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1.
Micromachines (Basel) ; 15(5)2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38793173

RESUMO

In this study, a 4H-SiC homoepitaxial layer was grown on a 150 mm 4° off-axis substrate using a horizontal hot wall chemical vapor deposition reactor. Comparing C3H8 and C2H4 as C sources, the sample grown with C2H4 exhibited a slower growth rate and lower doping concentration, but superior uniformity and surface roughness compared to the C3H8-grown sample. Hence, C2H4 is deemed more suitable for commercial epitaxial wafer growth. Increasing growth pressure led to decreased growth rate, worsened thickness uniformity, reduced doping concentration, deteriorated uniformity, and initially improved and then worsened surface roughness. Optimal growth quality was observed at a lower growth pressure of 40 Torr. Furthermore, the impact of buffer layer growth on epitaxial quality varied significantly based on different C/Si ratios, emphasizing the importance of selecting the appropriate conditions for subsequent device manufacturing.

2.
Polymers (Basel) ; 16(9)2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38732765

RESUMO

The long-term operation of motors induces substantial alterations in the surface conductivity and nonlinear coefficient of anti-corona paint, diminishing its efficacy and jeopardizing the longevity of large motors. Hence, the development of high-performance anti-corona paint holds paramount importance in ensuring motor safety. In this study, we integrate two nano-fillers, namely silicon carbide (SiC) and organic montmorillonite (O-MMT), into a composite matrix comprising micron silicon carbide and epoxy resin (SiC/EP). Subsequently, three distinct types of anti-corona paint are formulated: SiC/EP, Nano-SiC/EP, and O-MMT/SiC/EP. Remarkably, O-MMT/SiC/EP exhibits a glass transition temperature about 25 °C higher than that of SiC/EP, underscoring its superior thermal properties. Moreover, the introduction of nano-fillers markedly augments the surface conductivity of the anti-corona paint. Aging tests, conducted across varying temperatures, unveil a notable reduction in the fluctuation range of surface conductivity post-aging. Initially, the nonlinear coefficients exhibit a declining trend, succeeded by an ascending trajectory. The O-MMT/SiC/EP composite displays a maximum nonlinearity coefficient of 1.465 and a minimum of 1.382. Furthermore, the incorporation of nanofillers amplifies the dielectric thermal stability of epoxy resin composites, with O-MMT/SiC/EP showcasing the pinnacle of thermal endurance. Overall, our findings elucidate the efficacy of nano-fillers in enhancing the performance and longevity of anti-corona paint, particularly highlighting the exceptional attributes of the O-MMT/SiC/EP composite in bolstering motor safety through improved thermal stability and electrical properties.

4.
RSC Adv ; 14(23): 16574-16583, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38779386

RESUMO

In this study, the epitaxial growth of 6-inch n-type 4° off-axis Si-face substrates using a horizontal hot-wall LPCVD system was investigated. The study explored the epitaxial growth under different source gas flow rates, growth pressures, and pre-etching times, with particular emphasis on their effects on epitaxial growth rate, epitaxial layer thickness uniformity, doping concentration and uniformity, and epitaxial layer surface roughness. The observation was made that the increase in source gas flow rate led to variations in dopant concentration due to different transport models between nitrogen gas and source gas. Additionally, with the increase in etching time, overetching phenomena occurred, resulting in changes in both dopant concentration and uniformity. Furthermore, the relationships between these three factors and their corresponding indicators were explained by combining the CVD growth process with the laminar flow model. These observed patterns are beneficial for further optimizing growth conditions in industrial settings, ultimately enhancing the quality of the growth process.

