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1.
Adv Mater ; : e2404597, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38975985

RESUMO

Photomultiplication (PM)-type organic photodetectors (OPDs), which typically form a homogeneous distribution (HD) of n-type dopants in a p-type polymer host (HD PM-type OPDs), have achieved a breakthrough in device responsivity by surpassing a theoretical limit of external quantum efficiency (EQE). However, they face limitations in higher dark current and slower dynamic characteristics compared to p-n heterojunction (p-n HJ) OPDs due to inherent long lifetime of trapped electrons. To overcome this, we have developed a new PM-type OPD that demonstrates ultrafast dynamic properties through a vertical phase separation (VPS) strategy between the p-type polymer (host) and n-type acceptor (dopant), referred to as VPS PM-type OPDs. Notably, VPS PM-type OPDs show a remarkable increase (by three orders of magnitude) in -3 dB cut-off frequency (120 kHz) and over a 200-fold faster response time (rising time = 4.8 µs, falling time = 8.3 µs) compared to HD PM-type OPDs, while maintaining high EQE of 1,121% and specific detectivity of 2.53 × 1013 Jones at -10 V. The VPS PM OPD represents a groundbreaking advancement by demonstrating the coexistence of p-n HJ and PM modes within a single photoactive layer for the first time. This innovative approach holds the potential to enhance both static and dynamic properties of OPDs. This article is protected by copyright. All rights reserved.

2.
Se Pu ; 42(7): 646-657, 2024 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-38966973

RESUMO

Glycomics, an emerging "omics" technology that was developed after genomics and proteomics, is a discipline that studies the composition, structure, and functions of glycomes in cells, tissues, and organisms. Glycomics plays key roles in understanding the laws of major life activities, disease prevention and treatment, and drug quality control and development. At present, the structural analysis of glycans relies mainly on mass spectrometry. However, glycans have low abundance in biological samples. In addition, factors such as variable monosaccharide compositions, differences in glycosidic bond positions and modes, diverse branching structures, contribute to the complexity of the compositions and structures of glycans, posing great challenges to glycomics research. Liquid chromatography can effectively remove matrix interferences and enhance glycan separation to improve the mass spectrometric response of glycans. Thus, liquid chromatography and liquid chromatography coupled with mass spectrometry are important technical tools that have been actively applied to solve these problems; these technologies play indispensable roles in glycomics research. Different studies have highlighted similarities and differences in the applications of various types of liquid chromatography, which also reflects the versatility and flexibility of this technology. In this review, we first discuss the enrichment methods for glycans and their applications in glycomics research from the perspective of chromatographic separation mechanisms. We then compare the advantages and disadvantages of these methods. Some glycan-enrichment modes include affinity, hydrophilic interactions, size exclusion, and porous graphitized carbon adsorption. A number of newly developed materials exhibit excellent glycan-enrichment ability. We enumerate the separation mechanisms of reversed-phase high performance liquid chromatography (RP-HPLC), high performance anion-exchange chromatography (HPAEC), hydrophilic interaction chromatography (HILIC), and porous graphitic carbon (PGC) chromatography in the separation and analysis of glycans, and describe the applications of these methods in the separation of glycans, glycoconjugates, and glyco-derivatives. Among these methods, HILIC and PGC chromatography are the most widely used, whereas HPAEC and RP-HPLC are less commonly used. The HILIC and RP-HPLC modes are often used for the separation of derived glycans. The ionization efficiency and detectability of glycans are significantly improved after derivatization. However, the derivatization process is relatively cumbersome, and byproducts inevitably affect the accuracy and completeness of the detection results. HPAEC and PGC chromatography exhibit good separation effects on nonderivative glycans, but issues related to the detection integrity of low-abundance glycans owing to their poor detection effect continue to persist. Therefore, the appropriate analytical method for a specific sample or target analyte or mutual verification must be selected. Finally, we highlight the research progress in various chromatographic methods coupled with mass spectrometry for glycomics analysis. Significant progress has been made in glycomics research in recent years owing to advancements in the development of chromatographic separation techniques. However, several significant challenges remain. As the development of novel separation materials and methods continues, chromatographic techniques may be expected to play a critical role in future glycomics research.


