the prediction target. The Area Under the Curve (AUC) and accuracy of the training and validation sets of 7 ML algorithms were compared, and the optimal 1 was selected to develop the model. The calibration curve was used to evaluate the prediction accuracy of the model further. SHapley Additive exPlanations (SHAP) and Local Interpretable Model-agnostic Explanations (LIME) enhanced model interpretability. 496 patients with MTH in the Intensive Care Unit (ICU) were included. After screening, 17 clinical features were included in the construction of the ML model, and the Pearson correlation coefficient was <0.8, indicating that the correlation between the clinical features was small. eXtreme Gradient Boosting (XGBoost) outperformed other algorithms, achieving perfect scores in the training set (accuracy: 1.000, AUC: 1.000) and high scores in the validation set (accuracy: 0.734, AUC: 0.733). The calibration curves indicated good predictive calibration of the model. SHAP analysis identified the top 8 predictive factors: urine output, mean heart rate, maximum urea nitrogen, minimum oxygen saturation, minimum mean blood pressure, maximum total bilirubin, mean respiratory rate, and minimum pH. In addition, SHAP and LIME performed in-depth individual case analyses. This study demonstrates the effectiveness of ML methods in predicting mortality risk in ICU patients with MTH. It highlights the importance of predictors like urine output and mean heart rate. SHAP and LIME significantly enhanced the model's interpretability.


Assuntos
Hiperpotassemia , Unidades de Terapia Intensiva , Aprendizado de Máquina , Neoplasias , Humanos , Hiperpotassemia/diagnóstico , Hiperpotassemia/mortalidade , Feminino , Masculino , Unidades de Terapia Intensiva/estatística & dados numéricos , Pessoa de Meia-Idade , Prognóstico , Neoplasias/mortalidade , Neoplasias/complicações , Idoso , Mortalidade Hospitalar , Algoritmos
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