5.
Adv Sci (Weinh) ; : e2400972, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38718307

RESUMO

Bioinspired micropillar adhesives have shown broad application prospects in space capture and docking, due to their strong adhesion, good environmental adaptability, and reusability. However, when performing space missions, unavoidable contact collision with target objects may cause large deformation of the micropillars, resulting in the loss of adhesion ability. This study reports a novel micropillar adhesive through the in-plane combination of micropillars (IPCM) with different aspect ratios, consisting of small pillars for retaining strong adhesion and large ones for resisting overload-induced adhesion failure. It is demonstrated that the IPCM array can still maintain 85% of the adhesion peak after static large deformation compared to a general micropillar array composed of the same pillars. The impact of element size and layout of the IPCM, as well as detachment velocity on adhesion performance under high preload is discussed. Furthermore, finite element contact analysis qualitatively reproduces the experimentally observed micropillar deformations and attributes the overload-induced adhesion failure to the redistribution of surface normal stress. Finally, the potential application of the IPCM in dynamic capture is demonstrated on different objects. The proposed IPCM opens up new design concepts for practical applications of bioinspired adhesives in space capture and docking.

6.
Micromachines (Basel) ; 15(4)2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38675319

RESUMO

The critical structural parameters are optimized and studied using the numerical simulation method to improve the resolution and stability of the Micro-Thrust Measurement Platform (MTMP). Under two different ground random vibration environments, the parameters, such as pivot thickness, pendulum rod length, and pivot structure, are focused on analyzing the influence of the system's resolution and stability. The results show that when the thickness of the pivot is 0.04 mm or 0.2 mm, and the pendulum rod length is 2 m, the effect of ground random vibration on the MTMP is minimized. At 0.1 mHz, it can reach 0.0057 µN/Hz. In the series double-pivot structure, an appropriate increase in the distance between the sheets can further optimize the above conclusions. The results and analysis within this study can provide support for the engineering design of the MTMP.

7.
Trials ; 25(1): 275, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38650028

RESUMO

BACKGROUND: Parkinson's disease (PD) is a progressive, neurodegenerative illness marked by the loss of dopaminergic neurons, causing motor symptoms. Oral levodopa replacement therapy remains the gold standard in the treatment of PD. It is, nevertheless, a symptomatic treatment. There is currently no effective treatment for PD. Therefore, new therapies for PD are highly desirable. Low-intensity pulsed ultrasound (LIPUS) has been shown to improve behavioral functions in PD animal models. It is a new type of neuromodulation approach that combines noninvasiveness with high spatial precision. The purpose of this study is to establish a new clinical protocol for LIPUS in the treatment of movement disorders in patients with PD. METHODS: This protocol is a single-site, prospective, double-blind, randomized controlled trial (RCT). Forty-eight participants with clinically confirmed PD will be randomly allocated to one of two groups: LIPUS group or sham group. All of the participants continue to use pharmacological therapy as a fundamental treatment. The primary outcome is the difference between groups from baseline to 4 months in the change in the Unified Parkinson's Disease Rating Scale (UPDRS) motor score (part III). The secondary outcomes include the rating scales such as the Mini-Mental State Examination (MMSE), and other three rating scales, and medical examinations including high-density electroencephalography (hdEEG) and functional magnetic resonance imaging (fMRI). The primary safety outcome will be assessed at 4 months, and adverse events will be recorded. DISCUSSION: This study represents the clinical investigation into the efficacy of therapeutic LIPUS in the treatment of PD for the first time. If LIPUS is determined to be effective, it could offer a practical and innovative means of expanding the accessibility of ultrasound therapy by using a wearable LIPUS device within a home setting. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100052093. Registered on 17 October 2021.


Assuntos
Doença de Parkinson , Ensaios Clínicos Controlados Aleatórios como Assunto , Terapia por Ultrassom , Humanos , Doença de Parkinson/terapia , Doença de Parkinson/complicações , Método Duplo-Cego , Estudos Prospectivos , Resultado do Tratamento , Terapia por Ultrassom/métodos , Masculino , Dispositivos Eletrônicos Vestíveis , Idoso , Pessoa de Meia-Idade , Feminino , Fatores de Tempo , China
8.
Lancet ; 403(10439): 1855-1865, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38604212

