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1.
Quant Imaging Med Surg ; 14(7): 4749-4762, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-39022238

RESUMEN

Background: The preoperative identification of epidermal growth factor receptor (EGFR) mutations and subtypes based on magnetic resonance imaging (MRI) of brain metastases (BM) is necessary to facilitate individualized therapy. This study aimed to develop a deep learning model to preoperatively detect EGFR mutations and identify the location of EGFR mutations in patients with non-small cell lung cancer (NSCLC) and BM. Methods: We included 160 and 72 patients who underwent contrast-enhanced T1-weighted (T1w-CE) and T2-weighted (T2W) MRI at Liaoning Cancer Hospital and Institute (center 1) and Shengjing Hospital of China Medical University (center 2) to form a training cohort and an external validation cohort, respectively. A multiscale feature fusion network (MSF-Net) was developed by adaptively integrating features based on different stages of residual network (ResNet) 50 and by introducing channel and spatial attention modules. The external validation set from center 2 was used to assess the performance of MSF-Net and to compare it with that of handcrafted radiomics features. Receiver operating characteristic (ROC) curves, accuracy, precision, recall, and F1-score were used to evaluate the effectiveness of the models. Gradient-weighted class activation mapping (Grad-CAM) was used to demonstrate the attention of the MSF-Net model. Results: The developed MSF-Net generated a better diagnostic performance than did the handcrafted radiomics in terms of the microaveraged area under the curve (AUC) (MSF-Net: 0.91; radiomics: 0.80) and macroaveraged AUC (MSF-Net: 0.90; radiomics: 0.81) for predicting EGFR mutations and subtypes. Conclusions: This study provides an end-to-end and noninvasive imaging tool for the preoperative prediction of EGFR mutation status and subtypes based on BM, which may be helpful for facilitating individualized clinical treatment plans.

2.
Cancer Cell Int ; 24(1): 222, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38937761

RESUMEN

Triple negative breast cancer (TNBC) is a type of cancer that lacks receptor expression and has complex molecular mechanisms. Recent evidence shows that the ubiquitin-protease system is closely related to TNBC. In this study, we obtain a key ubiquitination regulatory substrate-ABI2 protein by bioinformatics methods, which is also closely related to the survival and prognosis of TNBC. Further, through a series of experiments, we demonstrated that ABI2 expressed at a low level in TNBC tumors, and it has the ability to control cell cycle and inhibit TNBC cell migration, invasion and proliferation. Molecular mechanism studies proved E3 ligase CBLC could increase the ubiquitination degradation of ABI2 protein. Meanwhile, RNA-seq and IP experiments indicated that ABI2, acting as a crucial factor of tumor suppression, can significantly inhibit PI3K/Akt signaling pathway via the interaction with Rho GTPase RAC1. Finally, based on TNBC drug target ABI2, we screened and found that FDA-approved drug Colistimethate sodium(CS) has significant potential in suppressing the proliferation of TNBC cells and inducing cell apoptosis, making it a promising candidate for impeding the progression of TNBC.

3.
Artículo en Inglés | MEDLINE | ID: mdl-38862429

RESUMEN

DNA sequencers have become increasingly important research and diagnostic tools over the past 20 years. In this study, we developed a single-molecule desktop sequencer, GenoCare 1600 (GenoCare), which utilizes amplification-free library preparation and two-color sequencing-by-synthesis chemistry, making it more user-friendly compared with previous single-molecule sequencing platforms for clinical use. Using the GenoCare platform, we sequenced an Escherichia coli standard sample and achieved a consensus accuracy exceeding 99.99%. We also evaluated the sequencing performance of this platform in microbial mixtures and coronavirus disease 2019 (COVID-19) samples from throat swabs. Our findings indicate that the GenoCare platform allows for microbial quantitation, sensitive identification of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, and accurate detection of virus mutations, as confirmed by Sanger sequencing, demonstrating its remarkable potential in clinical application.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/virología , COVID-19/diagnóstico , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Análisis de Secuencia de ADN/métodos , Escherichia coli/genética , Mutación
4.
Stem Cell Res Ther ; 15(1): 180, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38902824

