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1.
Nature ; 630(8017): 613-618, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38811737

RESUMEN

A large qubit capacity and an individual readout capability are two crucial requirements for large-scale quantum computing and simulation1. As one of the leading physical platforms for quantum information processing, the ion trap has achieved a quantum simulation of tens of ions with site-resolved readout in a one-dimensional Paul trap2-4 and of hundreds of ions with global observables in a two-dimensional (2D) Penning trap5,6. However, integrating these two features into a single system is still very challenging. Here we report the stable trapping of 512 ions in a 2D Wigner crystal and the sideband cooling of their transverse motion. We demonstrate the quantum simulation of long-range quantum Ising models with tunable coupling strengths and patterns, with or without frustration, using 300 ions. Enabled by the site resolution in the single-shot measurement, we observe rich spatial correlation patterns in the quasi-adiabatically prepared ground states, which allows us to verify quantum simulation results by comparing the measured two-spin correlations with the calculated collective phonon modes and with classical simulated annealing. We further probe the quench dynamics of the Ising model in a transverse field to demonstrate quantum sampling tasks. Our work paves the way for simulating classically intractable quantum dynamics and for running noisy intermediate-scale quantum algorithms7,8 using 2D ion trap quantum simulators.

2.
Chem Rev ; 123(23): 13209-13290, 2023 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-37862151

RESUMEN

Pulmonary surfactant is a critical component of lung function in healthy individuals. It functions in part by lowering surface tension in the alveoli, thereby allowing for breathing with minimal effort. The prevailing thinking is that low surface tension is attained by a compression-driven squeeze-out of unsaturated phospholipids during exhalation, forming a film enriched in saturated phospholipids that achieves surface tensions close to zero. A thorough review of past and recent literature suggests that the compression-driven squeeze-out mechanism may be erroneous. Here, we posit that a surfactant film enriched in saturated lipids is formed shortly after birth by an adsorption-driven sorting process and that its composition does not change during normal breathing. We provide biophysical evidence for the rapid formation of an enriched film at high surfactant concentrations, facilitated by adsorption structures containing hydrophobic surfactant proteins. We examine biophysical evidence for and against the compression-driven squeeze-out mechanism and propose a new model for surfactant function. The proposed model is tested against existing physiological and pathophysiological evidence in neonatal and adult lungs, leading to ideas for biophysical research, that should be addressed to establish the physiological relevance of this new perspective on the function of the mighty thin film that surfactant provides.


Asunto(s)
Surfactantes Pulmonares , Recién Nacido , Humanos , Surfactantes Pulmonares/química , Surfactantes Pulmonares/metabolismo , Fosfolípidos/química , Tensoactivos , Tensión Superficial , Fenómenos Químicos
3.
Biophys J ; 123(12): 1519-1530, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38664968

RESUMEN

The type II pneumocytes of the lungs secrete a mixture of lipids and proteins that together acts as a surfactant. The material forms a thin film on the surface of the liquid layer that lines the alveolar air sacks. When compressed by the decreasing alveolar surface area during exhalation, the films reduce surface tension to exceptionally low levels. Pulmonary surfactant is essential for preserving the integrity of the barrier between alveolar air and capillary blood during normal breathing. This review focuses on the major biophysical processes by which endogenous pulmonary surfactant achieves its function and the mechanisms involved in those processes. Vesicles of pulmonary surfactant adsorb rapidly from the alveolar liquid to form the interfacial film. Interfacial insertion, which requires the hydrophobic surfactant protein SP-B, proceeds by a process analogous to the fusion of two vesicles. When compressed, the adsorbed film desorbs slowly. Constituents remain at the surface at high interfacial concentrations that reduce surface tensions well below equilibrium levels. We review the models proposed to explain how pulmonary surfactant achieves both the rapid adsorption and slow desorption characteristic of a functional film.


