Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 74
Filtrar
1.
Proc Natl Acad Sci U S A ; 120(34): e2305142120, 2023 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-37585462

RESUMO

Introducing nitrogen fixation (nif  ) genes into eukaryotic genomes and targeting Nif components to mitochondria or chloroplasts is a promising strategy for engineering nitrogen-fixing plants. A prerequisite for achieving nitrogen fixation in crops is stable and stoichiometric expression of each component in organelles. Previously, we designed a polyprotein-based nitrogenase system depending on Tobacco Etch Virus protease (TEVp) to release functional Nif components from five polyproteins. Although this system satisfies the demand for specific expression ratios of Nif components in Escherichia coli, we encountered issues with TEVp cleavage of polyproteins targeted to yeast mitochondria. To overcome this obstacle, a version of the Nif polyprotein system was constructed by replacing TEVp cleavage sites with minimal peptide sequences, identified by knowledge-based engineering, that are susceptible to cleavage by the endogenous mitochondrial-processing peptidase. This replacement not only further reduces the number of genes required, but also prevents potential precleavage of polyproteins outside the target organelle. This version of the polyprotein-based nitrogenase system achieved levels of nitrogenase activity in E. coli, comparable to those observed with the TEVp-based polyprotein nitrogenase system. When applied to yeast mitochondria, stable and balanced expression of Nif components was realized. This strategy has potential advantages, not only for transferring nitrogen fixation to eukaryotic cells, but also for the engineering of other metabolic pathways that require mitochondrial compartmentalization.


Assuntos
Escherichia coli , Fixação de Nitrogênio , Fixação de Nitrogênio/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Saccharomyces cerevisiae/metabolismo , Poliproteínas/genética , Poliproteínas/metabolismo , Nitrogenase/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo , Nitrogênio/metabolismo
2.
Neuroimage ; 287: 120519, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38280690

RESUMO

Functional brain networks (FBNs) are spatial patterns of brain function that play a critical role in understanding human brain function. There are many proposed methods for mapping the spatial patterns of brain function, however they oversimplify the underlying assumptions of brain function and have various limitations such as linearity and independence. Additionally, current methods fail to account for the dynamic nature of FBNs, which limits their effectiveness in accurately characterizing these networks. To address these limitations, we present a novel deep learning and spatial-wise attention based model called Spatial-Temporal Convolutional Attention (STCA) to accurately model dynamic FBNs. Specifically, we train STCA in a self-supervised manner by utilizing a Convolutional Autoencoder to guide the STCA module in assigning higher attention weights to regions of functional activity. To validate the reliability of the results, we evaluate our approach on the HCP-task motor behavior dataset, the experimental results demonstrate that the STCA derived FBNs have higher spatial similarity with the templates and that the spatial similarity between the templates and the FBNs derived by STCA fluctuates with the task design over time, suggesting that STCA can reflect the dynamic changes of brain function, providing a powerful tool to better understand human brain function. Code is available at https://github.com/SNNUBIAI/STCAE.


Assuntos
Mapeamento Encefálico , Imageamento por Ressonância Magnética , Humanos , Mapeamento Encefálico/métodos , Imageamento por Ressonância Magnética/métodos , Reprodutibilidade dos Testes , Encéfalo/diagnóstico por imagem
3.
Molecules ; 29(9)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38731398

RESUMO

(1) Background: Alzheimer's disease (AD) is characterized by ß-amyloid (Aß) peptide accumulation and mitochondrial dysfunction during the early stage of disease. PINK1 regulates the balance between mitochondrial homeostasis and bioenergy supply and demand via the PINK1/Parkin pathway, Na+/Ca2+ exchange, and other pathways. (2) Methods: In this study, we synthesized positively charged carbon dots (CA-PEI CDs) using citric acid (CA) and polyethyleneimine (PEI) and used them as vectors to express PINK1 genes in the APP/PS1-N2a cell line to determine mitochondrial function, electron transport chain (ETC) activity, and ATP-related metabolomics. (3) Results: Our findings showed that the CA-PEI CDs exhibit the characteristics of photoluminescence, low toxicity, and concentrated DNA. They are ideal biological carriers for gene delivery. PINK1 overexpression significantly increased the mitochondrial membrane potential in APP/PS1-N2a cells and reduced reactive-oxygen-species generation and Aß1-40 and Aß1-42 levels. An increase in the activity of NADH ubiquinone oxidoreductase (complex I, CI) and cytochrome C oxidase (complex IV, CIV) induces the oxidative phosphorylation of mitochondria, increasing ATP generation. (4) Conclusions: These findings indicate that the PINK gene can alleviate AD by increasing bioenergetic metabolism, reducing Aß1-40 and Aß1-42, and increasing ATP production.