RESUMEN

BACKGROUND: Telomeres consist of repetitive DNA sequences at the chromosome ends to protect chromosomal stability, and primarily maintained by telomerase or occasionally by alternative telomere lengthening of telomeres (ALT) through recombination-based mechanisms. Additional mechanisms that may regulate telomere maintenance remain to be explored. Simultaneous measurement of telomere length and transcriptome in the same human embryonic stem cell (hESC) revealed that mRNA expression levels of UBQLN1 exhibit linear relationship with telomere length. METHODS: In this study, we first generated UBQLN1-deficient hESCs and compared with the wild-type (WT) hESCs the telomere length and molecular change at RNA and protein level by RNA-seq and proteomics. Then we identified the potential interacting proteins with UBQLN1 using immunoprecipitation-mass spectrometry (IP-MS). Furthermore, the potential mechanisms underlying the shortened telomeres in UBQLN1-deficient hESCs were analyzed. RESULTS: We show that Ubiquilin1 (UBQLN1) is critical for telomere maintenance in human embryonic stem cells (hESCs) via promoting mitochondrial function. UBQLN1 deficiency leads to oxidative stress, loss of proteostasis, mitochondria dysfunction, DNA damage, and telomere attrition. Reducing oxidative damage and promoting mitochondria function by culture under hypoxia condition or supplementation with N-acetylcysteine partly attenuate the telomere attrition induced by UBQLN1 deficiency. Moreover, UBQLN1 deficiency/telomere shortening downregulates genes for neuro-ectoderm lineage differentiation. CONCLUSIONS: Altogether, UBQLN1 functions to scavenge ubiquitinated proteins, preventing their overloading mitochondria and elevated mitophagy. UBQLN1 maintains mitochondria and telomeres by regulating proteostasis and plays critical role in neuro-ectoderm differentiation.


Asunto(s)
Proteínas Relacionadas con la Autofagia , Células Madre Embrionarias Humanas , Mitocondrias , Proteostasis , Homeostasis del Telómero , Telómero , Humanos , Células Madre Embrionarias Humanas/metabolismo , Células Madre Embrionarias Humanas/citología , Proteínas Relacionadas con la Autofagia/metabolismo , Proteínas Relacionadas con la Autofagia/genética , Mitocondrias/metabolismo , Telómero/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Estrés Oxidativo , Daño del ADN
5.
Free Radic Biol Med ; 221: 40-51, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-38759901

RESUMEN

Fine particulate matter (PM2.5), a significant component of air pollution particulate matter, is inevitable and closely associated with increasing male reproductive disorder. However, the testicular targets of PM2.5 and its toxicity related molecular mechanisms are still not fully understood. In this study, the conditional knockout (cKO) mice and primary Leydig cells were used to explore the testicular targets of PM2.5 and the related underlying mechanisms. First, apparent the structure impairment of seminiferous tubules, Leydig cells vacuolization, decline of serum testosterone and sperm quality reduction were found in male wild-type (WT) and Sirt1 knockout mice after exposure to PM2.5. Enrichment analyses revealed that differentially expressed genes (DEGs) were enriched in steroid hormone biosynthesis, ferroptosis, and HIF-1 signaling pathway in the mice testes after exposure to PM2.5, which were subsequently verified by the molecular biological analyses. Notably, similar enrichment analyses results were also observed in primary Leydig cells after treatment with PM2.5. In addition, Knockdown of Sirt1 significantly increased PM2.5-induced expression and activation of HIF-1α, which was in parallel to the changes of cellular iron levels, oxidative stress indicators and the ferroptosis markers. In conclusion, this highlights that PM2.5 triggers ferroptosis via SIRT1/HIF-1α signaling pathway to inhibit testosterone synthesis in males. These findings provide a novel research support for the study that PM2.5 causes male reproductive injury.


