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1.
J Biomed Opt ; 30(Suppl 1): S13702, 2025 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-39034960

RESUMEN

Significance: Near-infrared autofluorescence (NIRAF) utilizes the natural autofluorescence of parathyroid glands (PGs) to improve their identification during thyroid surgeries, reducing the risk of inadvertent removal and subsequent complications such as hypoparathyroidism. This study evaluates NIRAF's effectiveness in real-world surgical settings, highlighting its potential to enhance surgical outcomes and patient safety. Aim: We evaluate the effectiveness of NIRAF in detecting PGs during thyroidectomy and central neck dissection and investigate autofluorescence characteristics in both fresh and paraffin-embedded tissues. Approach: We included 101 patients diagnosed with papillary thyroid cancer who underwent surgeries in 2022 and 2023. We assessed NIRAF's ability to locate PGs, confirmed via parathyroid hormone assays, and involved both junior and senior surgeons. We measured the accuracy, speed, and agreement levels of each method and analyzed autofluorescence persistence and variation over 10 years, alongside the expression of calcium-sensing receptor (CaSR) and vitamin D. Results: NIRAF demonstrated a sensitivity of 89.5% and a negative predictive value of 89.1%. However, its specificity and positive predictive value (PPV) were 61.2% and 62.3%, respectively, which are considered lower. The kappa statistic indicated moderate to substantial agreement (kappa = 0.478; P < 0.001 ). Senior surgeons achieved high specificity (86.2%) and PPV (85.3%), with substantial agreement (kappa = 0.847; P < 0.001 ). In contrast, junior surgeons displayed the lowest kappa statistic among the groups, indicating minimal agreement (kappa = 0.381; P < 0.001 ). Common errors in NIRAF included interference from brown fat and eschar. In addition, paraffin-embedded samples retained stable autofluorescence over 10 years, showing no significant correlation with CaSR and vitamin D levels. Conclusions: NIRAF is useful for PG identification in thyroid and neck surgeries, enhancing efficiency and reducing inadvertent PG removals. The stability of autofluorescence in paraffin samples suggests its long-term viability, with false positives providing insights for further improvements in NIRAF technology.


Asunto(s)
Imagen Óptica , Glándulas Paratiroides , Espectroscopía Infrarroja Corta , Tiroidectomía , Humanos , Glándulas Paratiroides/cirugía , Glándulas Paratiroides/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Imagen Óptica/métodos , Adulto , Espectroscopía Infrarroja Corta/métodos , Adhesión en Parafina/métodos , Anciano , Cáncer Papilar Tiroideo/cirugía , Cáncer Papilar Tiroideo/patología , Cáncer Papilar Tiroideo/metabolismo , Receptores Sensibles al Calcio/metabolismo , Receptores Sensibles al Calcio/análisis
2.
Biomed Rep ; 22(1): 1, 2025 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-39483331

RESUMEN

Human organ tissue is vulnerable to hyperuricemia (HUA), which negatively impacts quality of life, particularly when it progresses to gout. Chicken uric acid formation and metabolism are similar to human uric acid metabolism; therefore, theoretically, the genesis and progression of human HUA and gout may be similar to those of poultry models. The present review explored HUA and gout and the progress of poultry-induced HUA and gout models. The present study reviewed procedures of modelling chicken gout and HUA and the detection indices and current concerns regarding these models. Notably, In the production of poultry hyperuricemia model, the combined method of water and food induction has a higher success rate and stability. Compared with mice induced HUA and gout models, poultry induced HUA and gout models had less kidney damage, and the models were stable and long-lasting.

