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1.
Brief Bioinform ; 25(4)2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-39038937

RESUMEN

Peptide drugs are becoming star drug agents with high efficiency and selectivity which open up new therapeutic avenues for various diseases. However, the sensitivity to hydrolase and the relatively short half-life have severely hindered their development. In this study, a new generation artificial intelligence-based system for accurate prediction of peptide half-life was proposed, which realized the half-life prediction of both natural and modified peptides and successfully bridged the evaluation possibility between two important species (human, mouse) and two organs (blood, intestine). To achieve this, enzymatic cleavage descriptors were integrated with traditional peptide descriptors to construct a better representation. Then, robust models with accurate performance were established by comparing traditional machine learning and transfer learning, systematically. Results indicated that enzymatic cleavage features could certainly enhance model performance. The deep learning model integrating transfer learning significantly improved predictive accuracy, achieving remarkable R2 values: 0.84 for natural peptides and 0.90 for modified peptides in human blood, 0.984 for natural peptides and 0.93 for modified peptides in mouse blood, and 0.94 for modified peptides in mouse intestine on the test set, respectively. These models not only successfully composed the above-mentioned system but also improved by approximately 15% in terms of correlation compared to related works. This study is expected to provide powerful solutions for peptide half-life evaluation and boost peptide drug development.


Asunto(s)
Péptidos , Animales , Semivida , Humanos , Ratones , Péptidos/metabolismo , Péptidos/química , Aprendizaje Profundo , Aprendizaje Automático
2.
BMC Med ; 22(1): 376, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39256772

RESUMEN

BACKGROUND: Neurogenic erectile dysfunction, characterized by neurological repair disorders and progressive corpus cavernosum fibrosis (CCF), is an unbearable disease with limited treatment success. IL-17A exhibits a complex role in tissue remodelling. Nevertheless, the precise role and underlying mechanisms of IL-17A in CCF under denervation remain unclear. METHODS: PCR array was employed to identified differentially expressed genes between neurogenic ED and normal rats. IL-17A expression and its main target cells were analyzed using Western blotting, immunofluorescence and immunohistochemistry. The phenotypic regulation of IL-17A on corpus cavernosum smooth muscle cells (CSMCs) was evaluated by cell cycle experiments and SA-ß-Gal staining. The mechanism of IL-17A was elucidated using non-target metabolomics and siRNA technique. Finally, IL-17A antagonist and ABT-263 (an inhibitor of B-cell lymphoma 2/w/xL) were utilized to enhance the therapeutic effect in a rat model of neurogenic ED. RESULTS: IL-17A emerged as the most significantly upregulated gene in the corpus cavernosum of model rats. It augmented the senescence transformation and fibrotic response of CSMCs, and exhibited a strong correlation with CCF. Mechanistically, IL-17A facilitated CCF by activating the mTORC2-ACACA signalling pathway, upregulating of CSMCs lipid synthesis and senescence transition, and increasing the secretion of fibro-matrix proteins. In vivo, the blockade of IL-17A-senescence signalling improved erectile function and alleviated CCF in neurogenic ED. CONCLUSIONS: IL-17A assumes a pivotal role in denervated CCF by activating the mTORC2-ACACA signalling pathway, presenting itself as a potential therapeutic target for effectively overcoming CCF and erection rehabilitation in neurogenic ED.


Asunto(s)
Disfunción Eréctil , Fibrosis , Interleucina-17 , Pene , Transducción de Señal , Animales , Masculino , Disfunción Eréctil/tratamiento farmacológico , Interleucina-17/metabolismo , Ratas , Transducción de Señal/efectos de los fármacos , Pene/inervación , Pene/patología , Diana Mecanicista del Complejo 2 de la Rapamicina/metabolismo , Ratas Sprague-Dawley , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/efectos de los fármacos , Senescencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad
3.
Mol Pharm ; 21(8): 4116-4127, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39031123