Asunto(s)
Ferroptosis , Subunidad alfa del Factor 1 Inducible por Hipoxia , Células Intersticiales del Testículo , Ratones Noqueados , Material Particulado , Transducción de Señal , Sirtuina 1 , Testosterona , Animales , Masculino , Testosterona/metabolismo , Testosterona/sangre , Material Particulado/toxicidad , Material Particulado/efectos adversos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Ratones , Sirtuina 1/metabolismo , Sirtuina 1/genética , Transducción de Señal/efectos de los fármacos , Ferroptosis/efectos de los fármacos , Ferroptosis/genética , Células Intersticiales del Testículo/metabolismo , Células Intersticiales del Testículo/efectos de los fármacos , Células Intersticiales del Testículo/patología , Testículo/metabolismo , Testículo/patología , Testículo/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos
6.
Neurobiol Dis ; 197: 106527, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38740347

RESUMEN

BACKGROUND: Neurotransmitter deficits and spatial associations among neurotransmitter distribution, brain activity, and clinical features in Parkinson's disease (PD) remain unclear. Better understanding of neurotransmitter impairments in PD may provide potential therapeutic targets. Therefore, we aimed to investigate the spatial relationship between PD-related patterns and neurotransmitter deficits. METHODS: We included 59 patients with PD and 41 age- and sex-matched healthy controls (HCs). The voxel-wise mean amplitude of the low-frequency fluctuation (mALFF) was calculated and compared between the two groups. The JuSpace toolbox was used to test whether spatial patterns of mALFF alterations in patients with PD were associated with specific neurotransmitter receptor/transporter densities. RESULTS: Compared to HCs, patients with PD showed reduced mALFF in the sensorimotor- and visual-related regions. In addition, mALFF alteration patterns were significantly associated with the spatial distribution of the serotonergic, dopaminergic, noradrenergic, glutamatergic, cannabinoid, and acetylcholinergic neurotransmitter systems (p < 0.05, false discovery rate-corrected). CONCLUSIONS: Our results revealed abnormal brain activity patterns and specific neurotransmitter deficits in patients with PD, which may provide new insights into the mechanisms and potential targets for pharmacotherapy.


Asunto(s)
Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/fisiopatología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Encéfalo/metabolismo , Imagen por Resonancia Magnética/métodos , Neurotransmisores/metabolismo , Imagen Multimodal/métodos
7.
Cell Death Dis ; 15(4): 289, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38653973

RESUMEN

GATA-binding protein 4 (GATA4) is recognized for its significant roles in embryogenesis and various cancers. Through bioinformatics and clinical data, it appears that GATA4 plays a role in breast cancer development. Yet, the specific roles and mechanisms of GATA4 in breast cancer progression remain elusive. In this study, we identify GATA4 as a tumor suppressor in the invasion and migration of breast cancer. Functionally, GATA4 significantly reduces the transcription of MMP9. On a mechanistic level, GATA4 diminishes MMP9 transcription by interacting with p65 at the NF-κB binding site on the MMP9 promoter. Additionally, GATA4 promotes the recruitment of HDAC1, amplifying the bond between p65 and HDAC1. This leads to decreased acetylation of p65, thus inhibiting p65's transcriptional activity on the MMP9 promoter. Moreover, GATA4 hampers the metastasis of breast cancer in vivo mouse model. In summary, our research unveils a novel mechanism wherein GATA4 curtails breast cancer cell metastasis by downregulating MMP9 expression, suggesting a potential therapeutic avenue for breast cancer metastasis.


Asunto(s)
Neoplasias de la Mama , Movimiento Celular , Factor de Transcripción GATA4 , Regulación Neoplásica de la Expresión Génica , Histona Desacetilasa 1 , Metaloproteinasa 9 de la Matriz , Invasividad Neoplásica , Humanos , Factor de Transcripción GATA4/metabolismo , Factor de Transcripción GATA4/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/genética , Femenino , Movimiento Celular/genética , Histona Desacetilasa 1/metabolismo , Histona Desacetilasa 1/genética , Animales , Acetilación , Línea Celular Tumoral , Ratones , Factor de Transcripción ReIA/metabolismo , Transcripción Genética , Regiones Promotoras Genéticas/genética , Ratones Desnudos , Ratones Endogámicos BALB C
8.
Front Immunol ; 15: 1382661, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38558797