Asunto(s)
Surfactantes Pulmonares , Surfactantes Pulmonares/metabolismo , Surfactantes Pulmonares/química , Humanos , Animales , Modelos Biológicos , Adsorción , Fenómenos Biofísicos , Tensión Superficial
4.
Artículo en Inglés | MEDLINE | ID: mdl-39159363

RESUMEN

Surfactant replacement therapy is crucial in managing neonatal respiratory distress syndrome (RDS). Currently licensed clinical surfactants in the United States and Europe, including Survanta, Infasurf, Curosurf, and Alveofact, are all derived from bovine or porcine sources. We conducted a comprehensive examination of the biophysical properties of these four clinical surfactant preparations under physiologically relevant conditions, utilizing constrained drop surfactometry (CDS). The assessed biophysical properties included the adsorption rate, quasi-static and dynamic surface activity, resistance to surfactant inhibition by meconium, and the morphology of the adsorbed surfactant films. This comparative study unveiled distinct in vitro biophysical properties of these clinical surfactants and revealed correlations between their chemical composition, lateral film structure, and biophysical functionality. Notably, at 1 mg/mL, Survanta exhibited a significantly lower adsorption rate compared to the other preparations at the same surfactant concentration. At 10 mg/mL, Infasurf, Curosurf, and Survanta all demonstrated excellent dynamic surface activity, while Alveofact exhibited the poorest quasi-static and dynamic surface activity. The suboptimal surface activity of Alveofact is found to be correlated with its unique monolayer-predominant morphology, in contrast to other surfactants forming multilayers. Curosurf, in particular, showcased superior resistance to biophysical inhibition by meconium compared to other preparations. Understanding the diverse biophysical behaviors of clinical surfactants provides crucial insights for precision and personalized design in treating RDS and other respiratory conditions. The findings from this study contribute valuable perspectives for development of more efficacious and fully synthetic surfactant preparations.

5.
Ann Neurol ; 93(3): 615-628, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36443898

RESUMEN

OBJECTIVE: Prospective studies of encephalitis are rare in regions where encephalitis is prevalent, such as low middle-income Southeast Asian countries. We compared the diagnostic yield of local and advanced tests in cases of pediatric encephalitis in Myanmar. METHODS: Children with suspected subacute or acute encephalitis at Yangon Children's Hospital, Yangon, Myanmar, were prospectively recruited from 2016-2018. Cohort 1 (n = 65) had locally available diagnostic testing, whereas cohort 2 (n = 38) had advanced tests for autoantibodies (ie, cell-based assays, tissue immunostaining, studies with cultured neurons) and infections (ie, BioFire FilmArray multiplex Meningitis/Encephalitis multiplex PCR panel, metagenomic sequencing, and pan-viral serologic testing [VirScan] of cerebrospinal fluid). RESULTS: A total of 20 cases (13 in cohort 1 and 7 in cohort 2) were found to have illnesses other than encephalitis. Of the 52 remaining cases in cohort 1, 43 (83%) had presumed infectious encephalitis, of which 2 cases (4%) had a confirmed infectious etiology. Nine cases (17%) had presumed autoimmune encephalitis. Of the 31 cases in cohort 2, 23 (74%) had presumed infectious encephalitis, of which one (3%) had confirmed infectious etiology using local tests only, whereas 8 (26%) had presumed autoimmune encephalitis. Advanced tests confirmed an additional 10 (32%) infections, 4 (13%) possible infections, and 5 (16%) cases of N-methyl-D-aspartate receptor antibody encephalitis. INTERPRETATION: Pediatric encephalitis is prevalent in Myanmar, and advanced technologies increase identification of treatable infectious and autoimmune causes. Developing affordable advanced tests to use globally represents a high clinical and research priority to improve the diagnosis and prognosis of encephalitis. ANN NEUROL 2023;93:615-628.


Asunto(s)
Enfermedades Autoinmunes del Sistema Nervioso , Enfermedades Transmisibles , Encefalitis , Encefalitis Infecciosa , Meningitis , Niño , Humanos , Meningitis/líquido cefalorraquídeo , Meningitis/diagnóstico , Estudios Prospectivos , Mianmar , Encefalitis/líquido cefalorraquídeo
6.
Glob Chang Biol ; 30(8): e17479, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39188225