3.
Front Plant Sci ; 15: 1481732, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39483671

RESUMEN

Introduction: Soil contamination with copper (Cu) threatens ecological security and human health. Rapeseed demonstrates potential in remediating copper-contaminated soil, and biochar-assisted phytoremediation is increasingly being employed to improve remediation efficiency. However, the combined application of them has not been thoroughly studied in terms of the synergistic effects and the mechanisms of their interaction. Methods: In this regard, this study conducted a pot experiment to evaluate biochar-assisted remediation under Cu-contaminated soil with varying biochar application rates; Furthermore, the plant physiological mechanism and soil physicochemical properties involved in the biocharrapeseed system was explored. Results: Our results showed that the exchangeable pool of copper in soil decreased by 10.0% and 12.3% with adding 5% biochar (BC1) and 10% biochar (BC2) relative to control (BC0), respectively, prior to rapeseed cultivation. The rapeseed cultivation for one season further reclaimed 4.9%, 9.0%, and 13.6% of the available copper in this soil by root extraction under the BC0, BC1, and BC2 treatments, respectively. The overall copper concentration in plants decreased by 23.7% under BC2 and 13.3% under BC1 compared to BC0. However, the plant's dry biomass at BC1 and BC2 treatments increased by 1.7-fold and 2.7-fold relative to BC0, which offset the negative impact of the decreased copper concentration on phytoremediation. Physiological analysis showed adding 10% biochar decreased the MDA content by 36% in the leaf and 49% in the root, compared to BC0. The transmission electron microscopy for cell wall ultrastructure in root tips showed that biochar addition in Cu-contaminated soil increased the mechanical strength of the celL wall, explicitly increasing the thickness of the secondary cell wall. Further cell wall components analysis revealed a remarkable increment of the pectin content in BC2 relative to BC0, increased by 56% in the leaf and 99% in the root, respectively. Additionally, 10% biochar application led to a roughly 2-fold increase in seed yield via ameliorating the soil physicochemical properties and increasing the rapeseed growth. Discussion: These findings offer insights into synergistic rapeseed-biochar use for Cu-contaminated soil remediation.

4.
Front Pharmacol ; 15: 1431706, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39484158

RESUMEN

Background: Traditional Chinese medicine (TCM) is used to treat mycoplasma pneumonia (MP) in children with favorable treatment outcome in China. In the present study, we evaluated the clinical efficacy of TCM combined with azithromycin (AZM) for the treatment of MP among children, providing high evidence-based reference for clinical treatment. Method: We retrieved eligible randomized controlled trials (RCTs) from CQVIP, CNKI, WanFang, NSTL, PubMed, Embase, and Embase databases from January 2000 to November 2023. Data extraction and quality assessment of the enrolled studies were independently by two reviewers. Review Manager 5.3 was used for meta-analysis. Result: A total of 51 RCTs involving 5,799 children aged 1-14 enrolled. Meta-analysis demonstrated that TCM combined with AZM improved the cure rate (odds ratio [OR] = 2.34, 95% CI: 2.06 to 2.64) and the effective rate (OR = 5.21, 95% CI: 4.22 to 6.43), shorted the disappearance duration of cough (WMD = -1.62, 95% CI: -1.90 to -1.34), the duration of fever (WMD = -1.62, 95% CI: -1.96 to -1.29), and the disappearance time of lung rales (WMD = -1.15, 95% CI: -1.32 to -0.98), improved CRP levels (WMD = -2.06, 95% CI: -2.57 to -1.55), IL-6 levels (WMD = -1.92,95% CI: -2.51 to -1.34), and TNF-α levels (WMD = -1.59, 95% CI: -2.14 to -1.04), and reduced adverse reactions (OR = 0.37, 95% CI: 0.32 to 0.44). Conclusion: TCM combined with AZM in the treatment of MP among children has favorable clinical efficacy and safety.

5.
J Mater Chem B ; 2024 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-39445792

RESUMEN

Owing to their inherent flexibility and excellent biocompatibility, liquid metals (LMs) have been explored at the frontiers of clinical therapy. Herein, a LM and tanshinone IIA (TA) drugs were dispersed into sodium alginate (SA) solution by ultrasonication to prepare SA/LM/TA, which is an injectable biomaterial for stable drug release and intrapericardial injection for the treatment of myocardial infarction (MI). The SA/LM/TA has a low viscosity and can be injected smoothly using a syringe. In rat models of MI, we demonstrated that SA/LM/TA injection in the pericardial cavity is a biosafe and effective method to deliver a carrier containing LM particles and TA drugs for MI treatment. After injection, the drug release is slow and stable in the pericardial cavity, increasing the cardiac retention of drugs. After surgery and treatment for 7 days, the cardiac function of rats improved compared with the control group and the TA direct injection group. The intrapericardial injection of SA/LM/TA improves cardiac functions and mitigates cardiac remodeling post myocardial infarction of rats. Overall, the present study establishes a therapeutic strategy for treatment of myocardial infarction by intrapericardial injection of SA/LM/TA and expands the application categories of LM biomaterials in disease treatments.