RESUMEN

Peptide-based therapeutics hold immense promise for the treatment of various diseases. However, their effectiveness is often hampered by poor cell membrane permeability, hindering targeted intracellular delivery and oral drug development. This study addressed this challenge by introducing a novel graph neural network (GNN) framework and advanced machine learning algorithms to build predictive models for peptide permeability. Our models offer systematic evaluation across diverse peptides (natural, modified, linear and cyclic) and cell lines [Caco-2, Ralph Russ canine kidney (RRCK) and parallel artificial membrane permeability assay (PAMPA)]. The predictive models for linear and cyclic peptides in Caco-2 and RRCK cell lines were constructed for the first time, with an impressive coefficient of determination (R2) of 0.708, 0.484, 0.553, and 0.528 in the test set, respectively. Notably, the GNN framework behaved better in permeability prediction with larger data sets and improved the accuracy of cyclic peptide prediction in the PAMPA cell line. The R2 increased by about 0.32 compared with the reported models. Furthermore, the important molecular structural features that contribute to good permeability were interpreted; the influence of cell lines, peptide modification, and cyclization on permeability were successfully revealed. To facilitate broader use, we deployed these models on the user-friendly KNIME platform (https://github.com/ifyoungnet/PharmPapp). This work provides a rapid and reliable strategy for systematically assessing peptide permeability, aiding researchers in drug delivery optimization, peptide preselection during drug discovery, and potentially the design of targeted peptide-based materials.


Asunto(s)
Permeabilidad de la Membrana Celular , Células CACO-2 , Perros , Humanos , Animales , Péptidos Cíclicos/metabolismo , Péptidos Cíclicos/química , Aprendizaje Automático , Redes Neurales de la Computación , Péptidos/química , Péptidos/metabolismo , Permeabilidad , Línea Celular , Membranas Artificiales , Algoritmos
4.
J Org Chem ; 89(11): 7780-7789, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38752832

RESUMEN

Methods for regioselective N-trideuteromethylation of tautomeric polyaza heterocycles are highly sought-after. Disclosed herein is an N-trideuterated methylation reaction of imidazoles and pyrazoles with high regioselectivity and deuterium purity using easily available CF3SO3CD3 as the -CD3 source. This method enables the easy synthesis of important deuterium-labeled azoles, including dimetridazole-d3, ipronidazole-d3, hydroxy dimetridazole-d3, and ronidazole-d3.

5.
Int J Mol Sci ; 25(17)2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39273441

RESUMEN

Antimicrobial resistance poses an escalating threat to human health, necessitating the development of novel antimicrobial agents capable of addressing challenges posed by antibiotic-resistant bacteria. Thanatin, a 21-amino acid ß-hairpin insect antimicrobial peptide featuring a single disulfide bond, exhibits broad-spectrum antibacterial activity, particularly effective against multidrug-resistant strains. The outer membrane biosynthesis system is recognized as a critical vulnerability in antibiotic-resistant bacteria, which thanatin targets to exert its antimicrobial effects. This peptide holds significant promise for diverse applications. This review begins with an examination of the structure-activity relationship and synthesis methods of thanatin. Subsequently, it explores thanatin's antimicrobial activity, detailing its various mechanisms of action. Finally, it discusses prospective clinical, environmental, food, and agricultural applications of thanatin, offering valuable insights for future research endeavors.


Asunto(s)
Péptidos Catiónicos Antimicrobianos , Farmacorresistencia Bacteriana Múltiple , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Humanos , Péptidos Catiónicos Antimicrobianos/farmacología , Péptidos Catiónicos Antimicrobianos/química , Antibacterianos/farmacología , Antibacterianos/química , Relación Estructura-Actividad , Animales , Bacterias/efectos de los fármacos , Péptidos Antimicrobianos/farmacología , Péptidos Antimicrobianos/química , Pruebas de Sensibilidad Microbiana
6.
BMC Surg ; 23(1): 110, 2023 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-37149588