RESUMEN

Terrestrial gross primary productivity (GPP) is the largest carbon flux in the global carbon cycle and plays a crucial role in terrestrial carbon sequestration. However, historical and future global GPP estimates still vary markedly. In this study, we reduced uncertainties in global GPP estimates by employing an innovative emergent constraint method on remote sensing-based GPP datasets (RS-GPP), using ground-based estimates of GPP from flux towers as the observational constraint. Using this approach, the global GPP in 2001-2014 was estimated to be 126.8 ± 6.4 PgC year-1, compared to the original RS-GPP ensemble mean of 120.9 ± 10.6 PgC year-1, which reduced the uncertainty range by 39.6%. Independent space- and time-based (different latitudinal zones, different vegetation types, and individual year) constraints further confirmed the robustness of the global GPP estimate. Building on these insights, we extended our constraints to project global GPP estimates in 2081-2100 under various Shared Socioeconomic Pathway (SSP) scenarios: SSP126 (140.6 ± 9.3 PgC year-1), SSP245 (153.5 ± 13.4 PgC year-1), SSP370 (170.7 ± 16.9 PgC year-1), and SSP585 (194.1 ± 23.2 PgC year-1). These findings have important implications for understanding and projecting climate change, helping to develop more effective climate policies and carbon reduction strategies.


Asunto(s)
Ciclo del Carbono , Cambio Climático , Tecnología de Sensores Remotos , Incertidumbre , Secuestro de Carbono , Modelos Teóricos
7.
Clin Radiol ; 79(9): e1167-e1175, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38942707

RESUMEN

AIM: A number of studies have reported that contrast-enhanced ultrasound (CEUS) imaging might be used for the early diagnosis of adnexal masses. A meta-analysis was performed to evaluate the diagnostic accuracy of CEUS combined with Ovarian-Adnexal Reporting and Data System (O-RADS) ultrasound risk stratification for adnexal masses. MATERIALS AND METHODS: Related articles were retrieved from PubMed, Web of Science, Embase, and the Cochrane Library in strict accordance with established standards, and data (including true positive, false positive, false negative, and true negative values) was extracted from the original articles. The Quality Assessment of Diagnostic Accuracy Studies 2 was used to evaluate the quality of articles and the possibility of bias. STATA 12.0 software was used to perform statistical analysis. RESULTS: Five articles that included 598 patients were analyzed in this meta-analysis. The pooled sensitivity and specificity of CEUS combined with O-RADS for the diagnosis of adnexal masses were 0.95 (95% confidence interval [CI]: 0.91-0.98) and 0.86 (95% CI: 0.79-0.91). Moreover, the positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio (DOR), and area under the curve (AUC) were 6.81 (95% CI: 4.61-10.08), 0.05 (95% CI: 0.03-0.11), 111.30 (95% CI: 65.32-189.65), and 0.97 (95% CI: 0.95-0.98), respectively. The pooled AUC and DOR for the detection of CEUS combined with O-RADS were superior to O-RADS US. CONCLUSION: Our findings revealed that O-RADS combined with CEUS can improve the diagnostic accuracy of ovarian adnexal masses.


Asunto(s)
Enfermedades de los Anexos , Medios de Contraste , Ultrasonografía , Humanos , Femenino , Ultrasonografía/métodos , Enfermedades de los Anexos/diagnóstico por imagen , Medición de Riesgo , Sensibilidad y Especificidad , Ovario/diagnóstico por imagen , Neoplasias Ováricas/diagnóstico por imagen
8.
Nano Lett ; 23(16): 7552-7560, 2023 08 23.
Artículo en Inglés | MEDLINE | ID: mdl-37494635

RESUMEN

Zwitterionic polymers have emerged as promising trans-mucus nanocarriers due to their superior antifouling properties. However, for pH-sensitive zwitterionic polymers, the effect of the pH microenvironment on their trans-mucus fate remains unclear. In this work, we prepared a library of zwitterionic polydopamine-modified silica nanoparticles (SiNPs-PDA) with an isoelectric point of 5.6. Multiple-particle tracking showed that diffusion of SiNPs-PDA in mucus with a pH value of 5.6 was 3 times faster than that in mucus with pH value 3.0 or 7.0. Biophysical analysis found that the trans-mucus behavior of SiNPs-PDA was mediated by hydrophobic and electrostatic interactions and hydrogen bonding between mucin and the particles. Furthermore, the particle distribution in the stomach, intestine, and lung demonstrated the pH-mediated mucus penetration behavior of the SiNPs-PDA. This study reveals the pH-mediated mucus penetration behavior of zwitterionic nanomaterials, which provides rational design strategies for zwitterionic polymers as nanocarriers in various mucus microenvironments.