Assuntos
Glicômica , Polissacarídeos , Glicômica/métodos , Polissacarídeos/análise , Polissacarídeos/química , Cromatografia Líquida/métodos , Espectrometria de Massas/métodos
3.
Sci Rep ; 14(1): 15766, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982175

RESUMO

Mining stress induces deformation and fracture of the overlaying rock, which will result in water filling the separation layer if the aquifer finds access to abscission space along the fracture channels. Accurate detection is crucial to prevent water hazards induced by water-bearing fractures. The 3-D time-domain finite-difference method with Yee's grid was adopted to calculate full-space transient electromagnetic response; meanwhile, a typical geologic and geophysical model with a water-bearing block in an separation layer was built according to regional tectonics and stratigraphic developments. By using numerical simulation, the induced voltage and apparent resistivity for both vertical and horizontal components were acquired, and then an approximate inversion was carried out based on the "smoke ring" theory. The results indicate that the diffusion velocity of induced voltage is significantly affected by the water-bearing body in the fracture, and the horizontal velocity of induced voltage is lower than the vertical one. The induced voltage curves indicate that the horizontal response to an anomaly body is stronger than the vertical one, leading to a high apparent resistivity resolution of conductivity contrast and separation layer boundary in the horizontal direction. The results of 3-D simulation making use of a measured data model also demonstrate that the horizontal component of apparent resistivity can reflect the electrical structure in a better way; however, its ability to recognize the concealed and fine conductor is rather weak. Accordingly, the observation method or numerical interpolation method needs to be further improved for data processing and interpretation.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38982922

RESUMO

The phenomenon of Liquid-Liquid Phase Separation (LLPS) serves as a vital mechanism for the spatial organization of biomolecules, significantly influencing the elementary processes within the cellular milieu. Intrinsically disordered proteins, or proteins endowed with intrinsically disordered regions, are pivotal in driving this biophysical process, thereby dictating the formation of non-membranous cellular compartments. Compelling evidence has linked aberrations in LLPS to the pathogenesis of various neurodegenerative diseases, underscored by the disordered proteins' proclivity to form pathological aggregates. This study meticulously evaluates the arsenal of contemporary experimental and computational methodologies dedicated to the examination of intrinsically disordered proteins within the context of LLPS. Through a discerning discourse on the capabilities and constraints of these investigative techniques, we unravel the intricate contributions of these ubiquitous proteins to LLPS and neurodegeneration. Moreover, we project a future trajectory for the field, contemplating on innovative research tools and their potential to elucidate the underlying mechanisms of LLPS, with the ultimate goal of fostering new therapeutic avenues for combating neurodegenerative disorders.

5.
World J Clin Cases ; 12(18): 3575-3581, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38983423

RESUMO

BACKGROUND: Intrabony defects beneath non-keratinized mucosa are frequently observed at the distal site of terminal molars. Consequently, the application of regenerative treatment using the modified wedge-flap technique is considered impractical for these specific dental conditions. CASE SUMMARY: This article proposes a modified surgical procedure aimed at exposing the distal intrabony defect by making a vertical incision in the keratinized buccal gingiva. The primary objective is to maintain gingival flap stability, thereby facilitating periodontal regeneration. The described technique was successfully employed in a case involving the left mandibular second molar, which presented with an intrabony defect without keratinized gingiva at the distal site. In this case, an incision was made on the disto-buccal gingival tissue, creating a tunnel-like separation of the distal non-keratinized soft tissue to expose the intrabony defect. Subsequently, bone grafting and guided tissue regeneration surgeries were performed, resulting in satisfactory bone fill at 9 mo postoperatively. CONCLUSION: This technique offers a regenerative opportunity for the intrabony defects beneath non-keratinized mucosa and is recommended for further research.