RESUMEN

AIM: The incidence and risk factors of low anterior resection syndrome (LARS) largely variate in different studies. In addition, there is lack of study on how patients evaluate the therapeutic effect of LARS. This single-center retrospective study aims to investigate the status of LARS in Chinese patients undergoing laparoscopic low anterior resection (LAR). METHODS: Consequent patients undergoing laparoscopic LAR and free from disease recurrence from January 2015 to May 2021 were issued with both LARS questionnaire and satisfaction survey. Related data were collected and analyzed. RESULTS: Both LARS questionnaires and self-made satisfaction survey were received from 261 eligible patients. The overall incidence of LARS was 47.1% (minor in 19.5%, major in 27.6%), decreased with the passage of postoperative time (64.7% within 12 months, and 41.7% within 12-36 months), and became stable 36 months later (39.7%). The most common symptoms were defecation clustering (n = 107/261, 41.0%) and defecation urgency (n = 101/261, 38.7%). According to the multivariable regression analysis, risk factors of major LARS were: 1 year increase in age (OR 1.035, 95% CI 1.004-1.068), protective stoma (OR 2.656, 95% CI 1.233-5.724) and T3 - 4 stage (OR 2.449, 95% CI 1.137-5.273). Most patients complained defecation disorder (87.3%) to doctors and 84.5% got suggestions or treatments for it. However, only 36.8% patients thought the treatments worked for them. CONCLUSIONS: LARS frequently occurs after laparoscopic LAR, while the therapeutic effect is not satisfying. Elder, advanced T-stage and protective stoma were risk factors for postoperative major LARS.


Asunto(s)
Neoplasias del Recto , Humanos , Anciano , Neoplasias del Recto/cirugía , Síndrome de Resección Anterior Baja , Estudios Retrospectivos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Recurrencia Local de Neoplasia , Calidad de Vida
7.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(2): 432-438, 2023 Mar.
Artículo en Zh | MEDLINE | ID: mdl-36949711

RESUMEN

Objective: To analyze the efficacy of using baseline calcitonin (bCtn) for auxiliary diagnosis of medullary thyroid cancer (MTC) in the hypercalcitoninemic population with thyroid nodules and to explore the relationship between preoperative levels of bCtn and carcinoembryonic antigen (CEA) and MTC staging. Methods: The clinical, pathological, imaging, and lab test data of 58 MTC patients and 84 non-MTC patients were retrospectively reviewed in the study. The patients were hospitalized at West China Hosptal, Sichuan University between 2011 and 2020. Receiver operating characteristic (ROC) curves were constructed to calculate the MTC diagnostic efficacy of bCtn and CEA. The differences in the preoperative bCtn and CEA levels of MTC patients with different primary tumor sites and regional lymph node involvement were compared. Results: The bCtn cutoff values were 31.54 pg/mL for men and 22.60 pg/mL for women for diagnosing MTC in the hypercalcitoninemic population with thyroid nodules. There were statistical differences in preoperative bCtn levels ( H=16.166, P=0.001) and in preoperative CEA levels ( H=9.447, P=0.024) in MTC patients of different T stages. There were statistical differences in preoperative bCtn levels ( H=7.919, P=0.019) and in preoperative CEA levels ( H=7.934, P=0.019) in MTC patients of different N stages. Conclusion: The best bCtn cutoff values for the diagnosis of MTC in the hypercalcitoninemic population with thyroid nodules and are 31.54 pg/mL for men and 22.60 pg/mL for women.


Asunto(s)
Neoplasias de la Tiroides , Nódulo Tiroideo , Masculino , Humanos , Femenino , Calcitonina , Nódulo Tiroideo/diagnóstico , Antígeno Carcinoembrionario , Diagnóstico Diferencial , Estudios Retrospectivos , Neoplasias de la Tiroides/diagnóstico , Biomarcadores de Tumor
8.
Small ; 18(24): e2201952, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35567327