Assuntos
Trifosfato de Adenosina , Carbono , Ácido Cítrico , Polietilenoimina , Proteínas Quinases , Pontos Quânticos , Animais , Humanos , Camundongos , Trifosfato de Adenosina/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Carbono/química , Linhagem Celular , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Polietilenoimina/química , Proteínas Quinases/metabolismo , Proteínas Quinases/genética , Pontos Quânticos/química , Espécies Reativas de Oxigênio/metabolismo
4.
Appl Opt ; 62(20): 5452-5458, 2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37706862

RESUMO

This study proposes what we believe to be a novel x-ray detection system that achieves a temporal resolution of 930 fs with photorefractive and four-wave mixing effects. The system comprises two parts: a signal-conversion system and signal-acquisition system. The signal-conversion system is based on the photorefractive effect, which converts x-ray evolution into the variation of infrared interference intensity. The signal-conversion sensor consists of ultra-fast response LT-GaAs and a high-resolution interference cavity, achieving a resolution of  767 fs. The signal-acquisition system consists of a time-domain amplification system based on four-wave mixing and a high-resolution signal-recording system with a resolution of 21 ps, providing a temporal resolution of 525 fs.

5.
Hereditas ; 160(1): 36, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37904201

RESUMO

BACKGROUND: RNA modifications, especially N6-methyladenosine, N1-methyladenosine and 5-methylcytosine, play an important role in the progression of cardiovascular disease. However, its regulatory function in dilated cardiomyopathy (DCM) remains to be undefined. METHODS: In the study, key RNA modification regulators (RMRs) were screened by three machine learning models. Subsequently, a risk prediction model for DCM was developed and validated based on these important genes, and the diagnostic efficiency of these genes was assessed. Meanwhile, the relevance of these genes to clinical traits was explored. In both animal models and human subjects, the gene with the strongest connection was confirmed. The expression patterns of important genes were investigated using single-cell analysis. RESULTS: A total of 4 key RMRs were identified. The risk prediction models were constructed basing on these genes which showed a good accuracy and sensitivity in both the training and test set. Correlation analysis showed that insulin-like growth factor binding protein 2 (IGFBP2) had the highest correlation with left ventricular ejection fraction (LVEF) (R = -0.49, P = 0.00039). Further validation expression level of IGFBP2 indicated that this gene was significantly upregulated in DCM animal models and patients, and correlation analysis validation showed a significant negative correlation between IGFBP2 and LVEF (R = -0.87; P = 6*10-5). Single-cell analysis revealed that this gene was mainly expressed in endothelial cells. CONCLUSION: In conclusion, IGFBP2 is an important biomarker of left ventricular dysfunction in DCM. Future clinical applications could possibly use it as a possible therapeutic target.


Assuntos
Cardiomiopatia Dilatada , Disfunção Ventricular Esquerda , Humanos , Biomarcadores , Cardiomiopatia Dilatada/genética , Cardiomiopatia Dilatada/diagnóstico , Células Endoteliais , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina , RNA , Volume Sistólico , Disfunção Ventricular Esquerda/genética , Função Ventricular Esquerda
6.
J Asian Nat Prod Res ; 25(12): 1217-1222, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37163366

RESUMO

A new abietane diterpenoid, 1ß, 11-epoxyabieta-12-hydroxy-8, 11, 13-triene-7-one (1), along with three known compounds (2-4), was isolated from Lycopodium complanatum. Their structures were confirmed by the analysis of 1D, 2D NMR and HRESIMS data, and comparison with previous spectral data. All compounds were tested for inhibitory activities against A549, HepG2 and MCF-7 tumor cell lines. [Figure: see text].