6.
World J Methodol ; 14(2): 94562, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38983657

RESUMO

BACKGROUND: Adipose-derived stem cells (ADSCs) and the stromal vascular fraction (SVF) have garnered substantial interest in regenerative medicine due to their potential to treat a wide range of conditions. Traditional enzymatic methods for isolating these cells face challenges such as high costs, lengthy processing time, and regu-latory complexities. AIM: This systematic review aimed to assess the efficacy and practicality of non-enzymatic, mechanical methods for isolating SVF and ADSCs, comparing these to conventional enzymatic approaches. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a comprehensive literature search was conducted across multiple databases. Studies were selected based on inclusion criteria focused on non-enzymatic isolation methods for SVF and ADSCs from adipose tissue. The risk of bias was assessed, and a qualitative synthesis of findings was performed due to the methodological heterogeneity of the included studies. RESULTS: Nineteen studies met the inclusion criteria, highlighting various mechanical techniques such as centrifugation, vortexing, and ultrasonic cavitation. The review identified significant variability in cell yield and viability, and the integrity of isolated cells across different non-enzymatic methods compared to enzymatic procedures. Despite some advantages of mechanical methods, including reduced processing time and avoidance of enzymatic reagents, the evidence suggests a need for optimization to match the cell quality and therapeutic efficacy achievable with enzymatic isolation. CONCLUSION: Non-enzymatic, mechanical methods offer a promising alternative to enzymatic isolation of SVF and ADSCs, potentially simplifying the isolation process and reducing regulatory hurdles. However, further research is necessary to standardize these techniques and ensure consistent, high-quality cell yields for clinical applications. The development of efficient, safe, and reproducible non-enzymatic isolation methods could significantly advance the field of regenerative medicine.

7.
Angew Chem Int Ed Engl ; : e202409894, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38984418

RESUMO

Porous liquids are new types of fluid sorbent investigated mainly for the separation of gas mixtures. Here, we explore their application to the separation of miscible liquids, MEG (monoethylene glycol)/water and EtOH/water) as proof of principle. Recovery of used MEG is industrially important but its extraction from water is difficult. PLs ZIF 8@PDMS (PL1, PDMS = polydimethylsilicone) or ZIF-8@sesame oil (PL2) each consisting of 25wt% of the hydrophobic microporous material ZIF-8 dispersed in PDMS/sesame oil, were formulated and found to be exceedingly physically stable. 5 nm PEEK membranes were used to provide permeable barriers between the PL and the alcohol/water phase. MEG was selectively extracted through the membrane from 50wt% MEG/water mixtures into the PL phase. It was effective for MEG/water mixtures as dilute as 3:97wt%. The PL could be regenerated and re-used, suggesting its potential for continuous cyclic extraction. Furthermore, PL3 (silicalite-1@PDMS) has demonstrated effectiveness in achieving selective alcohol extraction from beverages. It shows great potential for lowering the alcohol concentration in gin/wine due to its excellent chemical stability and nontoxicity. Overall, the enhanced adsorption properties of PLs due the presence of empty pores, which provides unusually high gas solubilities, also makes them, in principle, applicable to liquid-liquid separations.

8.
Sci Total Environ ; 946: 174479, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38969112

RESUMO

Here, we offer thoughts concerning a 'zero residual nanoadsorbent toxicity' environmental policy which we strongly advocate. Our discussions in support of this policy are based on the adage 'Prevention is better than cure'. Besides emphasizing the need for strict regulations (regional and international), research and development avenues are highlighted for the technology that can achieve 'zero tolerance' for residual nanoadsorbent levels escaping and building up in receiving ecosystems. We do not oppose nanoadsorbents. On the contrary, their water and wastewater purification potentials are well recognized. However, they should not be permitted to translocate downstream from the exit point of a final effluent.

