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1.
Cell ; 186(11): 2475-2491.e22, 2023 05 25.
Artículo en Inglés | MEDLINE | ID: mdl-37178688

RESUMEN

Holistic understanding of physio-pathological processes requires noninvasive 3D imaging in deep tissue across multiple spatial and temporal scales to link diverse transient subcellular behaviors with long-term physiogenesis. Despite broad applications of two-photon microscopy (TPM), there remains an inevitable tradeoff among spatiotemporal resolution, imaging volumes, and durations due to the point-scanning scheme, accumulated phototoxicity, and optical aberrations. Here, we harnessed the concept of synthetic aperture radar in TPM to achieve aberration-corrected 3D imaging of subcellular dynamics at a millisecond scale for over 100,000 large volumes in deep tissue, with three orders of magnitude reduction in photobleaching. With its advantages, we identified direct intercellular communications through migrasome generation following traumatic brain injury, visualized the formation process of germinal center in the mouse lymph node, and characterized heterogeneous cellular states in the mouse visual cortex, opening up a horizon for intravital imaging to understand the organizations and functions of biological systems at a holistic level.


Asunto(s)
Imagenología Tridimensional , Animales , Ratones , Imagenología Tridimensional/métodos , Microscopía Confocal/métodos
2.
Proc Natl Acad Sci U S A ; 121(18): e2400313121, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38652745

RESUMEN

Can liquid-like and gas-like states be distinguished beyond the critical point, where the liquid-gas phase transition no longer exists and conventionally only a single supercritical fluid phase is defined? Recent experiments and simulations report strong evidence of dynamical crossovers above the critical temperature and pressure. Despite using different criteria, many existing theoretical explanations consider a single crossover line separating liquid-like and gas-like states in the supercritical fluid phase. We argue that such a single-line scenario is inconsistent with the supercritical behavior of the Ising model, which has two crossover lines due to its symmetry, violating the universality principle of critical phenomena. To reconcile the inconsistency, we define two thermodynamic crossover lines in supercritical fluids as boundaries of liquid-like, indistinguishable, and gas-like states. Near the critical point, the two crossover lines follow critical scalings with exponents of the Ising universality class, supported by calculations of theoretical models and analyses of experimental data from the standard database. The upper line agrees with crossovers independently estimated from the inelastic X-ray scattering data of supercritical argon, and from the small-angle neutron scattering data of supercritical carbon dioxide. The lower line is verified by the equation of states for the compressibility factor. This work provides a fundamental framework for understanding supercritical physics in general phase transitions.

3.
Nat Methods ; 20(5): 747-754, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37002377

RESUMEN

Widefield microscopy can provide optical access to multi-millimeter fields of view and thousands of neurons in mammalian brains at video rate. However, tissue scattering and background contamination results in signal deterioration, making the extraction of neuronal activity challenging, laborious and time consuming. Here we present our deep-learning-based widefield neuron finder (DeepWonder), which is trained by simulated functional recordings and effectively works on experimental data to achieve high-fidelity neuronal extraction. Equipped with systematic background contribution priors, DeepWonder conducts neuronal inference with an order-of-magnitude-faster speed and improved accuracy compared with alternative approaches. DeepWonder removes background contaminations and is computationally efficient. Specifically, DeepWonder accomplishes 50-fold signal-to-background ratio enhancement when processing terabytes-scale cortex-wide functional recordings, with over 14,000 neurons extracted in 17 h.


Asunto(s)
Encéfalo , Calcio , Animales , Encéfalo/fisiología , Microscopía , Corteza Cerebral , Neuronas/fisiología , Mamíferos
4.
Nat Methods ; 20(12): 1957-1970, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37957429

RESUMEN

Fluorescence microscopy has become an indispensable tool for revealing the dynamic regulation of cells and organelles. However, stochastic noise inherently restricts optical interrogation quality and exacerbates observation fidelity when balancing the joint demands of high frame rate, long-term recording and low phototoxicity. Here we propose DeepSeMi, a self-supervised-learning-based denoising framework capable of increasing signal-to-noise ratio by over 12 dB across various conditions. With the introduction of newly designed eccentric blind-spot convolution filters, DeepSeMi effectively denoises images with no loss of spatiotemporal resolution. In combination with confocal microscopy, DeepSeMi allows for recording organelle interactions in four colors at high frame rates across tens of thousands of frames, monitoring migrasomes and retractosomes over a half day, and imaging ultra-phototoxicity-sensitive Dictyostelium cells over thousands of frames. Through comprehensive validations across various samples and instruments, we prove DeepSeMi to be a versatile and biocompatible tool for breaking the shot-noise limit.