RESUMEN

Electrically accelerated self-healable poly(ionic liquids) copolymers that exhibit resistor-capacitor (RC) circuit properties are developed. At low alternating current (AC) frequencies these materials behave as a resistor (R), whereas at higher frequencies as a capacitor (C). These properties are attributed to a combination of dipolar and electrostatic interactions in (1-[(2-methacryloyloxy)ethyl]-3-butylimidazolium bis(trifluoromethyl-sulfonyl)imide) copolymerized with methyl methacrylate (MMA) monomers to form p(MEBIm-TSFI/MMA)] copolymers. When the monomer molar ratio (MEBIm-TSFI:MMA) is 40/60, these copolymers are capable of undergoing multiple damage-repair cycles and self-healing is accelerated by the application of alternating 1.0-4.0 V electric field (EF). Self-healing in the absence of EFs is facilitated by van der Waals (vdW) interactions, but the application of AC EF induces back and forth movement of charges against the opposing force that result in dithering of electrostatic dipoles giving rise to interchain physical crosslinks. Electrostatic inter- and intrachain interactions facilitated by copolymerization of ionic liquid monomers with typically dielectric acrylic-based monomers result in enhanced cohesive energy densities that accelerate the recovery of vdW forces facilitating self-healing. Incorporating ionic liquids into commodity polymers offers promising uses as green conducting solid polyelectrolytes in self-healable energy storage, energy-harvesting devices, and many other applications.


Asunto(s)
Líquidos Iónicos , Iones , Polimerizacion , Polímeros , Electricidad Estática
9.
Neural Comput ; 34(5): 1170-1188, 2022 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-35231931

RESUMEN

Recent work on spiking neural networks (SNNs) has focused on achieving deep architectures. They commonly use backpropagation (BP) to train SNNs directly, which allows SNNs to go deeper and achieve higher performance. However, the BP training procedure is computing intensive and complicated by many trainable parameters. Inspired by global pooling in convolutional neural networks (CNNs), we present the spike probabilistic global pooling (SPGP) method based on a probability function for training deep convolutional SNNs. It aims to remove the difficulty of too many trainable parameters brought by multiple layers in the training process, which can reduce the risk of overfitting and get better performance for deep SNNs (DSNNs). We use the discrete leaky-integrate-fire model and the spatiotemporal BP algorithm for training DSNNs directly. As a result, our model trained with the SPGP method achieves competitive performance compared to the existing DSNNs on image and neuromorphic data sets while minimizing the number of trainable parameters. In addition, the proposed SPGP method shows its effectiveness in performance improvement, convergence, and generalization ability.


Asunto(s)
Redes Neurales de la Computación , Neuronas , Algoritmos
10.
BMC Geriatr ; 22(1): 893, 2022 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-36419004

RESUMEN

BACKGROUND: Sarcopenia is an age-related skeletal muscle disorder that involves a loss of muscle mass or strength and physiological function. Skeletal muscle deteriorates in both quantity and quality. The endocrine system is an important regulator of muscle metabolism. Therefore, we aimed to explore the relationship between biochemical markers and muscle mass in sarcopenia. METHODS: We used the AWGS 2014 as the diagnostic criteria for sarcopenia, considering both the loss in muscle mass, muscle strength and physical performance. A total of 2837 elderly female participants over 50 years of age from the West China Health and Aging Trend (WCHAT) study were included. Insulin, glucose, 25(OH)VD, procalcitonin, alanine aminotransferase, aspartate aminotransferase, total protein, prealbumin, albumin, thyroid-stimulating hormone, free triiodothyronine, free tetraiodothyronine, triglycerides, cholesterol, high-density lipoprotein, very low-density lipoprotein, cortisol, and follicle-stimulating hormone were measured. Based on the findings of univariate analysis, multivariate regression and receiver operating characteristic (ROC) curves were established. RESULTS: Participants with sarcopenia had significantly lower free triiodothyronine, insulin, total protein, albumin, prealbumin, albumin/prealbumin ratio (A/G), alanine aminotransferase, triglycerides, and very low-density lipoprotein concentrations (P < 0.05). Compared with those without sarcopenia, those with sarcopenia had significantly higher free tetraiodothyronine, cortisol, follicle-stimulating hormone (FSH), aspartate aminotransferase/alanine aminotransferase ratio (AST/ALT), and high-density lipoprotein concentrations (P < 0.05). Insulin (OR = 0.854), FSH (OR = 1.016), and the AST/ALT ratio (OR = 1.819) were independent risk factors for low muscle mass (P < 0.001). The AUC of insulin was the highest, followed by the AST/ALT ratio and FSH (0.691, 0.671, and 0.634, respectively), and the AUC of the mixture of the above three reached 0.736. CONCLUSION: In this cross-sectional study of elderly Chinese females aged over 50 years from the WCHAT, FSH, insulin, and AST/ALT ratio were associated with sarcopenia and risk factors for low muscle mass.


