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1.
Biol Trace Elem Res ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38954322

RESUMO

This study investigated heavy metal contamination in dried fish sold in Guangzhou, China, and evaluated the resultant non-carcinogenic and carcinogenic health risks. Dried fish samples were purchased from Baiyun, Tianhe, Panyu, and Yuexiu districts in Guangzhou, where the population is substantial. They were randomly acquired in bustling supermarkets and farmers' markets, targeting the most popular dried fish in these areas. Sixty samples from five dried fish types (Stolephorus chinensis, Thamnaconus modestus, Nemipterus-virgatus, river fish, Ctenopharyngodon idella) were analyzed for chromium (Cr), arsenic (As), cadmium (Cd), lead (Pb), and mercury (Hg) content. Quantification of the heavy metals were carried out by inductively coupled plasma mass spectrometry (ICP-MS) for Cr, As, Cd, and Pb, and an automatic mercury analyzer for Hg. The median concentration of these heavy metals in dried fish were 0.358 mg/kg, 2.653 mg/kg, 0.032 mg/kg, 0.083 mg/kg, and 0.042 mg/kg, respectively. Pollution severity was ranked as dried Nemipterus-virgatus > dried Stolephorus chinensis > dried Thamnaconus modestus > dried river fish > dried Ctenopharyngodon idella, with As being the most predominant pollutant. All fish types showed severe As pollution. Non-carcinogenic risks were identified in the consumption of dried Nemipterus-virgatus and dried Stolephorus chinensis for both genders, while potential carcinogenic risks were associated with four of the fish types. Women faced higher health risks than men from dried fish consumption. Consequently, we advise consumers to minimize their intake of dried fish and regulatory agencies conduct regular monitoring of heavy metal levels in commercially available dried fish to avert potential health risks.

2.
ACS Sens ; 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38970501

RESUMO

The combination of closed bipolar electrodes (cBPE) with electrochemiluminescence (ECL) imaging has demonstrated remarkable capabilities in the field of bioanalysis. Here, we established a cBPE-ECL platform for ultrasensitive detection of alkaline phosphatase (ALP) and two-dimensional imaging of epidermal growth factor receptor (EGFR). This cBPE-ECL system consists of a high-density gold nanowire array in anodic aluminum oxide (AAO) membrane as the cBPE coupled with ECL of highly luminescent cadmium selenide quantum dots (CdSe QDs) luminophores to achieve cathodic electro-optical conversion. When an enzyme-catalyzed amplification effect of ALP with 4-aminophenyl phosphate monosodium salt hydrate (p-APP) as the substrate and 4-aminophenol (p-AP) as the electroactive probe is introduced, a significant improvement of sensing sensitivity with a detection limit as low as 0.5 fM for ALP on the cBPE-ECL platform can be obtained. In addition, the cBPE-ECL sensing system can also be used to detect cancer cells with an impressive detection limit of 50 cells/mL by labeling ALP onto the EGFR protein on A431 human epidermal cancer cell membranes. Thus, two-dimensional (2D) imaging of the EGFR proteins on the cell surface can be achieved, demonstrating that the established cBPE-ECL sensing system is of high resolution for spatiotemporal cell imaging.

3.
Value Health ; 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38977183

RESUMO

OBJECTIVES: Health technology assessment (HTA) is increasingly crucial in medicine price negotiations in China, yet prior appraisals revealed national discrepancies on key economic evaluation issues: willingness-to-pay (WTP) threshold, pricing models for multi-indication medicines, and comparator selection principles. This study aims to collect expert opinions on these issues for future HTA evaluations. METHODS: A nationwide anonymous web-based survey encompassing experts across academia, HTA, consultancy/contract research organization (CRO)/industry, service provider and payer. In 2023, a generic invitation containing a web link to the questionnaire was disseminated via WeChat using convenience and snowball sampling. Agreement rates for questionnaire views were analyzed using descriptive statistics. The relationship between participants' responses and demographics was examined using appropriate logistic models. RESULTS: 303 responses were received from experts in 34 cities. Key expert views include: a suggested base WTP threshold ranging from 0.5 to 1.5 times GDP (52.1% agreement); elevated thresholds for childhood diseases, rare diseases, end-of-life diseases, and first-in-class medicines (FICs) (>78.0% agreement); a single pricing model for multi-indication medicines (60.4% agreement); consideration of multiple medicines as comparators (79.9% agreement); and avoiding the use of centrally procured medicines as comparators for medicines with a time-to-market under three years (71.0% agreement). Participants who are service provider had lower odds of selecting higher thresholds (OR: 0.26; P<0.01) compared with responders from consultancy/CRO/industry. CONCLUSIONS: Expert views indicate the need for substantial changes in China's current HTA methods, highlighting the need for increased investment in HTA processes and expertise cultivation.