RESUMO

BACKGROUND: Intravascular ultrasound-guided percutaneous coronary intervention has been shown to result in superior clinical outcomes compared with angiography-guided percutaneous coronary intervention. However, insufficient data are available concerning the advantages of intravascular ultrasound guidance for patients with an acute coronary syndrome. This trial aimed to investigate whether the use of intravascular ultrasound guidance, as compared with angiography guidance, improves the outcomes of percutaneous coronary intervention with contemporary drug-eluting stents in patients presenting with an acute coronary syndrome. METHODS: In this two-stage, multicentre, randomised trial, patients aged 18 years or older and presenting with an acute coronary syndrome at 58 centres in China, Italy, Pakistan, and the UK were randomly assigned to intravascular ultrasound-guided percutaneous coronary intervention or angiography-guided percutaneous coronary intervention. Patients, follow-up health-care providers, and assessors were masked to random assignment; however, staff in the catheterisation laboratory were not. The primary endpoint was target vessel failure, a composite of cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularisation at 1 year after randomisation. This trial is registered at ClinicalTrials.gov, NCT03971500, and is completed. FINDINGS: Between Aug 20, 2019 and Oct 27, 2022, 3505 patients with an acute coronary syndrome were randomly assigned to intravascular ultrasound-guided percutaneous coronary intervention (n=1753) or angiography-guided percutaneous coronary intervention (n=1752). 1-year follow-up was completed in 3504 (>99·9%) patients. The primary endpoint occurred in 70 patients in the intravascular ultrasound group and 128 patients in the angiography group (Kaplan-Meier rate 4·0% vs 7·3%; hazard ratio 0·55 [95% CI 0·41-0·74]; p=0·0001), driven by reductions in target vessel myocardial infarction or target vessel revascularisation. There were no significant differences in all-cause death or stent thrombosis between groups. Safety endpoints were also similar in the two groups. INTERPRETATION: In patients with an acute coronary syndrome, intravascular ultrasound-guided implantation of contemporary drug-eluting stents resulted in a lower 1-year rate of the composite outcome of cardiac death, target vessel myocardial infarction, or clinically driven revascularisation compared with angiography guidance alone. FUNDING: The Chinese Society of Cardiology, the National Natural Scientific Foundation of China, and Jiangsu Provincial & Nanjing Municipal Clinical Trial Project. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.


Assuntos
Síndrome Coronariana Aguda , Angiografia Coronária , Stents Farmacológicos , Intervenção Coronária Percutânea , Ultrassonografia de Intervenção , Humanos , Síndrome Coronariana Aguda/terapia , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/cirurgia , Intervenção Coronária Percutânea/métodos , Ultrassonografia de Intervenção/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Angiografia Coronária/métodos , Idoso , Resultado do Tratamento , China
9.
Int J Biol Macromol ; 267(Pt 2): 131658, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38636759

RESUMO

Moisture evaporation plays a crucial role in thermal management of human body, particularly in perspiration process. However, current fabrics aim for sweat removal and takes little account of basic thermo-regulation of sweat, resulted in their limited evaporation capacity and heat dissipation at moderate/intense scenarios. In this study, a hygroscopic cooling (h-cool) fabric based on multi-functional design, for personal perspiration management, was described. By using economic and effective weaving technology, directional moisture transport routes and heat conductive pathways were incorporated in the construct. The resultant fabric showed 10 times greater one-way transport index higher than cotton, Dri-FIT and Coolswitch fabrics, which contributed to highly enhanced evaporation ability (∼4.5 times than cotton), not merely liquid diffusion. As a result, h-cool fabric performed 2.1-4.2 °C cooling efficacy with significantly reduced sweat consuming than cotton, Dri-FIT and Coolswitch fabrics in the artificial sweating skin. Finally, the practical applications by actually wearing h-cool fabric showed great evaporative-cooling efficacy during different physical activities. Owing to the excellent thermo-moisture management ability, we expect the novel concept and construct of h-cool fabric can provide promising strategy for developing functional textiles with great "cool" and comfortable "dry" tactile sensation at various daily scenarios.


