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1.
Food Chem X ; 23: 101666, 2024 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-39170070

RESUMO

Zearalenone (ZEN) contamination in cereals poses a serious threat to human and animal health, yet existing rapid test methods still suffer from poor stability and low sensitivity. The studied sensor reduces inspection time while enabling applications for on-site grain inspection. Specifically, a ZEN detector that can sensitively detect ZEN content in grains was developed. Ion implantation is an effective method for modifying screen-printed electrodes (SPEs). Gold nanoparticles (AuNPs; 5-10 nm) were uniformly implanted using screen-printed electrodes as a catalytic oxidation medium to generate an electrochemical sensor. The surface structure of the modified electrode was characterized using scanning electron microscopy and X-ray photoelectron spectroscopy. The results showed that differential pulse voltammetry had good linear electrochemical response to ZEN at 10 ng/kg to 10 mg/kg, with a detection limit of 1.1 ng/kg. We used AuNP-SPE sensors to detect ZEN in grain samples such as maize and oats.

2.
Noncoding RNA Res ; 9(4): 1190-1202, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39026604

RESUMO

Background: Drug-induced liver injury (DILI) is a leading cause of drug development failures during clinical trials and post-market introduction. Current biomarkers, such as ALT and AST, lack the necessary specificity and sensitivity needed for accurate detection. Exosomes, which protect LncRNAs from RNase degradation, could provide reliable and easily accessible options for biomarkers. Materials and methods: RNA-sequencing was used to identify differentially expressed LncRNAs (DE-LncRNAs), followed by isolation of LncRNAs from plasma exosomes in this study. Exosome characterization was conducted by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot (WB). Bioinformatics analysis included functional enrichment and co-expression network analysis. Five rat models were established, and quantitative real-time PCR was used to verify the specificity and sensitivity of two candidate exosomal LncRNAs. Results: The APAP-induced hepatocellular injury model was successfully established for RNA-sequencing, leading to the identification of several differentially expressed exosomal LncRNAs. Eight upregulated exosomal DE-LncRNAs were selected for validation. Among them, NONRATT018001.2 (p < 0.05) and MSTRG.73954.4 (p < 0.05) exhibited a more than 2-fold increase in expression levels. In hepatocellular injury and intrahepatic cholestasis models, both NONRATT018001.2 and MSTRG.73954.4 showed earlier increases compared to serum biomarkers ALT and AST. However, no histological changes were observed until the final time point. In the fatty liver model, NONRATT018001.2 and MSTRG.73954.4 increased earlier than ALT and AST at 21 days. By the 7th day, minor steatosis was evident in liver tissue, while the expression levels of the two candidate exosomal LncRNAs exceeded 2 and 4 times, respectively. In the hepatic fibrosis model, NONRATT018001.2 and MSTRG.73954.4 showed increases at every time point. By the 49th day, hepatocellular necrosis and fibrosis were observed in the liver tissue, with NONRATT018001.2 showing an increase of more than 8 times. The specificity of the identified exosomal DE-LncRNAs was verified using a myocardial injury model and they showed no significant differences between the case and control groups. Conclusion: NONRATT018001.2 and MSTRG.73954.4 hold potential as biomarkers for distinguishing different types of organ injury induced by drugs, particularly enabling early prediction of liver injury. Further experiments, such as siRNA interference or gene knockout, are warranted to explore the underlying mechanisms of these LncRNAs.

3.
Heliyon ; 10(11): e31576, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38832282

RESUMO

Dendritic fibrous nanosilica (DFNS) was functionalized using microcrystalline chitosan, derived from shrimp exoskeletons, to act as a robust anchor, resulting in DFNS@Chitosan. In order to prevent the restacking of chitosan sheets, the supramolecular polymerized chitosan not only served as a spacer but was also incorporated into cement-based composites. The physical-chemical characteristics of DFNS@Chitosan were assessed through various analytical techniques such as TEM, SEM, TGA, FTIR, AFM, XPS, and EDX. The potency and auto-induced contraction of Cement-based composite materials fortified with DFNS@Chitosan were probed. The incorporation of DFNS@Chitosan resulted in an increase in both compressive and interfacial stretching potency of the cement-based composites. Furthermore, the presence of DFNS@Chitosan effectively inhibited the occurrence of auto-induced contraction in the cement-based paste. This research endeavor is anticipated to promote an alternative utilization of DFNS and shrimp waste shells in the development of sustainable building materials.