RESUMEN

Introduction: BTBD8 has been identified as a susceptible gene for inflammatory bowel diseases (IBD). However, the function of BTBD8 in normal development and IBD pathogenesis remains unknown. Methods: We administered drinking water with 3% dextran sodium sulfate (DSS) to wild-type (WT) and Btbd8 knockout (KO) mice for seven consecutive days to induce IBD. Subsequently, we further examined whether Btbd8 KO affects intestinal barrier and inflammation. Results: We demonstrated that Btbd8 deficiency partially protects mice from DSS-induced IBD, even though no obvious phenotypes were observed in Btbd8 KO mice. Btbd8 deletion leads to strengthened tight junctions between intestinal epithelial cells, elevated intestinal stem cell activity, and enhanced mucus layer. All these three mechanisms work together to improve the intestinal barrier integrity in Btbd8 KO mice. In addition, Btbd8 deficiency mitigates inflammation by reducing the expression of IL-1ß and IL-6 by macrophages. Discussion: Our studies validate the crucial role of Btbd8 in IBD pathogenesis, and reveal that Btbd8 deficiency may ameliorate DSS-induced IBD through improving the intestinal barrier integrity, as well as suppressing inflammatory response mediated by macrophages. These findings suggest that Btbd8 could be a promising therapeutic target for the treatment of IBD.


Asunto(s)
Colitis , Enfermedades Inflamatorias del Intestino , Animales , Ratones , Funcion de la Barrera Intestinal , Colitis/inducido químicamente , Colitis/genética , Colitis/tratamiento farmacológico , Inflamación/genética , Inflamación/patología , Intestinos/patología , Enfermedades Inflamatorias del Intestino/genética , Enfermedades Inflamatorias del Intestino/patología
9.
JCO Precis Oncol ; 8: e2300405, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38547420

RESUMEN

PURPOSE: Long noncoding RNAs (lncRNAs) were recently implicated in modifying pyroptosis. Nonetheless, pyroptosis-related lncRNAs and their possible clinical relevance persist largely uninvestigated in lung adenocarcinoma (LUAD). MATERIALS AND METHODS: A sum of 921 samples were collected from three independent data sets. We obtained pyroptosis-related genes from both the Molecular Signatures Database and relevant literature sources and used four machine learning techniques, comprising stepwise Cox, ridge regression, least absolute shrinkage and selection operator, and random forest. Multiple bioinformatics approaches were used to further investigate the underlying mechanisms. RESULTS: In total, 39 differentially expressed pyroptosis genes were identified by comparing normal and tumor samples. Correlation analysis revealed 933 pyroptosis-related lncRNAs. Furthermore, univariate Cox regression determined 11 lncRNAs that exhibited stable associations with prognosis in the three cohorts, which were used to construct the pyroptosis-derived lncRNA signature. After analyzing the optimal results from four machine learning algorithms, we ultimately selected random forest to develop the pyroptosis-derived lncRNA signature. This signature was proven to be an independent prognostic factor and exhibited robust performance in three cohorts. CONCLUSION: We provided novel insight and established a pyroptosis-derived lncRNA signature for patients with LUAD, exhibiting strong predictive capabilities in both the training and validation sets.


Asunto(s)
Adenocarcinoma , ARN Largo no Codificante , Humanos , Piroptosis , ARN Largo no Codificante/genética , Pronóstico , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Pulmón
10.
J Imaging Inform Med ; 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38381383

RESUMEN

The purpose of this study was to fuse conventional radiomic and deep features from digital breast tomosynthesis craniocaudal projection (DBT-CC) and ultrasound (US) images to establish a multimodal benign-malignant classification model and evaluate its clinical value. Data were obtained from a total of 487 patients at three centers, each of whom underwent DBT-CC and US examinations. A total of 322 patients from dataset 1 were used to construct the model, while 165 patients from datasets 2 and 3 formed the prospective testing cohort. Two radiologists with 10-20 years of work experience and three sonographers with 12-20 years of work experience semiautomatically segmented the lesions using ITK-SNAP software while considering the surrounding tissue. For the experiments, we extracted conventional radiomic and deep features from tumors from DBT-CCs and US images using PyRadiomics and Inception-v3. Additionally, we extracted conventional radiomic features from four peritumoral layers around the tumors via DBT-CC and US images. Features were fused separately from the intratumoral and peritumoral regions. For the models, we tested the SVM, KNN, decision tree, RF, XGBoost, and LightGBM classifiers. Early fusion and late fusion (ensemble and stacking) strategies were employed for feature fusion. Using the SVM classifier, stacking fusion of deep features and three peritumoral radiomic features from tumors in DBT-CC and US images achieved the optimal performance, with an accuracy and AUC of 0.953 and 0.959 [CI: 0.886-0.996], a sensitivity and specificity of 0.952 [CI: 0.888-0.992] and 0.955 [0.868-0.985], and a precision of 0.976. The experimental results indicate that the fusion model of deep features and peritumoral radiomic features from tumors in DBT-CC and US images shows promise in differentiating benign and malignant breast tumors.