Assuntos
Antineoplásicos Fitogênicos , Lycopodium , Humanos , Abietanos/farmacologia , Abietanos/química , Estrutura Molecular , Lycopodium/química , Linhagem Celular Tumoral , Células MCF-7 , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química
7.
Acta Neurochir (Wien) ; 164(5): 1297-1301, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34993621

RESUMO

BACKGROUND: The cure of an eloquent brain arteriovenous malformation (BAVM) and multiple intracranial aneurysms with preservation of neurological function and the minimal procedures is challenging. METHOD: A 53-year-old male was admitted to treat a left frontal language-area BAVM and concomitant five bilateral intracranial aneurysms. After repairing the ruptured right middle cerebral artery (MCA) bifurcation aneurysms and the other two unruptured ones, at the second-stage multimodality-guided awake hybrid operation, we successfully obliterated the left frontal BAVM and two other left MCA aneurysms. CONCLUSION: The multimodality-guided awake hybrid operation may be a promising technique to treat complicated cerebrovascular disease.


Assuntos
Malformações Arteriovenosas , Aneurisma Intracraniano , Malformações Arteriovenosas Intracranianas , Encéfalo , Humanos , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Malformações Arteriovenosas Intracranianas/complicações , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Malformações Arteriovenosas Intracranianas/cirurgia , Idioma , Masculino , Pessoa de Meia-Idade , Vigília
8.
Molecules ; 27(19)2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36234885

RESUMO

Five new furofurans lignans, Brasesquilignan A-E (1-5), were isolated from the aqueous ethanol extract of Selaginella braunii Baker. Their structures were elucidated by extensive analysis of NMR and HRESIMS data. Their absolute configurations were determined by CD spectra, enzymatic hydrolysis, and GCMS analysis. Furthermore, all compounds were evaluated for anti-proliferative activities against various human cancer cellsin vitro. Compounds 2 and 3 exhibited weak inhibitorypotency against five human cancer cells.


Assuntos
Lignanas , Selaginellaceae , Etanol , Humanos , Lignanas/química , Lignanas/farmacologia , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Selaginellaceae/química
9.
J Exp Bot ; 72(13): 4839-4852, 2021 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-33864461

RESUMO

Vacuolar storage of iron (Fe) is important for Fe homeostasis in plants. When sufficient, excess Fe could be stored in vacuoles for remobilization in the case of Fe deficiency. Although the mechanism of Fe remobilization from vacuoles is critical for crop development under low Fe stress, the transporters that mediate vacuolar Fe translocation into the cytosol in rice remains unknown. Here, we showed that under high Fe2+ concentrations, the Δccc1 yeast mutant transformed with the rice natural resistance-associated macrophage protein 2 gene (OsNRAMP2) became more sensitive to Fe toxicity. In rice protoplasts and transgenic plants expressing Pro35S:OsNRAMP2-GFP, OsNRAMP2 was localized to the tonoplast. Vacuolar Fe content in osnramp2 knockdown lines was higher than in the wild type, while the growth of osnramp2 knockdown plants was significantly influenced by Fe deficiency. Furthermore, the germination of osnramp2 knockdown plants was arrested. Conversely, the vacuolar Fe content of Pro35S:OsNRAMP2-GFP lines was significantly lower than in the wild type, and overexpression of OsNRAMP2 increased shoot biomass under Fe deficiency. Taken together, we propose that OsNRAMP2 transports Fe from the vacuole to the cytosol and plays a pivotal role in seed germination.


Assuntos
Oryza , Vacúolos , Regulação da Expressão Gênica de Plantas , Germinação , Homeostase , Ferro/metabolismo , Oryza/genética , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Sementes/metabolismo , Vacúolos/metabolismo
10.
Int J Clin Pract ; 75(11): e14570, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34165855