Asunto(s)
Insulina , Sarcopenia , Anciano , Femenino , Humanos , Persona de Mediana Edad , Alanina Transaminasa , Sarcopenia/diagnóstico , Sarcopenia/epidemiología , Prealbúmina , Triyodotironina , Hidrocortisona , Estudios Transversales , Aspartato Aminotransferasas , Músculo Esquelético , Triglicéridos , Albúminas , Lipoproteínas HDL , Hormona Folículo Estimulante , Lipoproteínas LDL
11.
Angew Chem Int Ed Engl ; 61(48): e202212079, 2022 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-36195828

RESUMEN

An approach allowing remote editing of stacked aromatic assemblies for heteroannular C-H functionalization would represent a transformative chemical toolbox that may make the diversification of complex molecules in a straightforward manner. However, such a C-H activation is usually less kinetically and thermodynamically favorable than homoannular ortho C-H activation and remains a fundamental challenge. Herein we disclose an engineer's approach, using a transient ligand as an interim bridge between two aryl rings (analogues to mountaintops) to anchor the metal center on the remote heteroannular C-H bond. As a proof-of-concept, we present the palladium-catalyzed heteroannular C-H olefination of stacked aromatic assemblies with olefins and allylation with vinyl acetates using L-tert-leucine acid as a transient ligand. Mechanistic investigations suggest an unusual olefin coordination-promoted interannular palladium migration process determinative for reversal of the site-selectivity.

12.
Macromol Rapid Commun ; 42(18): e2100054, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33749047

RESUMEN

Known for their adaptability to surroundings, capability of transport control of molecules, or the ability of converting one type of energy to another as a result of external or internal stimuli, responsive polymers play a significant role in advancing scientific discoveries that may lead to an array of diverge applications. This review outlines recent advances in the developments of selected commodity polymers equipped with stimuli-responsiveness to temperature, pH, ionic strength, enzyme or glucose levels, carbon dioxide, water, redox agents, electromagnetic radiation, or electric and magnetic fields. Utilized diverse applications ranging from drug delivery to biosensing, dynamic structural components to color-changing coatings, this review focuses on commodity acrylics, epoxies, esters, carbonates, urethanes, and siloxane-based polymers containing responsive elements built into their architecture. In the context of stimuli-responsive chemistries, current technological advances as well as a critical outline of future opportunities and applications are also tackled.


Asunto(s)
Polímeros de Estímulo Receptivo , Sistemas de Liberación de Medicamentos , Polímeros , Temperatura
13.
Angew Chem Int Ed Engl ; 59(44): 19460-19467, 2020 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-32400958

RESUMEN

The development of ultrastable carbon materials for potassium storage poses key limitations caused by the huge volume variation and sluggish kinetics. Nitrogen-enriched porous carbons have recently emerged as promising candidates for this application; however, rational control over nitrogen doping is needed to further suppress the long-term capacity fading. Here we propose a strategy based on pyrolysis-etching of a pyridine-coordinated polymer for deliberate manipulation of edge-nitrogen doping and specific spatial distribution in amorphous high-surface-area carbons; the obtained material shows an edge-nitrogen content of up to 9.34 at %, richer N distribution inside the material, and high surface area of 616 m2 g-1 under a cost-effective low-temperature carbonization. The optimized carbon delivers unprecedented K-storage stability over 6000 cycles with negligible capacity decay (252 mA h g-1 after 4 months at 1 A g-1 ), rarely reported for potassium storage.

