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1.
JMIR AI ; 3: e56590, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39259582

RESUMEN

BACKGROUND: A significant proportion of young at-risk patients and nonsmokers are excluded by the current guidelines for lung cancer (LC) screening, resulting in low-screening adoption. The vision of the US National Academy of Medicine to transform health systems into learning health systems (LHS) holds promise for bringing necessary structural changes to health care, thereby addressing the exclusivity and adoption issues of LC screening. OBJECTIVE: This study aims to realize the LHS vision by designing an equitable, machine learning (ML)-enabled LHS unit for LC screening. It focuses on developing an inclusive and practical LC risk prediction model, suitable for initializing the ML-enabled LHS (ML-LHS) unit. This model aims to empower primary physicians in a clinical research network, linking central hospitals and rural clinics, to routinely deliver risk-based screening for enhancing LC early detection in broader populations. METHODS: We created a standardized data set of health factors from 1397 patients with LC and 1448 control patients, all aged 30 years and older, including both smokers and nonsmokers, from a hospital's electronic medical record system. Initially, a data-centric ML approach was used to create inclusive ML models for risk prediction from all available health factors. Subsequently, a quantitative distribution of LC health factors was used in feature engineering to refine the models into a more practical model with fewer variables. RESULTS: The initial inclusive 250-variable XGBoost model for LC risk prediction achieved performance metrics of 0.86 recall, 0.90 precision, and 0.89 accuracy. Post feature refinement, a practical 29-variable XGBoost model was developed, displaying performance metrics of 0.80 recall, 0.82 precision, and 0.82 accuracy. This model met the criteria for initializing the ML-LHS unit for risk-based, inclusive LC screening within clinical research networks. CONCLUSIONS: This study designed an innovative ML-LHS unit for a clinical research network, aiming to sustainably provide inclusive LC screening to all at-risk populations. It developed an inclusive and practical XGBoost model from hospital electronic medical record data, capable of initializing such an ML-LHS unit for community and rural clinics. The anticipated deployment of this ML-LHS unit is expected to significantly improve LC-screening rates and early detection among broader populations, including those typically overlooked by existing screening guidelines.

2.
J Colloid Interface Sci ; 678(Pt A): 1132-1142, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39255752

RESUMEN

HYPOTHESIS: The co-flow step emulsification (CFSE) is very sensitive to the two-phase fluid interfaces, we conjecture that the CFSE hydrodynamic model depends on several key factors and the droplet generation process can be precisely controlled, thus to obtain droplet emulsions with the "ultra-high volume fraction of inner-phase" and "flexible droplet size" characteristics. The resulting droplets are expected to be applied to droplet digital PCR (ddPCR) with "high information density" and "wide dynamic range" advances. EXPERIMENTS: By combining numerical simulation and fluid dynamics experiments, we have investigated the crucial parameters affecting the CFSE two-phase interface and finally achieved the prediction and guidance for CFSE droplet production. FINDINGS: With the help of the CFSE device, multivolume droplet populations were produced on demand. Then, ddPCR tests were performed with DNA concentrations from 10 copies/µL to 20,000 copies/µL. The CFSE device owns an ultra-wide dynamic range (up to 5 orders of magnitude), showing excellent quantification ability of nucleic acid targets.

3.
Exp Eye Res ; 248: 110093, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39277098

RESUMEN

Keratoconus (KC) is a progressive, multifactorial and ectatic corneal disorder that characterized by steepening thinning of the cornea. It was previously demonstrated that oxidative stress has a strong link with KC progression. However, the molecular mechanism underlying oxidative stress response in KC remains unclear. Hence, the present study analyzed the heterogeneity of response of corneal stromal cells (CSCs) to oxidative stress in order to further illustrate how oxidative shape the pathophysiology of KC. Single-cell transcriptomics analysis revealed that CSCs demonstrated significant higher oxidative stress score in the KC group compared to the Ctrl group. The expression of oxidative markers verified by experiments illustrated elevated oxidative stress levels and insufficient antioxidant levels in CSCs of KC. In further single-cell transcriptomics analysis, we identified CYR61 to distinguish different subgroups of CSCs responding to oxidative stress. The cornea stroma cells in KC could be differentiated into CYR61high cells and CYR61low cells. Of note, the CYR61high cells showed lower score in collagen production process and higher score in collagen catabolic process. Further experiments illustrated that CYR61 was elevated in KC and associated with collagen production.

4.
J Hazard Mater ; 480: 135926, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39307018

RESUMEN

Cadmium (Cd) pollution poses a significant ecological risk to mangrove ecosystems. Trehalose has excellent potential to mitigate the adverse effects of heavy metals. Unfortunately, the mechanisms related to trehalose-mediated heavy metal tolerance in plants remain elusive. In the present study, we firstly found that Cd induced the accumulation of trehalose and the differential expression of trehalose biosynthesis genes in the roots of mangrove plant Avicennia marina. Then, we found that the application of exogenous trehalose could alleviate the negative effects of Cd on A. marina by phenotypic observation. In addition, photosynthetic parameters and cellular ultrastructure analyses demonstrated that exogenous trehalose could improve the photosynthesis and stabilize the chloroplast and nuclear structure of the leaves of A. marina. Besides, exogenous trehalose could inhibit the Cd2+ influx from the root to reduce the Cd2+ content in A. marina. Subsequently, substrate sensitivity assay combined with ion uptake analysis using yeast cells showed that several trehalose biosynthesis genes may have a regulatory function for Cd2+ transport. Finally, we further identified a positive regulatory factor, AmTPS6, which enhances the Cd tolerance in transgenic Arabidopsis thaliana. Taken together, these findings provide new understanding to the mechanism of Cd tolerance in mangrove A. marina at trehalose aspect and a theoretical basis for the conservation of mangroves in coastal wetlands.

5.
Nanomicro Lett ; 16(1): 268, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39136800

RESUMEN

The eye, a complex organ isolated from the systemic circulation, presents significant drug delivery challenges owing to its protective mechanisms, such as the blood-retinal barrier and corneal impermeability. Conventional drug administration methods often fail to sustain therapeutic levels and may compromise patient safety and compliance. Polysaccharide-based microneedles (PSMNs) have emerged as a transformative solution for ophthalmic drug delivery. However, a comprehensive review of PSMNs in ophthalmology has not been published to date. In this review, we critically examine the synergy between polysaccharide chemistry and microneedle technology for enhancing ocular drug delivery. We provide a thorough analysis of PSMNs, summarizing the design principles, fabrication processes, and challenges addressed during fabrication, including improving patient comfort and compliance. We also describe recent advances and the performance of various PSMNs in both research and clinical scenarios. Finally, we review the current regulatory frameworks and market barriers that are relevant to the clinical and commercial advancement of PSMNs and provide a final perspective on this research area.

6.
Neural Regen Res ; 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39104172

RESUMEN

α-Synuclein accumulation and transmission are vital to the pathogenesis of Parkinson's disease, although the mechanisms underlying misfolded α-synuclein accumulation and propagation have not been conclusively determined. The expression of low-density lipoprotein receptor-related protein 1, which is abundantly expressed in neurons and considered to be a multifunctional endocytic receptor, is elevated in the neurons of patients with Parkinson's disease. However, whether there is a direct link between low-density lipoprotein receptor- related protein 1 and α-synuclein aggregation and propagation in Parkinson's disease remains unclear. Here, we established animal models of Parkinson's disease by inoculating monkeys and mice with α-synuclein pre-formed fibrils and observed elevated low-density lipoprotein receptor-related protein 1 levels in the striatum and substantia nigra, accompanied by dopaminergic neuron loss and increased α-synuclein levels. However, low-density lipoprotein receptor-related protein 1 knockdown efficiently rescued dopaminergic neurodegeneration and inhibited the increase in α-synuclein levels in the nigrostriatal system. In HEK293A cells overexpressing α-synuclein fragments, low-density lipoprotein receptor-related protein 1 levels were upregulated only when the N-terminus of α-synuclein was present, whereas an α-synuclein fragment lacking the N-terminus did not lead to low-density lipoprotein receptor-related protein 1 upregulation. Furthermore, the N-terminus of α-synuclein was found to be rich in lysine residues, and blocking lysine residues in PC12 cells treated with α-synuclein pre-formed fibrils effectively reduced the elevated low-density lipoprotein receptor-related protein 1 and α-synuclein levels. These findings indicate that low-density lipoprotein receptor-related protein 1 regulates pathological transmission of α-synuclein from the striatum to the substantia nigra in the nigrostriatal system via lysine residues in the α-synuclein N-terminus.

7.
Neurosci Lett ; 839: 137917, 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39102941

RESUMEN

PTEN-induced kinase1 (PINK1) mutation is the main cause of autosomal recessive inheritance and early-onset Parkinson's disease. Mitochondrial respiratory chain complex I (CI) functional impairment has been considered to be an important factor in the pathogenesis of PD in recent years. In addition, NDUFS3 (nicotinamide adenine dinucleotide deoxylase iron-thionein 3) is one of the core subunits of mitochondrial CI. Therefore, this study explored the role of NDUFS3 gene in PINK1B9 transgenic Drosophila and its possible related mechanisms. In this study, the PD transgenic Drosophila model of MHC-Gal4/UAS system was selected to specifically activate the expression of PINK1B9 gene in the chest muscle tissue of Drosophila melanogaster. NDUFS3 RNAi interference was used to interfere with PINK1B9 transgenic Drosophila melanogaster and its effect on PD transgenic flies was studied. The results suggest that down-regulation of NDUFS3 gene expression may have a protective effect on PINK1B9 transgenic Drosophila melanogaster, and we speculate that down-regulation of NDUFS3 gene expression to reduce oxidative stress and restore mitochondrial function may be related to mitochondrial stress response.


Asunto(s)
Animales Modificados Genéticamente , Modelos Animales de Enfermedad , Proteínas de Drosophila , Drosophila melanogaster , Complejo I de Transporte de Electrón , Mitocondrias , Enfermedad de Parkinson , Animales , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/metabolismo , Mitocondrias/metabolismo , Mitocondrias/genética , Complejo I de Transporte de Electrón/metabolismo , Complejo I de Transporte de Electrón/genética , NADH Deshidrogenasa/genética , NADH Deshidrogenasa/metabolismo , Interferencia de ARN , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Estrés Oxidativo/genética
8.
Eur J Med Res ; 29(1): 430, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39175037

RESUMEN

Enzalutamide (Enz) is commonly utilized as the initial treatment strategy for advanced prostate cancer (PCa). However, a notable subset of patients may experience resistance to Enz, resulting in reduced effectiveness. Utilizing Gene Expression Omnibus (GEO) databases, we identified CBX2 as a crucial factor in mediating resistance to Enz, primarily due to its inhibitory effect on the P53 signaling pathway. Silencing of CBX2 using small interfering RNA (siRNA) led to elevated levels of P53 expression in LNCaP cells. This indicates that CBX2 may have a critical effect on PCa Enz resistance and could serve as a promising therapeutic target for individuals with Enz resistance.


Asunto(s)
Benzamidas , Biología Computacional , Resistencia a Antineoplásicos , Nitrilos , Feniltiohidantoína , Neoplasias de la Próstata , Humanos , Masculino , Feniltiohidantoína/uso terapéutico , Feniltiohidantoína/farmacología , Feniltiohidantoína/análogos & derivados , Resistencia a Antineoplásicos/genética , Biología Computacional/métodos , Benzamidas/uso terapéutico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/metabolismo , Nitrilos/uso terapéutico , Complejo Represivo Polycomb 1/genética , Complejo Represivo Polycomb 1/metabolismo , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética
9.
Front Hum Neurosci ; 18: 1429223, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38962148

RESUMEN

Objective: Neuromodulation has been proven to be a promising alternative treatment for adult patients with drug-resistant epilepsy (DRE). Deep brain stimulation (DBS) and responsive neurostimulation (RNS) were approved by many countries for the treatment of DRE. However, there is a lack of systematic studies illustrating the differences between them. This meta-analysis is performed to assess the efficacy and clinical characteristics of DBS and RNS in adult patients with DRE. Methods: PubMed, Web of Science, and Embase were retrieved to obtain related studies including adult DRE patients who accepted DBS or RNS. The clinical characteristics of these patients were compiled for the following statistical analysis. Results: A total of 55 studies (32 of DBS and 23 of RNS) involving 1,568 adult patients with DRE were included in this meta-analysis. There was no significant difference in seizure reduction and responder rate between DBS and RNS for DRE. The seizure reduction of DBS and RNS were 56% (95% CI 50-62%, p > 0.05) and 61% (95% CI 54-68%, p > 0.05). The responder rate of DBS and RNS were 67% (95% CI 58-76%, p > 0.05) and 71% (95% CI 64-78%, p > 0.05). Different targets of DBS did not show significant effect on seizure reduction (p > 0.05). Patients with DRE who accepted DBS were younger than those of RNS (32.9 years old vs. 37.8 years old, p < 0.01). The mean follow-up time was 47.3 months for DBS and 39.5 months for RNS (p > 0.05). Conclusion: Both DBS and RNS are beneficial and alternative therapies for adult DRE patients who are not eligible to accept resection surgery. Further and larger studies are needed to clarify the characteristics of different targets and provide tailored treatment for patients with DRE.

10.
Chem Commun (Camb) ; 60(60): 7753-7756, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-38973629

RESUMEN

An efficient cyclization for the synthesis of 1,2,4,5-tetra-substituted benzenes via copper catalyzed dimerization of γ,δ-unsaturated ketones has been described. This one-pot procedure employs the γ,δ-unsaturated ketones as the sole substrate with multiple C-C bond formation. This protocol features broad substrate scope and provides a facile and robust method to construct polysubstituted benzene derivatives under mild conditions.

11.
Materials (Basel) ; 17(14)2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-39063727

RESUMEN

Large forgings are crucial in aerospace applications; however, the residual stresses generated during their forming and heat treatment seriously affect their serviceability. Therefore, the non-destructive detection of residual stresses in large forgings is of far-reaching significance for ensuring the quality of forgings and realising precision machining. Although a variety of detection methods are available, there is still a lack of a programme that can comprehensively, accurately and non-destructively measure the residual stresses in large forgings. This study is dedicated to exploring the application of the bouncing impact indentation method in the non-destructive testing of residual stresses in large forgings. Through in-depth finite element simulations and orthogonal scheme analyses, we found that the elastic modulus, yield strength and work hardening indexes have significant effects on the impact indentation process. Further, we establish the dimensionless function of residual stress and indentation parameters, and successfully obtain the inversion algorithm of residual stress. The relative error of the calculated values of the indentation curves hm and hr in the simulation with reference values is not more than 3%, and the relative error of the corrected Pm inversion values for most virtual materials is not more than 5%. The folding elastic modulus and apparent elastic modulus obtained by inversion are controlled within 10%, which demonstrates a high value for engineering applications. In addition, we innovatively express the research results in the form of 3D stress diagrams, realising the digital expression of 3D residual stresses in large forgings based on feature point measurements and contour surface configurations, which provides intuitive and comprehensive data support for engineering practice.

12.
Clin Cancer Res ; 30(18): 4201-4214, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39024031

RESUMEN

PURPOSE: The purpose of this study was to investigate the remodeling of the multiple myeloma microenvironment after B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor T (CAR-T) cell therapy. EXPERIMENTAL DESIGN: We performed single-cell RNA sequencing on paired bone marrow specimens (n = 14) from seven patients with multiple myeloma before (i.e., baseline, "day -4") and after (i.e., "day 28") lymphodepleted BCMA CAR-T cell therapy. RESULTS: Our analysis revealed heterogeneity in gene expression profiles among multiple myeloma cells, even those harboring the same cytogenetic abnormalities. The best overall responses of patients over the 15-month follow-up are positively correlated with the abundance and targeted cytotoxic activity of CD8+ effector CAR-T cells on day 28 after CAR-T cell infusion. Additionally, favorable responses are associated with attenuated immunosuppression mediated by regulatory T cells, enhanced CD8+ effector T-cell cytotoxic activity, and elevated type 1 conventional dendritic cell (DC) antigen presentation ability. DC re-clustering inferred intramedullary-originated type 3 conventional DCs with extramedullary migration. Cell-cell communication network analysis indicated that BCMA CAR-T therapy mitigates BAFF/GALECTIN/MK pathway-mediated immunosuppression and activates MIF pathway-mediated anti-multiple myeloma immunity. CONCLUSIONS: Our study sheds light on multiple myeloma microenvironment dynamics after BCMA CAR-T therapy, offering clues for predicting treatment responsivity.


Asunto(s)
Antígeno de Maduración de Linfocitos B , Inmunoterapia Adoptiva , Mieloma Múltiple , Receptores Quiméricos de Antígenos , Microambiente Tumoral , Humanos , Mieloma Múltiple/terapia , Mieloma Múltiple/inmunología , Mieloma Múltiple/patología , Antígeno de Maduración de Linfocitos B/inmunología , Antígeno de Maduración de Linfocitos B/genética , Microambiente Tumoral/inmunología , Inmunoterapia Adoptiva/métodos , Receptores Quiméricos de Antígenos/inmunología , Receptores Quiméricos de Antígenos/genética , Femenino , Depleción Linfocítica , Persona de Mediana Edad , Masculino , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Anciano
13.
Mitochondrial DNA B Resour ; 9(6): 687-691, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38835639

RESUMEN

Arachis lutescens Krapov. & Rigoni 1958 is an important species due to their potentially extensive applications for cultivated peanut breeding. The whole chloroplast genome of A. lutescens was successfully assembled and annotated for the first time. The complete chloroplast genome of A. lutescens is a typically circular structure of 156,398 bp with a GC content of 36.3%. It comprises a large single-copy (LSC) region of 85,950 bp, a small single-copy (SSC) region of 18,800 bp, and two inverted repeat regions (IRs) of 25,824 bp, each. The plastome of A. lutescens contains a total of 125 genes, including 81 protein-coding genes, 36 tRNAs, and eight rRNAs. The phylogenetic analysis strongly supports the close relationship between A. lutescens and cultivated peanut clades. This study contributes to our understanding of the molecular characteristics and evolutionary relationships of this plant species.

14.
Opt Express ; 32(9): 15546-15554, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38859202

RESUMEN

Carbon-based inorganic CsPbIBr2 perovskite solar cells (C-IPSC) have attracted widespread attention due to their low cost and excellent thermal stability. Unfortunately, due to the soft ion crystal nature of perovskite, inherent bulk defects and energy level mismatch at the CsPbIBr2/carbon interface limit the performance of the device. In this study, we introduced aromatic benzyltrimethylammonium chloride (BTACl) as a passivation layer to passivate the surface and grain boundaries of the CsPbIBr2 film. Due to the reduction of perovskite defects and better energy level arrangement, carrier recombination is effectively suppressed and hole extraction is improved. The champion device achieves a maximum power conversion efficiency (PCE) of 11.30% with reduces hysteresis and open circuit voltage loss. In addition, unencapsulated equipment exhibits excellent stability in ambient air.

15.
Opt Express ; 32(12): 20618-20628, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38859439

RESUMEN

Quantum dot (QD) light-emitting diodes (QLEDs) are promising for next-generation lighting and displays. Considering the optimization design of both the QD and device structure is expected to improve the QLED's performance significantly but has rarely been reported. Here, we use the thick-shell QDs combined with a dual-hole transport layer device structure to construct a high-efficiency QLED. The optimized thick-shell QDs with CdS/CdSe/CdS/ZnS seed/spherical quantum well/shell/shell geometry exhibit a high photoluminescence quantum yield of 96% at a shell thickness of 5.9 nm. The intermediate emissive CdSe layer with coherent strain ensures defect-free growth of the thick CdS and ZnS outer shells. Based on the orthogonal solvents assisted Poly-TPD&PVK dual-hole transport layer device architecture, the champion QLED achieved a maximum external quantum efficiency of 22.5% and a maximum luminance of 259955 cd m-2, which are 1.6 and 3.7 times that of thin-shell QDs based devices with single hole transport layer, respectively. Our study provides a feasible idea for further improving the performance of QLED devices.

16.
Cell Biol Toxicol ; 40(1): 48, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38900277

RESUMEN

Aggregation of aberrant proteins is a common pathological hallmark in neurodegeneration such as polyglutamine (polyQ) and other repeat-expansion diseases. Here through overexpression of ataxin3 C-terminal polyQ expansion in Drosophila gut enterocytes, we generated an intestinal obstruction model of spinocerebellar ataxia type3 (SCA3) and reported a new role of nuclear-associated endosomes (NAEs)-the delivery of polyQ to the nucleoplasm. In this model, accompanied by the prominently increased RAB5-positive NAEs are abundant nucleoplasmic reticulum enriched with polyQ, abnormal nuclear envelope invagination, significantly reduced endoplasmic reticulum, indicating dysfunctional nucleocytoplasmic trafficking and impaired endomembrane organization. Consistently, Rab5 but not Rab7 RNAi further decreased polyQ-related NAEs, inhibited endomembrane disorganization, and alleviated disease model. Interestingly, autophagic proteins were enriched in polyQ-related NAEs and played non-canonical autophagic roles as genetic manipulation of autophagic molecules exhibited differential impacts on NAEs and SCA3 toxicity. Namely, the down-regulation of Atg1 or Atg12 mitigated while Atg5 RNAi aggravated the disease phenotypes both in Drosophila intestines and compound eyes. Our findings, therefore, provide new mechanistic insights and underscore the fundamental roles of endosome-centered nucleocytoplasmic trafficking and homeostatic endomembrane allocation in the pathogenesis of polyQ diseases.


Asunto(s)
Autofagia , Endosomas , Péptidos , Animales , Péptidos/metabolismo , Endosomas/metabolismo , Núcleo Celular/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Transporte Activo de Núcleo Celular , Drosophila melanogaster/metabolismo , Drosophila melanogaster/genética , Enfermedad de Machado-Joseph/metabolismo , Enfermedad de Machado-Joseph/genética , Enfermedad de Machado-Joseph/patología , Enterocitos/metabolismo , Modelos Animales de Enfermedad , Ataxina-3/metabolismo , Ataxina-3/genética , Drosophila/metabolismo
17.
Anticancer Res ; 44(7): 2775-2786, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38925849

RESUMEN

BACKGROUND/AIM: Ovarian cancer (OVC) is a common, aggressive, and heterogeneous malignancy, with a widely variable prognosis. With the advances of modern immunology, mast cells (MCs) have been shown to play a significant role in the prognosis of some malignant tumors. However, the role of mast cells in the prognosis of OVC is unknown. MATERIALS AND METHODS: In this study, MC-associated prognostic genes (MRGs) were used to classify OVC from The Cancer Genome Atlas (TCGA)-OVC cohort. Genes were evaluated using univariate cox regression analysis. Twenty-nine prognostic gene signatures were identified using LASSO-COX analysis. COX regression models and principal component analysis (PCA) algorithms were used to construct MRG scores and individual MRGs patterns. External validation was performed in the TCGA-breast cancer (BRCA) and IMvigor210 cohorts. Immunity analysis based on MRGs was performed using CIBERSORT, and GSVA methods, and immunotherapy response was evaluated using the TIDE website. RESULTS: Using TCGA-OVC data, we established a model for constructing MRG scores based on the twenty-nine identified prognostic gene signatures using the PCA algorithm. MRG scores were found to be strongly correlated with immune cell infiltration and were excellent predictors of prognosis in patients with OVC. Low MRG scores were associated with better prognosis and better response to immunotherapy and chemotherapy. CONCLUSION: MC-related prognosis signature characterizes the immune landscape and predicts the prognosis of OVC. Understanding the correlation between MC-related gene signatures and immunotherapy and chemotherapy may improve the development of personalized clinical treatment strategies.


Asunto(s)
Mastocitos , Neoplasias Ováricas , Humanos , Femenino , Mastocitos/inmunología , Mastocitos/patología , Pronóstico , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Neoplasias Ováricas/mortalidad , Biomarcadores de Tumor/genética , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Regulación Neoplásica de la Expresión Génica , Inmunoterapia/métodos , Perfilación de la Expresión Génica , Transcriptoma
18.
Front Oncol ; 14: 1365474, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38812777

RESUMEN

Genomic imprinting plays an important role in the growth and development of mammals. When the original imprint status of these genes is lost, known as loss of imprinting (LOI), it may affect growth, neurocognitive development, metabolism, and even tumor susceptibility. The LOI of imprint genes has gradually been found not only as an early event in tumorigenesis, but also to be involved in progression. More than 120 imprinted genes had been identified in humans. In this review, we summarized the most studied LOI of two gene clusters and 13 single genes in cancers. We focused on the roles they played, that is, as growth suppressors and anti-apoptosis agents, sustaining proliferative signaling or inducing angiogenesis; the molecular pathways they regulated; and especially their clinical significance. It is notable that 12 combined forms of multi-genes' LOI, 3 of which have already been used as diagnostic models, achieved good sensitivity, specificity, and accuracy. In addition, the methods used for LOI detection in existing research are classified into detection of biallelic expression (BAE), differentially methylated regions (DMRs), methylation, and single-nucleotide polymorphisms (SNPs). These all indicated that the detection of imprinting genes' LOI has potential clinical significance in cancer diagnosis, treatment, and prognosis.

19.
Sci Total Environ ; 934: 173283, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38759927

RESUMEN

Conventional concentration-oriented approaches for nitrate risk diagnosis only provide overall risk levels without identifying risk values of individual sources or sources accountable for potential health risks. Therefore, a hybrid model combining the end-member mixing model tool on Excel™ (EMMTE) with human health risk assessment (HHRA) was developed to assess the source-oriented health risks for groundwater nitrate, particularly in the Poyang Lake Plain (PLP) region. The results indicated that the EMMTE and the Bayesian stable isotope mixing model (MixSIAR) exhibited remarkable consistency in source apportionment of groundwater nitrate. The source contribution of groundwater nitrate in PLP was related to land use types, hydrogeological conditions, and soil properties. Notably, manure and sewage sources, contributing up to 53.4 %, represented the largest nitrate pollution sources, with a significant contribution of soil nitrogen and nitrogen fertilizers. The non-carcinogenic risk for four potential sources was below the acceptable threshold of 1. Given the factors including rainfall dilution and economic development, attention should be directed towards mitigating the health risks posed by manure and sewage. This study can verify the efficacy of EMMTE in source apportionment and offer valuable insights for decision-makers to regulate the largest sources of nitrate contamination and enhance groundwater management efficiency.


Asunto(s)
Monitoreo del Ambiente , Agua Subterránea , Nitratos , Contaminantes Químicos del Agua , Agua Subterránea/química , Nitratos/análisis , Contaminantes Químicos del Agua/análisis , Medición de Riesgo , Monitoreo del Ambiente/métodos , Humanos , Teorema de Bayes , China
20.
J Environ Manage ; 361: 121248, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38820798

RESUMEN

One of the main reasons for the decline in global freshwater biodiversity can be attributed to alterations in hydrological conditions resulting from dam construction. However, the majority of current research has focused on single or limited numbers of dams. Here, we carried out a seasonal fish survey, using environmental DNA (eDNA) method, on the Wujiang River mainstream (Tributaries of the Yangtze River, China) to investigate the impact of large-scale cascade hydropower development on changes in fish diversity patterns. eDNA survey revealed that native fish species have decreased in contrast to alien fish. There was also a shift in fish community structure, with declines of the dominant rheophilic fish species, an increase of the small-size fish species, and homogenization of species composition across reservoirs. Additionally, environmental factors, such as temperature, dissolved oxygen and reservoir age, had a significant effect on fish community diversity. This study provides basic information for the evaluation of the impact of cascade developments on fish diversity patterns.


Asunto(s)
Biodiversidad , Peces , Ríos , Animales , Peces/genética , China , ADN Ambiental/análisis
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