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1.
Cell ; 186(11): 2475-2491.e22, 2023 05 25.
Article in English | MEDLINE | ID: mdl-37178688

ABSTRACT

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.


Subject(s)
Imaging, Three-Dimensional , Animals , Mice , Imaging, Three-Dimensional/methods , Microscopy, Confocal/methods
2.
Proc Natl Acad Sci U S A ; 121(18): e2400313121, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38652745

ABSTRACT

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(12): 1957-1970, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37957429

ABSTRACT

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.


Subject(s)
Dictyostelium , Image Enhancement , Microscopy, Confocal/methods , Signal-To-Noise Ratio , Microscopy, Fluorescence , Image Processing, Computer-Assisted/methods
4.
Nat Methods ; 20(5): 747-754, 2023 05.
Article in English | MEDLINE | ID: mdl-37002377

ABSTRACT

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.


Subject(s)
Brain , Calcium , Animals , Brain/physiology , Microscopy , Cerebral Cortex , Neurons/physiology , Mammals
5.
Plant J ; 2024 Aug 22.
Article in English | MEDLINE | ID: mdl-39172024

ABSTRACT

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.
Article in English | MEDLINE | ID: mdl-37552606

ABSTRACT

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.
Article in English | MEDLINE | ID: mdl-38551337

ABSTRACT

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.
Article in English | MEDLINE | ID: mdl-37726238

ABSTRACT

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.
Article in English | MEDLINE | ID: mdl-37702141

ABSTRACT

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.


Subject(s)
Nanoparticles , Neoplasms , Nitriles , Humans , Porosity , Silicon Dioxide/chemistry , Immunotherapy , Nanoparticles/chemistry , Neoplasms/therapy , Skeleton
10.
Small ; 20(31): e2308690, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38470201

ABSTRACT

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.
Article in English | MEDLINE | ID: mdl-34400836

ABSTRACT

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.


Subject(s)
Action Potentials , Algorithms , Calcium/metabolism , Diagnostic Imaging/methods , Image Processing, Computer-Assisted/methods , Neurons/physiology , Signal-To-Noise Ratio , Animals , Female , Male , Mice , Mice, Transgenic , Neurons/cytology
12.
J Virol ; 97(10): e0109023, 2023 10 31.
Article in English | MEDLINE | ID: mdl-37787533

ABSTRACT

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.


Subject(s)
Coinfection , DNA-Binding Proteins , Hepacivirus , Hepatitis B virus , Hepatitis B , Hepatitis C , Immunity, Innate , Humans , Coinfection/immunology , Coinfection/virology , DNA-Binding Proteins/metabolism , Hepacivirus/immunology , Hepatitis B/complications , Hepatitis B/immunology , Hepatitis B/virology , Hepatitis B virus/immunology , Hepatitis B virus/physiology , Hepatitis C/complications , Hepatitis C/immunology , Hepatitis C/virology , Inflammasomes/metabolism , Interferon-gamma/immunology
13.
J Vasc Surg ; 80(1): 188-198.e1, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38301808

ABSTRACT

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.


Subject(s)
Amputation, Surgical , Endovascular Procedures , Femoral Artery , Peripheral Arterial Disease , Popliteal Artery , Vascular Calcification , Vascular Patency , Humans , Male , Female , Retrospective Studies , Femoral Artery/diagnostic imaging , Femoral Artery/physiopathology , Femoral Artery/surgery , Aged , Popliteal Artery/diagnostic imaging , Popliteal Artery/physiopathology , Popliteal Artery/surgery , Peripheral Arterial Disease/diagnostic imaging , Peripheral Arterial Disease/therapy , Peripheral Arterial Disease/physiopathology , Peripheral Arterial Disease/mortality , Vascular Calcification/diagnostic imaging , Vascular Calcification/therapy , Vascular Calcification/mortality , Endovascular Procedures/adverse effects , Time Factors , Middle Aged , Risk Factors , Aged, 80 and over , Limb Salvage , Treatment Outcome , Progression-Free Survival , Risk Assessment
14.
Eur Radiol ; 34(2): 761-769, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37597031

ABSTRACT

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.


Subject(s)
Carcinoma, Papillary , Radiofrequency Ablation , Thyroid Neoplasms , Humans , Female , Adult , Follow-Up Studies , Retrospective Studies , Thyroid Neoplasms/surgery , Thyroid Neoplasms/pathology , Radiofrequency Ablation/methods , Treatment Outcome
15.
Eur Radiol ; 34(7): 4716-4726, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38170265

ABSTRACT

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.


Subject(s)
Carcinoma, Papillary , Propensity Score , Radiofrequency Ablation , Thyroid Neoplasms , Humans , Female , Male , Thyroid Neoplasms/surgery , Thyroid Neoplasms/pathology , Retrospective Studies , Radiofrequency Ablation/methods , Middle Aged , Adult , Carcinoma, Papillary/surgery , Treatment Outcome , Disease Progression , Aged
16.
Bioorg Chem ; 151: 107686, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39111120

ABSTRACT

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.