Asunto(s)
Portadores de Fármacos , Nanopartículas , Portadores de Fármacos/química , Dióxido de Silicio/química , Polímeros/química , Nanopartículas/química , Moco , Concentración de Iones de Hidrógeno
9.
Biophys J ; 122(15): 3099-3107, 2023 08 08.
Artículo en Inglés | MEDLINE | ID: mdl-37353933

RESUMEN

Liquid ventilation is a mechanical ventilation technique in which the entire or part of the lung is filled with oxygenated perfluorocarbon (PFC) liquids rather than air in conventional mechanical ventilation. Despite its many ideal biophysicochemical properties for assisting liquid breathing, a general misconception about PFC is to use it as a replacement for pulmonary surfactant. Because of the high PFC-water interfacial tension (59 mN/m), pulmonary surfactant is indispensable in liquid ventilation to increase lung compliance. However, the biophysical function of pulmonary surfactant in liquid ventilation is still unknown. Here, we have studied the adsorption and dynamic surface activity of a natural surfactant preparation, Infasurf, at the PFC-water interface using constrained drop surfactometry. The constrained drop surfactometry is capable of simulating the intra-alveolar microenvironment of liquid ventilation under physiologically relevant conditions. It was found that Infasurf adsorbed to the PFC-water interface reduces the PFC-water interfacial tension from 59 mN/m to an equilibrium value of 9 mN/m within seconds. Atomic force microscopy revealed that after de novo adsorption, Infasurf forms multilayered structures at the PFC-water interface with an average thickness of 10-20 nm, depending on the adsorbing surfactant concentration. It was found that the adsorbed Infasurf film is capable of regulating the interfacial tension of the PFC-water interface within a narrow range, between ∼12 and ∼1 mN/m, during dynamic compression-expansion cycles that mimic liquid ventilation. These findings have novel implications in understanding the physiological and biophysical functions of the pulmonary surfactant film at the PFC-water interface, and may offer new translational insights into the development of liquid ventilation and liquid breathing techniques.


Asunto(s)
Fluorocarburos , Ventilación Liquida , Surfactantes Pulmonares , Surfactantes Pulmonares/química , Tensoactivos , Tensión Superficial , Agua/química
10.
Biophys J ; 122(10): 1772-1780, 2023 05 16.
Artículo en Inglés | MEDLINE | ID: mdl-37041745

RESUMEN

Pulmonary surfactant is a lipid-protein complex that forms a thin film at the air-water surface of the lungs. This surfactant film defines the elastic recoil and respiratory mechanics of the lungs. One generally accepted rationale of using oxygenated perfluorocarbon (PFC) as a respiratory medium in liquid ventilation is to take advantage of its low surface tensions (14-18 mN/m), which was believed to make PFC an ideal replacement of the exogenous surfactant. Compared with the extensive studies of the phospholipid phase behavior of the pulmonary surfactant film at the air-water surface, its phase behavior at the PFC-water interface is essentially unknown. Here, we reported the first detailed biophysical study of phospholipid phase transitions in two animal-derived natural pulmonary surfactant films, Infasurf and Survanta, at the PFC-water interface using constrained drop surfactometry. Constrained drop surfactometry allows in situ Langmuir-Blodgett transfer from the PFC-water interface, thus permitting direct visualization of lipid polymorphism in pulmonary surfactant films using atomic force microscopy. Our data suggested that regardless of its low surface tension, the PFC cannot be used as a replacement of pulmonary surfactant in liquid ventilation where the air-water surface of the lungs is replaced with the PFC-water interface that features an intrinsically high interfacial tension. The pulmonary surfactant film at the PFC-water interface undergoes continuous phase transitions at surface pressures less than the equilibrium spreading pressure of 50 mN/m and a monolayer-to-multilayer transition above this critical pressure. These results provided not only novel biophysical insight into the phase behavior of natural pulmonary surfactant at the oil-water interface but also translational implications into the further development of liquid ventilation and liquid breathing techniques.