Asunto(s)
Dictyostelium , Aumento de la Imagen , Microscopía Confocal/métodos , Relación Señal-Ruido , Microscopía Fluorescente , Procesamiento de Imagen Asistido por Computador/métodos
5.
Plant J ; 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39172024

RESUMEN

Cotton fiber (Gossypium hirsutum) serves as an ideal model for investigating the molecular mechanisms of plant cell elongation at the single-cell level. Brassinosteroids (BRs) play a crucial role in regulating plant growth and development. However, the mechanism by which BR influences cotton fiber elongation remains incompletely understood. In this study, we identified EXORDIUM-like (GhEXL3) through transcriptome analysis of fibers from BR-deficient cotton mutant pagoda 1 (pag1) and BRI1-EMS-SUPPRESSOR 1 (GhBES1.4, encoding a central transcription factor of BR signaling) overexpression cotton lines. Knockout of GhEXL3 using CRISPR/Cas9 was found to impede cotton fiber elongation, while its overexpression promoted fiber elongation, suggesting a positive regulatory function for GhEXL3 in fiber elongation. Furthermore, in vitro ovule culture experiments revealed that the overexpression of GhEXL3 partially counteracted the inhibitory effects of brassinazole (BRZ) on cotton fiber elongation, providing additional evidence of GhEXL3 involvement in BR signaling pathways. Moreover, our findings demonstrate that GhBES1.4 directly binds to the E-box (CACGTG) motif in the GhEXL3 promoter region and enhances its transcription. RNA-seq analysis revealed that overexpression of GhEXL3 upregulated the expression of EXPs, XTHs, and other genes associated with fiber cell elongation. Overall, our study contributes to understanding the mechanism by which BR regulates the elongation of cotton fibers through the direct modulation of GhEXL3 expression by GhBES1.4.

6.
Chem Rev ; 123(16): 9786-9879, 2023 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-37552606

RESUMEN

When molecules are coupled to an optical cavity, new light-matter hybrid states, so-called polaritons, are formed due to quantum light-matter interactions. With the experimental demonstrations of modifying chemical reactivities by forming polaritons under strong light-matter interactions, theorists have been encouraged to develop new methods to simulate these systems and discover new strategies to tune and control reactions. This review summarizes some of these exciting theoretical advances in polariton chemistry, in methods ranging from the fundamental framework to computational techniques and applications spanning from photochemistry to vibrational strong coupling. Even though the theory of quantum light-matter interactions goes back to the midtwentieth century, the gaps in the knowledge of molecular quantum electrodynamics (QED) have only recently been filled. We review recent advances made in resolving gauge ambiguities, the correct form of different QED Hamiltonians under different gauges, and their connections to various quantum optics models. Then, we review recently developed ab initio QED approaches which can accurately describe polariton states in a realistic molecule-cavity hybrid system. We then discuss applications using these method advancements. We review advancements in polariton photochemistry where the cavity is made resonant to electronic transitions to control molecular nonadiabatic excited state dynamics and enable new photochemical reactivities. When the cavity resonance is tuned to the molecular vibrations instead, ground-state chemical reaction modifications have been demonstrated experimentally, though its mechanistic principle remains unclear. We present some recent theoretical progress in resolving this mystery. Finally, we review the recent advances in understanding the collective coupling regime between light and matter, where many molecules can collectively couple to a single cavity mode or many cavity modes. We also lay out the current challenges in theory to explain the observed experimental results. We hope that this review will serve as a useful document for anyone who wants to become familiar with the context of polariton chemistry and molecular cavity QED and thus significantly benefit the entire community.