11.
Sci Total Environ ; 918: 170701, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38325452

RESUMEN

Epidemiological studies have found that long-term inhalation of PM2.5 is closely related to spermatogenesis disorders and infertility, but the underlying molecular mechanism is still unidentified. Testosterone, an essential reproductive hormone produced by Leydig cells, whose synthesis is disrupted by multiple environmental pollutants. In the current study, we explored the role of METTL3-m6A-SIRT1 axis-mediated abnormal autophagy in PM2.5-induced inhibition of testosterone production in in vivo and in vitro models. Our in vivo findings shown that long-term inhalation of PM2.5 decreased sperm count, increased sperm deformity rates, and altered testicular interstitial morphology accompanied by reduced testosterone in serum and testes. Further, data from the in vitro model displayed that exposure to PM2.5 caused an increase in m6A modification and METTL3 levels, followed by a decrease in testosterone levels and autophagy dysfunction in Leydig cells. The knockdown of METTL3 promotes autophagy flux and testosterone production in Leydig cells. Mechanistically, PM2.5 increased METTL3-induced m6A modification of SIRT1 mRNA in Leydig cells, bringing about abnormal autophagy. Subsequently, administration of SRT1720 (a SIRT1 activator) enhanced autophagy and further promoted testosterone biosynthesis. Collectively, our discoveries indicate that METTL3-m6A-SIRT1 axis-mediated autophagic flux contributes to PM2.5-induced inhibition of testosterone biosynthesis. This research offers a novel viewpoint on the mechanism of male reproductive injury following PM2.5 exposure.


Asunto(s)
Adenina/análogos & derivados , Células Intersticiales del Testículo , Testosterona , Masculino , Humanos , Sirtuina 1 , Semen , Material Particulado/toxicidad , Autofagia/fisiología
12.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(2): 221-224, 2024 Feb 10.
Artículo en Chino | MEDLINE | ID: mdl-38311563

RESUMEN

OBJECTIVE: To carry out prenatal diagnosis for a fetus with Meckel syndrome (MKS) and explore its genetic basis. METHODS: A pregnant woman presented at Suzhou Municipal Hospital in February 2018 was selected as the study subject. Clinical data was collected. Muscle tissue sample from the abortus and peripheral blood samples from the couple were collected. Genomic DNA was extracted and subjected to chromosomal microarray analysis (CMA) and whole exome sequencing. Candidate variant was verified by Sanger sequencing. RESULTS: The fetus was found to have microcephaly, oligohydramnios, polycystic kidneys and banana-shaped cerebellum at 18 weeks of gestation. After induction of labor, it was found to have encephalocele, renal cysts and polydactyly. CMA has found no abnormality. Whole exome sequencing revealed novel compound heterozygous variants c.296delA (p.Lys99SerfsTer6) and c.1243G>A (p.Val415Met) in the TMEM67 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.296delA variant was predicted to be pathogenic (PVS1+PM2_Supporting+PP4), whilst the c.1243G>A variant was predicted to be likely pathogenic (PM2_Supporting+PM3+PP3_Moderate+PP4). CONCLUSION: The c.296delA and c.1243G>A compound heterozygous variants of the TMEM67 gene probably underlay the MKS in this fetus.


Asunto(s)
Trastornos de la Motilidad Ciliar , Enfermedades Renales Poliquísticas , Retinitis Pigmentosa , Femenino , Embarazo , Humanos , Encefalocele/genética , Enfermedades Renales Poliquísticas/genética , Feto , Trastornos de la Motilidad Ciliar/genética , Mutación , Proteínas de la Membrana/genética
13.
J Hazard Mater ; 465: 133477, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38218033