Asunto(s)
Fluorocarburos , Surfactantes Pulmonares , Animales , Agua , Fosfolípidos , Tensoactivos , Tensión Superficial , Propiedades de Superficie
11.
Am J Physiol Lung Cell Mol Physiol ; 325(4): L508-L517, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37642656

RESUMEN

Exogenous surfactant therapy has been used as a standard clinical intervention for treating premature newborns with respiratory distress syndrome. The phospholipid concentrations of exogenous surfactants used in clinical practice are consistently higher than 25 mg/mL; while it was estimated that the phospholipid concentration of endogenous surfactant is approximately in the range between 15 and 50 mg/mL. However, most in vitro biophysical simulations of pulmonary surfactants were only capable of studying surfactant concentrations up to 3 mg/mL, one order of magnitude lower than the physiologically relevant concentration. Using a new in vitro biophysical model, called constrained drop surfactometry, in conjunction with atomic force microscopy and other technological advances, we have investigated the biophysical properties, ultrastructure, and topography of the pulmonary surfactant film adsorbed from the subphase at physiologically relevant high surfactant concentrations of 10-35 mg/mL. It was found that the effect of surfactant concentration on the dynamic surface activity of the surfactant film was only important when the surface area of the surfactant film varied no more than 15%, mimicking normal tidal breathing. The adsorbed surfactant film depicts a multilayer conformation consisting of a layer-by-layer assembly of stacked bilayers with the height of the multilayers proportional to the surfactant concentration. Our experimental data suggest that the biophysical function of these multilayer structures formed after de novo adsorption is to act as a buffer zone to store surface-active materials ejected from the interfacial monolayer under extreme conditions such as deep breathing.NEW & NOTEWORTHY An in vitro biophysical model, called constrained drop surfactometry, was developed to study the biophysical properties, ultrastructure, and topography of the pulmonary surfactant film adsorbed from the subphase at physiologically relevant high surfactant concentrations of 10-35 mg/mL. These results suggest that the biophysical function of multilayers formed after de novo adsorption is to act as a buffer zone to store surface-active materials ejected from the interfacial monolayer under extreme conditions such as deep breathing.

12.
Environ Sci Technol ; 57(42): 15882-15891, 2023 10 24.
Artículo en Inglés | MEDLINE | ID: mdl-37824199

RESUMEN

The attractiveness and abundance of flavors are primary factors eliciting youth to use e-cigarettes. Emerging studies in recent years revealed the adverse health impact of e-cigarette flavoring chemicals, including disruption of the biophysical function of pulmonary surfactants in the lung. Nevertheless, a comprehensive understanding of the biophysical impact of various flavoring chemicals is still lacking. We used constrained drop surfactometry as a new alternative method to study the biophysical impact of flavored e-cigarette aerosols on an animal-derived natural pulmonary surfactant. The dose of exposure to e-cigarette aerosols was quantified with a quartz crystal microbalance, and alterations to the ultrastructure of the surfactant film were visualized using atomic force microscopy. We have systematically studied eight representative flavoring chemicals (benzyl alcohol, menthol, maltol, ethyl maltol, vanillin, ethyl vanillin, ethyl acetate, and ethyl butyrate) and six popular recombinant flavors (coffee, vanilla, tobacco, cotton candy, menthol/mint, and chocolate). Our results suggested a flavor-dependent inhibitory effect of e-cigarette aerosols on the biophysical properties of the pulmonary surfactant. A qualitative phase diagram was proposed to predict the hazardous potential of various flavoring chemicals. These results provide novel implications in understanding the environmental, health, and safety impacts of e-cigarette aerosols and may contribute to better regulation of e-cigarette products.


Asunto(s)
Sistemas Electrónicos de Liberación de Nicotina , Surfactantes Pulmonares , Mentol , Aromatizantes/análisis , Aerosoles
13.
Environ Sci Technol ; 57(50): 21050-21060, 2023 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-38055865

RESUMEN

Microplastics (MPs) are ubiquitous environmental pollutants produced through the degradation of plastic products. Nanoplastics (NPs), commonly coexisting with MPs in the environment, are submicrometer debris incidentally produced from fragmentation of MPs. We studied the biophysical impacts of MPs/NPs derived from commonly used commercial plastic products on a natural pulmonary surfactant extracted from calf lung lavage. It was found that in comparison to MPs/NPs derived from lunch boxes made of polypropylene or from drinking water bottles made of poly(ethylene terephthalate), the MP/NP derived from foam packaging boxes made of polystyrene showed the highest adverse impact on the biophysical function of the pulmonary surfactant. Accordingly, intranasal exposure of MP/NP derived from the foam boxes also induced the most serious proinflammatory responses and lung injury in mice. Atomic force microscopy revealed that NP particles were adsorbed on the air-water surface and heteroaggregated with the pulmonary surfactant film. These results indicate that although the incidentally formed NPs only make up a small mass fraction, they likely play a predominant role in determining the nano-bio interactions and the lung toxicity of MPs/NPs by forming heteroaggregates at the alveolar-capillary interface. These findings may provide novel insights into understanding the health impact of MPs and NPs on the respiratory system.