14.
Biomacromolecules ; 20(7): 2577-2586, 2019 07 08.
Artículo en Inglés | MEDLINE | ID: mdl-31244021

RESUMEN

Clinically used bio-based tissue sealants bring in the risk of animal-borne infections, non-degradability, allergic reactions, tissue compression, tissue necrosis, and poor wet adhesion. Motivated by these unsatisfactory properties of existing tissue sealants, herein, we designed a library of solvent- and initiator-free hydrophobic mussel-inspired degradable tissue adhesives that can stick and seal the epidermis, pericardium, and Glisson's capsule under physiologically relevant wet conditions. By varying the molar ratio of the functional groups, we obtained polyester adhesive sealants with similar surface energy and varying viscosity. The careful examination of the wetting behavior of these polyester adhesive sealants on tissue surfaces showed that the polyester adhesive sealant with lower viscosity has higher intrinsic work of adhesion, which allowed them to adhere to strongly hydrated surfaces such as pericardium and Glisson's capsule. Because of the lower intrinsic work of adhesion, the polyester adhesive sealant with higher viscosity only adhered to the relatively hydrophobic surface (epidermis). The strong wet adhesion to tissue surfaces, cell-compatibility, hydrolytic degradability, and radical scavenging nature of these polyester adhesive sealants make them potential candidates for wound closure procedures.


Asunto(s)
Poliésteres/química , Poliésteres/farmacología , Adhesivos Tisulares/química , Adhesivos Tisulares/farmacología , Animales
15.
Macromol Rapid Commun ; 40(17): e1800770, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30698904

RESUMEN

Understanding correlation between the nanostructure of porous carbons and their ion transport behavior is critical for achieving high-performance supercapacitors. Herein, the relationship between size and shell thickness of carbon nanospheres (CNSs) and capacitive electrochemical performance is clarified. Structural uniform CNSs with controlled diameters, prepared via template-free interfacial copolymerization, are emerging as an ideal platform for investigating the ion transport behavior. It is found that ionic transport is significantly enhanced while the introduction of hollow cores with thinner shell, by virtue of the hollow nanopore-accelerated mass transport to reduce ion diffusion length. The proof-of-concept supercapacitors, constituted of carbons with diameter and shell thickness of 91 and 28 nm, respectively, can maintain highest capacitance retention ratio of 86% at a high sweep rate of 300 mVs-1 , also far outperforming the commercial activated carbon in terms of capacitance, rate capability, and surface efficiency, promising a brilliant application.


Asunto(s)
Carbono/química , Capacidad Eléctrica , Nanosferas/química , Nitrógeno/química , Polímeros/química , Técnicas Electroquímicas , Nanoestructuras , Porosidad
16.
Neural Netw ; 173: 106172, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38402808

RESUMEN

Spiking neural networks (SNNs) are brain-inspired models that utilize discrete and sparse spikes to transmit information, thus having the property of energy efficiency. Recent advances in learning algorithms have greatly improved SNN performance due to the automation of feature engineering. While the choice of neural architecture plays a significant role in deep learning, the current SNN architectures are mainly designed manually, which is a time-consuming and error-prone process. In this paper, we propose a spiking neural architecture search (NAS) method that can automatically find efficient SNNs. To tackle the challenge of long search time faced by SNNs when utilizing NAS, the proposed NAS encodes candidate architectures in a branchless spiking supernet which significantly reduces the computation requirements in the search process. Considering that real-world tasks prefer efficient networks with optimal accuracy under a limited computational budget, we propose a Synaptic Operation (SynOps)-aware optimization to automatically find the computationally efficient subspace of the supernet. Experimental results show that, in less search time, our proposed NAS can find SNNs with higher accuracy and lower computational cost than state-of-the-art SNNs. We also conduct experiments to validate the search process and the trade-off between accuracy and computational cost.