7.
Anal Chem ; 96(14): 5686-5693, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38551337

RESUMEN

Vacuum ultraviolet photoionization (VUV-PI) is a soft ionization technique that operates under pressures ranging from vacuum to ambient pressure. VUV-PI has played an essential role in direct sampling mass spectrometry. In this study, new ionization processes initiated by photoelectrons have been studied through the inclusion of a radio frequency (RF) electric field at different pressures. After deducting the contribution of single photoionization (SPI), the signal intensity of 1 ppmv toluene (C7H8+) in Ar was approximately 5-fold higher than that in N2. Mixed gases with different ionization energies (IEs) and excitation energies (EEs) were further investigated to reveal that metastable species were involved in the enhancement process. Reactant ions were produced by photoelectron impact ionization (PEI), which further triggered ion-molecule reactions, i.e., chemical ionization (CI). Metastable species were produced by photoelectron impact excitation (PEE), which further triggered Penning ionization (PenI). Analytes with IEs above 10.6 eV, such as CO2 (IE = 13.78 eV) and CHCl3 (IE = 11.37 eV), could be sensitively ionized by PenI with a sensitivity comparable to SPI. Except for the contribution of SPI, the dominant ionization process was switched from PEI-CI to PenI when the pressure was elevated from 50 to 500 Pa, as the electron energy gradually decreased and was only able to produce metastable states based on the kinetic energy balance equation of electrons. The conversion processes and conditions from PEI-CI to PenI will provide novel insights to develop new selective and sensitive VUV-PI sources and understand the ionization mechanism in other discharge ionization sources.

8.
Small ; 20(3): e2302550, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37726238

RESUMEN

The structural coloration of textiles with bionic photonic crystals (PCs) is expected to become a critical approach to the ecological coloration of textiles. Rapid and large-area preparation of PC structurally colored textiles can be achieved via self-assembly of high mass fractions of liquid photonic crystals (LPCs). However, the rapid and large-scale manufacturing of LPCs remains a challenge. In this work, the pH regulator is added in the process of emulsion polymerization to solve the problem of phase transformation caused by the thermal decomposition of the initiator to produce H+ , directly achieving 40 wt.% PS nanospheres in the dispersion. Then oligomers and small-molecule salts are removed from the system via dialysis, and the pre-crystallized LPC system is efficiently prepared. Adjusting the particle size and the mass fraction of nanospheres is shown to be an efficient way to control the optical properties of LPCs. The rapid and large-area preparation of PC structural color fabric and the patterned PC structural color fabric with an iridescent effect is implemented by using LPCs as the assembly intermediate. By constructing the encapsulation layer on the surface of the PC structural color fabric, the consistency of high structural stability and high color saturation of the PC is realized.

9.
Small ; 20(3): e2305567, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37702141

RESUMEN

Mesoporous silica nanoparticles (MSNs) have been widely praised as nanoadjuvants in vaccine/tumor immunotherapy thanks to their excellent biocompatibility, easy-to-modify surface, adjustable particle size, and remarkable immuno-enhancing activity. However, the application of MSNs is still greatly limited by some severe challenges including the unclear and complicated relationships of structure and immune effect. Herein, three commonly used MSNs with different skeletons including MSN with tetrasulfide bonds (TMSN), MSN containing ethoxy framework (EMSN), and pure -Si-O-Si- framework of MSN (MSN) are comprehensively compared to study the impact of chemical construction on immune effect. The results fully demonstrate that the three MSNs have great promise in improving cellular immunity for tumor immunotherapy. Moreover, the TMSN performs better than the other two MSNs in antigen loading, cellular uptake, reactive oxygen species (ROS) generation, lymph node targeting, immune activation, and therapeutic efficiency. The findings provide a new paradigm for revealing the structure-function relationship of mesoporous silica nanoadjuvants, paving the way for their future clinical application.