Assuntos
Suor , Têxteis , Humanos , Suor/química , Temperatura Alta , Molhabilidade , Sudorese
10.
J Biophotonics ; : e202300568, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38651324

RESUMO

We investigate the efficacy of photodynamic antimicrobial chemotherapy (PACT) and its combination with an antibiotic in the treatment of diabetic foot ulcers (DFUs) in rats using a novel cationic amino acid porphyrin-based photosensitizer. The research findings demonstrate that the combination of novel cationic photosensitizer-mediated PACT and an antibiotic exhibits significant therapeutic efficacy in treating deep ulcers in a rat model of DFUs. Moreover, the PACT + Antibiotic group displays enhanced angiogenesis, improved tissue maturation, and superior wound healing effect. Micro-computed tomography examination showed that the periosteal reaction was most obvious in the PACT + Antibiotic group. The cortical bone volume ratio (BV/TV), the bone mineral density, and trabecular thickness were significantly higher in the PACT + Antibiotic group than in the model group (p < 0.05). The combination of PACT and antibiotic plays a sensitizing therapeutic role, which provides a new idea for the clinical treatment of DFUs.

11.
Eye Vis (Lond) ; 11(1): 15, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38584290

RESUMO

PURPOSE: The corneal cap thickness is a vital parameter designed in small incision lenticule extraction (SMILE). The purpose was to investigate the changes in corneal subbasal nerve plexus (SNP) and stromal cells with different cap thicknesses and evaluate the optimized design for the surgery. METHODS: In this prospective, comparative, non-randomized study, a total of 108 eyes of 54 patients who underwent SMILE were allocated into three groups with different corneal cap thicknesses (110 µm, 120 µm or 130 µm group). The SNP and stromal cell morphological changes obtained from in vivo corneal confocal microscopy (IVCCM) along with their refractive outcomes were collected at 1 week, 1 month, 3 months and 6 months postoperatively. One-way analysis of variance (ANOVA) was used to compare the parameters among the three groups. RESULTS: The SNPs in the three groups all decreased after surgery and revealed a gradual increasing trend during the 6-month follow-up. The values of the quantitative nerve metrics were significantly lower in the 110 µm group than in the 120 µm and 130 µm groups, especially at 1 week postoperatively. No difference was detected between the 120 µm and 130 µm groups at any time point. Both Langerhans cells and keratocytes were activated after surgery, and the activation was alleviated during the follow-up. CONCLUSIONS: The SMILE surgeries with 110 µm, 120 µm or 130 µm cap thickness design achieved good efficacy, safety, accuracy and stability for moderate to high myopic correction while the thicker corneal cap was more beneficial for corneal nerve regeneration.

12.
Front Bioeng Biotechnol ; 12: 1352794, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38686117

RESUMO

As a solution to restore knee function and reduce pain, the demand for Total Knee Arthroplasty (TKA) has dramatically increased in recent decades. The high rates of dissatisfaction and revision makes it crucially important to understand the relationships between surgical factors and post-surgery knee performance. Tibial implant alignment in the sagittal plane (i.e., posterior tibia slope, PTS) is thought to play a key role in quadriceps muscle forces and contact conditions of the joint, but the underlying mechanisms and potential consequences are poorly understood. To address this biomechanical challenge, we developed a subject-specific musculoskeletal model based on the bone anatomy and precise implantation data provided within the CAMS-Knee datasets. Using the novel COMAK algorithm that concurrently optimizes joint kinematics, together with contact mechanics, and muscle and ligament forces, enabled highly accurate estimations of the knee joint biomechanics (RMSE <0.16 BW of joint contact force) throughout level walking and squatting. Once confirmed for accuracy, this baseline modelling framework was then used to systematically explore the influence of PTS on knee joint biomechanics. Our results indicate that PTS can greatly influence tibio-femoral translations (mainly in the anterior-posterior direction), while also suggesting an elevated risk of patellar mal-tracking and instability. Importantly, however, an increased PTS was found to reduce the maximum tibio-femoral contact force and improve efficiency of the quadriceps muscles, while also reducing the patellofemoral contact force (by approximately 1.5% for each additional degree of PTS during walking). This study presents valuable findings regarding the impact of PTS variations on the biomechanics of the TKA joint and thereby provides potential guidance for surgically optimizing implant alignment in the sagittal plane, tailored to the implant design and the individual deficits of each patient.