4.
J Phys Chem Lett ; 15(24): 6415-6423, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38864743

RESUMO

The exotic optoelectronic properties of antimonene, including strain-induced tunable bandgaps, broad nonlinear refractive response, etc., have evoked profound upsurges for decades. As the screw dislocations break the crystal symmetry and modify interlayer coupling, it is highly desirable to investigate the optical prospects of antimonene with screw dislocations. Herein, controllable epitaxy of spiral ß-antimonene is achieved on Fe3GaTe2 substrates. By fine-tuning growth temperatures, the evolutions of spiral ß-antimonene with non-centrosymmetric stacking are investigated via scanning tunneling microscopy. The effects of interfacial strain and dislocation motion during screw-dislocation-driven growth are also studied. Additionally, a modulation depth of 40.8% and mode locking at 1558 nm with a pulse width of 290 fs are observed in Er-doped pulsed fiber lasers generated with spiral Sb-based saturable absorbers, revealing superior performance that far outstrips reported Sb-based saturable absorbers to date. Our work sheds light on the preparation of Sb films with screw dislocations and demonstrates a promising approach toward fabricating ultrafast optical devices.

6.
Am J Cancer Res ; 14(4): 1712-1729, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38726277

RESUMO

Melanoma is the most aggressive type of skin cancer and has a high mortality rate once metastasis occurs. Hypoxia is a universal characteristic of the microenvironment of cancer and a driver of melanoma progression. In recent years, long noncoding RNAs (lncRNAs) have attracted widespread attention in oncology research. In this study, screening was performed and revealed seven hypoxia-related lncRNAs AC008687.3, AC009495.1, AC245128.3, AL512363.1, LINC00518, LINC02416 and MCCC1-AS1 as predictive biomarkers. A predictive risk model was constructed via univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses. Patients were grouped according to the model risk score, and Kaplan-Meier analysis was performed to compare survival between groups. Functional and pathway enrichment analyses were performed to compare gene set enrichment between groups. Moreover, a nomogram was constructed with the risk score as a variable. In both the training and validation sets, patients in the low-risk group had better overall survival than did those in the high-risk group (P<0.001). The 3-, 5- and 10-year area under the curve (AUC) values for the nomogram model were 0.821, 0.795 and 0.820, respectively. Analyses of immune checkpoints, immunotherapy response, drug sensitivity, and mutation landscape were also performed. The results suggested that the low-risk group had a better response to immunotherapeutic. In addition, the nomogram can effectively predict the prognosis and immunotherapy response of melanoma patients. The signature of seven hypoxia-related lncRNAs showed great potential value as an immunotherapy response biomarker, and these lncRNAs might be treatment targets for melanoma patients.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38662093

RESUMO

Ketamine has demonstrated rapid and sustained antidepressant effects, marking its emergence as an innovative treatment of depression. Despite the growing number of preclinical and clinical studies exploring the antidepressant effects of ketamine and its enantiomers, a comprehensive bibliometric analysis in this field has yet to be conducted. This study employs bibliometric methods and visualization tools to examine the literature and identify key topics related to the antidepressant effects of ketamine and its enantiomers. We sourced publications on the antidepressant effects of ketamine and its enantiomers from the Web of Science Core Collection (WOSCC) database, covering the period from 2000 to 2023. Tools such as VOSviewer, CiteSpace and the R package "bibliometrix" were utilized for visual analysis. The study included 4,274 publications, with a notable increase in publications peaking in 2022. Co-occurrence analysis highlighted two primary research focal points: the efficacy and safety of ketamine and its enantiomers in treating depression, and the mechanisms behind their antidepressant effects. In conclusion, this analysis revealed a significant increase in research on the antidepressant effects of ketamine and its enantiomers over the past two decades, leading to the approval of esketamine nasal spray for treatment-resistant depression. The rapid antidepressant effects of ketamine have spurred further studies into its mechanisms of action and the search for new antidepressants with fewer side effects.