4.
Artigo em Inglês | MEDLINE | ID: mdl-39001735

RESUMO

Coronary artery disease continues to be the leading cause of death globally. Identifying patients who are at risk of coronary artery disease remains a public health priority. At present, the focus of cardiovascular disease prevention relies heavily on probabilistic risk scoring despite no randomized controlled trials demonstrating their efficacy. The concept of using imaging to guide preventative therapy is not new, but has previously focused on indirect measures such as carotid intima-media thickening or coronary artery calcification. In recent trials, patients found to have coronary artery disease on computed tomography (CT) coronary angiography were more likely to be started on preventative therapy and had lower rates of cardiac events. This led to the design of the SCOT-HEART 2 (Scottish Computed Tomography of the Heart 2) trial, which aims to determine whether screening with the use of CT coronary angiography is more clinically effective than cardiovascular risk scoring to guide the use of primary preventative therapies and reduce the risk of myocardial infarction.

5.
Genes Genomics ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38990270

RESUMO

BACKGROUND: In humans, ACTN2 mutations are identified as highly relevant to a range of cardiomyopathies such as DCM and HCM, while their association with sudden cardiac death has been observed in forensic cases. Although ACTN2 has been shown to regulate sarcomere Z-disc organization, a causal relationship between ACTN2 dysregulation and cardiomyopathies under chronic stress has not yet been investigated. OBJECTIVE: In this work, we explored the relationship between Actn2 dysregulation and cardiomyopathies under dexamethasone treatment. METHODS: Previous cases of ACTN2 mutations were collected and the conservative analysis was carried out by MEGA 11, the possible impact on the stability and function of ACTN2 affected by these mutations was predicted by Polyphen-2. ACTN2 was suppressed by siRNA in H9c2 cells under dexamethasone treatment to mimic the chronic stress in vitro. Then the cardiac hypertrophic molecular biomarkers were elevated, and the potential pathways were explored by transcriptome analysis. RESULTS: Actn2 suppression impaired calcium uptake and increased hypertrophy in H9c2 cells under dexamethasone treatment. Concomitantly, hypertrophic molecular biomarkers were also elevated in Actn2-suppressed cells. Further transcriptome analysis and Western blotting data suggested that Actn2 suppression led to the excessive activation of the MAPK pathway and ERK cascade. In vitro pharmaceutical intervention with ERK inhibitors could partially reverse the morphological changes and inhibit the excessive cardiac hypertrophic molecular biomarkers in H9c2 cells. CONCLUSION: Our study revealed a functional role of ACTN2 under chronic stress, loss of ACTN2 function accelerated H9c2 hypertrophy through ERK signaling. A commercial drug, Ibudilast, was identified to reverse cell hypertrophy in vitro.

6.
Sheng Wu Gong Cheng Xue Bao ; 40(7): 2346-2356, 2024 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-39044596

RESUMO

To achieve rapid detection of enramycin in feed, we employed the competitive inhibition method to develop a colloidal gold immunochromatographic test strip based on the anti-enramycin A monoclonal antibody (anti-Er.A-mAb). Colloidal gold probes were prepared with a laboratory-prepared high-purity anti-Er.A-mAb. The effects of pH, antibody titer, and antigen concentration (test line) on the test strip performance were investigated. The colloidal gold test strip prepared with 8 µL potassium carbonate addition, 4 µg/mL antibody, 1.0 mg/mL antigen (test line), and 3 µL gold-labeled antibody showed acceptable specificity and a low limit of detection. The test strip showed the detection limit of 25 ng/mL for enramycin A, with a linear range of 25-300 ng/mL. The experiments on the feed with positive sample addition proved that the test strip had good repeatability and was more sensitive than high-performance liquid chromatography, being applicable for the rapid detection of enramycin in large batches of feed samples.