RESUMEN

Electrical fields (EFs)-assisted in-situ bioremediation of petroleum-contaminated groundwater, such as polycyclic aromatic hydrocarbons, has drawn increasing attention. However, the long-term stability, the EFs influence, and metabolic pathways are still poorly understood, hindering the further development of robust technology design. Herein, a series of EFs was applied to the phenanthrene-contaminated groundwater, and the corresponding system performance was investigated. The highest removal capacity of phenanthrene (phe) (7.63 g/(m3·d)) was achieved with EF_0.8 V biofilm at a hydrolytic retention time of 0.5 d. All the biofilms with four EFs exhibited a high removal efficiency of phe over 80% during a 100-d continuous-flow operation. Intermediates analysis revealed the main pathways of phe degradation: phthalate and salicylate via hydroxylation, methylation, carboxylation, and ring cleavage steps. Synergistic effects between phe-degraders (Dechloromonas), fermentative bacteria (Delftia), and electroactive microorganisms (Geobacter) were the main contributors to the complete phe mineralization. Genes encoding various proteins of methyl-accepting (mcp), response regulator (cheABDRY), and type IV pilus (pilABCMQV) were dominant, revealing the importance of cell motility and extracellular electron transfer. Metagenomics analysis unveiled phe-degrading genes, including ring reduction enzymes (bamBCDE), carboxylase of aromatics (ubiD), and methyltransferase protein (ubiE, pcm). These findings offered a molecular understanding of refractory organics' decompositions in EFs-governed biotechnology.


Asunto(s)
Agua Subterránea , Fenantrenos , Hidrocarburos Policíclicos Aromáticos , Contaminantes del Suelo , Biodegradación Ambiental , Contaminantes del Suelo/metabolismo , Fenantrenos/metabolismo , Hidrocarburos Policíclicos Aromáticos/análisis , Biopelículas , Microbiología del Suelo
14.
J Hazard Mater ; 466: 133598, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38280327

RESUMEN

Organophosphate triesters (tri-OPEs) threaten human health through dietary exposure, but little is known about their feed-to-food transfer and in vivo behavior in farm animals. Herein 135 laying hens were fed with contaminated feed (control group, low-level group and high-level group) to elucidate the bioaccumulation, distribution, and metabolism of the six most commonly reported tri-OPEs. The storage (breast muscle), metabolism and mobilization (liver and blood) and non-invasive (feather) tissues were collected. The exposure-increase (D1∼14) and depuration-decrease (D15∼42) trends indicated that feed exposure caused tri-OPE accumulation in animal tissues. Tissue-specific and moiety-specific behavior was observed for tri-OPEs. The highest transfer factor (TF) and transfer rate (TR) were observed in liver (TF: 14.8%∼82.3%; TR: 4.40%∼24.5%), followed by feather, breast muscle, and blood. Tris(2-chloroisopropyl) phosphate (TCIPP) had the longest half-life in feather (72.2 days), while triphenyl phosphate (TPhP) showed the shortest half-life in liver (0.41 days). Tri-OPEs' major metabolites (organophosphate diesters, di-OPEs) were simultaneously studied, which exhibited dose-dependent and time-dependent variations following administration. In breast muscle, the inclusion of di-OPEs resulted in TF increases of 735%, 1108%, 798%, and 286% than considering TCIPP, tributyl phosphate, tris(2-butoxyethyl) phosphate and tris(2-ethylhexyl) phosphate alone. Feather was more of a proxy of birds' long-term exposure to tri-OPEs, while short-term exposure was better reflected by di-OPEs. Both experimental and in silico modeling methods validated aryl-functional group facilitated the initial accumulation and metabolism of TPhP in the avian liver compared to other moiety-substituted tri-OPEs.


Asunto(s)
Pollos , Retardadores de Llama , Animales , Femenino , Humanos , Bioacumulación , Pollos/metabolismo , Ésteres/metabolismo , Biotransformación , Organofosfatos/metabolismo , Fosfatos , Retardadores de Llama/análisis , China , Monitoreo del Ambiente
15.
Fish Physiol Biochem ; 50(2): 705-719, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38294642

RESUMEN

Color changes and pattern formations can represent strategies of the utmost importance for the survival of individuals or of species. Previous studies have associated capture with the formation of blotches (areas with light color) of coral trout, but the regulatory mechanisms link the two are lacking. Here, we report that capture induced blotches formation within 4-5 seconds. The blotches disappeared after anesthesia dispersed the pigment cells and reappeared after electrical stimulation. Subsequently, combining immunofluorescence, transmission electron microscopy and chemical sympathectomy, we found blotches formation results from activation of catecholaminergic neurons below the pigment layer. Finally, the in vitro incubation and intraperitoneal injection of norepinephrine (NE) induced aggregation of chromatosomes and lightening of body color, respectively, suggesting that NE, a neurotransmitter released by catecholaminergic nerves, mediates blotches formation. Our results demonstrate that acute stress response-induced neuronal activity can drive rapid changes in body color, which enriches our knowledge of physiological adaptations in coral reef fish.