Asunto(s)
Nanopartículas , Neoplasias , Nitrilos , Humanos , Porosidad , Dióxido de Silicio/química , Inmunoterapia , Nanopartículas/química , Neoplasias/terapia , Esqueleto
10.
Small ; 20(31): e2308690, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38470201

RESUMEN

Traditional surface-enhanced Raman scattering (SERS) sensors rely heavily on the use of plasmonic noble metals, which have limitations due to their high cost and lack of physical and chemical stability. Hence, it is imperative to explore new materials as SERS platforms that can withstand high temperatures and harsh conditions. In this study, the SERS effect of molybdenum boride ceramic powders is presented with an enhancement factor of 5 orders, which is comparable to conventional noble metal substrates. The molybdenum boride powders synthesized through liquid-phase precursor and carbothermal reduction have ß-MoB, MoB2, and Mo2B5 phases. Among these phases, ß-MoB demonstrates the most significant SERS activity, with a detection limit for rhodamine 6G (R6G) molecules of 10-9 m. The impressive SERS enhancement can be attributed to strong molecule interactions and prominent charge interactions between R6G and the various phases of molybdenum boride, as supported by theoretical calculations. Additionally, Raman measurements show that the SERS activity remains intact after exposure to high temperature, strong acids, and alkalis. This research introduces a novel molybdenum boride all-ceramic SERS platform capable of functioning in harsh conditions, thereby showing the promising of boride ultrahigh-temperature ceramics for detection applications in extreme environments.

11.
Nat Methods ; 18(11): 1395-1400, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34400836

RESUMEN

Calcium imaging has transformed neuroscience research by providing a methodology for monitoring the activity of neural circuits with single-cell resolution. However, calcium imaging is inherently susceptible to detection noise, especially when imaging with high frame rate or under low excitation dosage. Here we developed DeepCAD, a self-supervised deep-learning method for spatiotemporal enhancement of calcium imaging data that does not require any high signal-to-noise ratio (SNR) observations. DeepCAD suppresses detection noise and improves the SNR more than tenfold, which reinforces the accuracy of neuron extraction and spike inference and facilitates the functional analysis of neural circuits.


Asunto(s)
Potenciales de Acción , Algoritmos , Calcio/metabolismo , Diagnóstico por Imagen/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Neuronas/fisiología , Relación Señal-Ruido , Animales , Femenino , Masculino , Ratones , Ratones Transgénicos , Neuronas/citología
12.
J Virol ; 97(10): e0109023, 2023 10 31.
Artículo en Inglés | MEDLINE | ID: mdl-37787533

RESUMEN

IMPORTANCE: Clinical data suggest that Hepatitis C virus (HCV) levels are generally lower in Hepatitis B virus (HBV) co-infected patients, but the mechanism is unknown. Here, we show that HBV, but not HCV, activated absent in melanoma-2. This in turn results in inflammasome-mediated cleavage of pro-IL-18, leading to an innate immune activation cascade that results in increased interferon-γ, suppressing both viruses.


Asunto(s)
Coinfección , Proteínas de Unión al ADN , Hepacivirus , Virus de la Hepatitis B , Hepatitis B , Hepatitis C , Inmunidad Innata , Humanos , Coinfección/inmunología , Coinfección/virología , Proteínas de Unión al ADN/metabolismo , Hepacivirus/inmunología , Hepatitis B/complicaciones , Hepatitis B/inmunología , Hepatitis B/virología , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/fisiología , Hepatitis C/complicaciones , Hepatitis C/inmunología , Hepatitis C/virología , Inflamasomas/metabolismo , Interferón gamma/inmunología
13.
J Vasc Surg ; 80(1): 188-198.e1, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38301808