Assuntos
Ração Animal , Anticorpos Monoclonais , Cromatografia de Afinidade , Coloide de Ouro , Coloide de Ouro/química , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/química , Cromatografia de Afinidade/métodos , Ração Animal/análise , Nebramicina/análise , Nebramicina/análogos & derivados , Contaminação de Alimentos/análise , Resíduos de Drogas/análise
7.
Chemistry ; : e202401935, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39042471

RESUMO

Low temperature has been a major challenge for lithium-ion batteries (LIBs) to maintain satisfied electrochemical performance, and the main reason is the deactivation of electrolyte with the decreasing temperature. To address this point, in present work, we develop a low-temperature resistant electrolyte which includes ethyl acetate (EA) and fluoroethylene carbonate (FEC) as solvent and lithium difluoro(oxalato)borate (LiDFOB) as the primary lithium salt. Due to the preferential decomposition of LiDFOB and FEC, a solid electrolyte interface rich in LiF is formed on the lithium metal anodes (LMAs) and lithium cobalt oxide (LCO) cathodes, contributing to higher stability and rapid desolvation of Li+ ions. The batteries with the optimized electrolyte can undergo cycling tests at -40 °C, with a capacity retention of 83.9 % after 200 cycles. Furthermore, the optimized electrolyte exhibits excellent compatibility with both LCO cathodes and graphite (Gr) anodes, enabling a Gr/LCO battery to maintain a capacity retention of 90.3 % after multiple cycles at -25 °C. This work proposes a cost-effective electrolyte that can activate potential LIBs in practical scenarios, especially in low-temperature environments.

8.
Sci Total Environ ; 947: 174512, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38972406

RESUMO

Neonicotinoid pesticides (NNPs) and microplastics (MPs) are two emerging contaminants in agricultural environment. However, the interaction between MPs (especially biodegradable plastics) and NNPs is currently unclear. Therefore, taking thiacloprid (THI) as an example of NNPs, this study explores the adsorption-desorption process and mechanism of NNPs on MPs (traditional and biodegradable plastics), and analyzed the main factors affecting the adsorption (pH, salinity and dissolved organic matter). In addition, by using diffusive gradients in thin-films device, this study assessed the impact of MPs on the bioavailability of NNPs in soil. The results showed that the maximum adsorption capacity of polyamide 6 (96.49 µg g-1) for THI was greater than that of poly (butylene adipate co-terephthalate) (88.78 µg g-1). Aging increased the adsorption amount of THI (5.53 %-15.8 %) due to the higher specific surface area and reduced contact angle of MPs, but the adsorption mechanism remained unchanged. The desorption amount of THI from MPs in simulated intestinal fluid is 1.30-1.36 times. The MPs in soil alter the distribution of THI in the soil, increasing the bioavailability of THI while inhibiting its degradation. The results highlighted the significance of examining the combined pollution caused by MPs and NNPs.

9.
ACS Nano ; 18(29): 19200-19207, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-38996344

RESUMO

Simultaneous detection and structural characterization of protein variants on a single platform are highly desirable but technically challenging. Herein, we present a single-molecule spectral system based on a gold plasmonic nanopore for analyzing two peptides and their single-point mutated variants. The gold plasmonic nanopore enabled the high-throughput acquisition of surface-enhanced Raman scattering (SERS) spectra at the single-molecule level by electrically driving analytes into hot spots. Furthermore, a statistical method based on Boolean operations was developed to extract prominent features from fluctuated single-molecule SERS spectra. The effects of the single-amino acid substitutions on both the intramolecular interactions and the peptide conformations were directly characterized by the nanopore system, and the results agreed with the predictions by AlphaFold2. This study highlights the mutual benefits of spectroscopy and nanopore technology, whereby the gold plasmonic nanopore offers a powerful tool for the structural analysis of single-molecule proteins.