8.
BMC Genomics ; 25(1): 373, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627659

RESUMO

The common dolphin (Delphinus delphis) is widely distributed worldwide and well adapted to various habitats. Animal genomes store clues about their pasts, and can reveal the genes underlying their evolutionary success. Here, we report the first high-quality chromosome-level genome of D. delphis. The assembled genome size was 2.56 Gb with a contig N50 of 63.85 Mb. Phylogenetically, D. delphis was close to Tursiops truncatus and T. aduncus. The genome of D. delphis exhibited 428 expanded and 1,885 contracted gene families, and 120 genes were identified as positively selected. The expansion of the HSP70 gene family suggested that D. delphis has a powerful system for buffering stress, which might be associated with its broad adaptability, longevity, and detoxification capacity. The expanded IFN-α and IFN-ω gene families, as well as the positively selected genes encoding tripartite motif-containing protein 25, peptidyl-prolyl cis-trans isomerase NIMA-interacting 1, and p38 MAP kinase, were all involved in pathways for antiviral, anti-inflammatory, and antineoplastic mechanisms. The genome data also revealed dramatic fluctuations in the effective population size during the Pleistocene. Overall, the high-quality genome assembly and annotation represent significant molecular resources for ecological and evolutionary studies of Delphinus and help support their sustainable treatment and conservation.


Assuntos
Golfinhos Comuns , Animais , Evolução Biológica , Cromossomos/genética , Imunidade Inata/genética , Filogenia
9.
Adv Mater ; 36(27): e2403078, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38583072

RESUMO

Composite polymer solid electrolytes (CPEs), possessing good rigid flexible, are expected to be used in solid-state lithium-metal batteries. The integration of fillers into polymer matrices emerges as a dominant strategy to improve Li+ transport and form a Li+-conducting electrode-electrolyte interface. However, challenges arise as traditional fillers: 1) inorganic fillers, characterized by high interfacial energy, induce agglomeration; 2) organic fillers, with elevated crystallinity, impede intrinsic ionic conductivity, both severely hindering Li+ migration. Here, a concept of super-ionic conductor soft filler, utilizing a Li+ conductivity nanocellulose (Li-NC) as a model, is introduced which exhibits super-ionic conductivity. Li-NC anchors anions, and enhances Li+ transport speed, and assists in the integration of cathode-electrolyte electrodes for room temperature solid-state batteries. The tough dual-channel Li+ transport electrolyte (TDCT) with Li-NC and polyvinylidene fluoride (PVDF) demonstrates a high Li+ transfer number (0.79) due to the synergistic coordination mechanism in Li+ transport. Integrated electrodes' design enables stable performance in LiNi0.5Co0.2Mn0.3O2|Li cells, with 720 cycles at 0.5 C, and 88.8% capacity retention. Furthermore, the lifespan of Li|TDCT|Li cells over 4000 h and Li-rich Li1.2Ni0.13Co0.13Mn0.54O2|Li cells exhibits excellent performance, proving the practical application potential of soft filler for high energy density solid-state lithium-metal batteries at room temperature.

10.
Eur J Drug Metab Pharmacokinet ; 49(3): 317-330, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38393637

RESUMO

BACKGROUND AND OBJECTIVE: HY-088 injection is an ultrasmall superparamagnetic iron oxide nanoparticle (USPIOs) composed of iron oxide crystals coated with polyacrylic acid (PAA) on the surface. The purpose of this study was to investigate the pharmacokinetics, tissue distribution, and mass balance of HY-088 injection. METHODS: The pharmacokinetics of [55Fe]-HY-088 and [14C]-HY-088 were investigated in 48 SD rats by intravenous injection of 8.5 (low-dose group), 25.5 (medium-dose group), and 85 (high-dose group) mg/100 µCi/kg. Tissue distribution was studied by intravenous injection of 35 mg/100 µCi/kg in 48 SD rats, and its tissue distribution in vivo was obtained by ex vivo tissue assay. At the same time, [14C]-HY-088 was injected intravenously at a dose of 25.5 mg/100 µCi/kg into 16 SD rats, and its tissue distribution in vivo was studied by quantitative whole-body autoradiography. [14C]-HY-088 and [55Fe]-HY-088 were injected intravenously into 24 SD rats at a dose of 35 mg/100 µCi/kg, and their metabolism was observed. RESULTS: In the pharmacokinetic study, [55Fe]-HY-088 reached the maximum observed concentration (Cmax) at 0.08 h in the low- and medium-dose groups of SD rats. [14C]-HY-088 reached Cmax at 0.08 h in the three groups of SD rats. The area under the concentration-time curve (AUC) of [55Fe]-HY-088 and [14C]-HY-088 increased with increasing dose. In the tissue distribution study, [55Fe]-HY-088 and [14C]-HY-088 were primarily distributed in the liver, spleen, and lymph nodes of both female and male rats. In the mass balance study conducted over 57 days, the radioactive content of 55Fe from [55Fe]-HY-088 was primarily found in the carcass, accounting for 86.42 ± 4.18% in females and 95.46 ± 6.42% in males. The radioactive recovery rates of [14C]-HY-088 in the urine of female and male rats were 52.99 ± 5.48% and 60.66 ± 2.23%, respectively. CONCLUSIONS: Following single intravenous administration of [55Fe]-HY-088 and [14C]-HY-088 in SD rats, rapid absorption was observed. Both [55Fe]-HY-088 and [14C]-HY-088 were primarily distributed in the liver, spleen, and lymph nodes. During metabolism, the radioactivity of [55Fe]-HY-088 is mainly present in the carcass, whereas the 14C-labeled [14C]-HY-088 shell PAA is eliminated from the body mainly through the urine.


