Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.150
Filtrar
1.
bioRxiv ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38746192

RESUMO

Objective: Recombinant monoclonal therapeutic antibodies like lecanemab, which target amyloid beta in Alzheimer's disease, offer a promising approach for modifying the disease progression. Due to its relatively short half-life, Lecanemab, administered as a bi-monthly infusion (typically 10mg/kg) has a relatively brief half-life. Interaction with abundant plasma proteins binder in the bloodstream can affect pharmacokinetics of drugs, including their half-life. In this study we investigated potential plasma protein binding interaction to lecanemab using lecanemab biosimilar. Methods: Lecanemab biosimilar used in this study was based on publicly available sequences. ELISA and Western blotting were used to assess lecanemab biosimilar immunoreactivity in the fractions human plasma sample obtained through size exclusion chromatography. The binding of lecanemab biosimilar to candidate binders was confirmed by Western blotting, ELISA, and surface plasmon resonance analysis. Results: Using a combination of equilibrium dialysis, ELISA, and Western blotting in human plasma, we first describe the presence of likely plasma protein binding partner to lecanemab biosimilar, and then identify fibrinogen as one of them. Utilizing surface plasmon resonance, we confirmed that lecanemab biosimilar does bind to fibrinogen, although with lower affinity than to monomeric amyloid beta. Interpretation: In the context of lecanemab therapy, these results imply that fibrinogen levels could impact the levels of free antibodies in the bloodstream and that fibrinogen might serve as a reservoir for lecanemab. More broadly, these results indicate that plasma protein binding may be an important consideration when clinically utilizing therapeutic antibodies in neurodegenerative disease.

2.
Chemphyschem ; : e202400143, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38726743

RESUMO

Electrocatalytic nitrogen reduction reaction (NRR) is a green and highly efficient way to replace the industrial Haber-Bosch process. Herein, clusters consisting of three transition metal atoms loaded on C2N as NRR electrocatalysts are investigated using density functional theory (DFT). Meanwhile, Ca was introduced as a promoter and the role of Ca in NRR was investigated. It was found that Ca anchored to the catalyst can act as an electron donor and effectively promote the activation of N2 on M3. In both M3@C2N and M3Ca@C2N (M = Fe, Co, Ni), the limiting potential (UL) is less negative than that of the Ru(0001) surface and has the ability to suppress the competitive hydrogen evolution reaction (HER). Among them, Fe3@C2N is suggested to be the most promising candidate for NRR with high thermal stability, strong N2 adsorption ability, low limiting potential, and good NRR selectivity. The concepts of trimetallic sites and alkaline earth metal promoters in this work provide theoretical guidance for the rational design of atomically active sites in electrocatalytic NRR.