Assuntos
Substituição de Aminoácidos , Ouro , Nanoporos , Peptídeos , Análise Espectral Raman , Ouro/química , Análise Espectral Raman/métodos , Peptídeos/química , Propriedades de Superfície
10.
Commun Biol ; 7(1): 807, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961177

RESUMO

Glaucoma is the leading cause of irreversible blindness and is characterized by progressive retinal ganglion cell (RGC) loss and retinal nerve fiber layer thinning. Currently, no existing treatment is effective for the preservation of RGCs. MicroRNA-22-3p (miR22) and small extracellular vesicles derived from mesenchymal stem cells (MSC-sEVs) have neuroprotective effects. In this study, we apply miR22-overexpressing MSC-sEVs in an N-methyl-D-aspartic acid (NMDA)-induced RGC injury model to assess their short-term therapeutic effects and explore the underlying mechanisms. We find that mice in the miR22-sEVs-treated group have thicker retinas, fewer apoptotic cells, more reserved RGCs, better retinal function, and lower expression levels of Bax and caspase-3. MiR22-sEVs treatment promotes viability, inhibits apoptosis and inhibits Bax and caspase-3 expression in RGC-5 cells. MiR22 targets mitogen-activated protein kinase kinase kinase 12 to inhibit apoptosis by regulating the mitogen-activated protein kinase (MAPK) signaling pathway. Collectively, our results suggest that miR22-sEVs ameliorate NMDA-induced RGC injury through the inhibition of MAPK signaling pathway-mediated apoptosis, providing a potential therapy for glaucoma and other diseases that involve RGC damage.


Assuntos
Vesículas Extracelulares , Sistema de Sinalização das MAP Quinases , Células-Tronco Mesenquimais , MicroRNAs , Células Ganglionares da Retina , Células Ganglionares da Retina/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , Células-Tronco Mesenquimais/metabolismo , Vesículas Extracelulares/metabolismo , Camundongos , Apoptose , Camundongos Endogâmicos C57BL , Glaucoma/genética , Glaucoma/metabolismo , Glaucoma/patologia , Glaucoma/terapia , Masculino
11.
J Phys Condens Matter ; 36(37)2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38888323

RESUMO

Interfacing the quantum anomalous Hall insulator with a conventional superconductor is known to be a promising manner for realizing a topological superconductor, which has been continuously pursued for years. Such a proximity route depends to a great extent on the control of the delicate interfacial coupling of the two constituents. However, a recent experiment reported the failure to reproduce such a topological superconductor, which is ascribed to the negligence of the electrical short by the superconductor in the theoretical proposal. Here, we reproduce this topological superconductor with attention to the interface control. The resulted conductance matrix under a wide magnetic field range agrees with the fingerprint of this topological superconductor. This allows us to develop a phase diagram that unveils three regions parameterized by various coupling limits, which not only supports the feasibility to fabricate the topological superconductor by proximity but also fully explains the origin of the previous debate. The present work provides a comprehensible guide on fabricating the topological superconductor.

12.
Front Cell Dev Biol ; 12: 1407428, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38887516

RESUMO

The mortality of hepatocellular carcinoma (HCC) is on the rise globally, particularly in the Western world, with etiology gradually shifting from virus-related liver diseases to metabolic disorders such as non-alcoholic fatty liver disease. Early detection of HCC is challenging, and effective prognostic indicators are currently lacking, urgently necessitating reliable markers to assist in treatment planning and clinical management. Here, we introduce hepatocellular carcinoma senescence genes (HSG) to assess cellular senescence in HCC and devise a hepatocellular carcinoma senescence score (HSS) for prognostic prediction. Higher HSS levels signify poorer prognosis and increased tumor proliferation activity. Additionally, we observe alterations in the tumor immune microenvironment with higher HSS levels, such as increased infiltration of Treg, potentially providing a basis for immunotherapy. Furthermore, we identify key genes, such as PTTG1, within the senescence gene set and demonstrate their regulatory roles in HCC cells and Treg through experimentation. In summary, we establish a scoring system based on hepatocellular carcinoma senescence genes for prognostic prediction in HCC, potentially offering guidance for clinical treatment planning.