6.
Artículo en Inglés | MEDLINE | ID: mdl-39438298

RESUMEN

INTRODUCTION: Progressive supranuclear palsy (PSP) is a neurodegenerative disorder with diverse clinical presentations that are linked to tau pathology. Recently, Subtype and Stage Inference (SuStaIn) algorithm, an innovative data-driven method, has been developed to model both the spatial-temporal progression and subtypes of disease. This study explores PSP progression using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging and the SuStaIn algorithm to identify PSP metabolic progression subtypes and understand disease mechanisms. METHODS: The study included 72 PSP patients and 70 controls, with an additional 24 PSP patients enrolled as a test set, undergoing FDG-PET, dopamine transporter (DAT) PET, and neuropsychological assessments. The SuStaIn algorithm was employed to analyze the FDG-PET data, identifying progression subtypes and sequences. RESULTS: Two PSP subtypes were identified: the cortical subtype with early prefrontal hypometabolism and the brainstem subtype with initial midbrain alterations. The cortical subtype displayed greater cognitive impairment and DAT reduction than the brainstem subtype. The test set demonstrates the robustness and reproducibility of the findings. Pathway analysis indicated that disruptions in dopaminergic cortico-basal ganglia pathways are crucial for elucidating the mechanisms of cognitive and behavioral impairment in PSP, leading to the two metabolic progression subtypes. CONCLUSION: This study identified two spatiotemporal progression subtypes of PSP based on FDG-PET imaging, revealing significant differences in metabolic patterns, striatal dopaminergic uptake, and clinical profiles, particularly cognitive impairments. The findings highlight the crucial role of dopaminergic cortico-basal ganglia pathways in PSP pathophysiology, especially in the cortical subtype, providing insights into PSP heterogeneity and potential avenues for personalized treatments.

7.
Cell Biochem Funct ; 42(7): e4127, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39420654

RESUMEN

Laccase is a copper-containing polyphenol oxidase that can oxidize phenolic and non-phenolic organic substrates. In the past decades, laccases had received considerable attention because of the ability to degrade various organic substances. Based on the codon preference of the Pichia pastoris expression system, this study optimized the gene structure of the laccase gene Lcc1 from Coprius cinerea through synthetic biology methods. A new gene Lcc1I was synthesized and heterologously expressed in P. pastoris. After 3 days of cultivation in a shake flask at 30°C, the transformants produced at a yield of 890 mg L-1protein. The highest production level of the recombinant laccase was 2760 U L-1. The molecular mass of the recombinant laccase was estimated at 60 kDa. The enzyme showed highest activity at pH 3.4 and 45°C. It possessed better stability at higher pH and lower temperature condition. Using 2,2'-azino-bis-(3-ethylbenzothiazoline)-6-sulphonate (ABTS) as the substrate, the Km and Vmax values were 0.136 mM and 9778 µM min-1 mg-1, respectively. The recombinant laccase could directly oxidize some triphenylmethane dyes like leuco-crystal violet (LCV) and leuco-malachite green (LMG). With the help of ABTS mediator, it could oxidize and degrade 77.7% crystal violet (CV) and 79.2% malachite green (MG) within 1 h. Our results indicate that optimization of the laccase gene achieves good expression results in the host system. The dye degradation model constructed in this study may also be applied to the degradation of other organic pollutants and toxic substances, providing new solutions for environmental remediation against the increasingly severe environmental pollution.


Asunto(s)
Colorantes , Coprinus , Lacasa , Compuestos de Tritilo , Lacasa/genética , Lacasa/metabolismo , Lacasa/química , Colorantes/metabolismo , Colorantes/química , Compuestos de Tritilo/metabolismo , Compuestos de Tritilo/química , Coprinus/enzimología , Coprinus/metabolismo , Coprinus/genética , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/genética , Concentración de Iones de Hidrógeno , Biodegradación Ambiental , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/química , Temperatura , Saccharomycetales
8.
Quant Imaging Med Surg ; 14(10): 7098-7110, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39429564

RESUMEN

Background: Patients with lung cancer face a heightened risk of developing sarcopenia. Despite this known risk, the impact of sarcopenia on the long-term prognosis of lung cancer patients, specifically concerning progression-free survival (PFS) and overall survival (OS), remains unclear. The primary objective of our study was to examine the correlation between metabolic parameters derived from 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and sarcopenia, as well as the prognostic value of sarcopenia in patients with surgically resected early-stage non-small cell lung cancer (NSCLC). Methods: In this retrospective cross-sectional study, we analyzed 187 NSCLC patients who underwent 18F-FDG PET/CT at the First Affiliated Hospital of Soochow University between March 2019 and October 2023. Patients were divided into two groups based on the presence (n=46) or absence (n=141) of sarcopenia. The correlation between sarcopenia, metabolic parameters, and patient characteristics was evaluated using chi-square and Mann-Whitney U tests. Survival analyses, including PFS and OS, were conducted using Kaplan-Meier analysis and Cox proportional hazards regression. Based on sarcopenia, metabolic parameters and patient characteristics, patients were classified into high-risk (n=28), intermediate-risk (n=121), and low-risk (n=38) groups. Results: Our analysis identified gender, body mass index (BMI), psoas Hounsfield unit (HU), and maximum standardized uptake value of the psoas major muscle (SUVmax-Muscle) as independent predictors of sarcopenia (P<0.05 for all). A nomogram model, utilizing these parameters, was constructed to predict sarcopenia. Survival analysis further demonstrated that total lesion glycolysis [hazard ratio (HR) =2.499; 95% confidence interval (CI): 2.014-3.267; P=0.016], sarcopenia (HR =3.323; 95% CI: 1.748-6.316; P<0.001), and programmed death ligand-1 (PD-L1) expression (HR =0.093; 95% CI: 0.012-0.698; P=0.021) emerged as independent predictors of OS in early-stage NSCLC. Notably, patients categorized as high-risk, characterized by elevated total lesion glycolysis, presence of sarcopenia, and PD-L1 positivity, exhibited a significantly poorer prognosis compared to the intermediate-risk (P<0.05) and low-risk groups (P<0.05). Conclusions: Our findings indicated an inverse relationship between SUVmax-Muscle or psoas HU with the incidence of sarcopenia in NSCLC patients. Additionally, total lesion glycolysis, sarcopenia, and PD-L1 expression were identified as independent prognostic factors for OS in early-stage NSCLC. The risk stratification model, incorporating total lesion glycolysis, sarcopenia, and PD-L1 expression, assumed a pivotal role in guiding personalized therapy decisions and post-treatment monitoring.

9.
Iran J Public Health ; 53(6): 1313-1321, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39430150

RESUMEN

Background: To explore the perioperative effect of the evaluation system of nursing quality in otorhinolaryngology patients. Methods: A total of 100 patients hospitalized in the Department of Otorhinolaryngology of the Third Affiliated Hospital of Qiqihar Medical College, Qiqihar City, China in 2019 were selected as the control group, and routine nursing mode was adopted. The control group was data before the implementation of this study. A total of 100 patients (experimental group) hospitalized in the Department of Otolaryngology in 2020 were selected to adopt the nursing model constructed by nursing quality evaluation system. The adverse mood of patients in the two groups were evaluated at admission and discharge, and postoperative pain and satisfaction were compared between the two groups. Results: Anxiety, depression and quality of life scores were improved in both groups, but the degree of improvement in experimental group was significantly higher than that in control group (t=481.759, 353.502, P<0.05), and the postoperative pain score in experimental group was lower than that in control group (t=54.086, P<0.05). The satisfaction of experimental group was better than that of control group (χ2=30.327, P<0.05). Conclusion: The nursing model based on the evaluation system of the nursing quality of otorhinolaryngology can relieve patients' adverse emotions, relieve postoperative pain of otorhinolaryngology patients, and improve patient satisfaction. Therefore, it is worth popularizing and applying in the future.

10.
Sci Adv ; 10(41): eadp8804, 2024 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-39383239

RESUMEN

Monitoring soft-tissue biomechanics is of interest in biomedical research and clinical treatment of diseases. An important focus is biointegrated strain gauges that track time-dependent mechanics of targeted tissues with deforming surfaces over multidirections. Existing methods provide limited gauge factors, tailored for sensing within specific directions under quasi-static conditions. We present development and applicability of implantable/wearable strain gauges that integrate multiple ultrathin monocrystalline silicon-based sensors aligned with different directions, in stretchable formats for dynamically monitoring direction angle-sensitive strain. We experimentally and computationally establish operational principles, with theoretical systems that enable determination of intensities and direction of applied strains at an omnidirectional scale. Wearable evaluations range from cardiac pulse to intraocular pressure monitoring of eyeballs. The device can evaluate cardiac disorders of myocardial infarction and hypoxia of living rats and locate the pathological orientation associated with infarction, in designs with possibilities as biodegradable implants for stable operation. These findings create clinical significance of the devices for monitoring complex dynamic biomechanics.


Asunto(s)
Silicio , Dispositivos Electrónicos Vestibles , Silicio/química , Animales , Ratas , Fenómenos Biomecánicos , Prótesis e Implantes , Humanos , Estrés Mecánico , Infarto del Miocardio
11.
Therap Adv Gastroenterol ; 17: 17562848241284229, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39386273

RESUMEN

Background: Fruquintinib is a third-line and subsequent targeted therapy for patients with metastatic colorectal cancer (mCRC). Identifying survival predictors after fruquintinib is crucial for optimizing the clinical use of this medication. Objectives: We aimed to identify factors influencing the prognosis of patients with mCRC treated with fruquintinib and to leverage these insights to develop a nomogram model for estimating survival rates in this patient population. Design: Multicenter retrospective observational study. Methods: We collected patient data from January 2019 to October 2023, with one healthcare institution's data serving as the training cohort and the other three hospitals' data serving as the multicenter validation cohort. The nomogram for overall survival was calculated from Cox regression models, and variable selection was screened using the univariate Cox regression analysis with additional variables based on clinical experience. Model performance was measured by the concordance index (C-index), calibration curves, decision curve analyses (DCA), and utility (patient stratification into low-risk vs high-risk groups). Results: Data were ultimately collected on 240 patients, with 144 patients included in the training cohort and 96 included in the multicenter validation cohort. Predictors included in the nomogram were CA199, body mass index, T stage, the primary site of the tumor, and other metastatic and pathological differentiation. The C-index of the nomogram in the training set and multicenter validation was 0.714 and 0.729, respectively. The models were fully calibrated and their predictions aligned closely with the observed data. DCA curves indicated the promising clinical benefits of the predictive model. Finally, the reliability of the model was also verified through the risk classification using the nomogram. Conclusions: We constructed a nomogram for mCRC treated with fruquintinib based on six variables that may be used to assist in personalizing the use of the drug.


A nomogram for predicting OS after application of fruquintinib in patients with mCRC The prognostic predictors of fruquintinib as a third-line and subsequent treatment agent for patients with mCRC have not been established. In this study, we explored possible factors influencing its prognosis and developed a nomogram model for estimating survival rates in this patient population. The nomogram, based on six key variables including CA199, BMI, T stage, primary tumor site, other metastatic sites, and pathological differentiation, was validated through a rigorous multicenter validation process. The nomogram has the potential to help clinicians personalize the use of fruquintinib for mCRC patients.

13.
J Cell Mol Med ; 28(19): e70137, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39392128

RESUMEN

Lymph node metastasis contributed to the leading cause and treatment failure in nasopharyngeal carcinoma (NPC). The microenvironment and the cellular communications of lymph node metastasized tumours determine the tumour progression and therapeutic effect, but the ecosystems about the lymph node metastasis (LNM) for NPC patients remain poorly characterized. Here, we integrated the transcriptomes of 47,618 single cells from eight samples related to NPC LNM. The dynamic immune ecosystems and immunosuppressive microenvironment including T cells, myeloid cells and B cells were observed in the lymph node metastatic samples compared with primary tumours. Additionally, the heterogeneity of epithelial cells was also revealed, and several clusters with expression programs that were associated with the progression-free survival of NPC patients were identified. Additionally, our data revealed the complex intercellular communications from primary to lymph node metastasis. The rewiring of CCL signalling which plays an important role in tumour metastasis was further identified. Altogether, we systematically characterized the ecosystem of NPC primary and lymph node metastasized tumours, which may shed light on the development of a therapeutic strategy to improve clinical outcomes of NPC patients with lymph node metastasis.


Asunto(s)
Ganglios Linfáticos , Metástasis Linfática , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Análisis de la Célula Individual , Microambiente Tumoral , Humanos , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patología , Carcinoma Nasofaríngeo/metabolismo , Microambiente Tumoral/genética , Análisis de la Célula Individual/métodos , Ganglios Linfáticos/patología , Ganglios Linfáticos/metabolismo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/metabolismo , Regulación Neoplásica de la Expresión Génica , Transcriptoma/genética , Perfilación de la Expresión Génica
14.
Food Chem ; 463(Pt 4): 141452, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39395348

RESUMEN

Differences in raw material characteristics directly affect the processing characteristics and quality of the final product. Therefore, it is important for the salmon industry to start regulating or grading from raw material side. In this study, the material characteristics and flavor quality of three different salmons: Atlantic salmon, red salmon, and pink salmon were evaluated. Trans-2,cis-6-nonadienal, octanal, and cis-4-heptenal contributed to the fishy aroma of roasted salmon, while fresh salmon was mainly caused by octanal. The oily aroma of fresh salmon was relevant to octanal, decanal, and 1-heptanol. The results indicated that the composition of phospholipids affect the flavor of roasted salmon, such as phosphatidylethanolamines and phosphatidylcholines, were closely related to the roasted and fishy aroma of roasted salmon. This study revealed that roasting could reduce the sensory quality difference between salmon by changing the textural property and volatile compound profile, provide guidance for production, grading, and consumption of salmon.

15.
ACS Nano ; 18(41): 28212-28227, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39363565

RESUMEN

The efficient delivery of RNA-based drugs to solid tumors remains a formidable obstacle. We aim to develop a safe and efficient oral drug delivery system compatible with RNA-based drugs that is urgently needed to overcome challenges such as enzymatic degradation and gastrointestinal barriers to facilitate effective treatment for treating colorectal cancer (CRC). To address these challenges, we utilized engineered modified Saccharomyces cerevisiae to evaluate the delivery efficacy of miR21-antagomir for treating CRC in preclinical mouse models, including adenomatosis polyposis coli mutant transgenic mice ApcMin/+ and in situ tumor-bearing mice. An orally deliverable gene delivery system, YS@NPs21, was designed. This gene delivery system demonstrated effectively suppressed tumor growth in both ApcMin/+ and in situ tumor-bearing mice models. This system exhibited tumor-targeting capability, effective inhibition of tumor growth, and low toxicity toward nontumor cells. Successful implementation of this innovative oral drug delivery system could offer a straightforward, safe, and RNA drug-compatible approach to CRC treatment, ultimately improving patient outcomes and reducing medical costs.


Asunto(s)
Neoplasias Colorrectales , Saccharomyces cerevisiae , Animales , Saccharomyces cerevisiae/genética , Ratones , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Administración Oral , Humanos , Técnicas de Transferencia de Gen , Ratones Transgénicos , MicroARNs/genética , MicroARNs/metabolismo , Antagomirs/farmacología , Antagomirs/química , Sistemas de Liberación de Medicamentos , Nanopartículas/química , Ratones Endogámicos C57BL , Proliferación Celular/efectos de los fármacos
16.
Comput Biol Med ; 183: 109268, 2024 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-39405731

RESUMEN

Machine learning is rapidly advancing the drug discovery process, significantly enhancing speed and efficiency. Innovation in computer-aided drug design is primarily driven by structure- and ligand-based approaches. When the number of known inhibitors for a target is limited, data augmentation strategies are often preferred to enhance model performance. In this study, we developed predictive machine learning models for structure-based drug discovery leveraging multiple traditional machine learning algorithms trained with target and ligand dynamics-aware datasets. To illustrate our approach, we present a composite model that combines classification and regression to predict YTHDF1 inhibitors, utilizing PLEC features. YTHDF1, a key m6A reader protein involved in mRNA translation, is implicated in various cancers, making it a promising therapeutic target. Traditional structure-based virtual screening (SBVS) using generic scoring functions has struggled to identify potent YTHDF1 inhibitors due to the protein's unique binding characteristics. To overcome this, we developed YTHDF1-specific machine learning scoring functions (MLSFs) to enhance SBVS efficacy. We employed various data augmentation techniques to generate a comprehensive dataset, incorporating multiple conformations of ligands and the YTHDF1 protein. We have trained 64 YTHDF1-specific MLSFs using four machine learning algorithms and evaluated them on ten test sets, focusing on their predictive and ranking power. Our results demonstrate that the artificial neural network with protein-ligand extended connectivity fingerprints (ANN-PLEC) outperforms other MLSFs, consistently achieving high area under the precision-recall curve (PR-AUC) of 0.87. This method shows promise for targets with limited quantities of active molecules, providing a viable path forward for drug discovery research. The ANN-PLEC scoring function is made freely available on GitHub for other researchers to access and utilize https://github.com/JuniML/SBVS-YTHDF1/.

17.
Artículo en Inglés | MEDLINE | ID: mdl-39423139

RESUMEN

High-fidelity (HiFi) sequencing has facilitated the assembly and analysis of the most repetitive region of the genome, the centromere. Nevertheless, our current understanding of human centromeres is based on a relatively small number of telomere-to-telomere assemblies, which has not yet captured its full diversity. In this study, we investigated the genomic diversity of human centromere higher order repeats (HORs) via both HiFi reads and haplotype-resolved assemblies from hundreds of samples drawn from ongoing pangenome-sequencing projects and reprocessed them via a novel HOR annotation pipeline, HiCAT-human. We used this wealth of data to provide a global survey of the centromeric HOR landscape; in particular, we found that 23 HORs presented significant copy number variability between populations. We detected three centromere genotypes with unbalanced population frequencies on chromosomes 5, 8, and 17. An inter-assembly comparison of HOR loci further revealed that while HOR array structures are diverse, they nevertheless tend to form a number of specific landscapes, each exhibiting different levels of HOR subunit expansion and possibly reflecting a cyclical evolutionary transition from homogeneous to nested structures and back.

18.
PLoS One ; 19(10): e0311722, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39418264

RESUMEN

By utilizing China's 2016 Implementation Plan for the Specific Rectification of Internet Financial Risks as an exogenous shock, we employ a difference-in-differences identification strategy to investigate the impact of FinTech regulation on banks' risk-taking. Our findings indicate that FinTech regulation strengthens banks' deposit franchises and funding liquidity. As reliable and interest-rate-insensitive funding sources, higher deposit franchises weaken banks' incentives for risk-taking. Further analysis, conducted to control for the potential interference of other policies, confirms the stable incremental effect of FinTech regulation. Moreover, we find that FinTech regulation tends to benefit banks with higher capital buffers and smaller sizes from a triple difference (difference-in-difference-in-difference) analysis. By focusing on the external effects of FinTech regulation, we aim to shed light on how regulatory gaps impact the formal financial system and highlight the importance of effectively regulating emerging financial entities.


Asunto(s)
Asunción de Riesgos , China , Humanos , Administración Financiera
19.
Genomics ; 116(6): 110953, 2024 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-39419194

RESUMEN

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its advanced stage, metabolic dysfunction-associated steatohepatitis (MASH), are increasingly recognized as a global health issue. This study examines the role of small RNAs in the spleen of MASH using a non-human primate model. We performed high-throughput small RNA sequencing on spleen tissues from MASH-primates, revealing significant alterations in the expression of small non-coding RNAs, especially miRNAs. Notably, miR-96, miR-182, miR-183, and miR-122 showed differential expression in MASH spleens. Predictive and validation studies have identified potential target genes, such as PTX3 and NFIX, that were significantly dysregulated in spleens of MASH. These findings characterized small RNAs in spleen of MASH and offer a novel insight for further research for MASH.

20.
Food Chem ; 464(Pt 1): 141620, 2024 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-39423521

RESUMEN

A multifunctional oxidase-mimicking Ag/Mn3O4 was prepared, catalyzing the 3, 3', 5, 5'-tetramethylbenzidine (TMB) chromogenic reaction. Six foodborne pathogenic bacteria species, including Escherichia coli, Staphylococcus aureus, Salmonella enterica, Listeria monocytogenes, Bacillus cereus, and Cronobacter sakazakii, were observed to differentially inhibit its oxidase-like activity, resulting in decelerating the TMB chromogenic reaction. Owing to these properties, the following achievements were achieved: colorimetric determination of these bacteria with high sensitivity can be achieved using Ag/Mn3O4 + TMB reaction system; precise identification of these bacteria at different concentrations, including individual bacterium, binary mixtures, and even multivariate mixtures, can be effectively realized by combining the Ag/Mn3O4-based colorimetric sensor array with principal component analysis (PCA); broad-spectrum inactivation of these bacteria can be remarkably realized through catalyzation of Ag/Mn3O4 to generate superoxide anion free radicals. Therefore, our proposed Ag/Mn3O4 holds significant application potential in the colorimetric determination, precise identification, and broad-spectrum inactivation of foodborne pathogenic bacteria.

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