3.
Med Phys ; 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38703397

RESUMO

BACKGROUND: Biology-guided radiotherapy (BgRT) is a novel radiotherapy delivery technique that utilizes the tumor itself to guide dynamic delivery of treatment dose to the tumor. The RefleXion X1 system is the first radiotherapy system developed to deliver SCINTIX® BgRT. The X1 is characterized by its split arc design, employing two 90-degree positron emission tomography (PET) arcs to guide therapeutic radiation beams in real time, currently cleared by FDA to treat bone and lung tumors. PURPOSE: This study aims to comprehensively evaluate the capabilities of the SCINTIX radiotherapy delivery system by evaluating its sensitivity to changes in PET contrast, its adaptability in the context of patient motion, and its performance across a spectrum of prescription doses. METHODS: A series of experimental scenarios, both static and dynamic, were designed to assess the SCINTIX BgRT system's performance, including an end-to-end test. These experiments involved a range of factors, including changes in PET contrast, motion, and prescription doses. Measurements were performed using a custom-made ArcCHECK insert which included a 2.2 cm spherical target and a c-shape structure that can be filled with a PET tracer with varying concentrations. Sinusoidal and cosine4 motion patterns, simulating patient breathing, was used to test the SCINTIX system's ability to deliver BgRT during motion-induced challenges. Each experiment was evaluated against specific metrics, including Activity Concentration (AC), Normalized Target Signal (NTS), and Biology Tracking Zone (BTZ) bounded dose-volume histogram (bDVH) pass rates. The accuracy of the delivered BgRT doses on ArcCHECK and EBT-XD film were evaluated using gamma 3%/2 mm and 3%/3 mm analysis. RESULTS: In static scenarios, the X1 system consistently demonstrated precision and robustness in SCINTIX dose delivery. The end-to-end delivery to the spherical target yielded good results, with AC and NTS values surpassing the critical thresholds of 5 kBq/mL and 2, respectively. Furthermore, bDVH analysis consistently confirmed 100% pass rates. These results were reaffirmed in scenarios involving changes in PET contrast, emphasizing the system's ability to adapt to varying PET avidities. Gamma analysis with 3%/2 mm (10% dose threshold) criteria consistently achieved pass rates > 91.5% for the static tests. In dynamic SCINTIX delivery scenarios, the X1 system exhibited adaptability under conditions of motion. Sinusoidal and cosine4 motion patterns resulted in 3%/3 mm gamma pass rates > 87%. Moreover, the comparison with gated stereotactic body radiotherapy (SBRT) delivery on a conventional c-arm Linac resulted in 93.9% gamma pass rates and used as comparison to evaluate the interplay effect. The 1 cm step shift tests showed low overall gamma pass rates of 60.3% in ArcCHECK measurements, while the doses in the PTV agreed with the plan with 99.9% for 3%/3 mm measured with film. CONCLUSIONS: The comprehensive evaluation of the X1 radiotherapy delivery system for SCINTIX BgRT demonstrated good agreement for the static tests. The system consistently achieved critical metrics and delivered the BgRT doses per plan. The motion tests demonstrated its ability to co-localize the dose where the PET signal is and deliver acceptable BgRT dose distributions.

4.
Chemosphere ; 358: 142207, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38697560

RESUMO

Fenazaquin, a potent insecticide widely used to control phytophagous mites, has recently emerged as a potential solution for managing Varroa destructor mites in honeybees. However, the comprehensive impact of fenazaquin on honeybee health remains insufficiently understood. Our current study investigated the acute and chronic toxicity of fenazaquin to honeybee larvae, along with its influence on larval hemolymph metabolism and gut microbiota. Results showed that the acute median lethal dose (LD50) of fenazaquin for honeybee larvae was 1.786 µg/larva, and the chronic LD50 was 1.213 µg/larva. Although chronic exposure to low doses of fenazaquin exhibited no significant effect on larval development, increasing doses of fenazaquin resulted in significant increases in larval mortality, developmental time, and deformity rates. At the metabolic level, high doses of fenazaquin inhibited nucleotide, purine, and lipid metabolism pathways in the larval hemolymph, leading to energy metabolism disorders and physiological dysfunction. Furthermore, high doses of fenazaquin reduced gut microbial diversity and abundance, characterized by decreased relative abundance of functional gut bacterium Lactobacillus kunkeei and increased pathogenic bacterium Melissococcus plutonius. The disrupted gut microbiota, combined with the observed gut tissue damage, could potentially impair food digestion and nutrient absorption in the larvae. Our results provide valuable insights into the complex and diverse effects of fenazaquin on honeybee larvae, establishing an important theoretical basis for applying fenazaquin in beekeeping.

5.
Materials (Basel) ; 17(9)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38730796

RESUMO

Experimental research and numerical simulations of the structural response to shock waves with pulse durations of hundreds of milliseconds, or even seconds, are extremely challenging. This paper takes typical single-layer and sandwich cylindrical shells as the research objects. The response rules of cylindrical shells under long-duration blast loadings were studied. The results show that when the pulse duration is greater than or equal to 4~5 times the first-order period of the structure, the maximum response of the structure tends to be consistent, that is, the maximum response of the cylindrical shells with different vibration shapes shows a saturation effect as the pulse duration increases. This study established the relationship between the saturation loading time and the inherent characteristics of the structure. It was found that the saturation effect was applicable under the following conditions, including different load waveforms, elastic-plastic deformation of the structure, and the loading object being a sandwich shell. This will help transform the long-duration explosion wave problem into a finite pulse-duration shock wave problem that can be realized by both experiments and numerical simulations.