9.
BMC Med Res Methodol ; 24(1): 145, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38970036

RESUMO

BACKGROUND: In binary classification for clinical studies, an imbalanced distribution of cases to classes and an extreme association level between the binary dependent variable and a subset of independent variables can create significant classification problems. These crucial issues, namely class imbalance and complete separation, lead to classification inaccuracy and biased results in clinical studies. METHOD: To deal with class imbalance and complete separation problems, we propose using a fuzzy logistic regression framework for binary classification. Fuzzy logistic regression incorporates combinations of triangular fuzzy numbers for the coefficients, inputs, and outputs and produces crisp classification results. The fuzzy logistic regression framework shows strong classification performance due to fuzzy logic's better handling of imbalance and separation issues. Hence, classification accuracy is improved, mitigating the risk of misclassified conditions and biased insights for clinical study patients. RESULTS: The performance of the fuzzy logistic regression model is assessed on twelve binary classification problems with clinical datasets. The model has consistently high sensitivity, specificity, F1, precision, and Mathew's correlation coefficient scores across all clinical datasets. There is no evidence of impact from the imbalance or separation that exists in the datasets. Furthermore, we compare the fuzzy logistic regression classification performance against two versions of classical logistic regression and six different benchmark sources in the literature. These six sources provide a total of ten different proposed methodologies, and the comparison occurs by calculating the same set of classification performance scores for each method. Either imbalance or separation impacts seven out of ten methodologies. The remaining three produce better classification performance in their respective clinical studies. However, these are all outperformed by the fuzzy logistic regression framework. CONCLUSION: Fuzzy logistic regression showcases strong performance against imbalance and separation, providing accurate predictions and, hence, informative insights for classifying patients in clinical studies.


Assuntos
Lógica Fuzzy , Humanos , Modelos Logísticos , Algoritmos
10.
J Chromatogr A ; 1730: 465112, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38972253

RESUMO

A macrocyclic peptide A was successfully purified in large quantities (∼30 g) in >95 % purity by an integrated two-step orthogonal purification process combining supercritical fluid chromatography (SFC) with medium-pressure reverse-phase liquid chromatography (MP-RPLC). MP-RPLC was used to fractionate the crude peptide A, remove unwanted trifluoroacetic acid (TFA) originating from the peptide A cleavage off the resin, and convert the peptide A into ammonium acetate salt form, prior to the final purification by SFC. A co-solvent of methanol/acetonitrile containing ammonium acetate and water in CO2 was developed on a Waters BEH 2-Ethylpyridine column. The developed SFC method was readily scaled up onto a 5 cm diameter column to process multi-gram quantities of the MP-RPLC fraction to reach > 95 % purity with a throughput/productivity of 0.96 g/h. The incorporation of SFC with MP-RPLC has been demonstrated to have a broader application in other large-scale polypeptide purifications.

11.
Adv Sci (Weinh) ; : e2405050, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38973148

RESUMO

Transition metal disulfide compounds (TMDCs) emerges as the promising candidate for new-generation flexible (opto-)electronic device fabrication. However, the harsh growth condition of TMDCs results in the necessity of using hard dielectric substrates, and thus the additional transfer process is essential but still challenging. Here, an efficient strategy for preparation and easy separation-transfer of high-uniform and quality-enhanced MoS2 via the precursor pre-annealing on the designed graphene inserting layer is demonstrated. Based on the novel strategy, it achieves the intact separation and transfer of a 2-inch MoS2 array onto the flexible resin. It reveals that the graphene inserting layer not only enhances MoS2 quality but also decreases interfacial adhesion for easy separation-transfer, which achieves a high yield of ≈99.83%. The theoretical calculations show that the chemical bonding formation at the growth interface has been eliminated by graphene. The separable graphene serves as a photocarrier transportation channel, making a largely enhanced responsivity up to 6.86 mA W-1, and the photodetector array also qualifies for imaging featured with high contrast. The flexible device exhibits high bending stability, which preserves almost 100% of initial performance after 5000 cycles. The proposed novel TMDCs growth and separation-transfer strategy lightens their significance for advances in curved and wearable (opto-)electronic applications.