13.
Nat Commun ; 15(1): 2495, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553445

RESUMO

Since the origin of life, temperatures on earth have fluctuated both on short and long time scales. How such changes affect the rate at which Darwinian evolution can bring forth new phenotypes remains unclear. On the one hand, high temperature may accelerate phenotypic evolution because it accelerates most biological processes. On the other hand, it may slow phenotypic evolution, because proteins are usually less stable at high temperatures and therefore less evolvable. Here, to test these hypotheses experimentally, we evolved a green fluorescent protein in E. coli towards the new phenotype of yellow fluorescence at different temperatures. Yellow fluorescence evolved most slowly at high temperature and most rapidly at low temperature, in contradiction to the first hypothesis. Using high-throughput population sequencing, protein engineering, and biochemical assays, we determined that this is due to the protein-destabilizing effect of neofunctionalizing mutations. Destabilization is highly detrimental at high temperature, where neofunctionalizing mutations cannot be tolerated. Their detrimental effects can be mitigated through excess stability at low temperature, leading to accelerated adaptive evolution. By modifying protein folding stability, temperature alters the accessibility of mutational paths towards high-fitness genotypes. Our observations have broad implications for our understanding of how temperature changes affect evolutionary adaptations and innovations.


Assuntos
Escherichia coli , Evolução Molecular , Temperatura , Escherichia coli/genética , Aptidão Genética , Fenótipo , Mutação , Proteínas de Fluorescência Verde/genética , Evolução Biológica
14.
South Med J ; 117(3): 165-171, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38428939

RESUMO

OBJECTIVES: Do-not-resuscitate (DNR) orders are used to express patient preferences for cardiopulmonary resuscitation. This study examined whether early DNR orders are associated with differences in treatments and outcomes among patients hospitalized with pneumonia. METHODS: This is a retrospective cohort study of 768,015 adult patients hospitalized with pneumonia from 2010 to 2015 in 646 US hospitals. The exposure was DNR orders present on admission. Secondary analyses stratified patients by predicted in-hospital mortality. Main outcomes included in-hospital mortality, length of stay, cost, intensive care admission, invasive mechanical ventilation, noninvasive ventilation, vasopressors, and dialysis initiation. RESULTS: Of 768,015 patients, 94,155 (12.3%) had an early DNR order. Compared with those without, patients with DNR orders were older (mean age 80.1 ± 10.6 years vs 67.8 ± 16.4 years), with higher comorbidity burden, intensive care use (31.6% vs 30.6%), and in-hospital mortality (28.2% vs 8.5%). After adjustment via propensity score weighting, these patients had higher mortality (odds ratio [OR] 2.39, 95% confidence interval [CI] 2.33-2.45) and lower use of intensive therapies such as vasopressors (OR 0.83, 95% CI 0.81-0.85) and invasive mechanical ventilation (OR 0.68, 95% CI 0.66-0.70). Although there was little relationship between predicted mortality and DNR orders, among those with highest predicted mortality, DNR orders were associated with lower intensive care use compared with those without (66.7% vs 80.8%). CONCLUSIONS: Patients with early DNR orders have higher in-hospital mortality rates than those without, but often receive intensive care. These orders have the most impact on the care of patients with the highest mortality risk.


