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1.
Brief Bioinform ; 25(4)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38990514

RESUMO

Protein-peptide interactions (PPepIs) are vital to understanding cellular functions, which can facilitate the design of novel drugs. As an essential component in forming a PPepI, protein-peptide binding sites are the basis for understanding the mechanisms involved in PPepIs. Therefore, accurately identifying protein-peptide binding sites becomes a critical task. The traditional experimental methods for researching these binding sites are labor-intensive and time-consuming, and some computational tools have been invented to supplement it. However, these computational tools have limitations in generality or accuracy due to the need for ligand information, complex feature construction, or their reliance on modeling based on amino acid residues. To deal with the drawbacks of these computational algorithms, we describe a geometric attention-based network for peptide binding site identification (GAPS) in this work. The proposed model utilizes geometric feature engineering to construct atom representations and incorporates multiple attention mechanisms to update relevant biological features. In addition, the transfer learning strategy is implemented for leveraging the protein-protein binding sites information to enhance the protein-peptide binding sites recognition capability, taking into account the common structure and biological bias between proteins and peptides. Consequently, GAPS demonstrates the state-of-the-art performance and excellent robustness in this task. Moreover, our model exhibits exceptional performance across several extended experiments including predicting the apo protein-peptide, protein-cyclic peptide and the AlphaFold-predicted protein-peptide binding sites. These results confirm that the GAPS model is a powerful, versatile, stable method suitable for diverse binding site predictions.


Assuntos
Peptídeos , Sítios de Ligação , Peptídeos/química , Peptídeos/metabolismo , Ligação Proteica , Biologia Computacional/métodos , Algoritmos , Proteínas/química , Proteínas/metabolismo , Aprendizado de Máquina
2.
Health Data Sci ; 4: 0121, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39011274

RESUMO

Background: Sex difference has long been recognized at cancer incidence, outcomes, and responses to therapy. Analyzing the somatic mutation profiles of large-scale cancer samples between the sexes have revealed several potential drivers of cancer with sex difference. However, it is still a demand for in-depth scrutinizing the sex-biased characteristics of genome instability to link the clinical differences for individual cancer type. Methods: Here, we utilized a published framework devised to specifically compare the copy number profiles between 2 groups to identify the sex-biased copy number alterations (CNAs) across 16 cancer types from the The Cancer Genome Atlas Program database, and dissected the impact of those CNAs. Results: Totally, 81 male-biased CNA regions and 23 female-biased CNA regions in 16 cancer types were found. Functional annotation analysis showed that several critical biological functions associated with sex-biased CNAs are shared in multiple cancer types, including immune-related pathways and regulation of cellular signaling. Most sex-biased CNAs have a substantial effect on transcriptional consequence, where the average of over 68% of genes have a linear relationship with CNAs across cancer types, and 14% of those genes are affected by the combination of the sex and copy number. Furthermore, 29 sex-biased CNA regions show latent capacity to be sex-specific prognostic biomarker such as CNA on 11q13.4 for head and neck cancer and lung cancer. Conclusions: This analysis offers new insights into the role of sex in cancer etiology and prognosis through a detailed characterization of sex differences in genome instability of diverse cancers.

3.
Clin Cardiol ; 47(7): e24308, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39011838

RESUMO

BACKGROUND: Right ventricular-pulmonary artery coupling (RVPAC) refers to the relationship between right ventricular systolic force and afterload. The ratio of echocardiograph-derived tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP) has been proposed as a noninvasive measurement of RVPAC and reported as an independent prognostic parameter of heart failure. However, it has not been adequately in detail evaluated in heart failure with preserved ejection fraction (HFpEF). We hypothesized that RVPAC may be used and proposed as an expression of key risk factors in patients with HFpEF. METHODS: We retrospectively analyzed TAPSE/PASP of 648 HFpEF patients hospitalized in Chongqing Hospital of Traditional Chinese Medicine from January 1, 2016 to January 1, 2017. All eligible patients were followed up for 5 years. The correlation between TAPSE/SPAP index and clinical indicators and outcomes was evaluated. RESULTS: The final analysis included 414 patients. Nonsurvivors had significantly lower TAPSE, TAPSE/PASP and higher PASP compared with survivors (p < 0.0001). ROC curve analysis showed that the optimal cutoff of TAPSE, PASP, and RVPAC to predict all-cause death were 16.5 mm, 37.5 mmHg, and 0.45 mm/mmHg, respectively. In multivariate Cox regression analyses adjusted for gender showed a significant, independent association of the RVPAC with the composite endpoint of all-cause death or HF-related recurrent hospitalization (HR: 0.006; 95% CI 0.001-0.057, p < 0.001). CONCLUSIONS: RVPAC, defined by the ratio of TAPSE to PASP, is the expression of a key risk factor in HFpEF patients, which is independently associated with the composite endpoint of all-cause death or HF-related recurrent hospitalization.