Asunto(s)
Contaminantes Ambientales , Surfactantes Pulmonares , Contaminantes Químicos del Agua , Animales , Ratones , Microplásticos , Plásticos , Polipropilenos
14.
Artículo en Zh | MEDLINE | ID: mdl-37006146

RESUMEN

Objective: To investigate the current situation of job involvement of nurses in military hospitals in Henan Province and analyze the influencing factors, so as to provide reference for improving the level of job involvement of military nurses. Methods: In February 2022, the employed nurses of 4 military hospitals in Henan Province were investigated by convenient sampling method. A total of 663 questionnaires were collected, including 632 valid questionnaires, with an effective recovery rate of 95.32%. The self-designed questionnaire was used to investigate the basic information of nurses, the Job Involvement Scale was used to investigate the job involvement of nurses, the Emotional Labor Scale for Nurses was used to investigate nurses' emotions, and the Work-Family Conflict Scale was used to investigate the work-family conflict of nurses. Independent sample t-test and univariate analysis of variance were used to compare the job involvement of military employed nurses with different demographic characteristics, Pearson correlation analysis was used to explore the correlation between emotional labor, work-family conflict and job involvement, and hierarchical regression analysis was used to explore the impact of relevant variables on the job involvement of military employed nurses. Results: The total average score of job involvement of military employed nurses was (3.68±1.13), and the scores of vitality, dedication and focus were (3.64±1.15), (3.74±1.25) and (3.67±1.21) respectively. The total score of emotional labor of nurses was 33-80 (62.95±8.12), with an average score of (3.93±0.51). The total score of work-family conflict was 18-94 (55.16±13.53), with an average score of (3.06±0.75). Professional emotional regulation, patient-centered emotional inhibition and standardized emotional play were positively related to the job involvement (r=0.46, 0.41, 0.22, P<0.01). Time-based conflict, stress-based conflict and behavior-based conflict had negative correlation with the job involvement (r=-0.12, -0.23, -0.20, P<0.01). In hierarchical regression analysis, after controlling demographic variables, emotional labor and work-family conflict accounted for 17.2% and 4.2% of the variation of job involvement. Conclusion: The job involvement of military employed nurses tends to be at a moderate level. Emotional labor and work-family conflict can significantly affect their job involvement.


Asunto(s)
Hospitales Militares , Enfermeras y Enfermeros , Estados Unidos , Humanos , Conflicto Familiar , Encuestas y Cuestionarios , Análisis de Regresión , Satisfacción en el Trabajo
15.
Biophys J ; 121(3): 439-450, 2022 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-34958775

RESUMEN

Tear film lipid layer (TFLL) is the outmost layer of the tear film. It plays a crucial role in stabilizing the tear film by reducing surface tension and retarding evaporation of the aqueous layer. Dysfunction of the TFLL leads to dysfunctional tear syndrome, with dry eye disease (DED) being the most prevalent eye disease, affecting 10%-30% of the world population. To date, except for treatments alleviating dry eye symptoms, effective therapeutic interventions in treating DED are still lacking. Therefore, there is an urgent need to understand the biophysical properties of the TFLL with the long-term goal to develop translational solutions in effectively managing DED. Here, we studied the composition-function correlations of an artificial TFLL, under physiologically relevant conditions, using a novel experimental methodology called constrained drop surfactometry. This artificial TFLL was composed of 40% behenyl oleate and 40% cholesteryl oleate, representing the most abundant wax ester and cholesteryl ester in the natural TFLL, respectively, and 15% phosphatidylcholine and 5% palmitic-acid-9-hydroxy-stearic-acid (PAHSA), which represent the two predominant polar lipid classes in the natural TFLL. Our study suggests that the major biophysical function of phospholipids in the TFLL is to reduce the surface tension, whereas the primary function of PAHSA is to optimize the rheological properties of the TFLL. These findings have novel implications in better understanding the physiological and biophysical functions of the TFLL and may offer new translational insight to the treatment of DED.