RESUMEN

OBJECTIVE: The aim of this study was to investigate whether intimal arterial calcification (IAC) and medial arterial calcification (MAC) are correlated with the various clinical outcomes following endovascular therapy (EVT) for peripheral arterial disease (PAD). METHODS: This single-center retrospective study comprised 154 consecutively hospitalized individuals with PAD who underwent EVT for de novo femoral-popliteal calcific lesions from January 2016 to July 2021. The predominant calcification patterns of IAC and MAC were assessed using a semi-quantitative computed tomography scoring system. The Kaplan-Meier method and Cox regression were conducted to evaluate the correlations between calcification patterns and medium- to long-term outcomes. RESULTS: The distribution of calcification patterns was as follows: IAC in 111 patients (72%) and MAC in 43 patients (28%). No remarkable variation was noted between the IAC and MAC groups regarding age (P = .84) and gender (P = .23). The MAC group indicated lower rates of 4-year primary patency, assisted primary patency, secondary patency, and amputation-free survival (AFS) compared with the IAC group (24% ± 7% vs 40% ± 6%; P = .003; 30% ± 8% vs 51% ± 6%; P = .001; 51% ± 8% vs 65% ± 5%; P = .004; and 43% ± 9% vs 76% ± 5%; P < .001, respectively). There was no significant difference in the rate of freedom from clinically driven target lesion revascularization between the MAC and IAC groups (63% ± 10% vs 73% ± 5%; P = .26). Stepwise multivariable Cox regression analysis demonstrated that MAC was associated with poor patency (hazard ratio, 1.81; 95% confidence interval, 1.12-2.93; P = .016) and AFS (hazard ratio, 2.80; 95% confidence interval, 1.52-5.16; P = .001). CONCLUSIONS: Compared with IAC, MAC is independently associated with lower medium- to long-term patency and AFS after EVT for de novo femoral-popliteal occlusive lesions.


Asunto(s)
Amputación Quirúrgica , Procedimientos Endovasculares , Arteria Femoral , Enfermedad Arterial Periférica , Arteria Poplítea , Calcificación Vascular , Grado de Desobstrucción Vascular , Humanos , Masculino , Femenino , Estudios Retrospectivos , Arteria Femoral/diagnóstico por imagen , Arteria Femoral/fisiopatología , Arteria Femoral/cirugía , Anciano , Arteria Poplítea/diagnóstico por imagen , Arteria Poplítea/fisiopatología , Arteria Poplítea/cirugía , Enfermedad Arterial Periférica/diagnóstico por imagen , Enfermedad Arterial Periférica/terapia , Enfermedad Arterial Periférica/fisiopatología , Enfermedad Arterial Periférica/mortalidad , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/terapia , Calcificación Vascular/mortalidad , Procedimientos Endovasculares/efectos adversos , Factores de Tiempo , Persona de Mediana Edad , Factores de Riesgo , Anciano de 80 o más Años , Recuperación del Miembro , Resultado del Tratamiento , Supervivencia sin Progresión , Medición de Riesgo
14.
Eur Radiol ; 34(2): 761-769, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37597031

RESUMEN

OBJECTIVE: To define a response-to-ablation system based on dynamic risk stratification proposed by the 2015 American Thyroid Association guidelines for predicting clinical outcomes and guiding follow-up strategies for patients with low-risk papillary thyroid microcarcinoma (PTMC) who underwent radiofrequency ablation (RFA). METHODS: This retrospective study reviewed patients with low-risk PTMC who underwent RFA between 2014 and 2018. We classified patients into three groups based on their response to therapy at the 1-year follow-up: complete, indeterminate, and incomplete. The primary endpoints were local tumor progression (LTP) and disease-free survival (DFS). RESULTS: Among the 748 patients (mean age, 43.7 years ± 9.8; 586 women), 4.0% (30/748) had LTP during a median follow-up of 5 years. The response was complete in 80.2% (600/748) of the patients, indeterminate in 18.1% (135/748), and incomplete in 1.7% (13/748). The LTP rate in the final follow-up was 1% (6/600), 8.1% (11/135), and 100% (13/13), respectively. The risk of LTP was significantly different in the incomplete response group (HR, 1825.82; 95% CI: 458.27, 7274.36; p < 0.001) and indeterminate response group (HR, 8.12; 95% CI: 2.99, 22.09; p < 0.001) than in the complete response group. There were significant differences in DFS among groups (p < 0.001). The proportion of variation explained and C-index of the system was high (27.66% and 0.79, respectively). CONCLUSIONS: We defined a response-to-ablation system that provides a new paradigm for the management of patients with PTMC who underwent RFA. Our data confirm that the system can effectively predict the risk of LTP and guide ongoing follow-up recommendations. KEY POINTS: • The response-to-ablation system can classify patients with low-risk PTMC who underwent RFA into complete, indeterminate, or incomplete response categories. • Results suggest that, in this population, this system can identify three separate cohorts of patients who have significantly different clinical outcomes. • The response-to-ablation system will help better tailor the ongoing follow-up recommendations.