Assuntos
Insuficiência Cardíaca , Artéria Pulmonar , Volume Sistólico , Função Ventricular Direita , Humanos , Masculino , Feminino , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/diagnóstico , Volume Sistólico/fisiologia , Artéria Pulmonar/fisiopatologia , Artéria Pulmonar/diagnóstico por imagem , Estudos Retrospectivos , Idoso , Função Ventricular Direita/fisiologia , Prognóstico , Fatores de Risco , Pessoa de Meia-Idade , Ecocardiografia , Ventrículos do Coração/fisiopatologia , Ventrículos do Coração/diagnóstico por imagem , China/epidemiologia , Seguimentos
4.
Food Microbiol ; 122: 104569, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38839228

RESUMO

Huangjiu is a spontaneously fermented alcoholic beverage, that undergoes intricate microbial compositional changes. This study aimed to unravel the flavor and quality formation mechanisms based on the microbial metabolism of Huangjiu. Here, metagenome techniques, chemometrics analysis, and headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) metabolomics combined with microbial metabolic network were employed to investigate the distinctions and relationship between the microbial profiles and the quality characteristics, flavor metabolites, functional metabolic patterns of Huangjiu across three regions. Significant variations (P < 0.05) were observed in metabolic rate of physicochemical parameters and biogenic amine concentration among three regions. 8 aroma compounds (phenethyl acetate, phenylethyl alcohol, isobutyl alcohol, ethyl octanoate, ethyl acetate, ethyl hexanoate, isoamyl alcohol, and diethyl succinate) out of 448 volatile compounds were identified as the regional chemical markers. 25 dominant microbial genera were observed through metagenomic analysis, and 13 species were confirmed as microbial markers in three regions. A metabolic network analysis revealed that Saccharomycetales (Saccharomyces), Lactobacillales (Lactobacillus, Weissella, and Leuconostoc), and Eurotiales (Aspergillus) were the predominant populations responsible for substrate, flavor (mainly esters and phenylethyl alcohol) metabolism, Lactobacillales and Enterobacterales were closely linked with biogenic amine. These findings provide scientific evidence for regional microbial contributions to geographical characteristics of Huangjiu, and perspectives for optimizing microbial function to promote Huangjiu quality.


Assuntos
Bactérias , Fermentação , Cromatografia Gasosa-Espectrometria de Massas , Redes e Vias Metabólicas , Metagenômica , Oryza , Compostos Orgânicos Voláteis , Vinho , Vinho/análise , Vinho/microbiologia , Compostos Orgânicos Voláteis/metabolismo , Compostos Orgânicos Voláteis/análise , Bactérias/classificação , Bactérias/metabolismo , Bactérias/genética , Bactérias/isolamento & purificação , Oryza/microbiologia , Oryza/química , Oryza/metabolismo , China , Paladar , Aromatizantes/metabolismo , Aromatizantes/química , Metabolômica/métodos , Odorantes/análise , Microbiota , Microextração em Fase Sólida , Aminas Biogênicas/análise , Aminas Biogênicas/metabolismo , População do Leste Asiático
5.
J Agric Food Chem ; 72(26): 14899-14911, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38913831

RESUMO

The synthetic community of lactic acid bacteria (LAB) is commonly utilized in the food industry for manipulating product properties. However, the intermediate interactions and ecological stability resulting from metabolic differences among various LAB types remain poorly understood. We aimed to analyze the metabolic behavior of single and combined lactic acid bacteria in China rice wine based on microbial succession. Three-stage succession patterns with obligate heterofermentative LAB dominating prefermentation and homofermentative LAB prevailing in main fermentation were observed. Facultative heterofermentative LAB exhibited significant growth. Pairwise coculture interactions revealed 63.5% positive, 34.4% negative, and 2.1% neutral interactions, forming nontransitive and transitive competition modes. Nontransitive competitive combinations demonstrated stability over ∼200 generations through amino acid (mainly aspartic acid, glutamine, and serine) cross-feeding and lactic acid detoxification, which also showed potential for controlling biogenic amines and developing LAB starter cultures. Our findings offer insights into the mechanistic underpinnings of LAB interaction networks.


Assuntos
Fermentação , Ácido Láctico , Lactobacillales , Oryza , Vinho , China , Ácido Láctico/metabolismo , Lactobacillales/metabolismo , Interações Microbianas , Oryza/microbiologia , Oryza/metabolismo , Oryza/química , Vinho/análise , Vinho/microbiologia
6.
Brief Bioinform ; 25(3)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38706323

RESUMO

In recent years, cyclic peptides have emerged as a promising therapeutic modality due to their diverse biological activities. Understanding the structures of these cyclic peptides and their complexes is crucial for unlocking invaluable insights about protein target-cyclic peptide interaction, which can facilitate the development of novel-related drugs. However, conducting experimental observations is time-consuming and expensive. Computer-aided drug design methods are not practical enough in real-world applications. To tackles this challenge, we introduce HighFold, an AlphaFold-derived model in this study. By integrating specific details about the head-to-tail circle and disulfide bridge structures, the HighFold model can accurately predict the structures of cyclic peptides and their complexes. Our model demonstrates superior predictive performance compared to other existing approaches, representing a significant advancement in structure-activity research. The HighFold model is openly accessible at https://github.com/hongliangduan/HighFold.


Assuntos
Dissulfetos , Peptídeos Cíclicos , Peptídeos Cíclicos/química , Dissulfetos/química , Software , Modelos Moleculares , Conformação Proteica , Algoritmos , Biologia Computacional/métodos
7.
Nat Commun ; 15(1): 3783, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38710722

RESUMO

General, catalytic and enantioselective construction of chiral α,α-dialkyl indoles represents an important yet challenging objective to be developed. Herein we describe a cobalt catalyzed enantioselective anti-Markovnikov alkene hydroalkylation via the remote stereocontrol for the synthesis of α,α-dialkyl indoles and other N-heterocycles. This asymmetric C(sp3)-C(sp3) coupling features high flexibility in introducing a diverse set of alkyl groups at the α-position of chiral N-heterocycles. The utility of this methodology has been demonstrated by late-stage functionalization of drug molecules, asymmetric synthesis of bioactive molecules, natural products and functional materials, and identification of a class of molecules exhibiting anti-apoptosis activities in UVB-irradiated HaCaT cells. Ligands play a vital role in controlling the reaction regioselectivity. Changing the ligand from bi-dentate L6 to tridentate L12 enables CoH-catalyzed Markovnikov hydroalkylation. Mechanistic studies disclose that the anti-Markovnikov hydroalkylation involves a migratory insertion process while the Markovnikov hydroalkylation involves a MHAT process.

8.
Int J Biol Macromol ; 264(Pt 2): 130693, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38458291

RESUMO

The accessory proteins of coronaviruses play a crucial role in facilitating virus-host interactions and modulating host immune responses. Previous study demonstrated that the NS7a protein of porcine deltacoronavirus (PDCoV) partially hindered the host immune response by impeding the induction of IFN-α/ß. However, the potential additional functions of NS7a protein in evading innate immunity have yet to be elucidated. This study aimed to investigate the mechanism of PDCoV NS7a protein regulating the JAK/STAT signaling pathway. We presented evidence that NS7a effectively inhibited ISRE promoter activity and ISGs transcription. NS7a hindered STAT1 phosphorylation, interacted with STAT2 and IRF9, and further impeded the formation and nuclear accumulation of ISGF3. Furthermore, comparative analysis of NS7a across different PDCoV strains revealed that the mutation of Leu4 to Pro4 led to an increase in the molecular weights of NS7a and disrupted its inhibition on the JAK/STAT signaling pathway. This finding implied that NS7a with key amino acids may be an indicator of virulence for PDCoV strains. Taken together, this study revealed a novel role of NS7a in antagonizing the IFN-I signaling pathway.


Assuntos
Deltacoronavirus , Janus Quinases , Transdução de Sinais , Animais , Suínos , Janus Quinases/genética , Fatores de Transcrição STAT/genética , Fator Gênico 3 Estimulado por Interferon
9.
Microb Cell Fact ; 23(1): 94, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38539197

RESUMO

BACKGROUND: Surfactin, a green lipopeptide bio-surfactant, exhibits excellent surface, hemolytic, antibacterial, and emulsifying activities. However, a lack of clear understanding of the synthesis regulation mechanism of surfactin homologue components has hindered the customized production of surfactin products with different biological activities. RESULTS: In this study, exogenous valine and 2-methylbutyric acid supplementation significantly facilitated the production of C14-C15 surfactin proportions (up to 75% or more), with a positive correlation between the homologue proportion and fortified concentration. Subsequently, the branched-chain amino acid degradation pathway and the glutamate synthesis pathway are identified as critical pathways in regulating C14-C15 surfactin synthesis by transcriptome analysis. Overexpression of genes bkdAB and glnA resulted in a 1.4-fold and 1.3-fold increase in C14 surfactin, respectively. Finally, the C14-rich surfactin was observed to significantly enhance emulsification activity, achieving an EI24 exceeding 60% against hexadecane, while simultaneously reducing hemolytic activity. Conversely, the C15-rich surfactin demonstrated an increase in both hemolytic and antibacterial activities. CONCLUSION: This study presents the first evidence of a potential connection between surfactin homologue synthesis and the conversion of glutamate and glutamine, providing a theoretical basis for targeting the synthesis regulation and structure-activity relationships of surfactin and other lipopeptide compounds.


Assuntos
Ácidos Graxos , Tensoativos , Ácidos Graxos/metabolismo , Tensoativos/metabolismo , Ácido Glutâmico/metabolismo , Lipopeptídeos , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Peptídeos Cíclicos/química , Bacillus subtilis/genética
10.
Nat Commun ; 15(1): 1306, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378680

RESUMO

Traffic light optimization is known to be a cost-effective method for reducing congestion and energy consumption in urban areas without changing physical road infrastructure. However, due to the high installation and maintenance costs of vehicle detectors, most intersections are controlled by fixed-time traffic signals that are not regularly optimized. To alleviate traffic congestion at intersections, we present a large-scale traffic signal re-timing system that uses a small percentage of vehicle trajectories as the only input without reliance on any detectors. We develop the probabilistic time-space diagram, which establishes the connection between a stochastic point-queue model and vehicle trajectories under the proposed Newellian coordinates. This model enables us to reconstruct the recurrent spatial-temporal traffic state by aggregating sufficient historical data. Optimization algorithms are then developed to update traffic signal parameters for intersections with optimality gaps. A real-world citywide test of the system was conducted in Birmingham, Michigan, and demonstrated that it decreased the delay and number of stops at signalized intersections by up to 20% and 30%, respectively. This system provides a scalable, sustainable, and efficient solution to traffic light optimization and can potentially be applied to every fixed-time signalized intersection in the world.

11.
Nano Lett ; 24(6): 1851-1858, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38315876

RESUMO

Interlayer excitons, with prolonged lifetimes and tunability, hold potential for advanced optoelectronics. Previous research on the interlayer excitons has been dominated by two-dimensional heterostructures. Here, we construct WSe2/GaN composite heterostructures, in which the doping concentration of GaN and the twist angle of bilayer WSe2 are employed as two ingredients for the manipulation of exciton behaviors and polarizations. The exciton energies in monolayer WSe2/GaN can be regulated continuously by the doping levels of the GaN substrate, and a remarkable increase in the valley polarizations is achieved. Especially in a heterostructure with 4°-twisted bilayer WSe2, a maximum polarization of 38.9% with a long lifetime is achieved for the interlayer exciton. Theoretical calculations reveal that the large polarization and long lifetime are attributed to the high exciton binding energy and large spin flipping energy during depolarization in bilayer WSe2/GaN. This work introduces a distinctive member of the interlayer exciton with a high degree of polarization and a long lifetime.

12.
J Mater Chem B ; 12(5): 1307-1316, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38226460

RESUMO

Bacterial infection is a key factor affecting wound healing. Conventional treatments might lead to the widespread emergence of drug-resistant bacteria due to the long-term and excessive use of antibiotics. It is necessary to develop an antibiotic-free method for effective treatment of bacterial wound infections. In this work, we constructed an antibiotic-free polysaccharide-based hydrogel dressing (ATB) with near-infrared light-actuated on-demand botanicals release and hyperthermia for the synergistic treatment of wound infections. The ATB hydrogel dressing was made up of agarose as a support matrix, berberine hydrochloride as the active botanicals and TA-Fe(III) nanoparticles as NIR laser-activated photothermal reagents. The ATB hydrogel dressing showed spatiotemporal botanicals release and excellent photothermal properties with NIR irradiation. With the results of in vitro and in vivo antibacterial experiments, the antibiotic-free ATB hydrogel could synergistically eliminate bacteria and accelerate wound healing. Overall, the near-infrared light-responsive ATB hydrogel could provide a promising antibiotic-free strategy for the treatment of bacterial wound infections.


Assuntos
Hipertermia Induzida , Infecção dos Ferimentos , Humanos , Hidrogéis/farmacologia , Compostos Férricos , Hipertermia , Polissacarídeos/farmacologia , Raios Infravermelhos , Bandagens , Antibacterianos/farmacologia , Infecção dos Ferimentos/tratamento farmacológico
13.
Nano Lett ; 24(4): 1415-1422, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38232178

RESUMO

Charge and spin are two intrinsic attributes of carriers governing almost all of the physical processes and operation principles in materials. Here, we demonstrate the manipulation of electronic and spin states in designed Co-quantum dot/WS2 (Co-QDs/WS2) heterostructures by employing a metal-dielectric composite substrate and via scanning tunneling microscope. By repeatedly scanning under a unipolar bias, switching the bias polarity, or applying a pulse through nonmagnetic or magnetic tips, the Co-QDs morphologies exhibit a regular and reproducible transformation between bright and dark dots. First-principles calculations reveal that these tunable characters are attributed to the variation of density of states and the transition of magnetic anisotropy energy induced by carrier accumulation. It also suggests that the metal-dielectric composite substrate is successful in creating the interfacial potential for carrier accumulation and realizes the electrically controllable modulations. These results will promote the exploration of electron-matter interactions in quantum systems and provide an innovative way to facilitate the development of spintronics.

14.
J Agric Food Chem ; 72(3): 1640-1650, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38213280

RESUMO

The O-glycosylation of polyphenols for the synthesis of glycosides has garnered substantial attention in food research applications. However, the practical utility of UDP-glycosyltransferases (UGTs) is significantly hindered by their low catalytic efficiency and suboptimal regioselectivity. The concurrent optimization of the regioselectivity and activity during the glycosylation of polyphenols presents a formidable challenge. Here, we addressed the long-standing activity-regioselectivity tradeoff in glycosyltransferase UGTBL1 through systematic enzyme engineering. The optimal combination of mutants, N61S/I62M/D63W/A208R/P218W/R282W (SMWRW1W2), yielded a 6.1-fold improvement in relative activity and a 17.3-fold increase in the ratio of gastrodin to para-hydroxybenzyl alcohol-4'-O-ß-glucoside (with 89.5% regioselectivity for gastrodin) compared to those of the wild-type enzyme and ultimately allowed gram-scale production of gastrodin (1,066.2 mg/L) using whole-cell biocatalysis. In addition, variant SMWRW1W2 exhibited a preference for producing phenolic glycosides from several substrates. This study lays the foundation for the engineering of additional UGTs and the practical applications of UGTs in regioselective retrofitting.


Assuntos
Álcoois Benzílicos , Glicosídeos , Glicosiltransferases , Difosfato de Uridina , Glucosídeos , Fenóis , Polifenóis
15.
Analyst ; 149(4): 1169-1178, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38205835

RESUMO

With the rapid development of nanotechnology and biomedicine, numerous gadolinium (Gd)-based nanoparticle MRI contrast agents have been widely investigated. Due to the unique physicochemical properties of nanoparticles and the complexity of biological systems, the biosafety of Gd-based nanoparticle MRI contrast agents has been paid more and more attention. Herein, for the first time, we employed an ultra-high performance liquid chromatography-electrospray ionization quadrupole time-of-flight/mass spectrometry (UPLC-ESI-QTOF/MS)-based metabolomics approach to investigate the potential toxicity of Gd-based nanoparticle MRI contrast agents. In this work, NaGdF4 and PEG-NaGdF4 nanoparticles were successfully constructed and selected as the representative Gd-based nanoparticle MRI contrast agents for the metabolomics analysis. Based on the results of metabolomics, more metabolic biomarkers and pathways were identified in the NaGdF4 group than those in the PEG-NaGdF4 group. Careful analysis of these metabolic biomarkers and pathways suggested that NaGdF4 nanoparticles induced disturbance of pyrimidine and purine metabolism, inflammatory response, and kidney injury to a certain extent compared with PEG-NaGdF4 nanoparticles. These results indicated that Gd-based nanoparticle contrast agents modified with PEG had better biosafety. Additionally, it was demonstrated that the discovery of characteristic metabolomics biomarkers induced by nanoparticles would provide a new approach for biosafety assessment and stimulate the development of nanomedicine.


Assuntos
Meios de Contraste , Nanopartículas , Meios de Contraste/toxicidade , Meios de Contraste/química , Contenção de Riscos Biológicos , Gadolínio/química , Nanopartículas/toxicidade , Nanopartículas/química , Imageamento por Ressonância Magnética/métodos , Biomarcadores
16.
Nucleic Acids Res ; 52(D1): D1365-D1369, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37819033

RESUMO

Systematic integration of lncRNA-disease associations is of great importance for further understanding their underlying molecular mechanisms and exploring lncRNA-based biomarkers and therapeutics. The database of long non-coding RNA-associated diseases (LncRNADisease) is designed for the above purpose. Here, an updated version (LncRNADisease v3.0) has curated comprehensive lncRNA (including circRNA) and disease associations from the burgeoning literatures. LncRNADisease v3.0 exhibits an over 2-fold increase in experimentally supported associations, with a total of 25440 entries, compared to the last version. Besides, each lncRNA-disease pair is assigned a confidence score based on experimental evidence. Moreover, all associations between lncRNAs/circRNAs and diseases are classified into general associations and causal associations, representing whether lncRNAs or circRNAs can directly lead to the development or progression of corresponding diseases, with 15721 and 9719 entries, respectively. In a case study, we used the data of LncRNADisease v3.0 to calculate the phenotypic similarity between human and mouse lncRNAs. This database will continue to serve as a valuable resource for potential clinical applications related to lncRNAs and circRNAs. LncRNADisease v3.0 is freely available at http://www.rnanut.net/lncrnadisease.


Assuntos
Bases de Dados de Ácidos Nucleicos , Doença , RNA Longo não Codificante , Animais , Humanos , Camundongos , Bases de Dados Genéticas , RNA Circular , RNA Longo não Codificante/genética , Doença/genética
17.
Cereb Cortex ; 33(24): 11570-11581, 2023 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-37851710

RESUMO

Facial palsy therapies based on cortical plasticity are in development, but facial synkinesis progress is limited. Studying neural plasticity characteristics, especially network organization and its constitutive elements (nodes/edges), is the key to overcome the bottleneck. We studied 55 participants (33 facial synkinesis patients, 22 healthy controls) with clinical assessments, functional magnetic resonance imaging (fMRI), and diffusion tensor imaging (DTI). We analyzed rich-club organization and metrics of structural brain networks (rich-club coefficients, strength, degree, density, and efficiency). Functional brain network metrics, including functional connectivity and its coupling with the structural network, were also computed. Patients displayed reduced strength and density of rich-club nodes and edges, as well as decreased global efficiency. All nodes exhibited decreased nodal efficiency in patients. Patients had significantly increased functional connectivity and decreased structural-functional coupling strength in rich-club nodes, rich-club edges, and feeder edges. Our study indicates that facial synkinesis patients have weakened structural connections but enhanced functional transmission from rich-club nodes. The loss of connections and efficiency in structural network may trigger compensatory increases in functional connectivity of rich-club nodes. Two potential biomarkers, rich-club edge density and structural-functional coupling strength, may serve as indicators of disease outcome. These findings provide valuable insights into synkinesis mechanisms and offer potential targets for cortical intervention.


Assuntos
Imagem de Tensor de Difusão , Sincinesia , Humanos , Sincinesia/diagnóstico por imagem , Sincinesia/patologia , Encéfalo , Imageamento por Ressonância Magnética , Vias Neurais/diagnóstico por imagem
18.
Medicine (Baltimore) ; 102(36): e35099, 2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37682162

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of short-term high-dose of dual antiplatelet therapy after 0.6 mg/kg rt-PA intravenous thrombolysis for acute ischemic stroke (AIS). METHODS: All 208 patients with AIS were randomized into group 1 (103 cases, after 0.6 mg/kg rt-PA, 300 mg of oral aspirin(ASP) q.d. and 225 mg of oral clopidogrel (CLO) q.d. for for 5 days, then 100 mg of oral ASP q.d. for the next 85 days and 75 mg of oral CLO q.d. for the next 16 days) and group 2 (105 cases, after 0.9 mg/kg rt-PA, 100 mg of oral ASP q.d. for 90 days and 75 mg of oral CLO q.d. for 21 days).The efficacy index was the mRS score, NIHSS score and recurrence risk of stroke, while the safety index was the incidence of bleeding events and mortality. All parameters were evaluated at 30 and 90 days after thrombolysis. Patients whose characteristics may provide the best treatment benefit were further analyzed using the logistic regression model in group 1. RESULTS: The proportion of mRS scores between 0 and 1 in group 1 was higher than that in group 2 at both 30 days (44.7% vs 32.4%, P < .05) and 90 days (50.5% vs 35.2%, P < .05). Compared to group 2, the proportion of NIHSS scores less than 4 was significantly higher in group 1 at both 30 days (37.9% vs 25.7%, P < .05) and 90 days (46.6% vs 30.5%, P < .05). At 90 days, Group 1 had a lower stroke recurrence risk than Group 2 (3.9% vs 10.5%, P < .05). The incidence of SICH was significantly different between the 2 groups at both 30 days (2.9% vs 9.5%, P < .05) and 90 days (2.9% vs 10.5%, P < .05). However, other bleeding events and mortality rates were not significantly different between the 2 groups. The lower the baseline NIHSS score and the shorter the OTT, the more favorable the outcomes obtained at 90 days. CONCLUSIONS: Compared to standard doses, short term high-dose dual antiplatelet therapy after 0.6 mg/kg rt-PA intravenous thrombolysis may be a good choice for AIS patients.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/tratamento farmacológico , Inibidores da Agregação Plaquetária/efeitos adversos , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/efeitos adversos , Clopidogrel/efeitos adversos , Terapia Trombolítica/efeitos adversos
19.
Mol Metab ; 77: 101796, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37696356

RESUMO

Hepatocellular carcinoma (HCC) is the second deadly cancer in the world and still lacks curative treatment. Aerobic glycolysis, or Warburg effect, is a major resistance mechanism induced by first-line treatment of HCC, sorafenib, and is regulated by the master regulator of metabolism, AMPK. Activation of AMPK is required for resistance; however, activation dynamics of AMPK and its regulation is rarely studied. Engineering cells to express an AMPK activity biosensor, we monitor AMPK activation in single HCC cells in a high throughput manner during sorafenib-induced drug resistance. Sorafenib induces transient activation of AMPK, duration of which is dependent on glucose. Inhibiting glycolysis shortens AMPK activation; whereas increasing glycolysis increases its activation duration. Our data highlight that activation duration of AMPK is important for cancer evasion of therapeutic treatment and glycolysis is a key regulator of activation duration of AMPK.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Carcinoma Hepatocelular/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Neoplasias Hepáticas/metabolismo , Resistencia a Medicamentos Antineoplásicos , Linhagem Celular Tumoral , Glicólise
20.
Ultrasonics ; 135: 107134, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37639832

RESUMO

Porosity is a crucial quality evaluation criterion in metal additive manufacturing. To investigate the propagation characteristics of ultrasonic longitudinal waves with different incident frequencies in AlSi10Mg prepared by selective laser melting, specimens with varying porosity were created using printing process adjustments. Ultrasonic longitudinal wave tests and COMSOL simulations based on 2.5 MHz, 3.5 MHz, 5 MHz, and 7.5 MHz incident frequencies were carried out to establish a linear relationship between average wave velocity, average attenuation coefficient, and porosity at different frequencies. Results indicate that sound velocity and porosity are inversely proportional for each frequency longitudinal wave, while the attenuation coefficient is proportional to the porosity. Linear fitting expressions suggest that the best fit for both sound velocity and attenuation coefficient occurs at 5 MHz. Simulation results demonstrate that using 5 MHz as the incident frequency can better balance detection sensitivity and linearity. These findings provide more data support for establishing the intrinsic connection between acoustic parameters and porosity of AlSi10Mg prepared by selective laser melting in the selected area and serve as a reference for selecting ultrasonic incident frequencies in practical inspection.

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