6.
Materials (Basel) ; 17(9)2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38730908

RESUMO

All-silicon terahertz absorbers have attracted considerable interest. We present a design and numerical study of an all-silicon polarization-insensitive terahertz metamaterial absorber. The meta-atoms of the metamaterial absorber are square silicon rings which can be viewed as gratings. By properly optimizing the structure of the meta-atom, we achieve a broadband absorptivity that is above 90% ranging from 0.77 THz to 2.53 THz, with a relative bandwidth of 106.7%. Impedance matching reduces the reflection of the terahertz waves and the (0, ±1)-order diffraction induce the strong absorption. The absorption of this absorber is insensitive to the polarization of the terahertz wave and has a large incident angle tolerance of up to 60 degrees. The all-silicon metamaterial absorber proposed here provides an effective way to obtain broadband absorption in the terahertz regime. Metamaterial absorbers have outstanding applications in terahertz communication and imaging.

7.
Environ Sci Technol ; 58(18): 7743-7757, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38652822

RESUMO

Permeabilities of various trace elements (TEs) through the blood-follicle barrier (BFB) play an important role in oocyte development. However, it has not been comprehensively described as well as its involved biological pathways. Our study aimed to construct a blood-follicle distribution model of the concerned TEs and explore their related biological pathways. We finally included a total of 168 women from a cohort of in vitro fertilization-embryo transfer conducted in two reproductive centers in Beijing City and Shandong Province, China. The concentrations of 35 TEs in both serum and follicular fluid (FF) samples from the 168 women were measured, as well as the multiomics features of the metabolome, lipidome, and proteome in both plasma and FF samples. Multiomics features associated with the transfer efficiencies of TEs through the BFB were selected by using an elastic net model and further utilized for pathway analysis. Various machine learning (ML) models were built to predict the concentrations of TEs in FF. Overall, there are 21 TEs that exhibited three types of consistent BFB distribution characteristics between Beijing and Shandong centers. Among them, the concentrations of arsenic, manganese, nickel, tin, and bismuth in FF were higher than those in the serum with transfer efficiencies of 1.19-4.38, while a reverse trend was observed for the 15 TEs with transfer efficiencies of 0.076-0.905, e.g., mercury, germanium, selenium, antimony, and titanium. Lastly, cadmium was evenly distributed in the two compartments with transfer efficiencies of 0.998-1.056. Multiomics analysis showed that the enrichment of TEs was associated with the synthesis and action of steroid hormones and the glucose metabolism. Random forest model can provide the most accurate predictions of the concentrations of TEs in FF among the concerned ML models. In conclusion, the selective permeability through the BFB for various TEs may be significantly regulated by the steroid hormones and the glucose metabolism. Also, the concentrations of some TEs in FF can be well predicted by their serum levels with a random forest model.


Assuntos
Aprendizado de Máquina , Oligoelementos , Humanos , Oligoelementos/metabolismo , Feminino , Líquido Folicular/metabolismo , Líquido Folicular/química , China , Multiômica
8.
Neuropsychiatr Dis Treat ; 20: 855-862, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38628602

RESUMO

Objective: We explored the correlation between the presence of isocitrate dehydrogenase-1 (IDH1) mutations and the incidence of postoperative epilepsy in patients with glioblastoma, as well as assessed the efficacy of preemptive administration of antiepileptic medications in mitigating the occurrence of postoperative epilepsy. Methods: Fifty-three patients who received a postoperative pathological diagnosis of glioblastoma, were enrolled in this study. Tumor specimens were subjected to IDH1 gene analysis. The patient cohort was stratified based on their IDH1 mutation status and the administration of prophylactic antiepileptic drugs during the postoperative phase. We subsequently conducted a comparative analysis of postoperative epileptic complications within each patient subgroup. Results: In the cohort of 53 patients under study, the occurrence of epilepsy was observed in 10 out of 21 patients carrying IDH1 mutations, while 5 out of 32 patients with wild-type IDH1 also experienced epilepsy, revealing a statistically significant difference (P < 0.05). Among the 27 patients who received prophylactic antiepileptic drugs, 6 of them developed epilepsy, whereas 9 out of 26 patients who did not receive prophylactic antiepileptic drugs exhibited concurrent epilepsy, with no statistically significant difference (P > 0.05). However, when performing a subgroup analysis, it was found that 3 out of 12 patients with IDH1 mutations who received prophylactic antiepileptic drugs experienced epilepsy, whereas 7 out of 9 patients who did not receive prophylactic antiepileptic drugs developed epilepsy, demonstrating a statistically significant difference (P < 0.05). Furthermore, within the group of 15 patients with wild-type IDH1, 3 patients who received prophylactic antiepileptic drugs developed epilepsy, while 2 cases of epilepsy occurred among the 17 patients who did not receive prophylactic antiepileptic drugs, with no statistically significant difference (P > 0.05). Conclusion: In individuals with IDH1 mutant glioblastoma who have undergone surgical resection, the implementation of preventive antiepileptic therapy demonstrates a potential to diminish the occurrence of postoperative epilepsy.