Assuntos
Pneumonia , Ordens quanto à Conduta (Ética Médica) , Adulto , Humanos , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Hospitalização , Comorbidade , Pneumonia/terapia
15.
Asian J Androl ; 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38445955

RESUMO

ABSTRACT: Failure of oocyte activation, including polyspermy and defects in pronuclear (PN) formation, triggers early embryonic developmental arrest. Many studies have shown that phospholipase C zeta 1 ( PLCZ1 ) mutations cause failure of PN formation following intracytoplasmic sperm injection (ICSI); however, whether PLCZ1 mutation is associated with polyspermy during in vitro fertilization (IVF) remains unknown. Whole-exome sequencing (WES) was performed to identify candidate mutations in couples with primary infertility. Sanger sequencing was used to validate the mutations. Multiple PLCZ1 -mutated sperm were injected into human and mouse oocytes to explore whether PN formation was induced. Assisted oocyte activation (AOA) after ICSI was performed to overcome the failure of oocyte activation. We identified three PLCZ1 mutations in three patients who experienced polyspermy during IVF cycles, including a novel missense mutation c.1154C>T, p.R385Q. PN formation failure was observed during the ICSI cycle. However, injection of multiple PLCZ1 -mutated sperm induced PN formation, suggesting that the Ca 2+ oscillations induced by the sperm exceeded the necessary threshold for PN formation. AOA after ICSI enabled normal fertilization, and all patients achieved successful pregnancies. These findings expand the mutational spectrum of PLCZ1 and suggest an important role for PLCZ1 in terms of blocking polyspermy. Furthermore, this study may benefit genetic diagnoses in cases of abnormal fertilization and provide potential appropriate therapeutic measures for these patients with sperm-derived polyspermy.

16.
Int J Biol Macromol ; 263(Pt 1): 130309, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38382779

RESUMO

Maintaining protein balance within a cell is essential for proper cellular function, and disruptions in the ubiquitin-proteasome pathway, which is responsible for degrading and recycling unnecessary or damaged proteins, can lead to various diseases. Deubiquitinating enzymes play a vital role in regulating protein homeostasis by removing ubiquitin chains from substrate proteins, thereby controlling important cellular processes, such as apoptosis and DNA repair. Among these enzymes, ubiquitin-specific protease 7 (USP7) is of particular interest. USP7 is a cysteine protease consisting of a TRAF region, catalytic region, and C-terminal ubiquitin-like (UBL) region, and it interacts with tumor suppressors, transcription factors, and other key proteins involved in cell cycle regulation and epigenetic control. Moreover, USP7 has been implicated in the pathogenesis and progression of various diseases, including cancer, inflammation, neurodegenerative conditions, and viral infections. Overall, characterizing the functions of USP7 is crucial for understanding the pathophysiology of diverse diseases and devising innovative therapeutic strategies. This article reviews the structure and function of USP7 and its complexes, its association with diseases, and its known inhibitors and thus represents a valuable resource for advancing USP7 inhibitor development and promoting potential future treatment options for a wide range of diseases.


Assuntos
Proteostase , Ubiquitina , Peptidase 7 Específica de Ubiquitina/genética , Peptidase 7 Específica de Ubiquitina/química , Peptidase 7 Específica de Ubiquitina/metabolismo , Ubiquitina/química , Domínio Catalítico , Ubiquitina Tiolesterase/química
17.
Front Endocrinol (Lausanne) ; 15: 1361115, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38298380
18.
Dalton Trans ; 53(11): 5202-5211, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38385284