13.
Molecules ; 29(12)2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38930980

RESUMO

Two-dimensional MXenes have become an important material for electrochemical sensing of biomolecules due to their excellent electric properties, large surface area and hydrophilicity. However, the simultaneous detection of multiple biomolecules using MXene-based electrodes is still a challenge. Here, a simple solvothermal process was used to synthesis the Ti3C2Tx coated with TiO2 nanosheets (Ti3C2Tx@TiO2 NSs). The surface modification of TiO2 NSs on Ti3C2Tx can effectively reduce the self-accumulation of Ti3C2Tx and improve stability. Glassy carbon electrode was modified by Ti3C2Tx@TiO2 NSs (Ti3C2Tx@TiO2 NSs/GCE) and was able simultaneously to detect dopamine (DA), ascorbic acid (AA) and uric acid (UA). Under concentrations ranging from 200 to 1000 µM, 40 to 300 µM and 50 to 400 µM, the limit of detection (LOD) is 2.91 µM, 0.19 µM and 0.25 µM for AA, DA and UA, respectively. Furthermore, Ti3C2Tx@TiO2 NSs/GCE demonstrated remarkable stability and reliable reproducibility for the detection of AA/DA/UA.


Assuntos
Ácido Ascórbico , Dopamina , Nanoestruturas , Titânio , Ácido Úrico , Titânio/química , Ácido Úrico/análise , Ácido Úrico/química , Dopamina/análise , Ácido Ascórbico/análise , Ácido Ascórbico/química , Nanoestruturas/química , Limite de Detecção , Técnicas Eletroquímicas/métodos , Eletrodos , Reprodutibilidade dos Testes , Técnicas Biossensoriais/métodos
14.
BMC Immunol ; 25(1): 37, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38937711

RESUMO

BACKGROUND: Although immune checkpoint inhibitors (ICIs) have brought survival benefits to non-small cell lung cancer (NSCLC), disease progression still occurs, and there is no consensus on the treatment options for these patients. We designed a network meta-analysis (NMA) to evaluate systemic treatment options for NSCLC after failure of ICIs. METHODS: PubMed, Embase, Web of Science and Cochrane Library databases were searched, then literature screening was followed by NMA. We included all Phase II and III randomized controlled trials (RCTs). Progression-free survival (PFS) and overall survival (OS) used hazard ratio (HR) for evaluation. Objective response rate (ORR) and adverse events (AEs) used odds ratio (OR) and relative risk (RR) effect sizes, respectively. R software was applied to compare the Bayesian NMA results. RESULTS: We finally included 6 studies. 1322 patients received ICI plus Chemotherapy (ICI + Chemo), ICI plus Anti-angiogenic monoclonal antibody (ICI + Antiangio-Ab), ICI plus Tyrosine kinase inhibitor (ICI + TKI), Tyrosine kinase inhibitor plus Chemotherapy (TKI + Chemo), Standard of Care (SOC), Chemotherapy (Chemo). TKI + Chemo is associated with longer PFS, higher ORR (surface under cumulative ranking curve [SUCRA], 99.7%, 88.2%), ICI + TKI achieved the longest OS (SUCRA, 82.7%). ICI + Antiangio-Ab was granted the highest safety rating for adverse events (AEs) of any grade, AEs greater than or equal to grade 3 and AEs of any grade leading to discontinuation of treatment (SUCRA, 95%, 82%, 93%). CONCLUSIONS: For NSCLC after failure of ICIs, TKI + Chemo was associated with longer PFS and higher ORR, while ICI + TKI was associated with the longest OS. In terms of safety, ICI + Antiangio-Ab was the highest.