Asunto(s)
Lípidos , Lágrimas , Reología , Propiedades de Superficie , Tensión Superficial
16.
Biophys J ; 121(3): 451-458, 2022 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-34968427

RESUMEN

Fatty acid esters of hydroxy fatty acids (FAHFAs) are a newly discovered class of endogenous lipids that consist of two acyl chains connected through a single ester bond. Being a unique species of FAHFAs, (O-acyl)-ω-hydroxy fatty acids (OAHFAs) differ from other FAHFAs in that their hydroxy fatty acid backbones are ultralong and their hydroxy esterification is believed to be solely at the terminal (ω-) position. Only in recent years with technological advances in lipidomics have OAHFAs been identified as an important component of the tear film lipid layer (TFLL). It was found that OAHFAs account for approximately 4 mol% of the total lipids and 20 mol% of the polar lipids in the TFLL. However, their biophysical function and contribution to the TFLL is still poorly understood. Here we studied the molecular biophysical mechanisms of OAHFAs using palmitic-acid-9-hydroxy-stearic-acid (PAHSA) as a model. PAHSA and OAHFAs share key structural similarities that could result in comparable biophysical properties and molecular mechanisms. With combined biophysical experiments, atomic force microscopy observations, and all-atom molecular dynamics simulations, we found that the biophysical properties of a dynamic PAHSA monolayer under physiologically relevant conditions depend on a balance between kinetics and thermal relaxation. PAHSA molecules at the air-water surface demonstrate unique polymorphic behaviors, which can be explained by configurational transitions of the molecules under various lateral pressures. These findings could have novel implications in understanding biophysical functions that FAHFAs, in general, or OAHFAs, specifically, play in the TFLL.


Asunto(s)
Ácidos Grasos , Lágrimas , Biofisica , Ésteres/química , Ácidos Grasos/química , Lágrimas/química , Agua
17.
Am J Physiol Lung Cell Mol Physiol ; 323(2): L165-L177, 2022 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-35762601

RESUMEN

With an increasing prevalence of electronic cigarette (e-cigarette) use, especially among youth, there is an urgent need to better understand the biological risks and pathophysiology of health conditions related to e-cigarettes. A majority of e-cigarette aerosols are in the submicron size and would deposit in the alveolar region of the lung, where they must first interact with the endogenous pulmonary surfactant. To date, little is known whether e-cigarette aerosols have an adverse impact on the pulmonary surfactant. We have systematically studied the effect of individual e-cigarette ingredients on an animal-derived clinical surfactant preparation, bovine lipid extract surfactant, using a combination of biophysical and analytical techniques, including in vitro biophysical simulations using constrained drop surfactometry, molecular imaging with atomic force microscopy, chemical assays using carbon nuclear magnetic resonance and circular dichroism, and in silico molecular dynamics simulations. All data collectively suggest that flavorings used in e-cigarettes, especially menthol, play a predominant role in inhibiting the biophysical function of the surfactant. The mechanism of biophysical inhibition appears to involve menthol interactions with both phospholipids and hydrophobic proteins of the natural surfactant. These results provide novel insights into the understanding of the health impact of e-cigarettes and may contribute to better regulation of e-cigarette products.


Asunto(s)
Sistemas Electrónicos de Liberación de Nicotina , Surfactantes Pulmonares , Aerosoles , Animales , Bovinos , Mentol , Surfactantes Pulmonares/metabolismo , Tensoactivos
18.
Anal Chem ; 94(4): 2078-2086, 2022 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-35029972

RESUMEN

The hydrophobicity of nanoparticles (NPs) is one of the most important physicochemical properties that determines their agglomeration state under various environmental conditions. When studying nano-bio interactions, it is found that the hydrophobicity of NPs plays a predominant role in mediating the biological response and toxicity of the NPs. Although many methods have been developed to qualitatively or quantitatively determine hydrophobicity, there is not yet a scientific consensus on the standard of characterizing the hydrophobicity of NPs. We have developed a novel optical method, called the maximum particle dispersion (MPD), for quantitatively characterizing the hydrophobicity of NPs. The principle of measurement of the MPD method lies in the control of the aggregation state of the NPs via manipulating the van der Waals interactions between NPs across a dispersion liquid. We have scrutinized the mechanism of the MPD method using a combination of dynamic light scattering and atomic force microscopy and further verified the MPD method using a completely independent dye adsorption method. The MPD method demonstrated great promise to be developed into an easy-to-use and cost-effective method for quantitatively characterizing the hydrophobicity of NPs.