9.
Sensors (Basel) ; 24(8)2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38676192

RESUMO

A new method based on a digital twin is proposed for fault diagnosis, in order to compensate for the shortcomings of the existing methods for fault diagnosis modeling, including the single fault type, low similarity, and poor visual effect of state monitoring. First, a fault diagnosis test platform is established to analyze faults under constant and variable speed conditions. Then, the obtained data are integrated into the Unity3D platform to realize online diagnosis and updated with real-time working status data. Finally, an industrial test of the digital twin model is conducted, allowing for its comparison with other advanced methods in order to verify its accuracy and application feasibility. It was found that the accuracy of the proposed method for the entire reducer was 99.5%, higher than that of other methods based on individual components (e.g., 93.5% for bearings, 96.3% for gear shafts, and 92.6% for shells).

10.
Sci China Life Sci ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38676814

RESUMO

Plant genomics and crop breeding are at the intersection of biotechnology and information technology. Driven by a combination of high-throughput sequencing, molecular biology and data science, great advances have been made in omics technologies at every step along the central dogma, especially in genome assembling, genome annotation, epigenomic profiling, and transcriptome profiling. These advances further revolutionized three directions of development. One is genetic dissection of complex traits in crops, along with genomic prediction and selection. The second is comparative genomics and evolution, which open up new opportunities to depict the evolutionary constraints of biological sequences for deleterious variant discovery. The third direction is the development of deep learning approaches for the rational design of biological sequences, especially proteins, for synthetic biology. All three directions of development serve as the foundation for a new era of crop breeding where agronomic traits are enhanced by genome design.

11.
Pharmacol Res ; 203: 107164, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38569981

RESUMO

The impact of mitochondrial dysfunction on the pathogenesis of cardiovascular disease is increasing. However, the precise underlying mechanism remains unclear. Mitochondria produce cellular energy through oxidative phosphorylation while regulating calcium homeostasis, cellular respiration, and the production of biosynthetic chemicals. Nevertheless, problems related to cardiac energy metabolism, defective mitochondrial proteins, mitophagy, and structural changes in mitochondrial membranes can cause cardiovascular diseases via mitochondrial dysfunction. Mitofilin is a critical inner mitochondrial membrane protein that maintains cristae structure and facilitates protein transport while linking the inner mitochondrial membrane, outer mitochondrial membrane, and mitochondrial DNA transcription. Researchers believe that mitofilin may be a therapeutic target for treating cardiovascular diseases, particularly cardiac mitochondrial dysfunctions. In this review, we highlight current findings regarding the role of mitofilin in the pathogenesis of cardiovascular diseases and potential therapeutic compounds targeting mitofilin.


Assuntos
Doenças Cardiovasculares , Proteínas Mitocondriais , Proteínas Musculares , Humanos , Animais , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Proteínas Musculares/metabolismo , Proteínas Musculares/genética , Proteínas Mitocondriais/metabolismo , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/efeitos dos fármacos
12.
Adv Mater ; : e2402515, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38616719

RESUMO

The artificial brain is conceived as advanced intelligence technology, capable to emulate in-memory processes occurring in the human brain by integrating synaptic devices. Within this context, improving the functionality of synaptic transistors to increase information processing density in neuromorphic chips is a major challenge in this field. In this article, Li-ion migration promoting long afterglow organic light-emitting transistors, which display exceptional postsynaptic brightness of 7000 cd m-2 under low operational voltages of 10 V is presented. The postsynaptic current of 0.1 mA operating as a built-in threshold switch is implemented as a firing point in these devices. The setting-condition-triggered long afterglow is employed to drive the photoisomerization process of photochromic molecules that mimic neurotransmitter transfer in the human brain for realizing a key memory rule, that is, the transition from long-term memory to permanent memory. The combination of setting-condition-triggered long afterglow with photodiode amplifiers is also processed to emulate the human responding action after the setting-training process. Overall, the successful integration in neuromorphic computing comprising stimulus judgment, photon emission, transition, and encoding,  to emulate the complicated decision tree of the human brain is demonstrated.

13.
ACS Sens ; 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38644577

RESUMO

A core-shell nanostructure of gold nanoparticles@covalent organic framework (COF) loaded with palladium nanoparticles (AuNPs@COF-PdNPs) was designed for the rapid monitoring of catalytic reactions with surface-enhanced Raman spectroscopy (SERS). The nanostructure was prepared by coating the COF layer on AuNPs and then in situ synthesizing PdNPs within the COF shell. With the respective SERS activity and catalytic performance of the AuNP core and COF-PdNPs shell, the nanostructure can be directly used in the SERS study of the catalytic reaction processes. It was shown that the confinement effect of COF resulted in the high dispersity of PdNPs and outstanding catalytic activity of AuNPs@COF-PdNPs, thus improving the reaction rate constant of the AuNPs@COF-PdNPs-catalyzed hydrogenation reduction by 10 times higher than that obtained with Au/Pd NPs. In addition, the COF layer can serve as a protective shell to make AuNPs@COF-PdNPs possess excellent reusability. Moreover, the loading of PdNPs within the COF layer was found to be in favor of avoiding intermediate products to achieve a high total conversion rate. AuNPs@COF-PdNPs also showed great catalytic activities toward the Suzuki-Miyaura coupling reaction. Taken together, the proposed core-shell nanostructure has great potential in monitoring and exploring catalytic processes and interfacial reactions.

14.
Proteomics ; : e2300184, 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38643383

RESUMO

Unconventional secretory proteins (USPs) are vital for cell-to-cell communication and are necessary for proper physiological processes. Unlike classical proteins that follow the conventional secretory pathway via the Golgi apparatus, these proteins are released using unconventional pathways. The primary modes of secretion for USPs are exosomes and ectosomes, which originate from the endoplasmic reticulum. Accurate and rapid identification of exosome-mediated secretory proteins is crucial for gaining valuable insights into the regulation of non-classical protein secretion and intercellular communication, as well as for the advancement of novel therapeutic approaches. Although computational methods based on amino acid sequence prediction exist for predicting unconventional proteins secreted by exosomes (UPSEs), they suffer from significant limitations in terms of algorithmic accuracy. In this study, we propose a novel approach to predict UPSEs by combining multiple deep learning models that incorporate both protein sequences and evolutionary information. Our approach utilizes a convolutional neural network (CNN) to extract protein sequence information, while various densely connected neural networks (DNNs) are employed to capture evolutionary conservation patterns.By combining six distinct deep learning models, we have created a superior framework that surpasses previous approaches, achieving an ACC score of 77.46% and an MCC score of 0.5406 on an independent test dataset.

15.
Front Plant Sci ; 15: 1327507, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38562563

RESUMO

Introduction: Rice (Oryza sativa) serves as a vital staple crop that feeds over half the world's population. Optimizing rice breeding for increasing grain yield is critical for global food security. Heading-date-related or Flowering-time-related traits, is a key factor determining yield potential. However, traditional manual phenotyping methods for these traits are time-consuming and labor-intensive. Method: Here we show that aerial imagery from unmanned aerial vehicles (UAVs), when combined with deep learning-based panicle detection, enables high-throughput phenotyping of heading-date-related traits. We systematically evaluated various state-of-the-art object detectors on rice panicle counting and identified YOLOv8-X as the optimal detector. Results: Applying YOLOv8-X to UAV time-series images of 294 rice recombinant inbred lines (RILs) allowed accurate quantification of six heading-date-related traits. Utilizing these phenotypes, we identified quantitative trait loci (QTL), including verified loci and novel loci, associated with heading date. Discussion: Our optimized UAV phenotyping and computer vision pipeline may facilitate scalable molecular identification of heading-date-related genes and guide enhancements in rice yield and adaptation.

16.
Environ Sci Technol ; 58(19): 8207-8214, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38647545

RESUMO

Short-term exposure to air pollution is associated with a decline in cognitive function. Standardized test scores have been employed to evaluate the effects of air pollution exposure on cognitive performance. Few studies aimed to prove whether air pollution is responsible for reduced test scores; none have implemented a "gold-standard" method for assessing the association such as a randomized, double-blind intervention. This study used a "gold-standard" method─randomized, double-blind crossover─to assess whether reducing short-term indoor particle concentrations results in improved test scores in college students in Tianjin, China. Participants (n = 162) were randomly assigned to one of two similar classrooms and completed a standardized English test on two consecutive weekends. Air purifiers with active or sham (i.e., filter removed) particle filtration were placed in each classroom. The filtration mode was switched between the two test days. Linear mixed-effect models were used to evaluate the effect of the intervention mode on the test scores. The results show that air purification (i.e., reducing PM) was significantly associated with increases in the z score for combined (0.11 [95%CI: 0.02, 0.21]) and reading (0.11 [95%CI: 0.00, 0.22]) components. In conclusion, a short-term reduction in indoor particle concentration led to improved test scores in students, suggesting an improvement in cognitive function.


Assuntos
Poluição do Ar em Ambientes Fechados , Estudos Cross-Over , Material Particulado , Estudantes , Humanos , Método Duplo-Cego , Masculino , Feminino , China , Poluentes Atmosféricos/análise , Adulto Jovem , Poluição do Ar
17.
Biochem Pharmacol ; 223: 116133, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38494066

RESUMO

Despite the exact biological role of HNF1 homolog A (HNF1A) in the regulatory mechanism of glioblastoma (GBM), the molecular mechanism, especially the downstream regulation as a transcription factor, remains to be further elucidated. Immunohistochemistry was used to detect the expression and clinical relevance of HNF1A in GBM patients. CCK8, TUNEL, and subcutaneous tumor formation in nude mice were used to evaluate the effect of HNF1A on GBM in vitro and in vivo. The correction between HNF1A and epidermal growth factor receptor pathway substrate 8 (EPS8) was illustrated by bioinformatics analysis and luciferase assay. Further mechanism was explored that the transcription factor HNF1A regulated the expression of EPS8 and downstream signaling pathways by directly binding to the promoter region of EPS8. Our comprehensive analysis of clinical samples in this study showed that upregulated expression of HNF1A was associated with poor survival in GBM patients. Further, we found that knockdown of HNF1A markedly suppressed the malignant phenotype of GBM cells in vivo and in vitro as well as promoted apoptosis of tumor cells, which was reversed by upregulation of HNF1A. Mechanistically, HNF1A could significantly activate PI3K/AKT signaling pathway by specifically binding to the promoter regions of EPS8. Moreover, overexpression of EPS8 was able to reverse the apoptosis of tumor cells caused by HNF1A knockdown, thereby exacerbating the GBM progression. Correctively, our study has clarified the explicit mechanism by which HNF1A promotes GBM malignancy and provides a new therapeutic target for further clinical application.


Assuntos
Glioblastoma , Proteínas Proto-Oncogênicas c-akt , Animais , Camundongos , Humanos , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Glioblastoma/genética , Glioblastoma/patologia , Camundongos Nus , Proliferação de Células , Linhagem Celular Tumoral , Transdução de Sinais , Fatores de Transcrição/metabolismo , Regulação Neoplásica da Expressão Gênica , Fator 1-alfa Nuclear de Hepatócito/genética , Fator 1-alfa Nuclear de Hepatócito/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo
18.
Toxics ; 12(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38535930