Asunto(s)
Carcinoma Papilar , Ablación por Radiofrecuencia , Neoplasias de la Tiroides , Humanos , Femenino , Adulto , Estudios de Seguimiento , Estudios Retrospectivos , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Ablación por Radiofrecuencia/métodos , Resultado del Tratamiento
15.
Eur Radiol ; 34(7): 4716-4726, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38170265

RESUMEN

OBJECTIVES: To assess the safety and efficacy of radiofrequency ablation (RFA) for capsular-located papillary thyroid microcarcinoma (PTMC) in a large cohort and to compare its outcomes with those of noncapsular-located PTMC. METHODS: We retrospectively reviewed patients who underwent RFA for solitary capsular-located and noncapsular-located low-risk PTMC (n = 1095) from June 2014 to October 2020. To balance confounding variables between capsular and noncapsular groups, we employed the 1:1 propensity score matching approach. We evaluated and compared tumor changes, disease progression, and complications in both groups. Furthermore, we analyzed the association between capsular location and disease progression using multivariable Cox regression. RESULTS: During a mean follow-up time of 29.86 ± 16.14 months and 29.73 ± 15.69 months, no substantial difference was observed between capsular and noncapsular groups in the latest volume (0.83 ± 3.66 mm3 vs. 0.85 ± 3.67 mm3, p = 0.44) and volume reduction ratio (99.29 ± 4.04% vs. 99.43 ± 3.03%, p = 0.43), and cumulative disappearance rate (87.87% vs. 86.07%, p = 0.31). In addition, no significant differences were observed in complication incidence (1.35% vs. 1.12%, p = 0.76) and progression-free survival (p = 0.53). Based on adjusted multivariate Cox proportional hazard analysis, the association between capsular location and disease progression was nonsignificant (all p > 0.05). CONCLUSION: This study demonstrates that the short-term outcomes of RFA for capsular-located PTMCs are comparable to those of noncapsular-located PTMCs. These findings indicate that RFA may be a viable and effective alternative for eligible patients with solitary capsular-located PTMC. CLINICAL RELEVANCE STATEMENT: Radiofrequency ablation may serve as a safe and effective alternative treatment method for eligible patients with capsular-located and noncapsular-located papillary thyroid microcarcinoma. KEY POINTS: • The safety and efficacy of radiofrequency ablation for capsular-located and noncapsular-located papillary thyroid microcarcinomas were comparable. • Disease progression did not differ significantly between capsular-located and noncapsular-located papillary thyroid microcarcinomas. • The incidence of complications for capsular-located papillary thyroid microcarcinoma was low.


Asunto(s)
Carcinoma Papilar , Puntaje de Propensión , Ablación por Radiofrecuencia , Neoplasias de la Tiroides , Humanos , Femenino , Masculino , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Estudios Retrospectivos , Ablación por Radiofrecuencia/métodos , Persona de Mediana Edad , Adulto , Carcinoma Papilar/cirugía , Resultado del Tratamiento , Progresión de la Enfermedad , Anciano
16.
BMC Med Res Methodol ; 24(1): 192, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39217327

RESUMEN

BACKGROUND: Many existing healthcare ranking systems are notably intricate. The standards for peer review and evaluation often differ across specialties, leading to contradictory results among various ranking systems. There is a significant need for a comprehensible and consistent mode of specialty assessment. METHODS: This quantitative study aimed to assess the influence of clinical specialties on the regional distribution of patient origins based on 10,097,795 outpatient records of a large comprehensive hospital in South China. We proposed the patient regional index (PRI), a novel metric to quantify the regional influence of hospital specialties, using the principle of representative points of a statistical distribution. Additionally, a two-dimensional measure was constructed to gauge the significance of hospital specialties by integrating the PRI and outpatient volume. RESULTS: We calculated the PRI for each of the 16 specialties of interest over eight consecutive years. The longitudinal changes in the PRI accurately captured the impact of the 2017 Chinese healthcare reforms and the 2020 COVID-19 pandemic on hospital specialties. At last, the two-dimensional assessment model we devised effectively illustrates the distinct characteristics across hospital specialties. CONCLUSION: We propose a novel, straightforward, and interpretable index for quantifying the influence of hospital specialties. This index, built on outpatient data, requires only the patients' origin, thereby facilitating its widespread adoption and comparison across specialties of varying backgrounds. This data-driven method offers a patient-centric view of specialty influence, diverging from the traditional reliance on expert opinions. As such, it serves as a valuable augmentation to existing ranking systems.