RESUMO

BACKGROUND: Acute kidney injury (AKI) is one of the most serious perioperative complications. 20% to 40% of high-risk patients who undergo non-cardiac surgery have AKI and those with AKI are eight-times more likely to die within 30 days after surgery. It may be related to intraoperative hypotension, which is mainly caused by vasodilatory and cardiodepressant effects of anaesthesia, and/or hypovolemia. Strict intraoperative blood pressure management strategy (strict BP management) is a potential option to prevent postoperative AKI. This strategy refers to additional administration of vasoactive agents under the premise of a protocolised fluid delivery. The efficacy of strict BP management for preventing postoperative AKI in non-cardiac surgery patients was assessed by a meta-analysis. METHODS: We systematically retrieved randomised controlled trials (RCTs) and compared strict BP management with conventional therapy control on effect of postoperative AKI in non-cardiac surgery patients, which were published on PubMed, EMBASE, Cochrane library and Web of Science databases before October 5, 2020. Ultimately, a meta-analysis of all RCTs eligible for inclusion criteria was performed. RESULTS: Five RCTs, comprising 1485 patients, were included in the meta-analysis. Strict BP management was associated with a reduced incidence of postoperative AKI [relative risk (RR) = 0.73, 95% confidence interval (CI): 0.58-0.92, P = .007]. No significant difference was found between strict BP management group and conventional therapy control in mortality at longest follow-up available (RR = 0.92, 95% CI: 0.68-1.25, P = .60). In the subset analysis, the studies using supranormal BP management target was significantly lower in the incidence of postoperative AKI (RR = 0.65, 95% CI: 0.51-0.82, P = .0003) CONCLUSION: Strict BP management is significantly more effective than conventional therapy for the prevention of postoperative AKI. Supranormal target of intraoperative BP management may be considered a more appealing option for the prevention of AKI.


Assuntos
Injúria Renal Aguda , Hipotensão , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/prevenção & controle , Pressão Sanguínea , Humanos , Hipotensão/etiologia , Hipotensão/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle
11.
Int J Mol Sci ; 22(20)2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34681614

RESUMO

The l-type amino acid transporter 1 (LAT1) is a membranous transporter that transports neutral amino acids for cells and is dysregulated in various types of cancer. Here, we first observed increased LAT1 expression in pemetrexed-resistant non-small cell lung cancer (NSCLC) cells with high cancer stem cell (CSC) activity, and its mRNA expression level was associated with shorter overall survival in the lung adenocarcinoma dataset of the Cancer Genome Atlas database. The inhibition of LAT1 by a small molecule inhibitor, JPH203, or by RNA interference led to a significant reduction in tumorsphere formation and the downregulation of several cancer stemness genes in NSCLC cells through decreased AKT serine/threonine kinase (AKT)/mammalian target of rapamycin (mTOR) activation. The treatment of the cell-permeable leucine derivative promoted AKT/mTOR phosphorylation and reversed the inhibitory effect of JPH203 in the reduction of CSC activity in pemetrexed-resistant lung cancer cells. Furthermore, we observed that LAT1 silencing caused the downregulation of programmed cell death 1 ligand 1 (PD-L1) on lung cancer cells. The PD-L1+/LAT1+ subpopulation of NSCLC cells displayed great CSC activity with increased expression of several cancer stemness genes. These data suggest that LAT1 inhibitors can serve as anti-CSC agents and could be used in combination with immune checkpoint inhibitors in lung cancer therapy.


Assuntos
Antígeno B7-H1/metabolismo , Transportador 1 de Aminoácidos Neutros Grandes/metabolismo , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/genética , Benzoxazóis/farmacologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Transportador 1 de Aminoácidos Neutros Grandes/química , Transportador 1 de Aminoácidos Neutros Grandes/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Células-Tronco Neoplásicas/citologia , Células-Tronco Neoplásicas/metabolismo , Pemetrexede/farmacologia , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Tirosina/análogos & derivados , Tirosina/farmacologia
12.
Acta Anaesthesiol Scand ; 64(10): 1414-1421, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32659854

RESUMO

BACKGROUND: In the monitored anesthesia care (MAC) setting for awake craniotomy (AC), maintaining airway patency in sedated patients remains challenging. This randomized controlled trial aimed to compare the validity of the below-epiglottis transnasal tube insertion (the tip of the tube placed between the epiglottis and vocal cords) and the nasopharyngeal airway (simulated by the above-epiglottis transnasal tube with the tip of the tube placed between the epiglottis and the free edge of the soft palate) with respect to maintaining upper airway patency for moderately sedated patients undergoing AC. METHODS: Sixty patients scheduled for elective AC were randomized to receive below-epiglottis (n = 30) or above-epiglottis (n = 30) transnasal tube insertion before surgery. Moderate sedation was maintained in the pre- and post-awake phases. The primary outcome was the upper airway obstruction (UAO) remission rate (relieved obstructions after tube insertion/the total number of obstructions before tube insertion). RESULTS: The UAO remission rate was higher in the below-epiglottis group [100% (12/12) vs 45% (5/11); P = .005]. The tidal volume values monitored through the tube were greater in the below-epiglottis group during the pre-awake phase (P < .001). End-tidal carbon dioxide (EtCO2 ) monitored through the tube was higher in the below-epiglottis group at bone flap removal (P < .001). During the awake phase, patients' ability to speak was not impeded. No patient had serious complications related to the tube. CONCLUSION: The below-epiglottis tube insertion is a more effective method to maintain upper airway patency than the nasopharyngeal airway for moderately sedated patients undergoing AC.