12.
Adv Sci (Weinh) ; : e2308279, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38973194

RESUMO

The coacervation of alpha-synuclein (αSyn) into cytotoxic oligomers and amyloid fibrils are considered pathological hallmarks of Parkinson's disease. While aggregation is central to amyloid diseases, liquid-liquid phase separation (LLPS) and its interplay with aggregation have gained increasing interest. Previous work shows that factors promoting or inhibiting aggregation have similar effects on LLPS. This study provides a detailed scanning of a wide range of parameters, including protein, salt and crowding concentrations at multiple pH values, revealing different salt dependencies of aggregation and LLPS. The influence of salt on aggregation under crowding conditions follows a non-monotonic pattern, showing increased effects at medium salt concentrations. This behavior can be elucidated through a combination of electrostatic screening and salting-out effects on the intramolecular interactions between the N-terminal and C-terminal regions of αSyn. By contrast, this study finds a monotonic salt dependence of LLPS due to intermolecular interactions. Furthermore, it observes time evolution of the two distinct assembly states, with macroscopic fibrillar-like bundles initially forming at medium salt concentration but subsequently converting into droplets after prolonged incubation. The droplet state is therefore capable of inhibiting aggregation or even dissolving aggregates through heterotypic interactions, thus preventing αSyn from its dynamically arrested state.

13.
Angew Chem Int Ed Engl ; : e202411724, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38973233

RESUMO

Covalent organic frameworks (COFs), at the forefront of porous materials, hold tremendous potential in membrane separation; however, achieving high continuity in COF membranes remains crucial for efficient gas separation. Here, we present a unique approach termed assembly-dissociation-reconstruction for fabricating COF membranes tailored for CO2/N2 separation. A parent COF is designed from two-node aldehyde and three-node amine monomers and dissociated to high-aspect-ratio nanosheets. Subsequently, COF nanosheets are orderly reconstructed into a crack-free membrane by surface reaction under water evaporation. The membrane exhibits high crystallinity, open pores and a strong affinity for CO2 adsorption over N2, resulting in CO2 permeance exceeding 1060 GPU and CO2/N2 selectivity surpassing 30.6. The efficacy of this strategy offers valuable guidance for the precise fabrication of gas-separation membranes.

14.
Adv Sci (Weinh) ; : e2400140, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38973255

RESUMO

Most clinical PARP inhibitors (PARPis) trap PARP1 in a chromatin-bound state, leading to PARPi-mediated cytotoxicity. PARPi resistance impedes the treatment of ovarian cancer in clinical practice. However, the mechanism by which cancer cells overcome PARP1 trapping to develop PARPi resistance remains unclear. Here, it is shown that high levels of KAT6A promote PARPi resistance in ovarian cancer, regardless of its catalytic activity. Mechanistically, the liquid-liquid phase separation (LLPS) of KAT6A, facilitated by APEX1, inhibits the cytotoxic effects of PARP1 trapping during PARPi treatment. The stable KAT6A-PARP1-APEX1 complex reduces the amount of PARP1 trapped at the DNA break sites. In addition, inhibition of KAT6A LLPS, rather than its catalytic activity, impairs DNA damage repair and restores PARPi sensitivity in ovarian cancer both in vivo and in vitro. In conclusion, the findings demonstrate the role of KAT6A LLPS in fostering PARPi resistance and suggest that repressing KAT6A LLPS can be a potential therapeutic strategy for PARPi-resistant ovarian cancer.

15.
Artigo em Inglês | MEDLINE | ID: mdl-38975704

RESUMO

Microfluidics have been widely used for cell sorting and capture. In this work, numerical simulations of cell transport in microfluidic devices were studied considering cell sizes, deformability, and five different device designs. Among these five designs, deterministic lateral displacement device (DLD) and hyperuniform device (HU) performed better in promoting cell-micropost collision due to the continuously shifted micropost positions as compared with regular grid, staggered, and hexagonal layout designs. However, the grid and the hexagonal layouts showed best in differentiating cells by their size dependent velocity due to the size exclusion effect for cell transport in clear and straight paths in the flow direction. A systematic study of the velocity differentiation under different dimensionless groups was performed showing that the velocity difference is dominated by the micropost separation distance perpendicular to the direction of flow. Microfluidic experiments also confirmed the velocity differentiation results. The study can provide guiding principles for microfluidic design.