Asunto(s)
Antozoos , Lubina , Animales , Trucha , Norepinefrina/farmacología , Lubina/fisiología , Arrecifes de Coral
16.
Environ Res ; 241: 117641, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-37972808

RESUMEN

The presence of excessive concentrations of nitrate poses a threat to both the environment and human health, and the bioelectrochemical systems (BESs) are attractive green technologies for nitrate removal. However, the denitrification efficiency in the BESs is still limited by slow biofilm formation and nitrate removal. In this work, we demonstrate the efficacy of novel combination of magnetite nanoparticles (nano-Fe3O4) with the anode-cathode polarity period reversal (PPR-Fe3O4) for improving the performance of BESs. After only two-week cultivation, the highest cathodic current density (7.71 ± 1.01 A m-2) and NO3--N removal rate (8.19 ± 0.97 g m-2 d-1) reported to date were obtained in the PPR-Fe3O4 process (i.e., polarity period reversal with nano-Fe3O4 added) at applied working voltage of -0.2 and -0.5 V (vs Ag/AgCl) under bioanodic and biocathodic conditions, respectively. Compared with the polarity reversal once only process, the PPR process (i.e., polarity period reversal in the absence of nano-Fe3O4) enhanced bioelectroactivity through increasing biofilm biomass and altering microbial community structure. Nano-Fe3O4 could enhance extracellular electron transfer as a result of promoting the formation of extracellular polymers containing Fe3O4 and reducing charge transfer resistance of bioelectrodes. This work develops a novel biocathode denitrification strategy to achieve efficient nitrate removal after rapid cultivation.


Asunto(s)
Desnitrificación , Nitratos , Humanos , Nitratos/química , Electrodos
17.
Cell Signal ; 114: 110967, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-37949382

RESUMEN

BACKGROUND: Multiple PDZ Domain Crumbs Cell Polarity Complex Component (MPDZ) is involved in a few human cancers. However, the features and potential mechanisms of MPDZ in progression of colorectal cancer (CRC) remains unknown. METHODS: The prognostic role of MPDZ in CRC was determined by Kaplan-Meier and univariate regression analysis. Enrichment analysis was performed to characterize crucial pathways of MPDZ. Immune infiltration and immunotherapeutic outcome were further evaluated. CCK8, EDU, transwell, and wound healing assay were used to assess the influence of MPDZ on pernicious performance of CRC cells. CD8+ T cells and CRC cells were co-cultured to explore the effect of MPDZ on the tumor microenvironment. qRT-PCR, western blot, immunoprecipitation (IP), and methylated RNA immunoprecipitation (me-RIP) were implemented in seeking for the potential mechanisms of MPDZ in CRC. RESULTS: CRC patients with elevated MPDZ expression suffered from significantly worse prognosis. Enrichment analysis revealed that MPDZ involved in pathways related to metastasis and cell cycle in CRC. In addition, MPDZ expression were related to several immunoinhibitors and had the ability to predict immunotherapy response. Finally, in vitro assays demonstrated that MPDZ knockdown inhibited migration, invasion and immune evasion of CRC cells. Mechanistically, MPDZ knockdown enhanced YAP1 phosphorylation by increased LATS1 expression. Moreover, m6A-MPDZ mRNA may be recognized and degraded by m6A recognition protein YTHDF2. CONCLUSIONS: MPDZ was critical for CRC development and could be a promising candidate for the treatment of CRC patients.