Assuntos
Manuseio das Vias Aéreas , Vigília , Sedação Consciente , Craniotomia , Epiglote , Humanos , Intubação Intratraqueal
13.
Phytother Res ; 30(2): 331-40, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26676220

RESUMO

Cinnamomum verum is used to make the spice cinnamon and has been used as a traditional Chinese herbal medicine. We evaluated the anticancer effect of 2-methoxycinnamaldehyde (2-MCA), a constituent of the bark of the plant, and its underlying molecular biomarkers associated with carcinogenesis in human lung adenocarcinoma A549 cells. The results show that 2-MCA suppressed proliferation and induced apoptosis as indicated by an upregulation of pro-apoptotic Bax and Bak genes and downregulation of anti-apoptotic Bcl-2 and Bcl-XL genes, mitochondrial membrane potential loss, cytochrome c release, activation of caspase-3 and -9, and morphological characteristics of apoptosis, including plasma membrane blebbing and long comet tail. In addition, 2-MCA also induced lysosomal vacuolation with increased volume of acidic compartment (VAC) and suppressions of nuclear transcription factors nuclear factor-κB (NF-κB) and both topoisomerase I and II activities. Further study reveals that the growth-inhibitory effect of 2-MCA was also evident in a nude mice model. Taken together, the data suggest that the growth-inhibitory effect of 2-MCA against A549 cells is accompanied by downregulations of NF-κB binding activity and proliferative control involving apoptosis and both topoisomerase I and II activities, together with an upregulation of lysosomal vacuolation and VAC. Our data suggest that 2-MCA could be a potential agent for anticancer therapy.


Assuntos
Acroleína/análogos & derivados , Antineoplásicos Fitogênicos/farmacologia , Cinnamomum zeylanicum/química , Inibidores da Topoisomerase/farmacologia , Acroleína/farmacologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma de Pulmão , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular Tumoral/efeitos dos fármacos , Citocromos c/metabolismo , DNA Topoisomerases Tipo I/metabolismo , DNA Topoisomerases Tipo II/metabolismo , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Nus , NF-kappa B/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Front Pharmacol ; 15: 1366035, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38863978

RESUMO

Background: Sacubitril-valsartan has been widely reported for reducing the risk of cardiovascular death and improving left ventricular remodeling in patients with heart failure (HF). However, the effect of sacubitril-valsartan in patients with acute myocardial infarction (AMI) remains controversial. Therefore, we conducted this meta-analysis to investigate whether sacubitril-valsartan could reverse left ventricular remodeling and reduce cardiovascular adverse events in AMI patients after primary percutaneous coronary intervention (PPCI). Materials and methods: Two researchers independently retrieved the relevant literature from PubMed, Embase, The Cochrane Library, China National Knowledge Infrastructure (CNKI), and the Wanfang database. The retrieval time was limited from inception to 1 June 2023. Randomized controlled trials (RCTs) meeting the inclusion criteria were included and analyzed. Results: In total, 21 RCTs involving 2442 AMI patients who underwent PPCI for revascularization were included in this meta-analysis. The meta-analysis showed that compared with the angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB), sacubitril-valsartan treatment in AMI patients after PPCI significantly reduced left ventricular end-diastolic dimension (LVEDD) (weighted mean difference (WMD) -3.11, 95%CI: -4.05∼-2.16, p < 0.001), left ventricular end-diastolic volume (LVEDV) (WMD -7.76, 95%CI: -12.24∼-3.27, p = 0.001), left ventricular end-systolic volume (LVESV) (WMD -6.80, 95%CI: -9.45∼-4.15, p < 0.001) and left ventricular end-systolic dimension (LVESD) (WMD -2.53, 95%CI: -5.30-0.24, p < 0.001). Subgroup analysis according to the dose of sacubitril-valsartan yielded a similar result. Meanwhile, PPCI patients using sacubitril-valsartan therapy showed lower risk of major adverse cardiac events (MACE) (OR = 0.36, 95%CI: 0.28-0.46, p < 0.001), myocardial reinfarction (OR = 0.54, 95%CI: 0.30-0.98, p = 0.041) and HF (OR = 0.35, 95%CI: 0.26-0.47, p < 0.001) without increasing the risk of renal insufficiency, hyperkalemia, or symptomatic hypotension. At the same time, the change of LV ejection fraction (LVEF) (WMD 3.91, 95%CI: 3.41-4.41, p < 0.001), 6 min walk test (6MWT) (WMD 43.56, 95%CI: 29.37-57.76, p < 0.001) and NT-proBNP level (WMD -130.27, 95%CI: -159.14∼-101.40, p < 0.001) were statistically significant. Conclusion: In conclusion, our meta-analysis indicates that compared with ACEI/ARB, sacubitril-valsartan may be superior to reverse left ventricular remodeling, improve cardiac function, and effectively reduce the risk of MACE, myocardial reinfarction, and HF in AMI patients after PPCI during follow-up without increasing the risk of adverse reactions including renal insufficiency, hyperkalemia, and symptomatic hypotension.