Asunto(s)
Algoritmos , Redes Neurales de la Computación , Automatización , Ingeniería
17.
Front Public Health ; 12: 1368933, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39114511

RESUMEN

Objective: Sarcopenia is a gradually advancing systemic disorder affecting skeletal muscles, primarily distinguished by diminished muscle mass and functional decline. As of present, a universally accepted diagnostic criterion for sarcopenia has yet to be established. From the perspective of the constitution theory in traditional Chinese medicine (TCM), the Yin-deficiency constitution is believed to have a significant correlation with the development of sarcopenia. The primary objective of this study was to examine the potential association between sarcopenia and Yin-deficiency constitution. Methods: The present study is a cross-sectional analysis. The Asian Working Group for Sarcopenia (AWGS) recommended a diagnostic criterion for sarcopenia. A total of 141 participants over 50 years of age were diagnosed with sarcopenia. To determine the constitution of each patient, classification and determination standards were used in traditional Chinese medicine. In this study, a combination of logistic regression and propensity score matching (PSM) was employed to analyze a dataset comprising 1,372 eligible observations. The diagnostic efficacy of the test in distinguishing sarcopenia was assessed through receiver operating characteristic (ROC) curve analysis. Results: The relationship between Yin-deficiency constitution and sarcopenia was examined using logistic regression analysis. In the crude model, the odds ratio (OR) was found to be 3.20 (95% confidence interval [CI]: 1.70-6.03). After adjusting for various confounding factors, including gender, sex, 6 m walking test/(m/s), SMI, and maximum grip strength/kg, the OR increased to 9.70 (95% CI: 3.20-69.38). The associations between seven other biased traditional Chinese medicine (TCM) constitutions and sarcopenia were not found to be statistically significant in the fully adjusted model. The propensity score matching (PSM) analysis yielded consistent results with the logistic regression analysis. Receiver operating characteristic (ROC) curve analysis showed that the AUC of the Yin-deficiency constitution combined with age and gender reached 0.707. Conclusion: Among the nine TCM constitutions examined, the Yin-deficiency constitution demonstrates an independent association with sarcopenia. Yin-deficiency constitution may serve as a potential risk factor for the development of sarcopenia. To establish a causal relationship, further experimental investigations are warranted. The diagnostic performance of sarcopenia is effectively demonstrated by the Yin-deficiency constitution combined with age and gender.


Asunto(s)
Medicina Tradicional China , Sarcopenia , Humanos , Sarcopenia/diagnóstico , Estudios Transversales , Femenino , Masculino , Anciano , Persona de Mediana Edad , Deficiencia Yin/diagnóstico , Curva ROC , Anciano de 80 o más Años
18.
Chem Sci ; 15(27): 10547-10555, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38994415

RESUMEN

In this work, we present a design concept of introducing linear structures into the orthogonal configuration of 9,9'-spirobifluorene (SBF), aiming to enhance carrier mobilities while maintaining high triplet energies (E T), which are two critical parameters for optimizing host materials in organic light-emitting diodes (OLEDs). To validate our proposed design, four pivotal model molecules of 1,4-diaryl SBFs were synthesized via interannular C-H arylation of bi(hetero)aryl-2-formaldehydes, a task challenging to accomplish using previous synthetic methodologies. The orthogonal configuration and the steric hindrance of SBF lead to high E T through the conjugation breaking at C1 and C4 positions, rendering 1,4-diaryl SBFs suitable as universal pure hydrocarbon (PHC) hosts for red, green, and blue (RGB) phosphorescent OLEDs (PhOLEDs). Meanwhile, the linearity and relatively good planarity of the para-quaterphenyl structure promote high carrier mobilities through orderly intermolecular packing. The synergistic effects of linearity and orthogonality in 1-(para-biphenyl)-4-phenyl-SBF result in exceptional device performance with external quantum efficiencies (EQEs) of 26.0%, 26.1%, and 22.5% for RGB PhOLEDs, respectively. Notably, the green PhOLED exhibits minimal efficiency roll-off, positioning its device performances among the state-of-the-art in PHC hosts.