Asunto(s)
Macrodatos , COVID-19 , Humanos , China , COVID-19/epidemiología , SARS-CoV-2 , Instituciones de Atención Ambulatoria/estadística & datos numéricos , Instituciones de Atención Ambulatoria/normas , Pandemias , Medicina/estadística & datos numéricos , Especialización/estadística & datos numéricos , Pacientes Ambulatorios/estadística & datos numéricos , Reforma de la Atención de Salud
17.
Bioorg Chem ; 151: 107686, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39111120

RESUMEN

A series of novel quinazoline-derived EGFR/HER-2 dual-target inhibitors were designed and synthesized by heterocyclic-containing tail approach. The inhibitory activities against four human epidermal growth factor receptor (HER) isozymes (EGFR, HER-2, HER-3 and HER-4) of all new compounds so designed were investigated in vitro. Compound 12k was found to be the most effective and rather selective dual-target inhibitor of EGFR and HER-2 with inhibitory constant (IC50) values of 6.15 and 9.78 nM, respectively, which was more potent than the clinical used agent Lapatinib (IC50 = 8.41 and 9.41 nM). Meanwhile, almost all compounds showed excellent antiproliferative activities against four cancer cell models (A549, NCI-H1975, SK-BR-3 and MCF-7) and low damage to healthy cells. Among them, compound 12k also exhibited the most prominent antitumor activity. Moreover, the hit compound 12k could bind to EGFR and HER-2 stably in molecular docking and dynamics studies. The following wound healing assay revealed that compound 12k could inhibit the migration of SK-BR-3 cells. Further studies found that compound 12k could arrest cell cycle in the G0/G1 phase and induce SK-BR-3 cells apoptosis. Notably, compound 12k could effectively inhibit breast cancer growth with little toxicity in the SK-BR-3 cell xenograft model. Taken together, in vitro and in vivo results disclosed that compound 12k had high drug potential as a dual-target inhibitor of EGFR/HER-2 to inhibit breast cancer growth.


Asunto(s)
Antineoplásicos , Proliferación Celular , Relación Dosis-Respuesta a Droga , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Receptores ErbB , Inhibidores de Proteínas Quinasas , Quinazolinas , Receptor ErbB-2 , Humanos , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Quinazolinas/farmacología , Quinazolinas/química , Quinazolinas/síntesis química , Receptor ErbB-2/antagonistas & inhibidores , Receptor ErbB-2/metabolismo , Proliferación Celular/efectos de los fármacos , Relación Estructura-Actividad , Estructura Molecular , Animales , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Ratones , Línea Celular Tumoral , Simulación del Acoplamiento Molecular , Apoptosis/efectos de los fármacos , Compuestos Heterocíclicos/farmacología , Compuestos Heterocíclicos/química , Compuestos Heterocíclicos/síntesis química , Femenino
18.
Environ Res ; 262(Pt 2): 119913, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39233030

RESUMEN

This study investigates the enhancement of ozone adsorption on diverse TiO2 crystal interfaces through an innovative electrochemical modulation approach. The research focuses on the effects of applied electric field strength and reaction sites on ozone interfacial adsorption energies for Ti/Anatase TiO2 (0 0 1) and Ti/Rutile TiO2 (1 1 0) interfaces. The findings reveal that positive electric fields significantly enhance ozone adsorption on both interfaces, with adsorption energies increasing by up to 18% for Ti/Anatase TiO2 (0 0 1) and 15% for Ti/Rutile TiO2 (1 1 0). Notably, double water molecule sites (≡(H2O)2) play a crucial role in this enhancement process. The study demonstrates that the applied electric field alters the charge distribution at the TiO2 catalytic interface, thereby increasing interfacial charge density and promoting charge migration to ozone. Furthermore, this process leads to enhanced overlap and hybridization between ≡(H2O)2 sites and the s and p orbitals of ozone molecules, resulting in the formation of chemical bonds with lower Fermi levels. These comprehensive results demonstrate the broad applicability of the electrochemical interfacial ozone adsorption enhancement method across different crystal types and surfaces. Consequently, this study provides essential data to support the advancement of greener and more energy-efficient heterogeneous catalytic ozonation processes, potentially contributing to significant improvements in ozone-based water treatment technologies.