15.
Front Neurol ; 15: 1375723, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38742049

RESUMO

Background: Glioblastoma (GBM) is a highly malignant brain tumor, and immune cells play a crucial role in its initiation and progression. The immune system's cellular components, including various types of lymphocytes, macrophages, and dendritic cells, among others, engage in intricate interactions with GBM. However, the precise nature of these interactions remains to be conclusively determined. Method: In this study, a comprehensive two-sample Mendelian Randomization (MR) analysis was conducted to elucidate the causal relationship between immune cell features and the incidence of GBM. Utilizing publicly available genetic data, we investigated the causal associations between 731 immune cell signatures and the risk of GBM. Subsequently, we conducted a reverse Mendelian randomization analysis to rule out reverse causation. Finally, it was concluded that there is a unidirectional causal relationship between three subtypes of immune cells and GBM. Comprehensive sensitivity analyses were employed to validate the results robustness, heterogeneity, and presence of horizontal pleiotropy. To enhance the accuracy of our results, we concurrently subjected them to Bayesian analysis. Results: After conducting MR analyses, we identified 10 immune phenotypes that counteract glioblastoma, with the most protective being FSC-A on Natural Killer T cells (OR = 0.688, CI = 0.515-0.918, P = 0.011). Additionally, we found 11 immune cell subtypes that promote GBM incidence, including CD62L- HLA DR++ monocyte % monocyte (OR = 1.522, CI = 1.004-2.307, P = 0.048), CD4+CD8+ T cell % leukocyte (OR = 1.387, CI = 1.031-1.866, P = 0.031). Following the implementation of reverse MR analysis, where glioblastoma served as the exposure variable and the outcomes included 21 target immune cell subtypes, we discerned that only three cell subtypes (CD45 on CD33+ HLA DR+ CD14dim, CD33+ HLA DR+ Absolute Count, and IgD+ CD24+ B cell Absolute Count) exhibited a unidirectional causal association with glioblastoma. Conclusion: Our study has genetically demonstrated the close relationship between immune cells and GBM, guiding future clinical research.