Assuntos
Teorema de Bayes , Carcinoma Pulmonar de Células não Pequenas , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/imunologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
15.
J Colloid Interface Sci ; 673: 583-593, 2024 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-38897060

RESUMO

Ti-based Metal-organic frameworks (Ti-MOF) have been extensively investigated for producing hydrogen via solar water splitting, while their intrinsic activities are still retarded by the poor performance of photocarriers separation and utilization. Herein, a donor-acceptor (D-A) supramolecular photocatalyst is successfully constructed via encapsulating fullerene (C60) into MIL-125-NH2 and meanwhile depositing individual Pt atoms as cocatalyst. The as-prepared C60@MIL-125-NH2-Pt exhibits remarkable activity in photocatalytic water splitting, with a H2 formation rate of 1180 µmol g-1 h-1, which is âˆ¼ 12 times higher than that of the pristine MIL-125-NH2. Further investigations indicate that the host-guest interactions between C60 and MIL-125-NH2 strengthen the built-in electric field, which greatly facilitates the separation and migration of photogenerated charge carriers. In addition, the cocatalyst of individual Pt atoms not only further promotes the separation and transport of carriers but also enhances the contact between water and the catalyst. All of these factors directly contribute to the superior activity of C60@MIL-125-NH2-Pt. This work provides a new perspective for constructing D-A supramolecular photocatalysts for enhanced charge separation and making full use of photoelectrons to realize efficient hydrogen production.

16.
Environ Sci Technol ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38860911

RESUMO

Foliar assimilation of elemental mercury (Hg0) from the atmosphere plays a critical role in the global Hg biogeochemical cycle, leading to atmospheric Hg removal and soil Hg insertion. Recent studies have estimated global foliar Hg assimilation; however, large uncertainties remained due to coarse accounting of observed foliar Hg concentrations, posing a substantial challenge in constraining the global Hg budget. Here, we integrated a comprehensive observation database of foliar Hg concentrations and machine learning algorithms to predict the first spatial distribution of foliar Hg concentrations on a global scale, contributing to the first estimate of global Hg pools in foliage. The global average of foliar Hg concentrations was estimated to be 24.0 ng g-1 (7.5-56.5 ng g-1), and the global total in foliar Hg pools reached 4561.3 Mg (1455.2-9062.8 Mg). The spatial distribution showed the hotspots in tropical regions, including the Amazon, Central Africa, and Southeast Asia. A range of 2268.5-2727.0 Mg yr-1 was estimated for annual foliar Hg assimilation accounting for the perennial continuous assimilation by evergreen vegetation foliage. The first spatial maps of foliar Hg concentrations and Hg pools may aid in understanding the global biogeochemical cycling of Hg, especially in the context of climate change and global vegetation greening.

17.
Artigo em Inglês | MEDLINE | ID: mdl-38865229

RESUMO

Developing AI models for digital pathology has traditionally relied on single-scale analysis of histopathology slides. However, a whole slide image is a rich digital representation of the tissue, captured at various magnification levels. Limiting our analysis to a single scale overlooks critical information, spanning from intricate high-resolution cellular details to broad low-resolution tissue structures. In this study, we propose a model-agnostic multiresolution feature aggregation framework tailored for the analysis of histopathology slides in the context of breast cancer, on a multicohort dataset of 2038 patient samples. We have adapted 9 state-of-the-art multiple instance learning models on our multi-scale methodology and evaluated their performance on grade prediction, TP53 mutation status prediction and survival prediction. The results prove the dominance of the multiresolution methodology, and specifically, concatenating or linearly transforming via a learnable layer the feature vectors of image patches from a high (20x) and low (10x) magnification factors achieve improved performance for all prediction tasks across domain-specific and imagenet-based features. On the contrary, the performance of uniresolution baseline models was not consistent across domain-specific and imagenet-based features. Moreover, we shed light on the inherent inconsistencies observed in models trained on whole-tissue-sections when validated against biopsy-based datasets. Despite these challenges, our findings underscore the superiority of multiresolution analysis over uniresolution methods. Finally, cross-scale analysis also benefits the explainability aspects of attention-based architectures, since one can extract attention maps at the tissue- and cell-levels, improving the interpretation of the model's decision. The code and results of this study can be found at github.com/tsikup/multiresolution_histopathology.