Asunto(s)
Nanopartículas , Adsorción , Interacciones Hidrofóbicas e Hidrofílicas , Microscopía de Fuerza Atómica/métodos , Nanopartículas/química , Tamaño de la Partícula
19.
Liver Int ; 42(11): 2548-2561, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36004563

RESUMEN

Acyl-CoA thioesterase 9 (ACOT9) is a critical regulator of cellular utilization of fatty acids by catalysing the hydrolysis of acyl-CoA thioesters to non-esterified fatty acid and coenzyme A (CoA). Recently, ACOT9 was reported to participate in the pathogenesis of non-alcoholic liver disease (NAFLD), which arises from aberrant lipid metabolism and serves as a risk factor for hepatocellular carcinoma (HCC). However, the functions of ACOT9 in carcinogenesis and aberrant lipid metabolism in HCC remain unexplored. Here, we found that ACOT9 expression is significantly elevated in HCC at least partially due to the down-regulation of miR-449c-3p. Upregulation of ACOT9 is closely associated with poor prognosis for patients with HCC. Knockdown of ACOT9 expression in HCC cells significantly decreased cell proliferation, colony formation, migration and invasion, mainly through suppression of G1-to-S cell cycle transition and epithelial-to-mesenchymal transition (EMT). By contrast, forced ACOT9 expression promoted HCC growth and metastasis. In addition, we found that ACOT9 reprogrammed lipid metabolism in HCC cells by increasing de novo lipogenesis. Furthermore, we demonstrated that increased lipogenesis was involved in ACOT9-promoted HCC growth and metastasis. Altogether, we demonstrate that ACOT9 plays a critical oncogenic role in the promotion of tumour growth and metastasis by reprogramming lipid metabolism in HCC, indicating ACOT9 as a potential therapeutic target in treatment of HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , Acilcoenzima A/metabolismo , Carcinogénesis , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Transición Epitelial-Mesenquimal , Ácidos Grasos/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Metabolismo de los Lípidos , Neoplasias Hepáticas/patología , MicroARNs/genética , MicroARNs/metabolismo , Metástasis de la Neoplasia
20.
Climacteric ; 25(4): 376-382, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-34694955

RESUMEN

OBJECTIVE: This study was performed to assess the effects of vitamin D deficiency/insufficiency combined with a high body mass index (BMI) on paraspinal muscle (PSM) atrophy and pain intensity in postmenopausal women with lower back pain (LBP). METHODS: In total, 365 postmenopausal women were analyzed in the study. We divided the women into four groups according to BMI and vitamin D status. Outcome measurements included PSM atrophy, fatty infiltration (FI) and severity of LBP. Binary logistic regression was used to analyze the odds ratio (OR), and the interaction between the BMI and vitamin D status was tested. RESULTS: Compared with the control group, the high BMI with vitamin D deficiency/insufficiency group had a significantly increased risk of FI > grade 2 (OR = 10.69, p < 0.001), hand grip strength of <16 kg (OR = 8.96, p < 0.001), Short Physical Performance Battery score of ≤8 (OR = 3.69, p < 0.001) and visual analog scale (VAS) score of >3 (OR = 4.76, p < 0.001). A significant positive additive interaction was found between the BMI and vitamin D status on PSM atrophy. CONCLUSION: Vitamin D deficiency/insufficiency combined with a high BMI was associated with PSM atrophy and LBP intensity in postmenopausal women. The interaction analysis showed a positive additive interaction between BMI and vitamin D status.


Asunto(s)
Deficiencia de Vitamina D , Vitamina D , Índice de Masa Corporal , Femenino , Fuerza de la Mano/fisiología , Humanos , Atrofia Muscular , Dimensión del Dolor/efectos adversos , Músculos Paraespinales , Posmenopausia , Deficiencia de Vitamina D/complicaciones , Vitaminas
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