Assuntos
Nanopartículas Magnéticas de Óxido de Ferro , Ratos Sprague-Dawley , Animais , Distribuição Tecidual , Masculino , Ratos , Feminino , Nanopartículas Magnéticas de Óxido de Ferro/química , Injeções Intravenosas , Nanopartículas de Magnetita/química , Dextranos/farmacocinética , Resinas Acrílicas/química , Resinas Acrílicas/farmacocinética
11.
Animals (Basel) ; 14(4)2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38396609

RESUMO

Microplastics (MPs) pollution is of global concern, which poses serious threats to various marine organisms, including many threatened apex predators. In this study, MPs were investigated from nine cetaceans of four different species, comprising one common dolphin (Delphinus delphis), two pygmy sperm whales (Kogia breviceps), one ginkgo-toothed beaked whale (Mesoplodon ginkgodens), and five Indo-Pacific humpback dolphins (Sousa chinensis) stranded along the western coast of the Taiwan Strait from the East China Sea based on Fourier transform infrared (FTIR) spectroscopy analysis. Mean abundances of 778 identified MPs items were 86.44 ± 12.22 items individual-1 and 0.43 ± 0.19 items g-1 wet weight of intestine contents, which were found predominantly to be transparent, fiber-shaped polyethylene terephthalate (PET) items usually between 0.5 and 5 mm. The abundance of MPs was found at a slightly higher level and significantly correlated with intestine contents mass (p = 0.0004*). The MPs source was mainly likely from synthetic fibers-laden sewage discharged from intense textile industries. Our report represents the first study of MPs in pelagic and deep-diving cetaceans in China, which not only adds baseline data on MPs for cetaceans in Asian waters but also highlights the further risk assessment of MPs consumption in these threatened species.

12.
Toxicol Appl Pharmacol ; 484: 116840, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38307258

RESUMO

Isoprenaline hydrochloride (IH) is a ß-adrenergic receptor agonist commonly used in the treatment of hypotension, shock, asthma, and other diseases. However, IH-induced cardiotoxicity limits its application. A large number of studies have shown that long noncoding RNA (lncRNA) regulates the occurrence and development of cardiovascular diseases. This study aimed to investigate whether abnormal lncRNA expression is involved in IH-mediated cardiotoxicity. First, the Sprague-Dawley (SD) rat myocardial injury model was established. Circulating exosomes were extracted from the plasma of rats and identified. In total, 108 differentially expressed (DE) lncRNAs and 150 DE mRNAs were identified by sequencing. These results indicate that these lncRNAs and mRNAs are substantially involved in chemical cardiotoxicity. Further signaling pathway and functional studies indicated that lncRNAs and mRNAs regulate several biological processes, such as selective mRNA splicing through spliceosomes, participate in sphingolipid metabolic pathways, and play a certain role in the circulatory system. Finally, we obtained 3 upregulated lncRNAs through reverse transcription-quantitative PCR (RT-qPCR) verification and selected target lncRNA-mRNA pairs according to the regulatory relationship of lncRNA/mRNA, some of which were associated with myocardial injury. This study provides valuable insights into the role of lncRNAs as novel biomarkers of chemical-induced cardiotoxicity.


Assuntos
Exossomos , RNA Longo não Codificante , Ratos , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Isoproterenol/toxicidade , Redes Reguladoras de Genes , Ratos Sprague-Dawley , Cardiotoxicidade , Exossomos/genética , Exossomos/metabolismo , RNA Mensageiro/metabolismo
13.
Small ; 20(29): e2310825, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38342581

RESUMO

Bifunctional electrocatalysts with excellent activity and durability are highly desirable for alkaline overall water splitting, yet remain a significant challenge. In this contribution, palm-like Mo5N6/Ni3S2 heterojunction arrays anchored in conductive Ni foam (denoted as Mo5N6-Ni3S2 HNPs/NF) are developed. Benefiting from the optimized electronic structure configuration, hierarchical branched structure and abundant heterogeneous interfaces, the as-synthesized Mo5N6-Ni3S2 HNPs/NF electrode exhibits remarkably stable bifunctional electrocatalytic activity in 1 m KOH solution. It only requires ultralow overpotentials of 59 and 190 mV to deliver a current density of 10 mA cm-2 for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in 1 m KOH solution, respectively. Importantly, the overall water splitting electrolyzer assembled by Mo5N6-Ni3S2 HNPs/NF exhibits an exceptionally low cell voltage (1.48 V@10 mA cm-2) and outstanding durability, surpassing most of the reported Ni-based bifunctional materials. Density functional theory (DFT) further confirms the heterostructure can optimize the Gibbs free energies of H and O-containing intermediates (OH, O, OOH) during HER and OER processes, thereby accelerating the catalytic kinetics of electrochemical water splitting. The findings provide a new design strategy toward low-cost and excellent catalysts for overall water splitting.

14.
Poult Sci ; 103(2): 103286, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38100949

RESUMO

In this study, we evaluated the enrichment efficiency of lutein in eggs and its function in preventing fatty liver hemorrhagic syndrome (FLHS) in aged laying hens. Five groups of laying hens (65 wk old) were fed basal diets supplemented with 0, 30, 60, 90, or 120 mg/kg of lutein. The supplementation period lasted 12 wk followed by 2 wk of lutein depletion in feed. The results revealed that lutein efficiently enriched the egg yolks and improved their color with a significant increase in relative redness (P < 0.001). Lutein accumulation increased in the egg yolk until day 10, then depletion reached a minimum level after 14 d. Overall, zeaxanthin content in all the groups was similar throughout the experimental period. However, triglycerides and total cholesterol were significantly decreased in the liver (P < 0.05) but not significantly different in the serum (P > 0.05). In the serum, the lipid metabolism enzyme acetyl-CoA synthetase was significantly reduced (P < 0.05), whereas dipeptidyl-peptidase 4 was not significantly different (P > 0.05), and there was no statistical difference of either enzyme in the liver (P > 0.05). Regarding oxidation and inflammation-related indexes, malondialdehyde, tumor necrosis factors alpha, interleukin-6, and interleukin-1 beta were decreased, whereas superoxide dismutase and total antioxidant capacity increased in the liver (P < 0.001). The function of lutein for the same indexes in serum was limited. It was concluded that lutein efficiently enriched the egg yolk of old laying hens to improve their color and reached the highest level on day 10 without being subject to a significant conversion into zeaxanthin. At the same time, lutein prevented liver steatosis in aged laying hens by exerting strong antioxidant and anti-inflammatory functions, but also through the modulation of lipid metabolism, which may contribute to reducing the incidence of FLHS in poultry.


Assuntos
Anormalidades Múltiplas , Anormalidades Craniofaciais , Fígado Gorduroso , Transtornos do Crescimento , Comunicação Interventricular , Luteína , Feminino , Animais , Luteína/metabolismo , Antioxidantes/metabolismo , Galinhas/metabolismo , Zeaxantinas/metabolismo , Suplementos Nutricionais/análise , Dieta/veterinária , Gema de Ovo/metabolismo , Fígado Gorduroso/prevenção & controle , Fígado Gorduroso/veterinária , Ração Animal/análise
15.
Exp Ther Med ; 27(1): 32, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38125338

RESUMO

Endoscopic retrograde cholangiopancreatography (ERCP) has become a common treatment method for common bile duct stones. However, ERCP is also associated with a high risk of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). Identification of risk factors is essential for reducing the incidence of PEP. The present study aimed to summarize the risk factors for PEP by performing a meta-analysis. Therefore, studies published between 2000 and 2022 were screened in PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang Digital Periodicals and the Weipu Database, with no language restrictions. Newcastle-Ottawa Scale was used to assess the quality of the included studies. Stata 17.0 software was utilized for the meta-analysis of 14 possible risk factors. Overall, 15 high-quality studies were included into the present meta-analysis. The results showed that female [odds ratio (OR), 1.42; 95% CI, 1.23-1.64), age <60 years (OR, 1.53; 95% CI, 1.06-2.21), difficult intubation (OR, 4.87; 95% CI, 2.73-8.68), ≥3 cannulation attempts (OR, 9.64; 95% CI, 4.16-22.35), cannulation time ≥10 min (OR, 2.37; 95% CI, 1.67-3.35), history of pancreatitis (OR, 2.95; 95% CI, 1.06-5.51), pancreatic duct visualization (OR, 3.63; 95% CI, 2.47-5.34) and sphincter of Oddi dysfunction (OR, 5.72; 95% CI, 1.80-18.24) are potential risk factors for PEP (P<0.05). In conclusion, the present meta-analysis suggests that PEP can be affected by several risk factors, particularly the technique-related factors such as the frequency and time of cannulation. Therefore, effective precautions should be taken as early as possible to reduce the incidence of PEP.

16.
Front Immunol ; 14: 1307588, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38235137

RESUMO

Background: Cancer-associated fibroblasts (CAFs) contribute to the progression and treatment of breast cancer (BRCA); however, risk signatures and molecular targets based on CAFs are limited. This study aims to identify novel CAF-related biomarkers to develop a risk signature for predicting the prognosis and therapeutic response of patients with BRCA. Methods: CAF-related genes (CAFRGs) and a risk signature based on these genes were comprehensively analyzed using publicly available bulk and single-cell transcriptomic datasets. Modular genes identified from bulk sequencing data were intersected with CAF marker genes identified from single-cell analysis to obtain reliable CAFRGs. Signature CAFRGs were screened via Cox regression and least absolute shrinkage and selection operator (LASSO) analyses. Multiple patient cohorts were used to validate the prognosis and therapeutic responsiveness of high-risk patients stratified based on the CAFRG-based signature. In addition, the relationship between the CAFRG-based signature and clinicopathological factors, tumor immune landscape, functional pathways, chemotherapy sensitivity and immunotherapy sensitivity was examined. External datasets were used and sample experiments were performed to examine the expression pattern of MFAP4, a key CAFRG, in BRCA. Results: Integrated analyses of single-cell and bulk transcriptomic data as well as prognostic screening revealed a total of 43 prognostic CAFRGs; of which, 14 genes (TLN2, SGCE, SDC1, SAV1, RUNX1, PDLIM4, OSMR, NT5E, MFAP4, IGFBP6, CTSO, COL12A1, CCDC8 and C1S) were identified as signature CAFRGs. The CAFRG-based risk signature exhibited favorable efficiency and accuracy in predicting survival outcomes and clinicopathological progression in multiple BRCA cohorts. Functional enrichment analysis suggested the involvement of the immune system, and the immune infiltration landscape significantly differed between the risk groups. Patients with high CAF-related risk scores (CAFRSs) exhibited tumor immunosuppression, enhanced cancer hallmarks and hyposensitivity to chemotherapy and immunotherapy. Five compounds were identified as promising therapeutic agents for high-CAFRS BRCA. External datasets and sample experiments validated the downregulation of MFAP4 and its strong correlation with CAFs in BRCA. Conclusions: A novel CAF-derived gene signature with favorable predictive performance was developed in this study. This signature may be used to assess prognosis and guide individualized treatment for patients with BRCA.


Assuntos
Neoplasias da Mama , Fibroblastos Associados a Câncer , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Prognóstico , Biomarcadores , Perfilação da Expressão Gênica , Proteínas de Transporte , Glicoproteínas , Proteínas da Matriz Extracelular
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