18.
Anal Chem ; 96(24): 9808-9816, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38833718

RESUMO

Visualization of the mitochondrial state is crucial for tracking cell life processes and diagnosing disease, while fluorescent probes that can accurately assess mitochondrial status are currently scarce. Herein, a fluorescent probe named "SYN" was designed and prepared, which can target mitochondria via the mitochondrial membrane potential. Upon pathology or external stimulation, SYN can be released from the mitochondria and accumulate in the nucleolus to monitor the status of mitochondria. During this process, the brightness of the nucleolus can then serve as an indicator of mitochondrial damage. SYN has demonstrated excellent photostability in live cells as well as an extremely inert fluorescence response to bioactive molecules and the physiological pH environment of live cells. Spectroscopic titration and molecular docking studies have revealed that SYN can be lit up in nucleoli due to the high viscosity of the nucleus and the strong electrostatic interaction with the phosphate backbone of RNA. This probe is expected to be an exceptional tool based on its excellent imaging properties for tracking mitochondrial state in live cells.


Assuntos
Nucléolo Celular , Corantes Fluorescentes , Mitocôndrias , Mitocôndrias/metabolismo , Mitocôndrias/química , Humanos , Corantes Fluorescentes/química , Nucléolo Celular/metabolismo , Células HeLa , Simulação de Acoplamento Molecular , Imagem Óptica , Potencial da Membrana Mitocondrial
19.
Mater Horiz ; 11(14): 3287-3297, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38842407

RESUMO

Eukaryotic cells regulate various cellular processes through membrane-bound and membrane-less organelles, enabling active signal communication and material exchange. Lysosomes and lipid droplets are representative organelles, contributing to cell lipophagy when their interaction and metabolism are disrupted. Our limited understanding of the interacting behaviours and physicochemical properties of different organelles during lipophagy hinders accurate diagnosis and treatment of related diseases. In this contribution, we report a fluorescent probe, PTZ, engineered for dual-targeting of lipid droplets and lysosomes. PTZ can track liquid-liquid phase separation and respond to polarity shifts through ratiometric fluorescence emission, elucidating the lipophagy process from the perspective of organelle behavior and physicochemical properties. Leveraging on the multifunctionality of PTZ, we have successfully tracked the polarity and dynamic changes of lysosomes and lipid droplets during lipophagy. Furthermore, an unknown homogeneous transition of lipid droplets and lysosomes was discovered, which provided a new perspective for understanding lipophagy processes. And this work is expected to serve as a reference for diagnosis and treatment of lipophagy-related diseases.


Assuntos
Corantes Fluorescentes , Gotículas Lipídicas , Lisossomos , Humanos , Lisossomos/metabolismo , Gotículas Lipídicas/metabolismo , Transição de Fase , Autofagia/fisiologia , Células HeLa
20.
J Am Chem Soc ; 146(29): 19998-20008, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-38865282

RESUMO

As the dimensionality of materials generally affects their characteristics, thin films composed of low-dimensional nanomaterials, such as nanowires (NWs) or nanoplates, are of great importance in modern engineering. Among various bottom-up film fabrication strategies, interfacial assembly of nanoscale building blocks holds great promise in constructing large-scale aligned thin films, leading to emergent or enhanced collective properties compared to individual building blocks. As for 1D nanostructures, the interfacial self-assembly causes the morphology orientation, effectively achieving anisotropic electrical, thermal, and optical conduction. However, issues such as defects between each nanoscale building block, crystal orientation, and homogeneity constrain the application of ordered films. The precise control of transdimensional synthesis and the formation mechanism from 1D to 2D are rarely reported. To meet this gap, we introduce an interfacial-assembly-induced interfacial synthesis strategy and successfully synthesize quasi-2D nanofilms via the oriented attachment of 1D NWs on the liquid interface. Theoretical sampling and simulation show that NWs on the liquid interface maintain their lowest interaction energy for the ordered crystal plane (110) orientation and then rearrange and attach to the quasi-2D nanofilm. This quasi-2D nanofilm shows enhanced electric conductivity and unique optical properties compared with its corresponding 1D geometry materials. Uncovering these growth pathways of the 1D-to-2D transition provides opportunities for future material design and synthesis at the interface.

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