16.
Polymers (Basel) ; 16(8)2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38674958

RESUMO

Polymer flooding has achieved considerable success in medium-high permeability reservoirs. However, when it comes to low-permeability reservoirs, polymer flooding suffers from poor injectivity due to the large molecular size of the commonly used high-molecular-weight (high-MW) partially hydrolyzed polyacrylamides (HPAM). Herein, an amphiphilic polymer (LMWAP) with a low MW (3.9 × 106 g/mol) was synthesized by introducing an amphiphilic monomer (Allyl-OP-10) and a chain transfer agent into the polymerization reaction. Despite the low MW, LMWAP exhibited better thickening capability in brine than its counterparts HPAM-1800 (MW = 1.8 × 107 g/mol) and HPAM-800 (MW = 8 × 106 g/mol) due to the intermolecular hydrophobic association. LMWAP also exhibited more significant shear-thinning behavior and stronger elasticity than the two counterparts. Furthermore, LMWAP possesses favorable oil-water interfacial activity due to its amphiphilicity. The oil-water interfacial tension (IFT) could be reduced to 0.88 mN/m and oil-in-water (O/W) emulsions could be formed under the effect of LMWAP. In addition, the reversible hydrophobic association endows the molecular chains of LMWAP with dynamic association-disassociation transition ability. Therefore, despite the similar hydrodynamic sizes in brine, LMWAP exhibited favorable injectivity under low-permeability conditions, while the counterpart HPAM-1800 led to fatal plugging. Furthermore, LMWAP could enhance oil recovery up to 21.5%, while the counterpart HPAM-800 could only enhance oil recovery by up to 11.5%, which could be attributed to the favorable interfacial activity of LMWAP.

17.
Viruses ; 16(3)2024 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-38543841

RESUMO

Machine learning (ML) is a key focus in predicting protein mutations and aiding directed evolution. Research on potential virus variants is crucial for vaccine development. In this study, the machine learning software PyPEF was employed to conduct mutation analysis within the receptor-binding domain (RBD) of the Spike glycoprotein of SARS-CoV-2. Over 48,960,000 variants were predicted. Eight prospective variants that could surface in the future underwent modeling and molecular dynamics simulations. The study forecasts that the latest variant, ISOY2P5O1, may potentially emerge around 17 November 2023, with an approximate window of uncertainty of ±22 days. The ISOY8P5O2 variant displayed an increased binding capacity in the dry assay, with a total predicted binding energy of -110.306 kcal/mol. This represents an 8.25% enhancement in total binding energy compared to the original SARS-CoV-2 strain discovered in Wuhan (-101.892 kcal/mol). Reverse research confirmed the structural significance of mutation sites using ML models, particularly in the context of protein folding. The study validated regression methods (SVR, RF, and PLS) with different data structures. This study investigates the effectiveness of the "ML-Guided Design Correctly Predicts Combinatorial Effects Strategy" compared to the "ML-Guided Design Correctly Predicts Natural Evolution Prediction Strategy". To enhance machine learning, we created a timestamping algorithm and two auxiliary programs using advanced techniques to rapidly process extensive data, surpassing batch sequencing capabilities. This study not only advances machine learning in guiding protein evolution but also holds potential for forecasting future viruses and vaccine development.


Assuntos
COVID-19 , Glicoproteína da Espícula de Coronavírus , Humanos , Glicoproteína da Espícula de Coronavírus/genética , Estudos Prospectivos , SARS-CoV-2/genética , Aprendizado de Máquina , Mutação , Glicoproteínas , Ligação Proteica
18.
J Neural Eng ; 21(2)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38407988

RESUMO

Objective: Using functional magnetic resonance imaging (fMRI) and deep learning to discover the spatial pattern of brain function, or functional brain networks (FBNs) has been attracted many reseachers. Most existing works focus on static FBNs or dynamic functional connectivity among fixed spatial network nodes, but ignore the potential dynamic/time-varying characteristics of the spatial networks themselves. And most of works based on the assumption of linearity and independence, that oversimplify the relationship between blood-oxygen level dependence signal changes and the heterogeneity of neuronal activity within voxels.Approach: To overcome these problems, we proposed a novel spatial-wise attention (SA) based method called Spatial and Channel-wise Attention Autoencoder (SCAAE) to discover the dynamic FBNs without the assumptions of linearity or independence. The core idea of SCAAE is to apply the SA to generate FBNs directly, relying solely on the spatial information present in fMRI volumes. Specifically, we trained the SCAAE in a self-supervised manner, using the autoencoder to guide the SA to focus on the activation regions. Experimental results show that the SA can generate multiple meaningful FBNs at each fMRI time point, which spatial similarity are close to the FBNs derived by known classical methods, such as independent component analysis.Main results: To validate the generalization of the method, we evaluate the approach on HCP-rest, HCP-task and ADHD-200 dataset. The results demonstrate that SA mechanism can be used to discover time-varying FBNs, and the identified dynamic FBNs over time clearly show the process of time-varying spatial patterns fading in and out.Significance: Thus we provide a novel method to understand human brain better. Code is available athttps://github.com/WhatAboutMyStar/SCAAE.