19.
Adv Sci (Weinh) ; : e2405596, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39021325

RESUMEN

Excited-state intramolecular proton transfer (ESIPT) has attracted great attention in fluorescent sensors and luminescent materials due to its unique photobiological and photochemical features. However, the current structures are far from meeting the specific demands for ESIPT molecules in different scenarios; the try-and-error development method is labor-intensive and costly. Therefore, it is imperative to devise novel approaches for the exploration of promising ESIPT fluorophores. This research proposes an artificial intelligence approach aiming at exploring ESIPT molecules efficiently. The first high-quality ESIPT dataset and a multi-level prediction system are constructed that realized accurate identification of ESIPT molecules from a large number of compounds under a stepwise distinguishing from conventional molecules to fluorescent molecules and then to ESIPT molecules. Furthermore, key structural features that contributed to ESIPT are revealed by using the SHapley Additive exPlanations (SHAP) method. Then three strategies are proposed to ensure the ESIPT process while keeping good safety, pharmacokinetic properties, and novel structures. With these strategies, >700 previously unreported ESIPT molecules are screened from a large pool of 570 000 compounds. The ESIPT process and biosafety of optimal molecules are successfully validated by quantitative calculation and experiment. This novel approach is expected to bring a new paradigm for exploring ideal ESIPT molecules.

20.
Aging Med (Milton) ; 7(3): 334-340, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38975312

RESUMEN

Objective: Sarcopenia is a geriatric syndrome that occurs with age and is characterized by a gradual decline in muscle mass, power, and functionality. It serves as a prominent contributor to frailty, disability, and mortality among older individuals. Currently, no standardized global guidelines exist for the diagnosis of sarcopenia. This study aimed to establish the correlation between sarcopenia and the constitutions of traditional Chinese medicine (TCM), considering the connection between physical functioning and sarcopenia. Methods: A total of 1441 participants in this study were diagnosed with sarcopenia. The Asian Working Group for Sarcopenia (AWGS) proposed a sarcopenia definition algorithm. To determine the constitution of each participant, classification and determination standards were used in traditional Chinese medicine. This study evaluated the demographics, lifestyles, and self-reported medical history of individuals diagnosed with sarcopenia through a self-administered questionnaire. The constitution of the participants was determined using TCM classification and determination standards. Subsequently, we analyzed the results of univariate analysis and multivariate regression and constructed a receiver operating characteristic (ROC) curve. Results: Participants who were diagnosed with sarcopenia had substantially lower original Neutral constitution scores (P < 0.050). In comparison to those without sarcopenia, individuals with sarcopenia exhibited notably elevated original Qi-deficiency, Yang-deficiency, Yin-deficiency, Blood-stagnation, and Qi-stagnation scores in contrast to those in the healthy group (P < 0.050). The identified risk factors associated with sarcopenia included the following: Neutral (OR = 0.903), Qi-deficiency (in males, OR = 1.126), Yang-deficiency (OR = 1.062), Phlegm-dampness (in males, OR = 0.833), and Blood-stagnation (in females, OR = 1.089). The highest area under the curve (AUC) was observed for the original neutral constitution score, followed by the Yang-deficiency and blood-stagnation scores (0.644, 0.613, and 0.611, respectively). Additionally, the AUC for the combined original scores of all nine constitutions among males reached 0.778. Conclusions: In this cross-sectional study of older people with higher original Qi-deficiency, Yin deficiency, Yang-deficiency, Blood-stagnation, and Qi-stagnation were associated with sarcopenia. Notably, various TCM constitutions are significantly linked to sarcopenia. There was a significant occurrence of various body constitution types among individuals diagnosed with sarcopenia. The mixture of the nine original constitution scores exhibited good diagnostic performance for sarcopenia in males.

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