16.
Mikrochim Acta ; 191(8): 454, 2024 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-38976069

RESUMO

An intelligent colorimetric sensing platform integrated with in situ immunomagnetic separation function was developed for ultrasensitive detection of Escherichia coli O157: H7 (E. coli O157: H7) in food. Captured antibody modified magnetic nanoparticles (cMNPs) and detection antibody/horseradish peroxidase (HRP) co-functionalized AuNPs (dHAuNPs) were firstly synthesized for targeted enrichment and colorimetric assay of E. coli O157: H7, in which remarkable signal amplification was realized by loading large amounts of HRP on the surface of AuNPs. Coupling with the optical collimation attachments and embedded magnetic separation module, a highly integrated optical device was constructed, by which in situ magnetic separation and high-quality imaging of 96-well microplates containing E. coli O157: H7 was achieved with a smartphone. The concentration of E. coli O157: H7 could be achieved in one-step by performing digital image colorimetric analysis of the obtained image with a custom-designed app. This biosensor possesses high sensitivity (1.63 CFU/mL), short detecting time (3 h), and good anti-interference performance even in real-sample testing. Overall, the developed method is expected to be a novel field detection platform for foodborne pathogens in water and food as well as for the diagnosis of infections due to its portability, ease of operation, and high feasibility.


Assuntos
Técnicas Biossensoriais , Colorimetria , Escherichia coli O157 , Microbiologia de Alimentos , Ouro , Peroxidase do Rábano Silvestre , Separação Imunomagnética , Nanopartículas Metálicas , Escherichia coli O157/isolamento & purificação , Colorimetria/métodos , Ouro/química , Peroxidase do Rábano Silvestre/química , Separação Imunomagnética/métodos , Técnicas Biossensoriais/métodos , Nanopartículas Metálicas/química , Contaminação de Alimentos/análise , Limite de Detecção , Smartphone , Anticorpos Imobilizados/imunologia , Anticorpos Imobilizados/química , Nanopartículas de Magnetita/química
17.
Plant Cell ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38976557

RESUMO

Transcription factors (TFs) tightly control plant development by regulating gene expression. The phase separation of TFs plays a vital role in gene regulation. Many plant TFs have the potential to form phase-separated protein condensates; however, little is known about which TFs are regulated by phase separation and how it affects their roles in plant development. Here, we report that the rice (Oryza sativa) single Myb TF TELOMERE REPEAT-BINDING FACTOR 2 (TRBF2) is highly expressed in fast-growing tissues at the seedling stage. TRBF2 is a transcriptional repressor that binds to the transcriptional start site of thousands of genes. Mutation of TRBF2 leads to pleiotropic developmental defects and misexpression of many genes. TRBF2 displays characteristics consistent with phase separation in vivo and forms phase-separated condensates in vitro. The H1/H5 domain of TRBF2 plays a crucial role in phase separation, chromatin targeting and gene repression. Replacing the H1/H5 domain by a phase-separated intrinsically disordered region from Arabidopsis (Arabidopsis thaliana) AtSERRATE partially recovers the function of TRBF2 in gene repression in vitro and in transgenic plants. We also found that TRBF2 is required for trimethylation of histone H3 Lys27 (H3K27me3) deposition at specific genes and genome-wide. Our findings reveal that phase separation of TRBF2 facilitates gene repression in rice development.

18.
Proc Natl Acad Sci U S A ; 121(29): e2401834121, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38976739

RESUMO

Lung adenocarcinoma (LUAD) is the leading cause of cancer-related death worldwide, but the underlying molecular mechanisms remain largely unclear. The transcription factor (TF) specificity protein 1 (SP1) plays a crucial role in the development of various cancers, including LUAD. Recent studies have indicated that master TFs may form phase-separated macromolecular condensates to promote super-enhancer (SE) assembly and oncogene expression. In this study, we demonstrated that SP1 undergoes phase separation and that its zinc finger 3 in the DNA-binding domain is essential for this process. Through Cleavage Under Targets & Release Using Nuclease (CUT&RUN) using antibodies against SP1 and H3K27ac, we found a significant correlation between SP1 enrichment and SE elements, identified the regulator of the G protein signaling 20 (RGS20) gene as the most likely target regulated by SP1 through SE mechanisms, and verified this finding using different approaches. The oncogenic activity of SP1 relies on its phase separation ability and RGS20 gene activation, which can be abolished by glycogen synthase kinase J4 (GSK-J4), a demethylase inhibitor. Together, our findings provide evidence that SP1 regulates its target oncogene expression through phase separation and SE mechanisms, thereby promoting LUAD cell progression. This study also revealed an innovative target for LUAD therapies through intervening in SP1-mediated SE formation.