RESUMO

Various geostatistical models have been used in epidemiological research to evaluate ambient air pollutant exposures at a fine spatial scale. Few studies have investigated the performance of different exposure models on population-weighted exposure estimates and the resulting potential misclassification across various modeling approaches. This study developed spatial models for NO2 and PM2.5 and conducted exposure assessment in Beijing, China. It explored three spatial modeling approaches: variable dimension reduction, machine learning, and conventional linear regression. It compared their model performance by cross-validation (CV) and population-weighted exposure estimates. Specifically, partial least square (PLS) regression, random forests (RF), and supervised linear regression (SLR) models were developed based on an ordinary kriging (OK) framework for NO2 and PM2.5 in Beijing, China. The mean squared error-based R2 (R2mse) and root mean squared error (RMSE) in leave-one site-out cross-validation (LOOCV) were used to evaluate model performance. These models were used to predict the ambient exposure levels in the urban area and to estimate the misclassification of population-weighted exposure estimates in quartiles between them. The results showed that the PLS-OK models for NO2 and PM2.5, with the LOOCV R2mse of 0.82 and 0.81, respectively, outperformed the other models. The population-weighted exposure to NO2 estimated by the PLS-OK and RF-OK models exhibited the lowest misclassification in quartiles. For PM2.5, the estimates of potential misclassification were comparable across the three models. It indicated that the exposure misclassification made by choosing different modeling approaches should be carefully considered, and the resulting bias needs to be evaluated in epidemiological studies.

19.
ACS Sens ; 9(3): 1321-1330, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38471126

RESUMO

A groundbreaking demonstration of the utilization of the metal-organic framework MIL-101(Fe) as an exceptionally perceptive visual label in colorimetric lateral flow assays (LFA) is described. This pioneering approach enables the precise identification of transglutaminase 2 (TGM2), a recognized biomarker for chronic kidney disease (CKD), in urine specimens, which offers a remarkably sensitive naked-eye detection mechanism. The surface of MIL-101(Fe) was modified with oxalyl chloride, adipoyl chloride, and poly(acrylic) acid (PAA); these not only improved the labeling material stability in a complex matrix but also achieved a systematic control in the detection limit of the TGM2 concentration using our LFA platform. The advanced LFA with the MIL-101(Fe)-PAA label can detect TGM2 concentrations down to 0.012, 0.009, and 0.010 nM in Tris-HCl buffer, urine, and desalted urine, respectively, which are approximately 55-fold lower than those for a conventional AuNP-based LFAs. Aside from rapid TGM2 detection (i.e., within 20 min), the performance of the MIL-101(Fe)-PAA-based LFA on reproducibility [coefficients of variation (CV) < 2.9%] and recovery (95.9-103.2%) along with storage stability within 25 days of observation (CV < 6.0%) shows an acceptable parameter range for quantitative analysis. A sophisticated sensing method grounded in machine learning principles was also developed, specifically aimed at precisely deducing the TGM2 concentration by analyzing immunoreaction sites. More importantly, our developed LFA offers potential for clinical measurement of TGM2 concentration in normal human urine and CKD patients' samples.


Assuntos
Aprendizado de Máquina , Estruturas Metalorgânicas , Proteína 2 Glutamina gama-Glutamiltransferase , Insuficiência Renal Crônica , Humanos , Colorimetria/métodos , Ferro , Proteína 2 Glutamina gama-Glutamiltransferase/urina , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/urina , Reprodutibilidade dos Testes
20.
ChemSusChem ; : e202301778, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38433647

RESUMO

Photocatalysis has the advantages of practical, sustainable and environmental protection, so it plays a significant role in energy transformation and environmental utilization. CeO2 has attracted widespread attention for its unique 4 f electrons, rich defect structures, high oxygen storage capacity and great chemical stability. In this paper, we review the structure of CeO2 and the common methods for the preparation of CeO2-based composites in the first part. In particular, we highlight the co-precipitation method, template method, and sol-gel method methods. Then, in the second part, we introduce the application of CeO2-based composites in photocatalysis, including photocatalytic CO2 reduction, hydrogen production, degradation, selective organic reaction, and photocatalytic nitrogen fixation. In addition, we discuss several modification techniques to improve the photocatalytic performance of CeO2-based composites, such as elemental doping, defect engineering, constructing heterojunction and morphology regulation. Finally, the challenges faced by CeO2-based composites are analyzed and their development prospects are prospected. This review provides a systematic summary of the recent advance of CeO2-based composites in the field of photocatalysis, which can provide useful references for the rational design of efficient CeO2-based composite photocatalysts for sustainable development.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...