Assuntos
Mapeamento Encefálico , Fenômenos Fisiológicos do Sistema Nervoso , Humanos , Mapeamento Encefálico/métodos , Encéfalo/fisiologia , Imageamento por Ressonância Magnética/métodos , Atenção
19.
J Clin Anesth ; 95: 111467, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38593491

RESUMO

STUDY OBJECTIVE: To assess the impact of preoperative infection with the contemporary strain of severe acute respiratory coronavirus 2 (SARS-CoV-2) on postoperative mortality, respiratory morbidity and extrapulmonary complications after elective, noncardiac surgery. DESIGN: An ambidirectional observational cohort study. SETTING: A tertiary and teaching hospital in Shanghai, China. PATIENTS: All adult patients (≥ 18 years of age) who underwent elective, noncardiac surgery under general anesthesia at Huashan Hospital of Fudan University from January until March 2023 were screened for eligibility. A total of 2907 patients were included. EXPOSURE: Preoperative coronavirus disease 2019 (COVID-19) positivity. MEASUREMENTS: The primary outcome was 30-day postoperative mortality. The secondary outcomes included postoperative pulmonary complications (PPCs), myocardial injury after noncardiac surgery (MINS), acute kidney injury (AKI), postoperative delirium (POD) and postoperative sleep quality. Multivariable logistic regression was used to assess the risk of postoperative mortality and morbidity imposed by preoperative COVID-19. MAIN RESULTS: The risk of 30-day postoperative mortality was not associated with preoperative COVID-19 [adjusted odds ratio (aOR), 95% confidence interval (CI): 0.40, 0.13-1.28, P = 0.123] or operation timing relative to diagnosis. Preoperative COVID-19 did not increase the risk of PPCs (aOR, 95% CI: 0.99, 0.71-1.38, P = 0.944), MINS (aOR, 95% CI: 0.54, 0.22-1.30; P = 0.168), or AKI (aOR, 95% CI: 0.34, 0.10-1.09; P = 0.070) or affect postoperative sleep quality. Patients who underwent surgery within 7 weeks after COVID-19 had increased odds of developing delirium (aOR, 95% CI: 2.26, 1.05-4.86, P = 0.036). CONCLUSIONS: Preoperative COVID-19 or timing of surgery relative to diagnosis did not confer any added risk of 30-day postoperative mortality, PPCs, MINS or AKI. However, recent COVID-19 increased the risk of POD. Perioperative brain health should be considered during preoperative risk assessment for COVID-19 survivors.


Assuntos
COVID-19 , Procedimentos Cirúrgicos Eletivos , Complicações Pós-Operatórias , Humanos , COVID-19/mortalidade , COVID-19/epidemiologia , COVID-19/complicações , Feminino , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Idoso , China/epidemiologia , Estudos de Coortes , Adulto , Fatores de Risco , Período Pré-Operatório
20.
IEEE Trans Pattern Anal Mach Intell ; 45(4): 5282-5295, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35925851

RESUMO

Existing unsupervised person re-identification methods only rely on visual clues to match pedestrians under different cameras. Since visual data is essentially susceptible to occlusion, blur, clothing changes, etc., a promising solution is to introduce heterogeneous data to make up for the defect of visual data. Some works based on full-scene labeling introduce wireless positioning to assist cross-domain person re-identification, but their GPS labeling of entire monitoring scenes is laborious. To this end, we propose to explore unsupervised person re-identification with both visual data and wireless positioning trajectories under weak scene labeling, in which we only need to know the locations of the cameras. Specifically, we propose a novel unsupervised multimodal training framework (UMTF), which models the complementarity of visual data and wireless information. Our UMTF contains a multimodal data association strategy (MMDA) and a multimodal graph neural network (MMGN). MMDA explores potential data associations in unlabeled multimodal data, while MMGN propagates multimodal messages in the video graph based on the adjacency matrix learned from histogram statistics of wireless data. Thanks to the robustness of the wireless data to visual noise and the collaboration of various modules, UMTF is capable of learning a model free of the human label on data. Extensive experimental results conducted on two challenging datasets, i.e., WP-ReID and Campus4K demonstrate the effectiveness of the proposed method.

SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa