Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 672
Filtrar
1.
Proc Natl Acad Sci U S A ; 121(4): e2311732121, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38232289

RESUMO

Rechargeable lithium (Li) metal batteries face challenges in achieving stable cycling due to the instability of the solid electrolyte interphase (SEI). The Li-ion solvation structure and its desolvation process are crucial for the formation of a stable SEI on Li metal anodes and improving Li plating/stripping kinetics. This research introduces an interfacial desolvation coating technique to actively modulate the Li-ion solvation structure at the Li metal interface and regulate the participation of the electrolyte solvent in SEI formation. Through experimental investigations conducted using a carbonate electrolyte with limited compatibility to Li metal, the optimized desolvation coating layer, composed of 12-crown-4 ether-modified silica materials, selectively displaces strongly coordinating solvents while simultaneously enriching weakly coordinating fluorinated solvents at the Li metal/electrolyte interface. This selective desolvation and enrichment effect reduce solvent participation to SEI and thus facilitate the formation of a LiF-dominant SEI with greatly reduced organic species on the Li metal surface, as conclusively verified through various characterization techniques including XPS, quantitative NMR, operando NMR, cryo-TEM, EELS, and EDS. The interfacial desolvation coating technique enables excellent rate cycling stability (i.e., 1C) of the Li metal anode and prolonged cycling life of the Li||LiCoO2 pouch cell in the conventional carbonate electrolyte (E/C 2.6 g/Ah), with 80% capacity retention after 333 cycles.

2.
J Biol Chem ; 300(4): 107150, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38462164

RESUMO

Histone 2A monoubiquitination (uH2A) underscores a key epigenetic regulation of gene expression. In this report, we show that the deubiquitinase for uH2A, ubiquitin-specific peptidase 16 (USP16), is modified by O-linked N-acetylglucosamine (O-GlcNAc). O-GlcNAcylation involves the installation of the O-GlcNAc moiety to Ser/Thr residues. It crosstalks with Ser/Thr phosphorylation, affects protein-protein interaction, alters enzyme activity or protein folding, and changes protein subcellular localization. In our study, we first confirmed that USP16 is glycosylated on Thr203 and Ser214, as reported in a previous chemoenzymatic screen. We then discovered that mutation of the O-GlcNAcylation site Thr203, which is adjacent to deubiquitination-required Cys204, reduces the deubiquitination activity toward H2AK119ub in vitro and in cells, while mutation on Ser214 had the opposite effects. Using USP16 Ser552 phosphorylation-specific antibodies, we demonstrated that O-GlcNAcylation antagonizes cyclin-dependent kinase 1-mediated phosphorylation and promotes USP16 nuclear export. O-GlcNAcylation of USP16 is also required for deubiquitination of Polo-like kinase 1, a mitotic master kinase, and the subsequent chromosome segregation and cytokinesis. In summary, our study revealed that O-GlcNAcylation of USP16 at Thr203 and Ser214 coordinates deubiquitination of uH2A and Polo-like kinase 1, thus ensuring proper cell cycle progression.


Assuntos
Acetilglucosamina , Ubiquitina Tiolesterase , Ubiquitinação , Humanos , Acetilglucosamina/metabolismo , Transporte Ativo do Núcleo Celular , Ciclo Celular , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Glicosilação , Células HEK293 , Células HeLa , Histonas/metabolismo , Fosforilação , Quinase 1 Polo-Like , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Ubiquitina Tiolesterase/metabolismo , Ubiquitina Tiolesterase/genética
3.
Acc Chem Res ; 57(13): 1851-1869, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38902854

RESUMO

ConspectusThe directed synthesis and functionalization of porous crystalline materials pose significant challenges for chemists. The synergistic integration of different functionalities within an ordered molecular material holds great significance for expanding its applications as functional materials. The presence of coordination bonds connected by inorganic and organic components in molecular materials can not only increase the structural diversity of materials but also modulate the electronic structure and band gap, which further regulates the physical and chemical properties of molecular materials. In fact, porous crystalline materials with coordination bonds, which inherit the merits of both organic and inorganic materials, already showcase their superior advantages in optical, electrical, and magnetic applications. In addition to the inorganic components that provide structural rigidity, organic ligands of various types serve as crucial connectors in the construction of functional porous crystalline materials. In addition, redox activity can endow organic linkers with electrochemical activity, thereby making them a perfect platform for the study of charge transfer with atom-resolved single-crystal structures, and they can additionally serve as stimuli-responsive sites in sensor devices and smart materials.In this Account, we introduce the synthesis, structural characteristics, and applications of porous crystalline materials based on the famous redox-active units, tetrathiafulvalene (TTF) and its analogues, by primarily focusing on metal-organic frameworks (MOFs) and covalent organic frameworks (COFs). TTF, a sulfur-rich conjugated molecule with two reversible and easily accessible oxidation states (i.e., radical TTF•+ cation and TTF2+ dication), and its analogues boast special electrical characteristics that enable them to display switchable redox activity and stimuli-responsive properties. These inherent properties contribute to the enhancement of the optical, electrical, and magnetic characteristics of the resultant porous crystalline materials. Moreover, delving into the charge transfer phenomena, which is key for the electrochemical process within these materials, uncovers a myriad of potential functional applications. The Account is organized into five main sections that correspond to the different properties and applications of these materials: optical, electrical, and magnetic functionalities; energy storage and conversion; and catalysis. Each section provides detailed discussions of synthetic methods, structural characteristics, the physical and chemical properties, and the functional performances of highlighted examples. The Account also discusses future directions by emphasizing the exploration of novel organic units, the transformation between radical cation TTF•+ and dication TTF2+, and the integration of multifunctionalities within these frameworks to foster the development of smart materials for enhanced performance across diverse applications. Through this Account, we aim to highlight the massive potential of TTF and its analogues-based porous crystals in chemistry and material science.

4.
Small ; 20(4): e2303153, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37721195

RESUMO

The global pandemic and excessive use of antibiotics have raised concerns about environmental health, and efforts are being made to develop alternative bactericidal agents for disinfection. Metal-based nanomaterials and their derivatives have emerged as promising candidates for antibacterial agents due to their broad-spectrum antibacterial activity, environmental friendliness, and excellent biocompatibility. However, the reported antibacterial mechanisms of these materials are complex and lack a comprehensive understanding from a coherent perspective. To address this issue, a new perspective is proposed in this review to demonstrate the toxic mechanisms and antibacterial activities of metal-based nanomaterials in terms of energy conversion and electron transfer. First, the antimicrobial mechanisms of different metal-based nanomaterials are discussed, and advanced research progresses are summarized. Then, the biological intelligence applications of these materials, such as biomedical implants, stimuli-responsive electronic devices, and biological monitoring, are concluded based on trappable electrical signals from electron transfer. Finally, current improvement strategies, future challenges, and possible resolutions are outlined to provide new insights into understanding the antimicrobial behaviors of metal-based materials and offer valuable inspiration and instructional suggestions for building future intelligent environmental health.


Assuntos
Anti-Infecciosos , Nanoestruturas , Elétrons , Nanoestruturas/toxicidade , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Metais
5.
J Transl Med ; 22(1): 368, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637886

RESUMO

In this study, we investigated CD70 as a promising target for renal cell carcinoma (RCC) therapy and developed a potent chimeric antigen receptor T (CAR-T) cells for potential clinical testing. CD70, found to be highly expressed in RCC tumors, was associated with decreased survival. We generated CAR-T cells expressing VHH sequence of various novel nanobodies from immunized alpaca and a single-chain variable fragment (scFv) derived from human antibody (41D12). In our in vitro experiments, anti-CD70 CAR-T cells effectively eliminated CD70-positive tumor cells while sparing CD70-negative cells. The nanobody-based CAR-T cells demonstrated significantly higher production of cytokines such as IL-2, IFN-γ and TNF-ɑ during co-culture, indicating their potential for enhanced functionality. In xenograft mouse model, these CAR-T cells exhibited remarkable anti-tumor activity, leading to the eradication of RCC tumor cells. Importantly, human T cell expansion after infusion was significantly higher in the VHH groups compared to the scFv CAR-T group. Upon re-challenging mice with RCC tumor cells, the VHH CAR-T treated group remained tumor-free, suggesting a robust and long-lasting anti-tumor response. These findings provide strong support for the potential of nanobody-based CD70 CAR-T cells as a promising therapeutic option for RCC. This warrants further development and consideration for future clinical trials and applications.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Receptores de Antígenos Quiméricos , Humanos , Animais , Camundongos , Carcinoma de Células Renais/terapia , Linfócitos T , Linhagem Celular Tumoral , Neoplasias Renais/terapia , Imunoterapia Adotiva , Ensaios Antitumorais Modelo de Xenoenxerto , Ligante CD27
6.
Nat Mater ; 22(5): 570-575, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36781950

RESUMO

The introduction of superconductivity to the Dirac surface states of a topological insulator leads to a topological superconductor, which may support topological quantum computing through Majorana zero modes1,2. The development of a scalable material platform is key to the realization of topological quantum computing3,4. Here we report on the growth and properties of high-quality (Bi,Sb)2Te3/graphene/gallium heterostructures. Our synthetic approach enables atomically sharp layers at both hetero-interfaces, which in turn promotes proximity-induced superconductivity that originates in the gallium film. A lithography-free, van der Waals tunnel junction is developed to perform transport tunnelling spectroscopy. We find a robust, proximity-induced superconducting gap formed in the Dirac surface states in 5-10 quintuple-layer (Bi,Sb)2Te3/graphene/gallium heterostructures. The presence of a single Abrikosov vortex, where the Majorana zero modes are expected to reside, manifests in discrete conductance changes. The present material platform opens up opportunities for understanding and harnessing the application potential of topological superconductivity.

7.
Phys Rev Lett ; 132(23): 237401, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38905697

RESUMO

Continuous-state network spreading models provide critical numerical and analytic insights into transmission processes in epidemiology, rumor propagation, knowledge dissemination, and many other areas. Most of these models reflect only local features such as adjacency, degree, and transitivity, so can exhibit substantial error in the presence of global correlations typical of empirical networks. Here, we propose mitigating this limitation via a network property ideally suited to capturing spreading. This is the network correlation dimension, which characterizes how the number of nodes within range of a source typically scales with distance. Applying the approach to susceptible-infected-recovered processes leads to a spreading model which, for a wide range of networks and epidemic parameters, can provide more accurate predictions of the early stages of a spreading process than important established models of substantially higher complexity. In addition, the proposed model leads to a basic reproduction number that provides information about the final state not available from popular established models.

8.
Mol Biol Rep ; 51(1): 697, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802698

RESUMO

Natural medicines are a valuable resource for the development of new drugs. However, factors such as low solubility and poor bioavailability of certain constituents have hindered their efficacy and potential as pharmaceuticals. Structural modification of natural products has emerged as an important research area for drug development. Phosphorylation groups, as crucial endogenous active groups, have been extensively utilized for structural modification and development of new drugs based on natural molecules. Incorporating phosphate groups into natural molecules not only enhances their stability, bioavailability, and pharmacological properties, but also improves their biological activity by altering their charge, hydrogen bonding, and spatial structure. This review summarizes the phosphorylation mechanism, modification approaches, and biological activity enhancement of natural medicines. Notably, compounds such as polysaccharides, flavonoids, terpenoids, anthraquinones, and coumarins exhibit increased antioxidation, anticancer, antiviral, immune regulatory, Antiaging, enzyme inhibition, bacteriostasis, liver protection, and lipid-lowering effects following phosphorylation modification.


Assuntos
Produtos Biológicos , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Produtos Biológicos/metabolismo , Fosforilação , Humanos , Animais , Flavonoides/química , Flavonoides/metabolismo , Flavonoides/farmacologia , Polissacarídeos/química , Polissacarídeos/metabolismo , Antioxidantes/farmacologia , Antioxidantes/química , Antraquinonas/química , Antraquinonas/farmacologia
9.
Artigo em Inglês | MEDLINE | ID: mdl-38948962

RESUMO

BACKGROUND: FMX101 4%, as a topical foam formulation of minocycline, has been approved by US Food and Drug Administration for the treatment of moderate-to-severe acne vulgaris (AV). OBJECTIVE: To evaluate the efficacy and safety of FMX101 4% in treating Chinese subjects with moderate-to-severe facial AV. METHODS: This was a multi-centre, randomized, double-blind, vehicle-controlled phase 3 study in Chinese subjects with moderate-to-severe AV. Eligible subjects were randomized 2:1 to receive either FMX101 4% or vehicle foam treatment for 12 weeks. The primary efficacy endpoint was the change in inflammation lesion count (ILC) from baseline at week 12. The key secondary endpoint was the treatment success rate according to Investigator's Global Assessment (IGA) at week 12. RESULTS: In total, 372 subjects were randomized into two groups (FMX101 4% group, n = 248; vehicle group, n = 124). After 12 weeks treatment, the reduction in ILC from baseline was statistically significant in favour of FMX101 4%, compared with vehicle foam (-21.0 [0.08] vs. -12.3 [1.14]; LSM [SE] difference, -8.7 [1.34]; 95% CI [-11.3, -6.0]; p < 0.001). FMX101 4% treatment yielded significantly higher IGA treatment success rate at week 12 as compared to the control treatment (8.06% vs. 0%). Applying FMX101 4% also resulted in significant reduction in noninflammatory lesion count (nILC) versus vehicle foam at week 12 (-19.4 [1.03] vs. -14.9 [1.47]; LSM [SE] difference, -4.5 [1.74]; 95% CI [-8.0, -1.1]; p = 0.009). Most treatment-emergent adverse events (TEAEs) were mild-to-moderate in severity, and no treatment-related treatment-emergent serious adverse event (TESAE) occurred. Thus, FMX101 4% was considered to be a safe and well-tolerated product during the 12-week treatment period. CONCLUSION: FMX101 4% treatment for 12 weeks could lead to significantly reduced ILC and nILC, and improved IGA treatment success rate in Chinese subjects with moderate-to-severe facial AV. It also showed a well acceptable safe and tolerability profile.

10.
Sex Health ; 212024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38538087

RESUMO

Coronavirus disease 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains an ongoing global public health challenge. This disease causes damage not only to the respiratory system, affecting the normal physiological function of the lungs, but also to other vital organs, such as the heart and testicles. Existing studies have shown that co-expression of angiotensin-converting enzyme 2 and transmembrane serine protease 2 is the main mechanism by which SARS-CoV-2 invades host cells. Angiotensin-converting enzyme 2-expressing cells are widespread in the corpus cavernosum, reproductive tract and testis of men, which has raised concerns. Furthermore, abnormal sex hormone levels and decreased semen parameters were observed in coronavirus disease 2019 patients. This study comprehensively assessed the effects of SARS-CoV-2 infection on the testis, semen parameters, sex hormone levels and erectile function, and discussed possible transmission routes during sexual intercourse and the effect of vaccination on male fertility.


Assuntos
COVID-19 , Humanos , Masculino , COVID-19/prevenção & controle , SARS-CoV-2 , Enzima de Conversão de Angiotensina 2 , Peptidil Dipeptidase A , Fertilidade , Hormônios Esteroides Gonadais , Vacinação
11.
Sensors (Basel) ; 24(7)2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38610296

RESUMO

The contact wire wear is an important parameter to ensure the safety operation of electric railways. The contact wire may break if the wear is serious, which leads to transportation interruptions. This study proposes an optical measurement method of contact wire wear, using stereovision technology. The matching method of stereovision based on line-scan cameras is proposed. A lookup-table method is developed to exactly determine the image resolution caused by the contact wire being in different spatial positions. The wear width of the contact wire is extracted from catenaries' images, and the residual thickness of the contact wire is calculated. The method was verified by field tests. The round-robin tests of the residual thickness at the same location present excellent measurement repetitiveness. The maximum difference value between dynamic test results and ground measurement results is 0.13 mm. This research represents a potential way to implement condition-based maintenance for contact wire wear in the future in order to improve the maintenance efficiency and ensure the safety of catenary infrastructure.

12.
Nano Lett ; 23(15): 7120-7128, 2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37490464

RESUMO

Electrocatalytic nitric oxide reduction (eNORR) to ammonia (NH3) provides an environmental route to alleviate NO pollution and yield great-value chemicals. The evolution of eNORR has been primarily hindered, however, by the poor reaction kinetics and low solubility of the NO in aqueous electrolytes. Herein, we have rationally designed a cobalt-based composite with a heterostructure as a highly efficient eNORR catalyst. In addition, by integrating boron to modulate the electronic structure, the catalyst CoB/Co@C delivered a significant NH3 yield of 315.4 µmol h-1 cm-2 for eNORR and an outstanding power density of 3.68 mW cm-2 in a Zn-NO battery. The excellent electrochemical performance of CoB/Co@C is attributed to the enrichment of NO by cobalt and boron dual-site adsorption and fast charge-transfer kinetics. It is demonstrated that the boron is pivotal in the enhancement of NO, the suppression of hydrogen evolution, and Co oxidation to boost eNORR performance.

13.
Molecules ; 29(12)2024 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-38930821

RESUMO

2,6-pyridine dicarboxylic acid (DPA) is an exceptional biomarker of notorious anthrax spores. Therefore, the rapid, sensitive, and selective quantitative detection of DPA is extremely significant and urgent. This paper reports a Zn(II) metal-organic framework with the formula of {[Zn6(NDA)6(DPBT)3] 2H2O·3DMF}n (MOF-1), which consists of 2,6-naphthalenedicarboxylic acid (2,6-NDA), 4,7-di(4-pyridyl)-2,1,3-benzothiadiazole (DPBT), and Zn(II) ions. Structural analysis indicated that MOF-1 is a three-dimensional (3D) network which crystallized in the monoclinic system with the C2/c space group, revealing high pH, solvent, and thermal stability. Luminescence sensing studies demonstrated that MOF-1 had the potential to be a highly selective, sensitive, and recyclable fluorescence sensor for the identification of DPA. Furthermore, fluorescent test paper was made to detect DPA promptly with color changes. The enhancement mechanism was established by the hydrogen-bonding interaction and photoinduced electron transfer transition between MOF-1 and DPA molecules.


Assuntos
Biomarcadores , Estruturas Metalorgânicas , Tiadiazóis , Zinco , Estruturas Metalorgânicas/química , Zinco/química , Zinco/análise , Tiadiazóis/química , Antraz/diagnóstico , Ácidos Picolínicos/química , Ácidos Picolínicos/análise , Bacillus anthracis , Modelos Moleculares
14.
Arch Orthop Trauma Surg ; 144(1): 171-177, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37792059

RESUMO

OBJECTIVE: Deep venous thrombosis (DVT) is a common complication in patients with spinal fractures caused by high-energy injuries. Early identification of patients at high risk of postoperative DVT is essential for the prevention of thrombosis. This study aimed to develop and validate a prediction model based on a nomogram to predict DVT in patients with spinal fractures caused by high-energy injuries. METHODS: Clinical data were collected from 936 patients admitted to our hospital between January 2016 and December 2021 with spinal fractures caused by high-energy injuries. Multivariate logistic regression analysis was used to identify the risk factors for postoperative DVT and to develop a nomogram. The predictive performance of the nomogram was evaluated by the receiver operating characteristic (ROC) curve and calibration curve. RESULTS: The incidence of preoperative DVT was 15.38% (144/936). The postoperative incidence of DVT was 20.5% (192/936). The multivariate analysis revealed that age, operation time, blood transfusion, duration of bed rest, American Spinal Injury Association (ASIA) score and D-dimer were risk factors for postoperative DVT. The area under the ROC curve of the nomogram was 0.835 and the calibration curve showed good calibration. CONCLUSIONS: The nomogram showed a good ability to predict postoperative DVT in patients with spinal fractures caused by high-energy injuries, which may benefit pre- and postoperative DVT prophylaxis strategy development.


Assuntos
Fraturas da Coluna Vertebral , Trombose Venosa , Humanos , Fraturas da Coluna Vertebral/complicações , Fraturas da Coluna Vertebral/cirurgia , Nomogramas , Fatores de Risco , Medição de Risco , Trombose Venosa/epidemiologia , Trombose Venosa/etiologia , Estudos Retrospectivos
15.
Entropy (Basel) ; 26(2)2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38392416

RESUMO

Correlations between exchange rates are valuable for illuminating the dynamics of international trade and the financial dynamics of countries. This paper explores the changing interactions of the US foreign exchange market based on detrended cross-correlation analysis. First, we propose an objective way to choose a time scale parameter appropriate for comparing different samples by maximizing the summed magnitude of all DCCA coefficients. We then build weighted signed networks under this optimized time scale, which can clearly display the complex relationships between different exchange rates. Our study shows negative cross-correlations have become pyramidally rare in the past three decades. Both the number and strength of positive cross-correlations have grown, paralleling the increase in global interconnectivity. The balanced strong triads are identified subsequently after the network centrality analysis. Generally, while the strong development links revealed by foreign exchange have begun to spread to Asia since 2010, Europe is still the center of world finance, with the euro and Danish krone consistently maintaining the closest balanced development relationship. Finally, we propose a fluctuation propagation algorithm to investigate the propagation pattern of fluctuations in the inferred exchange rate networks. The results show that, over time, fluctuation propagation patterns have become simpler and more predictable.

16.
J Antimicrob Chemother ; 78(12): 2890-2894, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37875024

RESUMO

OBJECTIVES: To determine the genomic features of IMP-4-producing Klebsiella pneumoniae isolates recovered from paediatric patients and the transmission dynamics of blaIMP-4. METHODS: IMP-producing K. pneumoniae isolates were collected from paediatric patients in Shanghai Children's Medical Center from 2013 to 2020. WGS was performed for all isolates, and the complete genomes of three IMP-4-producing isolates were generated. The distribution of blaIMP-4-harbouring plasmids was determined, and a conjugation assay was employed to investigate the horizontal transfer of blaIMP-4-harbouring plasmids. RESULTS: We collected 21 blaIMP-carrying K. pneumoniae isolates, with IMP-4 (16/21, 76.2%) as the predominant subtype, followed by IMP-8 (n = 3) and IMP-26 (n = 2). IMP-4-producing isolates displayed a diverse population structure and all blaIMP-4 genes were located on plasmids, including IncN (n = 9), IncHI5 (n = 5), IncFII(K) (n = 1) and IncFII(pKP91) (n = 1), although only IncN plasmids were conjugative. Clonal transmission of ST101 strains carrying IncHI5 blaIMP-4-harbouring plasmids was observed, and the acquisition of blaIMP-4 by the international high-risk ST101 clone constituted a novel combination of ST101 clone and carbapenemase genes. Plasmid analysis demonstrated that the conjugal transfer of the IncHI5 blaIMP-4-harbouring plasmid might be blocked by the ST101 bacterial host. CONCLUSIONS: The horizontal transfer of IncN plasmids and clonal spread of the international high-risk ST101 clone facilitated the nosocomial dissemination of blaIMP-4 among K. pneumoniae. The emerging IMP-4-producing ST101 clone displays diverse combinations of carbapenemase genes, and this clone could be a continually evolving threat and warrants prospective monitoring.


Assuntos
Infecção Hospitalar , Infecções por Enterobacteriaceae , Infecções por Klebsiella , Humanos , Criança , Klebsiella pneumoniae/genética , Infecções por Enterobacteriaceae/microbiologia , Transferência Genética Horizontal , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Estudos Prospectivos , China/epidemiologia , beta-Lactamases/genética , Plasmídeos/genética , Proteínas de Bactérias/genética , Infecções por Klebsiella/epidemiologia , Testes de Sensibilidade Microbiana , Antibacterianos
17.
Brief Bioinform ; 22(2): 1543-1559, 2021 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-33197934

RESUMO

Systems medicine (SM) has emerged as a powerful tool for studying the human body at the systems level with the aim of improving our understanding, prevention and treatment of complex diseases. Being able to automatically extract relevant features needed for a given task from high-dimensional, heterogeneous data, deep learning (DL) holds great promise in this endeavour. This review paper addresses the main developments of DL algorithms and a set of general topics where DL is decisive, namely, within the SM landscape. It discusses how DL can be applied to SM with an emphasis on the applications to predictive, preventive and precision medicine. Several key challenges have been highlighted including delivering clinical impact and improving interpretability. We used some prototypical examples to highlight the relevance and significance of the adoption of DL in SM, one of them is involving the creation of a model for personalized Parkinson's disease. The review offers valuable insights and informs the research in DL and SM.


Assuntos
Aprendizado Profundo , Análise de Sistemas , Algoritmos , Biomarcadores/metabolismo , Doença/classificação , Registros Eletrônicos de Saúde , Genômica , Humanos , Metabolômica , Redes Neurais de Computação , Medicina de Precisão/métodos , Proteômica , Transcriptoma
18.
Br J Clin Pharmacol ; 89(10): 3165-3174, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37309663

RESUMO

AIMS: To investigate the drug-drug interaction (DDI) of ciprofol injectable emulsion and mefenamic acid capsules in healthy subjects. METHODS: Twenty healthy subjects were enrolled in this single-centre, open-label, two-period DDI study. Ciprofol (0.4 mg kg-1 ) was administered as a single dose on days 1 and 5. A 500-mg oral loading dose of mefenamic acid was given on day 4 followed by a 250-mg maintenance dose every 6 h (a total of eight doses). Blood samples for pharmacokinetic analyses were collected. Depth of anaesthesia was monitored using the Modified Observer's Assessment of Alertness and Sedation (MOAA/S) scale and Bispectral Index scores (BISs). RESULTS: Compared with administration of ciprofol alone, administration with mefenamic acid showed no significant difference in exposure. The geometric mean ratios (GMRs) and their 90% confidence intervals (CIs) for maximum plasma concentration (Cmax ), area under the plasma concentration-time curve calculated from 0 to the last measurement point (AUC0-last ) and AUC to infinity (AUC0-inf ) were 91.6% (86.5-96.9%), 103.3% (100.3-106.4%) and 107.0% (101.2-113.2%), respectively. The MOAA/S and BIS curves for the two treatment periods essentially coincided, indicating that the anaesthesia effect of ciprofol was not affected by mefenamic acid. Seven subjects (35%) reported eight adverse events (AEs) when ciprorol was administered alone and 12 subjects (60%) reported 18 AEs when ciprofol was administered in combination with mefenamic acid. All AEs were mild. CONCLUSIONS: Mefenamic acid, a UGT1A9 inhibitor, had no significant effect on the pharmacokinetics and pharmacodynamics of ciprofol in healthy subjects. Ciprofol was safe and well tolerated when administered with mefenamic acid.


Assuntos
Ácido Mefenâmico , Humanos , Ácido Mefenâmico/efeitos adversos , Voluntários Saudáveis , Emulsões , Cápsulas , Interações Medicamentosas , Estudos Cross-Over , Área Sob a Curva
19.
J Org Chem ; 88(16): 11913-11923, 2023 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-37498087

RESUMO

An NHC-catalyzed atroposelective synthesis of axially chiral α-carbolinones from α,ß-unsaturated iminoindole derivatives and α-chloroaldehydes was developed. The reaction proceeds through a cascade process including [4 + 2] annulation and then oxidative dehydrogenation with concomitant central-to-axial chirality conversion under mild conditions. The developed method opens a new avenue to efficiently access axially chiral α-carbolinones in moderate to good enantioselectivities.

20.
Inorg Chem ; 62(17): 6544-6548, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37067156

RESUMO

Two new functionalized platinum(II) rectangles, Pt1 and Pt2, were designed and synthesized from phenanthro crown ether- and biphenyl polyether-bridged bicarboxylate ligands, respectively. The fluorescence titration study of rectangles Pt1 and Pt2 with alkali- and alkaline-earth-metal cations indicated that Pt1 can selectively recognize Na+, while Pt2 has selective binding ability for Mg2+. These selectivity findings suggest that the comparative size and conformational nature of the polyether receptor cavity have a crucial influence on the cation selection.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA