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1.
Pest Manag Sci ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39007292

RESUMO

BACKGROUND: Unmanned aerial vehicles (UAVs) for pesticide application show promising potential in tobacco pest management. However, the impact of flight parameters on spray efficacy requires further investigation. Three field experiments were conducted from the rosette to the maturation stage of tobacco to systematically assess spray efficacy under varying flight heights, speeds, and application volumes. Using a multi-index weight analysis method, optimal operational parameter combinations for different tobacco growth stages were evaluated and compared with backpack electric sprayers. RESULTS: For the rosette stage, the recommended parameter is a flight speed of 5 m s-1, a flight height of 2 m, and a liquid application volume of 30 L hm-2; during the vigorous growth stage, the suggested parameter includes a flight speed of 3 m s-1, a flight height of 2 m, and a liquid application volume of 22.5 L hm-2. In the maturing stage, optimal parameter consists of a flight speed of 3 m s-1, a flight height of 3.5 m, and a liquid application volume of 30 L hm-2. Furthermore, UAV spraying achieves higher droplet deposition on both sides of tobacco leaves compared to traditional electric backpack sprayers. CONCLUSIONS: Adjusting UAV spraying parameters for different tobacco growth stages is crucial. These results can provide the methods for the precise control technology of tobacco pests at different growth stages. © 2024 Society of Chemical Industry.

2.
Pathol Res Pract ; 260: 155461, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39038388

RESUMO

Goblet cell adenocarcinoma (GCA) is a distinctive type of endocrine-exocrine mixed tumor, exhibiting intermediate morphological features between neuroendocrine tumor and adenocarcinoma. It predominantly arises in the appendix, but primary extra-appendiceal GCA is extremely rare. Here, we presented six cases of primary extra-appendiceal GCA from 2016 to 2022. Notably, one case was originating in the bladder which was the first report of primary GCA to occur outside the digestive tract. The tumors frequently displayed variable goblet cell morphology, characterized by cytoplasmic mucin accumulation and basally located nucleus. Low-grade components typically exhibited glandular or clustered patterns without prominent fibrotic responses. High-grade components demonstrated cribriform, cluster and single-file arrangement accompanied by marked fibrous reactions. Immunohistochemically, the tumors showed positivity for both neuroendocrine markers(synaptophysin, chromogranin A, CD56 )and adenoids markers(CDX-2, CK20). Next-generation sequencing revealed the most prevalent mutated genes within GCAs were TP53. Due to their morphological and immunohistochemical similarities to primary appendiceal GCA counterparts, we propose a distinct category for extra-appendiceal Goblet cell adenocarcinoma.

3.
Mol Cancer ; 23(1): 139, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38970106

RESUMO

BACKGROUND: Radioresistance is the leading cause of death in advanced cervical cancer (CC). Dysregulation of RNA modification has recently emerged as a regulatory mechanism in radiation and drug resistance. We aimed to explore the biological function and clinical significance of 5-methylcytosine (m5C) in cervical cancer radiosensitivity. METHODS: The abundance of RNA modification in radiotherapy-resistant and sensitive CC specimens was quantified by liquid chromatography-tandem mass spectrometry. The essential RNA modification-related genes involved in CC radiosensitivity were screened via RNA sequencing. The effect of NSUN6 on radiosensitivity was verified in CC cell lines, cell-derived xenograft (CDX), and 3D bioprinted patient-derived organoid (PDO). The mechanisms of NSUN6 in regulating CC radiosensitivity were investigated by integrative m5C sequencing, mRNA sequencing, and RNA immunoprecipitation. RESULTS: We found a higher abundance of m5C modification in resistant CC samples, and NSUN6 was the essential m5C-regulating gene concerning radiosensitivity. NSUN6 overexpression was clinically correlated with radioresistance and poor prognosis in cervical cancer. Functionally, higher NSUN6 expression was associated with radioresistance in the 3D PDO model of cervical cancer. Moreover, silencing NSUN6 increased CC radiosensitivity in vivo and in vitro. Mechanistically, NDRG1 was one of the downstream target genes of NSUN6 identified by integrated m5C-seq, mRNA-seq, and functional validation. NSUN6 promoted the m5C modification of NDRG1 mRNA, and the m5C reader ALYREF bound explicitly to the m5C-labeled NDRG1 mRNA and enhanced NDRG1 mRNA stability. NDRG1 overexpression promoted homologous recombination-mediated DNA repair, which in turn led to radioresistance in cervical cancer. CONCLUSIONS: Aberrant m5C hypermethylation and NSUN6 overexpression drive resistance to radiotherapy in cervical cancer. Elevated NSUN6 expression promotes radioresistance in cervical cancer by activating the NSUN6/ALYREF-m5C-NDRG1 pathway. The low expression of NSUN6 in cervical cancer indicates sensitivity to radiotherapy and a better prognosis.


Assuntos
5-Metilcitosina , Proteínas de Ciclo Celular , Regulação Neoplásica da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intracelular , RNA Mensageiro , Tolerância a Radiação , Neoplasias do Colo do Útero , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/patologia , Humanos , Feminino , Tolerância a Radiação/genética , 5-Metilcitosina/metabolismo , 5-Metilcitosina/análogos & derivados , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Animais , Camundongos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Linhagem Celular Tumoral , Prognóstico , Ensaios Antitumorais Modelo de Xenoenxerto , Metiltransferases/genética , Metiltransferases/metabolismo
4.
Int J Biol Macromol ; : 133883, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39033895

RESUMO

Tumour immunotherapy is an effective and essential treatment for cancer. However, the heterogeneity of tumours and the complex and changeable tumour immune microenvironment (TME) creates many uncertainties in the clinical application of immunotherapy, such as different responses to tumour immunotherapy and significant differences in individual efficacy. It makes anti-tumour immunotherapy face many challenges. Immunometabolism is a critical determinant of immune cell response to specific immune effector molecules, significantly affecting the effects of tumour immunotherapy. It is attributed mainly to the fact that metabolites can regulate the function of immune cells and immune-related molecules through the protein post-translational modifications (PTMs) pathway. This study systematically summarizes a variety of novel protein PTMs including acetylation, propionylation, butyrylation, succinylation, crotonylation, malonylation, glutarylation, 2-hydroxyisobutyrylation, ß-hydroxybutyrylation, benzoylation, lactylation and isonicotinylation in the field of tumour immune regulation and immunotherapy. In particular, we elaborate on how different PTMs in the TME can affect the function of immune cells and lead to immune evasion in cancer. Lastly, we highlight the potential treatment with the combined application of target-inhibited protein modification and immune checkpoint inhibitors (ICIs) for improved immunotherapeutic outcomes.

5.
Artigo em Inglês | MEDLINE | ID: mdl-39020510

RESUMO

Artificial solid electrolyte interphase (SEI) layers have been widely regarded as an effective protection for lithium (Li) metal anodes. In this work, an artificial SEI film consisting of dense Li6.4La3Zr1.4Ta0.6O12 (LLZTO) nanoparticles and polymerized styrene butadiene rubber is designed, which has good mechanical and chemical stability to effectively prevent Li anode corrosion by the electrolyte. The LLZTO-based SEI film can not only guide Li to uniformly deposit at the interface but also accelerate the electrochemical reaction kinetics due to its high Li+ conductivity. In particular, the high Young's modulus of the LLZTO-based SEI will regulate e- distribution in the continuous Li plating/stripping process and achieve uniform deposition of Li. As a consequence, the Li anode with LLZTO-based SEI (Li@LLZTO) enables symmetric cells to demonstrate a stable overpotential of 25 mV for 600 h at a current density of 1 mA cm-2 for 1 mA h cm-2. The Li@LLZTO||LFP (LiFePO4) full cell exhibits a capacity of 106 mA h g-1 after 800 cycles at 5 C with retention as high as 90%. Our strategy here suggests that the artificial SEI with high Young's modulus effectively inhibits the formation of Li dendrites and provides some guidance for the design of higher performance Li metal batteries.

6.
Br J Radiol ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38885406

RESUMO

OBJECTIVES: To find the optimal acceleration factor (AF) of the compressed SENSE (CS) technique for uterine isotropic high-resolution 3D T2-weighted imaging (3D-ISO-T2WI). METHODS: A total of 91 female volunteers from the XXX, XXX and XXX were recruited. A total of 44 volunteers received uterus sagittal 3D-ISO-T2WI scans on 3.0 T MRI device with different CS AFs (including SENSE3, CS3, CS4, CS5, CS6, and CS7), 51 received 3D-ISO-T2WI scans with different degrees of fat suppression (none, light, moderate, and severe), while 4 volunteers received both series of scans. Image quality was subjectively evaluated with a three-point scoring system. Junction zone signal-to-noise ratio (SNR) and contrast to noise ratio (CNR) and myometrial SNR were also calculated. Intraclass correlation coefficients (ICC) were used to analyze the consistency of the measurement results by two observers. ANOVA test or Friedman rank sum test was used to compare the differences in subjective scores, SNR and CNR under different AFs/different degrees of fat suppression. RESULTS: Images by AFs of CS3, CS4, and CS5 had the highest SNR and CNR. Among them, CS5 had the shortest scan time. CS5 also had one of the highest subjective scores. There was no significant difference in SNR and CNR among images acquired with different degrees of fat suppression. Also, images with moderate fat suppression had the highest subjective scores. CONCLUSION: The CS5 combined with moderate fat suppression is recommended for routine female pelvic 3D-ISO-T2WI scan. ADVANCES IN KNOWLEDGE: The CS5 has the highest images quality and has the shortest scan time, which is the best AF. Moderate fat suppression has the highest subjective scores. The CS5 and moderate fat suppression are the best combination for female pelvic 3D-ISO-T2WI scan.

7.
Int J Biol Macromol ; : 133477, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38942413

RESUMO

The highly efficient removal of oils such as oils or dyes from wastewater has aroused wide concern and is of great significance for clean production and environmental remediation. The synthesis of a novel aerogel (designated as HEC/LS) is reported herein, achieved through a sol-gel method followed by freeze-drying utilizing loofa and hydroxyethyl cellulose as the raw materials. The new HEC/LS aerogel exhibits excellent porosity and specific surface area, with a porosity of 88.70 %, a total pore area of 0.607 m2 g-1, and a specific surface area of 230 m2 g-1. The prepared HEC/LS aerogel exhibits exceptional hydrophilicity and self-floatability, facilitating its rapid absorption of water up to 21 times its own weight within a mere 3 s. Additionally, it demonstrates good adsorption performance for methylene blue (MB), with a maximum adsorption capacity of 83.30 mg g-1. Subsequently, a new hydrophobic microorganisms-loaded composite aerogel (namely, Bn-HEC/LS) was obtained by doping microorganisms into the as-prepared HEC/LS in multiple enrichment followed by a hydrophobic and oleophilic surface modification. Based on its rich porous structure and oleophilic wettability, the as-synthesized Bn-HEC/LS exhibits excellent selective adsorption and degradation properties for the oil contamination, the diesel oil could be selectively absorbed in the Bn-HEC/LS and degraded by the loaded microorganisms. Among them, B5-HEC/LS displays the highest removal efficiency of 94.50 % within 180 h, while free microorganisms and HEC/LS aerogels show degradation efficiencies of only 21.70 % and 48.10 %, respectively. The fixation of microorganisms in the aerogel increases their number within the material and enhances the relative microorganisms removal capacity. The hydrophobic and lipophilic modifications improve the selective adsorption performance of the aerogel on diesel oil, resulting in a significantly high removal rate of Bn-HEC/LS for diesel oil. The results indicate that the immobilization of microorganisms into aerogel improves the activity of microorganisms, and the hydrophobic and oleophilic modification enhances the selective adsorption performance of aerogel to diesel oil, thus resulting in a very high removal rate of Bn-HEC/LS for diesel oil. This study is expected to provide a now possibility for the green and efficient bioremediation of oils.

8.
J Colloid Interface Sci ; 672: 600-609, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38857568

RESUMO

Solar-light driven oxidation of benzylic alcohols over photocatalysts endows significant prospects in value-added organics evolution owing to its facile, inexpensive and sustainable process. However, the unsatisfactory performance of actual photocatalysts due to the inefficient charge separation, low photoredox potential and sluggish surface reaction impedes the practical application of this process. Herein, we developed an innovative Z-Scheme Cs3BiBr9 nanoparticles@porous C3N4 tubes (CBB-NP@P-tube-CN) heterojunction photocatalyst for highly selective benzyl alcohol oxidation. Such composite combining increased photo-oxidation potential, Z-Scheme charge migration route as well as the structural advantages of porous tubular C3N4 ensures the accelerated mass and ions diffusion kinetics, the fast photoinduced carriers dissociation and sufficient photoredox potentials. The CBB-NP@P-tube-CN photocatalyst demonstrates an exceptional performance for selective photo-oxidation of benzylic alcohol into benzaldehyde with 19, 14 and 3 times higher benzylic alcohols conversion rate than those of C3N4 nanotubes, Cs3Bi2Br9 and Cs3Bi2Br9@bulk C3N4 photocatalysts, respectively. This work offers a sustainable photocatalytic system based on lead-free halide perovskite toward large scale solar-light driven value-added chemicals production.

10.
Cell Biol Int ; 48(8): 1198-1211, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38825780

RESUMO

Ferroptosis is a novel form of programmed cell death and is considered to be a druggable target for colorectal cancer (CRC) therapy. However, the role of ferroptosis in CRC and its underlying mechanism are not fully understood. In the present study we found that a protein enriched in the Golgi apparatus, Golgi phosphoprotein 3 (GOLPH3), was overexpressed in human CRC tissue and in several CRC cell lines. The expression of GOLPH3 was significantly correlated with the expression of ferroptosis-related genes in CRC. The overexpression of GOLPH3 in Erastin-induced Caco-2 CRC cells reduced ferroptotic phenotypes, whereas the knockdown of GOLPH3 potentiated ferroptosis in HT-29 CRC cells. GOLPH3 induced the expression of prohibitin-1 (PHB1) and prohibitin-2 (PHB2), which also inhibited ferroptosis in Erastin-treated CRC cells. Moreover, GOLPH3 interacted with PHB2 and nuclear factor erythroid 2-related factor 2 (NRF2) in Caco-2 cells. These observations indicate that GOLPH3 is a negative regulator of ferroptosis in CRC cells. GOLPH3 protects these cells from ferroptosis by inducing the expression of PHB1 and PHB2, and by interacting with PHB2 and NRF2.


Assuntos
Neoplasias Colorretais , Ferroptose , Proteínas de Membrana , Piperazinas , Proibitinas , Proteínas Repressoras , Humanos , Ferroptose/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Células CACO-2 , Piperazinas/farmacologia , Proteínas Repressoras/metabolismo , Proteínas Repressoras/genética , Fator 2 Relacionado a NF-E2/metabolismo , Linhagem Celular Tumoral , Células HT29 , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
11.
Food Res Int ; 188: 114505, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38823848

RESUMO

Consumers care about the texture of fresh fish flesh, but a rapid quantitative analytical method for this has not been properly established. In this study, texture-associated biomarkers were selected by DIA-based proteomics for possible future application. Results indicated a significant decline in texture and moisture characteristics with extended storage under chilled and iced conditions, and flesh quality was categorized into three intervals. A total of 8 texture-associated biomarkers were identified in the chilled storage group, and 3 distinct ones in the iced storage group. Biomarkers were further refined based on their expression levels. Isobutyryl-CoA dehydrogenase, mitochondrial and [Phosphatase 2A protein]-leucine-carboxy methyltransferase were identified as effective texture-associated biomarkers for chilled fish, and Staphylococcal nuclease domain-containing protein 1 for iced fish. This study provided suitable proteins as indicators of fresh fish flesh texture, which could help establish a rapid and convenient texture testing method in future studies.


Assuntos
Biomarcadores , Carpas , Proteínas de Peixes , Proteômica , Alimentos Marinhos , Animais , Carpas/metabolismo , Proteômica/métodos , Biomarcadores/análise , Proteínas de Peixes/metabolismo , Alimentos Marinhos/análise , Armazenamento de Alimentos/métodos
12.
Front Pharmacol ; 15: 1337883, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38828452