Subject(s)
Antineoplastic Agents , Cell Proliferation , Dose-Response Relationship, Drug , Drug Design , Drug Screening Assays, Antitumor , ErbB Receptors , Protein Kinase Inhibitors , Quinazolines , Receptor, ErbB-2 , Humans , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Quinazolines/pharmacology , Quinazolines/chemistry , Quinazolines/chemical synthesis , Receptor, ErbB-2/antagonists & inhibitors , Receptor, ErbB-2/metabolism , Cell Proliferation/drug effects , Structure-Activity Relationship , Molecular Structure , Animals , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Mice , Cell Line, Tumor , Molecular Docking Simulation , Apoptosis/drug effects , Heterocyclic Compounds/pharmacology , Heterocyclic Compounds/chemistry , Heterocyclic Compounds/chemical synthesis , Female
17.
Int J Hyperthermia ; 41(1): 2270671, 2024.
Article in English | MEDLINE | ID: mdl-38214143

ABSTRACT

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.


Subject(s)
Carcinoma, Papillary , Radiofrequency Ablation , Thyroid Neoplasms , Humans , Trachea/surgery , Trachea/pathology , Thyroid Neoplasms/radiotherapy , Thyroid Neoplasms/surgery , Thyroid Neoplasms/pathology , Radiofrequency Ablation/methods , Disease Progression , Retrospective Studies , Treatment Outcome
18.
Mikrochim Acta ; 191(5): 263, 2024 04 15.
Article in English | MEDLINE | ID: mdl-38619658

ABSTRACT

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.


Subject(s)
Metal-Organic Frameworks , Phenylenediamines , Quantum Dots , Fluorescent Dyes , Nitrogen Dioxide , Formaldehyde
19.
Int J Phytoremediation ; 26(2): 241-249, 2024.
Article in English | MEDLINE | ID: mdl-37463004

ABSTRACT

Sedum plumbizincicola is a cadmium (Cd) and zinc hyperaccumulator that can activate Cd by rhizosphere acidification. However, there is little understanding of the Cd leaching risk from polluted soil during phytoextraction process. Here, pot and column experiments were conducted to monitor soil Cd leaching characteristics under different rainfall simulation conditions during S. plumbizincicola phytoextraction. Soil Cd leaching increased significantly with increasing simulated rainfall intensity. Compared with normal rainfall (NR), weak rainfall (WR) resulted in a 34.3% decrease in Cd uptake by S. plumbizincicola and also led to a 68.7% decline in Cd leaching. In contrast, Cd leaching under heavy rainfall (HR) was 2.12 times that of NR in the presence of S. plumbizincicola. After two successive growing periods, phytoextraction resulted in a 53.5-66.4% decline in the amount of soil Cd leached compared with controls in which S. plumbizincicola was absent. Even compared with maize cropping as a control, S. plumbizincicola did not instigate a significant increase in Cd leaching. The contribution of Cd leaching loss to the decline in soil total Cd concentration was negligible after phytoextraction in the pot experiment. Overall, the results contribute to our understanding of soil Cd leaching risk by phytoextraction with S. plumbizincicola.


Repeated phytoextraction by hyperaccumulator Sedum plumbizincicola is an important remediation technology to remove Cd from contaminated soils. At the same time, Sedum plumbizincicola can also activate soil Cd by rhizosphere acidification. However, studies on the leaching risk of soil activated Cd during the phytoextraction process are very few. This study looked at the effects of Sedum plumbizincicola growth on soil Cd leaching with the changes in rainfall simulation and plant type. Results showed that repeated phytoextraction with Sedum plumbizincicola did not increase Cd leaching from contaminated soil.


Subject(s)
Sedum , Soil Pollutants , Cadmium , Soil Pollutants/analysis , Biodegradation, Environmental , Soil
20.
Nano Lett ; 23(21): 10034-10043, 2023 11 08.
Article in English | MEDLINE | ID: mdl-37903236

ABSTRACT

Metabolic reprogramming, as one of the characteristics of cancer, is associated with tumorigenesis, growth, or migration, and the modulation of metabolic pathways has emerged as a novel approach for cancer therapy. However, the conventional metabolism-mediated apoptosis process in tumor cells exhibits limited immunogenicity and inadequate activation of antitumor immunity. Herein, phospholipid-coated sodium citrate nanoparticles (PSCT NPs) are successfully prepared, which dissolve in tumor cells and then release significant amounts of citrate ions and Na+ ions. Massive quantities of ions lead to increased intracellular osmotic pressure, which activates the caspase-1/gasdermin D (GSDMD) mediated pyroptosis pathway. Simultaneously, citrate induces activation of the caspase-8/gasdermin C (GSDMC) pathway. The combined action of these two pathways synergistically causes intense pyroptosis, exhibiting remarkable antitumor immune responses and tumor growth inhibition. This discovery provides new insight into the potential of nanomaterials in modulating metabolism and altering cell death patterns to enhance antitumor immunotherapy.


Subject(s)
Nanoparticles , Neoplasms , Humans , Pyroptosis , Sodium Citrate , Gasdermins , Intracellular Signaling Peptides and Proteins , Neoplasms/drug therapy , Immunotherapy , Nanoparticles/therapeutic use , Ions , Biomarkers, Tumor , Pore Forming Cytotoxic Proteins
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