RESUMO

The realization of thermally stable Tb3+-doped green emission at high temperatures in solid-state lighting is still a crucial challenge. Nevertheless, the study on modulating the thermally stable luminescence at high temperatures is seldom reported. The position of the intervalence charge transfer (IVCT) energy level is used to systematically investigate the thermal quenching performance of Tb3+-activated green-emitting phosphors with varying concentration gradients of Gd1-xTaO4:xTb3+ (x = 0.1%, 0.5%, and 2%) in this study. The IVCT energy levels were determined according to the empirical formula to show a decreasing trend, consistent with the position of the IVCT energy levels measured in the excitation and diffuse reflectance spectra. Moreover, the thermal quenching performance of different wavelength excitation positions (host absorption, 4f-5d of Tb3+, and Tb3+-Ta5+ IVCT band) is quite different. The modulation of thermal quenching performance among distinct phosphors when subjected to host excitation or IVCT excitation can be elucidated through optimal positions within the energy levels associated with IVCT. The diverse concentration gradient samples exhibit varying degrees of thermal quenching performance in the variable-temperature spectra. The fluorescence lifetimes of the samples are generally comparable but slightly lower. The quantum efficiency rapidly improves as the Tb concentration increases. The underlying mechanism governing this phenomenon is elucidated by constructing a model that encapsulates the interplay between the compensating and quenching channels, in addition to the energy conversion of Tb3+ into Gd3+. The abovementioned results indicate that the dual driving scheme of the doping concentration and excitation wavelength is an effective means to regulate the thermal quenching performance of Tb-activated green-emitting tantalate phosphors.

19.
Cell Rep ; 43(2): 113714, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38306271

RESUMO

Drug resistance is the leading problem in non-small-cell lung cancer (NSCLC) therapy. The contribution of histone methylation in mediating malignant phenotypes of NSCLC is well known. However, the role of histone methylation in NSCLC drug-resistance mechanisms remains unclear. Here, our data show that EZH2 and G9a, two histone methyltransferases, are involved in the drug resistance of NSCLC. Gene manipulation results indicate that the combination of EZH2 and G9a promotes tumor growth and mediates drug resistance in a complementary manner. Importantly, clinical study demonstrates that co-expression of both enzymes predicts a poor outcome in patients with NSCLC. Mechanistically, G9a and EZH2 interact and promote the silencing of the tumor-suppressor gene SMAD4, activating the ERK/c-Myc signaling pathway. Finally, SU08, a compound targeting both EZH2 and G9a, is demonstrated to sensitize resistant cells to therapeutic drugs by regulating the SMAD4/ERK/c-Myc signaling axis. These findings uncover the resistance mechanism and a strategy for reversing NSCLC drug resistance.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Transdução de Sinais , Proteínas Proto-Oncogênicas c-myc/genética , Histonas , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Proteína Smad4/genética , Proteína Potenciadora do Homólogo 2 de Zeste
20.
ACS Omega ; 9(6): 7230-7238, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38371808

RESUMO

Diterpenoid tanshinones (DTs) are a bioactive fraction extracted from Salvia miltiorrhiza. High-performance liquid chromatography analysis revealed the presence of four compounds, namely, tanshinone IIA, tanshinone I, cryptotanshinone, and dihydrotanshinone. In this study, we aimed to propose a possible mechanism for the anti-lung cancer effect of DT. To do so, we utilized a lung cancer nude mice model and a lung cancer cell line (PC9) to investigate the effect of DT on lung cancer. We employed immunohistochemistry, enzyme-linked immunosorbent assay, hematoxylin and eosin staining, and immunofluorescence to analyze the pharmacological role of DT in the inhibition of lung cancer growth. The results showed that DT inhibited tumor growth, induced apoptosis in the nude mice model, and reduced inflammatory cell infiltration. Additionally, DT inhibited PC9 lung cancer cells, growth, proliferation, and migration. The mechanism of action of DT involves not only directly inhibiting cell proliferation and migration but also improving the tumor microenvironment. DT significantly increased the expression of important intestinal gap junction proteins, such as zonula occludens 1 (ZO-1) and occludin I. This upregulation contributes to the reinforcement of the intestinal mucosal barrier, thereby reducing the paracellular transport of lipopolysaccharides (LPS) through the intestine. Consequently, the decreased LPS levels lead to the inhibition of NF-κB expression and downregulation of macrophage polarization, as indicated by the decreased expression of CD68. In conclusion, this study has confirmed that DT has anti-lung cancer properties by improving the inflammatory tumor microenvironment via regulating macrophage polarization and inhibiting LPS-associated immune response. These results provide new insights into the mechanism of DT action against lung cancer.

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