Assuntos
Adenocarcinoma de Pulmão , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares , Proteínas RGS , Fator de Transcrição Sp1 , Fator de Transcrição Sp1/metabolismo , Fator de Transcrição Sp1/genética , Humanos , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Proteínas RGS/metabolismo , Proteínas RGS/genética , Linhagem Celular Tumoral , Animais , Elementos Facilitadores Genéticos , Progressão da Doença , Camundongos , Separação de Fases
19.
Sci Rep ; 14(1): 15702, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977747

RESUMO

The present study investigates the efficacy of newly developed Zr-based metal-organic frameworks, specifically MIP-206, and its amine-modified counterpart, MIP-206-NH2, for the re-covery of antimony (Sb) from both synthetic and actual mining wastewater. Batch method studies were employed to examine the effect of waste media pH, Sb concentration, process kinetics, and the performance of the regeneration solution. MIP-206-NH2 exhibited impressive separation capabilities, achieving 102.18 mg/g and 63.23 mg/g for Sb (V) and Sb (III), respectively. In contrast, the pristine MIP-206 reached maximum values of 26.26 mg/g for Sb (V) and 16.95 mg/g for Sb (III). The separation process was well-described by the Langmuir equation, and the kinetics followed the pseudo-second-order model. Although the amine modification resulted in a decrease in the surface area of MIP-206 from 1345.21 to 1169.86 m2/g, SEM and XRD analyses confirmed that the structural integrity of MIP-206-NH2 remained unchanged. In terms of reusability, MIP-206-NH2 maintained up to 90% of its separation performance over 9 cycles, while MIP-206 demonstrated effectiveness for 7 cycles. The regeneration solution exhibited a capacity of approximately 0.63 mol/L for Sb (V) and 0.71 mol/L for Sb (III). Furthermore, MIP-206 and MIP-206-NH2 demonstrated successful application in selectively separating Sb from real mining wastewater.

20.
Int J Cardiol Heart Vasc ; 53: 101447, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38979528

RESUMO

Introduction: Yeo's Index, product of the mitral leaflet separation index and dimensionless index, is a novel measure of the severity of rheumatic mitral stenosis (MS). We assess Yeo's index in patients with rheumatic MS with or without mixed valve disease. Methods: In a retrospective cohort study, Yeo's index was measured in 237 cases of rheumatic MS - 124 in a transthoracic echocardiography validation cohort using mitral valve area (MVA) by pressure half-time and planimetry as comparator and 113 in a transesophageal echocardiography (TEE) validation cohort using TEE three-dimensional MVA as comparator. Patients were considered to have mixed valve disease if they had MS and concomitant mitral regurgitation or aortic valve disease. Results: There were 113 patients with isolated MS and 124 patients with mixed valve disease. Overall, Yeo's index ≤ 0.26 cm showed 93.0 % sensitivity and 87.5 % specificity for identifying severe MS (MVA ≤ 1.5 cm2). In isolated MS, Yeo's index ≤ 0.26 cm showed sensitivity of 94.6 % and specificity of 90.0 % for identifying severe MS, while in mixed valve disease sensitivity was 90.6 % and specificity 86.7 %. Overall, Yeo's index ≤ 0.15 cm showed 83.6 % sensitivity and 94.3 % specificity for very severe MS (MVA ≤ 1.0 cm2). In isolated MS, the threshold of ≤0.15 cm showed sensitivity of 84.4 % and specificity of 92.6 % for very severe MS, while in mixed valve disease sensitivity was 81.3 % and specificity 95.3 %. The presence of atrial fibrillation did not influence the performance of Yeo's index. Conclusion: Yeo's Index accurately differentiates severity of rheumatic MS with or without mixed valve disease.

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