19.
Int J Hyperthermia ; 41(1): 2270671, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38214143

RESUMEN

OBJECTIVE: To evaluate the outcomes of radiofrequency ablation (RFA) for papillary thyroid microcarcinoma (PTMC) adjacent to the trachea and compare them with those of PTMC distant from the trachea. METHODS: Patients who received RFA for solitary low-risk PTMC between June 2014 and July 2020 were reviewed and classified into adjacent and distant groups. To balance between-group confounders, the propensity score matching approach was employed. Volume, volume reduction ratio (VRR), tumor disappearance, complications, and disease progression were assessed and compared between the groups. Furthermore, factors affecting disease progression were evaluated. RESULTS: A total of 122 and 470 patients were included in the adjacent and distant groups, respectively. Overall VRR was 99.5% ± 3.1 and cumulative tumor disappearance rate was 99.4% after a mean follow-up time of 40.1 months ± 16.2. Overall disease progression and complications incidence were 3.7% and 1.0%, respectively. No substantial differences were observed between the two groups in the latest volume (0.8 mm3 ± 4.1 vs. 0.9 mm3 ± 4.2, p = .77), VRR (99.7% ± 1.6 vs. 99.5% ± 2.7, p = .75), cumulative tumor disappearance rate (92.6% vs. 94.2%, p = .58), and incidence of disease progression (4.1% vs. 4.5%, p = .70) and complication (1.7% vs. 0.8%, p = .86) after 1:2 matching. Additionally, tracheal adjacency exhibited no association with disease progression in multivariate Cox regression analysis (p = .73). CONCLUSION: For eligible patients with PTMC located adjacent to or distant from the trachea, RFA may offer a safe and effective alternative treatment method.


Asunto(s)
Carcinoma Papilar , Ablación por Radiofrecuencia , Neoplasias de la Tiroides , Humanos , Tráquea/cirugía , Tráquea/patología , Neoplasias de la Tiroides/radioterapia , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Ablación por Radiofrecuencia/métodos , Progresión de la Enfermedad , Estudios Retrospectivos , Resultado del Tratamiento
20.
Mikrochim Acta ; 191(5): 263, 2024 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-38619658

RESUMEN

A green and sensitive ratio fluorescence strategy was proposed for the detection of formaldehyde (FA) in food based on a kind of metal-organic frameworks (MOFs), MIL-53(Fe)-NO2, and nitrogen-doped Ti3C2 MXene quantum dots (N-Ti3C2 MQDs) with a blue fluorescence at 450 nm. As a type of MOFs with oxidase-like activity, MIL-53(Fe)-NO2 can catalyze o-phenylenediamine (OPD) into yellow fluorescent product 2,3-diaminophenazine (DAP) with a fluorescent emission at 560 nm. DAP has the ability to suppress the blue light of N-Ti3C2 MQDs due to inner filter effect (IFE). Nevertheless, Schiff base reaction can occur between FA and OPD, inhibiting DAP production. This results in a weakening of the IFE which reverses the original fluorescence color and intensity of DAP and N-Ti3C2 MQDs. So, the ratio of fluorescence intensity detected at respective 450 nm and 560 nm was designed as the readout signal to detect FA in food. The linear range of FA detection was 1-200 µM, with a limit of detection of 0.49 µM. The method developed was successfully used to detect FA in food with satisfactory results. It indicates that MIL-53(Fe)-NO2, OPD, and N-Ti3C2 MQDs (MON) system constructed by integrating the mimics enzyme, enzyme substrate, and fluorescent quantum dots has potential application for FA detection in practical samples.


Asunto(s)
Estructuras Metalorgánicas , Fenilendiaminas , Puntos Cuánticos , Colorantes Fluorescentes , Dióxido de Nitrógeno , Formaldehído
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