Asunto(s)
Linfocitos T CD8-positivos , Neoplasias Colorrectales , Humanos , Linfocitos T CD8-positivos/metabolismo , Linfocitos T CD8-positivos/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias Colorrectales/patología , Proteínas de la Membrana/metabolismo , Fosforilación , Factores de Transcripción/metabolismo , Microambiente Tumoral , Proteínas Señalizadoras YAP/metabolismo
18.
ISA Trans ; 144: 86-95, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37914615

RESUMEN

A fuzzy adaptive tracking control scheme is studied for a family of uncertain systems with immeasurable system states. The controller takes up few computation and transmission resources to achieve prescribed boundaries of the dynamic and steady-state performance indicators. Compared with the existing schemes, the low computational complexity is reflected in the following two points: (1) a fuzzy state observer is introduced, where only the estimation of states are incorporated into the input space of fuzzy logic systems (FLSs). (2) The problem of complexity explosion can be avoided without utilizing additional command filters or auxiliary dynamic surface control techniques. In addition, using the event-triggered control scheme, the data in the transmission is significantly reduced. Finally, the effectiveness of the scheme is fully verified by simulation.

19.
Artículo en Inglés | MEDLINE | ID: mdl-38083773

RESUMEN

Neoadjuvant chemotherapy (NAC) is the standard treatment for breast cancer patients. Patients achieving complete pathological response (pCR) after NAC usually have a good prognosis. However, automatic pCR prediction has been a challenging problem due to lacking well annotations in 3D MRI. Thus far, unifying different annotation information to predict the tumor's early response to NAC has not been systematically addressed. This paper proposes a weakly and semi-supervised joint learning method that integrates attentional features from multi-parametric MRI with radiomic features for predicting pCR to NAC in breast cancer patients. The attention-based multi-instance learning (MIL) is first developed to generate informative MRI bag-level features and mine key instances. The mean-teacher framework is then employed to segment tumor regions in a semi-supervised setting for extracting radiomic features. We perform experiments on 442 patients' data and show that our method achieves an AUC value of 0.85 in pCR prediction, which is superior to comparative methods. It is also shown that learning from multi-parametric MRI outperforms that of single-parameter MRI in pCR prediction.


Asunto(s)
Neoplasias de la Mama , Imágenes de Resonancia Magnética Multiparamétrica , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Resultado del Tratamiento , Imagen por Resonancia Magnética/métodos , Mama/patología
20.
Chemosphere ; 345: 140428, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37858765

RESUMEN

Persistent organic pollutant perfluorooctane sulfonate (PFOS) is strongly associated with male reproductive disorders, but the related mechanisms are still not fully understood. In this study, we used in vivo and in vitro models to explore the role of organic anion transporting polypeptide 3a1 (Oatp3a1) on PFOS-induced male reproductive injury. Thirty male C57BL/6 (B6) mice were orally given PFOS (0-10 mg/kg/bw) for 28 days. Body weight, organ index, sperm count, histology, and blood-testis barrier (BTB) integrity were evaluated. Primary Sertoli cells were used to describe the related molecular mechanisms of male reproductive injury caused by PFOS. Our results showed that PFOS induced a decrease in sperm count, morphological damage to testicular Sertoli cells, and disruption of BTB. In the in vitro model, exposure to PFOS significantly increased Oatp3a1 mRNA and protein levels and decreased miR-23a-3p expression in Sertoli cells, accompanied by reduced trans-epithelial electrical resistance (TEER) value. By performing the 14C-PFOS uptake experiment, we showed that 14C-PFOS uptake in HEK293-Oatp3a1 cells was apparently higher than in HEK293-MOCK cells. Meanwhile, treating Sertoli cells with Oatp3a1 siRNA significantly decreased Oatp3a1 expression and rescued PFOS-induced decreases in TEER value. As such, the present study highlights that Oatp3a1 may play an important role in the toxic effect of PFOS on Sertoli cells, advancing our understanding of molecular mechanisms for PFOS-induced male reproductive disorders.


Asunto(s)
Ácidos Alcanesulfónicos , Fluorocarburos , Transportadores de Anión Orgánico , Masculino , Humanos , Ratones , Animales , Células de Sertoli , Células HEK293 , Ratones Endogámicos C57BL , Semen , Ácidos Alcanesulfónicos/metabolismo , Fluorocarburos/metabolismo , Transportadores de Anión Orgánico/genética , Transportadores de Anión Orgánico/metabolismo , Transportadores de Anión Orgánico/farmacología
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