RESUMO

Background: The interaction between environmental endocrine-disrupting chemicals, such as Bisphenol A (BPA), and their influence on cancer progression, particularly regarding the GOLPH3 gene in colorectal cancer, remains unclear. Methods: We performed an integrated analysis of transcriptional profiling, clinical data, and bioinformatics analyses utilizing data from the Comparative Toxicogenomics Database and The Cancer Genome Atlas. The study employed ClueGO, Gene Set Enrichment Analysis, and Gene Set Variation Analysis for functional enrichment analysis, alongside experimental assays to examine the effects of BPA exposure on colorectal cancer cell lines, focusing on GOLPH3 expression and its implications for cancer progression. Results: Our findings demonstrated that BPA exposure significantly promoted the progression of colorectal cancer by upregulating GOLPH3, which in turn enhanced the malignant phenotype of colorectal cancer cells. Comparative analysis revealed elevated GOLPH3 protein levels in cancerous tissues versus normal tissues, with single-cell analysis indicating widespread GOLPH3 presence across various cell types in the cancer microenvironment. GOLPH3 was also associated with multiple carcinogenic pathways, including the G2M checkpoint. Furthermore, our investigation into the colorectal cancer microenvironment and genomic mutation signature underscored the oncogenic potential of GOLPH3, exacerbated by BPA exposure. Conclusion: This study provides novel insights into the complex interactions between BPA exposure and GOLPH3 in the context of colorectal cancer, emphasizing the need for heightened awareness and measures to mitigate BPA exposure risks. Our findings advocate for further research to validate these observations in clinical and epidemiological settings and explore potential therapeutic targets within these pathways.

13.
Front Cardiovasc Med ; 11: 1388164, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38826816

RESUMO

Background: This study aimed to explore the knowledge and attitude (KA) toward postoperative antithrombotic management and prevention among coronary artery disease (CAD) patients who underwent coronary revascularization. Methods: This cross-sectional study enrolled CAD outpatients and inpatients between May and December 2023 at Kailuan Medical Group at Tangshan. Basic demographic characteristics and KA scores were collected through a self-made questionnaire. Results: This study included 523 valid questionnaires. The mean knowledge and attitude scores were 13.20 ± 6.20 (range: 0-26) and 43.68 ± 6.01 (range: 21-50), respectively, indicating poor knowledge and favorable attitude. Multivariable logistic regression analysis showed that junior high school education (OR = 2.160, P = 0.035), high school or technical school education (OR = 2.356, P = 0.039), and monthly average income >5,000 RMB (OR = 3.407, P = 0.002) were independently associated with knowledge. Knowledge (OR = 1.095, P = 0.002), BMI ≥ 24.0 kg/m2 (OR = 0.372, P = 0.011), junior high school (OR = 3.699, P = 0.002), high school or technical school (OR = 2.903, P = 0.028), high associate degree or above education (OR = 6.068, P = 0.014), monthly average income 3,000-5,000 RMB (OR = 0.296, P = 0.005), monthly average income > 5,000 RMB (OR = 0.225, P = 0.021), with hypertension (OR = 0.333, P = 0.003), blood tests every 2-3 weeks (OR = 10.811, P = 0.011), blood tests every month (OR = 4.221, P = 0.024), and blood tests every 2-3 months (OR = 3.342, P = 0.033) were independently associated with attitude. Conclusion: CAD patients who underwent coronary revascularization had poor knowledge but favorable attitudes toward postoperative antithrombotic management and prevention. The study underscores the need for targeted education, especially for individuals with lower education and income levels, ultimately improving patient compliance and cardiovascular outcomes.

14.
BMC Plant Biol ; 24(1): 511, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38844870

RESUMO

The invasion of Mikania micrantha by climbing and covering trees has rapidly caused the death of many shrubs and trees, seriously endangering forest biodiversity. In this study, M. micrantha seedlings were planted together with local tree species (Cryptocarya concinna) to simulate the process of M. micrantha climbing under the forest. We found that the upper part of the M. micrantha stem lost its support after climbing to the top of the tree, grew in a turning and creeping manner, and then grew branches rapidly to cover the tree canopy. Then, we simulated the branching process through turning treatment. We found that a large number of branches had been formed near the turning part of the M. micrantha stem (TP). Compared with the upper part of the main stem (UP), the contents of plant hormones (auxin, cytokinin, gibberellin), soluble sugars (sucrose, glucose, fructose) and trehalose-6-phosphate (T6P) were significantly accumulated at TP. Further combining the transcriptome data of different parts of the main stem under erect or turning treatment, a hypothetical regulation model to illustrate how M. micrantha can quickly cover trees was proposed based on the regulation of sugars and hormones on plant branching; that is, the lack of support after ascending the top of the tree led to turning growth of the main stem, and the enhancement of sugars and T6P levels in the TP may first drive the release of nearby dormant buds. Plant hormone accumulation may regulate the entrance of buds into sustained growth and maintain the elongation of branches together with sugars to successfully covering trees.


Assuntos
Espécies Introduzidas , Mikania , Árvores , Mikania/crescimento & desenvolvimento , Árvores/crescimento & desenvolvimento , Reguladores de Crescimento de Plantas/metabolismo
15.
Mol Cancer ; 23(1): 111, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38778348

RESUMO

BACKGROUND: Poly (ADP-ribose) polymerase inhibitor (PARPi) resistance poses a significant challenge in ovarian carcinoma (OC). While the role of DOT1L in cancer and chemoresistance is acknowledged, its specific role in PARPi resistance remains unclear. This study aims to elucidate the molecular mechanism of DOT1L in PARPi resistance in OC patients. METHODS: This study analyzed the expression of DOT1L in PARPi-resistant cell lines compared to sensitive ones and correlated it with clinical outcomes in OC patients. Comprehensive in vitro and in vivo functional experiments were conducted using cellular and mouse models. Molecular investigations, including RNA sequencing, chromatin immunoprecipitation (ChIP) and Cleavage Under Targets and Tagmentation (CUT&Tag) assays, were employed to unravel the molecular mechanisms of DOT1L-mediated PARPi resistance. RESULTS: Our investigation revealed a robust correlation between DOT1L expression and clinical PARPi resistance in non-BRCA mutated OC cells. Upregulated DOT1L expression in PARPi-resistant tissues was associated with diminished survival in OC patients. Mechanistically, we identified that PARP1 directly binds to the DOT1L gene promoter, promoting transcription independently of its enzyme activity. PARP1 trapping induced by PARPi treatment amplified this binding, enhancing DOT1L transcription and contributing to drug resistance. Sequencing analysis revealed that DOT1L plays a crucial role in the transcriptional regulation of PLCG2 and ABCB1 via H3K79me2. This established the PARP1-DOT1L-PLCG2/ABCB1 axis as a key contributor to PARPi resistance. Furthermore, we discovered that combining a DOT1L inhibitor with PARPi demonstrated a synergistic effect in both cell line-derived xenograft mouse models (CDXs) and patient-derived organoids (PDOs). CONCLUSIONS: Our results demonstrate that DOT1L is an independent prognostic marker for OC patients. The PARP1-DOT1L/H3K79me2-PLCG2/ABCB1 axis is identified as a pivotal contributor to PARPi resistance. Targeted inhibition of DOT1L emerges as a promising therapeutic strategy for enhancing PARPi treatment outcomes in OC patients.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Neoplasias Ovarianas , Poli(ADP-Ribose) Polimerase-1 , Inibidores de Poli(ADP-Ribose) Polimerases , Ensaios Antitumorais Modelo de Xenoenxerto , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/mortalidade , Feminino , Resistencia a Medicamentos Antineoplásicos/genética , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Animais , Camundongos , Poli(ADP-Ribose) Polimerase-1/metabolismo , Poli(ADP-Ribose) Polimerase-1/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Prognóstico , Histona-Lisina N-Metiltransferase
16.
SLAS Technol ; : 100149, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38796035

RESUMO

OBJECTIVE: This study aims to diagnose Rotator Cuff Tears (RCT) and classify the severity of RCT in patients with Osteoporosis (OP) through the analysis of shoulder joint anteroposterior (AP) X-ray-based localized proximal humeral bone mineral density (BMD) measurements and clinical information based on machine learning (ML) models. METHODS: A retrospective cohort of 89 patients was analyzed, including 63 with both OP and RCT (OPRCT) and 26 with OP only. The study analyzed a series of shoulder radiographs from April 2021 to April 2023. Grayscale values were measured after plotting ROIs based on AP X-rays of shoulder joint. Five kinds of ML models were developed and compared based on their performance in predicting the occurrence and severity of RCT from ROIs' greyscale values and clinical information (age, gender, advantage side, lumbar BMD, and acromion morphology (AM)). Further analysis using SHAP values illustrated the significant impact of selected features on model predictions. RESULTS: R1-6 had a positive correlation with BMD respectively. The nine variables, including greyscale R1-6, age, BMD, and AM, were used in the prediction models. The RF model was determined to be superior in effectively diagnosing RCT in OP patients, with high AUC scores of 0.998, 0.889, and 0.95 in the training, validation, and testing sets, respectively. SHAP values revealed that the most influential factors on the diagnostic outcomes were the grayscale values of all cancellous bones in ROIs. A column-line graph prediction model based on nine variables was constructed, and DCA curves indicated that RCT prediction in OP patients was favored based on this model. Furthermore, the RF model was also the most superior in predicting the types of RCT within the OPRCT group, with an accuracy of 86.364% and 73.684% in the training and test sets, respectively. SHAP values indicated that the most significant factor affecting the predictive outcomes was the AM, followed by the grayscale values of the greater tubercle, among others. CONCLUSIONS: ML models, particularly the RF algorithm, show significant promise in diagnosing RCT occurrence and severity in OP patients using conventional shoulder X-rays based on the nine variables. This method presents a cost-effective, accessible, and non-invasive diagnostic strategy that has the potential to substantially enhance the early detection and management of RCT in OP patient population.

17.
Nanoscale ; 16(21): 10448-10457, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38752569

RESUMO

With continuous advances in medical technology, non-invasive embolization has emerged as a minimally invasive treatment, offering new possibilities in cancer therapy. Fluorescent labeling can achieve visualization of therapeutic agents in vivo, providing technical support for precise treatment. This paper introduces a novel in situ non-invasive embolization composite material, Au NPs@(mPEG-PLGTs), created through the electrostatic combination of L-cysteine-modified gold nanoparticles (Au NPs) and methoxy polyethylene glycol amine-poly[(L-glutamic acid)-(L-tyrosine)] (mPEG-PLGTs). Experiments were undertaken to confirm the biocompatibility, degradability, stability and performance of this tumor therapy. The research results demonstrated a reduction in tumor size as early as the fifth day after the initial injection, with a significant 90% shrinkage in tumor volume observed after a 20-day treatment cycle, successfully inhibiting tumor growth and exhibiting excellent anti-tumor effects. Utilizing near-infrared in vivo imaging, Au NPs@(mPEG-PLGTs) displayed effective fluorescence tracking within the bodies of nude BALB-c mice. This study provides a novel direction for the further development and innovation of in situ non-invasive embolization in the field, highlighting its potential for rapid, significant therapeutic effects with minimal invasiveness and enhanced safety.


Assuntos
Ouro , Nanopartículas Metálicas , Camundongos Endogâmicos BALB C , Camundongos Nus , Polietilenoglicóis , Ouro/química , Animais , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Camundongos , Polietilenoglicóis/química , Linhagem Celular Tumoral , Humanos , Concentração de Íons de Hidrogênio , Embolização Terapêutica , Ácido Poliglutâmico/química , Ácido Poliglutâmico/análogos & derivados
18.
Front Cardiovasc Med ; 11: 1297218, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38694566

RESUMO

Introduction: To investigate the prognostic value of the consistency between the residual quantitative flow ratio (QFR) and postpercutaneous coronary intervention (PCI) QFR in patients undergoing revascularization. Methods: This was a single-center, retrospective, observational study. All enrolled patients were divided into five groups according to the ΔQFR (defined as the value of the post-PCI QFR minus the residual QFR): (1) Overanticipated group; (2) Slightly overanticipated group; (3) Consistent group; (4) Slightly underanticipated group; and (5) Underanticipated group. The primary outcome was the 5-year target vessel failure (TVF). Results: A total of 1373 patients were included in the final analysis. The pre-PCI QFR and post-PCI QFR were significantly different among the five groups. TVF within 5 years occurred in 189 patients in all the groups. The incidence of TVF was significantly greater in the underanticipated group than in the consistent group (P = 0.008), whereas no significant differences were found when comparing the underanticipated group with the other three groups. Restricted cubic spline regression analysis showed that the risk of TVF was nonlinearly related to the ΔQFR. A multivariate Cox regression model revealed that a ΔQFR≤ -0.1 was an independent risk factor for TVF. Conclusions: The consistency between the residual QFR and post-PCI QFR may be associated with the long-term prognosis of patients. Patients whose post-PCI QFR is significantly lower than the residual QFR may be at greater risk of TVF. An aggressive PCI strategy for lesions is anticipated to have less functional benefit and may not result in a better clinical outcome.

19.
Medicine (Baltimore) ; 103(19): e38042, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38728482

RESUMO

Postmenopausal osteoporosis (PMOP) is a common metabolic inflammatory disease. In conditions of estrogen deficiency, chronic activation of the immune system leads to a hypo-inflammatory phenotype and alterations in its cytokine and immune cell profile, although immune cells play an important role in the pathology of osteoporosis, studies on this have been rare. Therefore, it is important to investigate the role of immune cell-related genes in PMOP. PMOP-related datasets were downloaded from the Gene Expression Omnibus database. Immune cells scores between high bone mineral density (BMD) and low BMD samples were assessed based on the single sample gene set enrichment analysis method. Subsequently, weighted gene co-expression network analysis was performed to identify modules highly associated with immune cells and obtain module genes. Differential analysis between high BMD and low BMD was also performed to obtain differentially expressed genes. Module genes are intersected with differentially expressed genes to obtain candidate genes, and functional enrichment analysis was performed. Machine learning methods were used to filter out the signature genes. The receiver operating characteristic (ROC) curves of the signature genes and the nomogram were plotted to determine whether the signature genes can be used as a molecular marker. Gene set enrichment analysis was also performed to explore the potential mechanism of the signature genes. Finally, RNA expression of signature genes was validated in blood samples from PMOP patients and normal control by real-time quantitative polymerase chain reaction. Our study of PMOP patients identified differences in immune cells (activated dendritic cell, CD56 bright natural killer cell, Central memory CD4 T cell, Effector memory CD4 T cell, Mast cell, Natural killer T cell, T follicular helper cell, Type 1 T-helper cell, and Type 17 T-helper cell) between high and low BMD patients. We obtained a total of 73 candidate genes based on modular genes and differential genes, and obtained 5 signature genes by least absolute shrinkage and selection operator and random forest model screening. ROC, principal component analysis, and t-distributed stochastic neighbor embedding down scaling analysis revealed that the 5 signature genes had good discriminatory ability between high and low BMD samples. A logistic regression model was constructed based on 5 signature genes, and both ROC and column line plots indicated that the model accuracy and applicability were good. Five signature genes were found to be associated with proteasome, mitochondria, and lysosome by gene set enrichment analysis. The real-time quantitative polymerase chain reaction results showed that the expression of the signature genes was significantly different between the 2 groups. HIST1H2AG, PYGM, NCKAP1, POMP, and LYPLA1 might play key roles in PMOP and be served as the biomarkers of PMOP.


Assuntos
Biomarcadores , Densidade Óssea , Osteoporose Pós-Menopausa , Humanos , Feminino , Osteoporose Pós-Menopausa/genética , Osteoporose Pós-Menopausa/sangue , Osteoporose Pós-Menopausa/imunologia , Densidade Óssea/genética , Biomarcadores/sangue , Pessoa de Meia-Idade , Perfilação da Expressão Gênica/métodos , Curva ROC , Idoso , Aprendizado de Máquina
20.
Nat Plants ; 10(5): 815-827, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38745100

RESUMO

A comprehensive understanding of inflorescence development is crucial for crop genetic improvement, as inflorescence meristems give rise to reproductive organs and determine grain yield. However, dissecting inflorescence development at the cellular level has been challenging owing to a lack of specific marker genes to distinguish among cell types, particularly in different types of meristems that are vital for organ formation. In this study, we used spatial enhanced resolution omics-sequencing (Stereo-seq) to construct a precise spatial transcriptome map of the developing maize ear primordium, identifying 12 cell types, including 4 newly defined cell types found mainly in the inflorescence meristem. By extracting the meristem components for detailed clustering, we identified three subtypes of meristem and validated two MADS-box genes that were specifically expressed at the apex of determinate meristems and involved in stem cell determinacy. Furthermore, by integrating single-cell RNA transcriptomes, we identified a series of spatially specific networks and hub genes that may provide new insights into the formation of different tissues. In summary, this study provides a valuable resource for research on cereal inflorescence development, offering new clues for yield improvement.


Assuntos
Inflorescência , Meristema , Transcriptoma , Zea mays , Zea mays/genética , Zea mays/crescimento & desenvolvimento , Zea mays/metabolismo , Inflorescência/genética , Inflorescência/crescimento & desenvolvimento , Meristema/genética , Meristema/crescimento & desenvolvimento , Meristema/metabolismo , Regulação da Expressão Gênica de Plantas , Perfilação da Expressão Gênica
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