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1.
Innovation (Camb) ; 5(3): 100620, 2024 May 06.
Article En | MEDLINE | ID: mdl-38706954

In the last decade, organoid research has entered a golden era, signifying a pivotal shift in the biomedical landscape. The year 2023 marked a milestone with the publication of thousands of papers in this arena, reflecting exponential growth. However, amid this burgeoning expansion, a comprehensive and accurate overview of the field has been conspicuously absent. Our review is intended to bridge this gap, providing a panoramic view of the rapidly evolving organoid landscape. We meticulously analyze the organoid field from eight distinctive vantage points, harnessing our rich experience in academic research, industrial application, and clinical practice. We present a deep exploration of the advances in organoid technology, underpinned by our long-standing involvement in this arena. Our narrative traverses the historical genesis of organoids and their transformative impact across various biomedical sectors, including oncology, toxicology, and drug development. We delve into the synergy between organoids and avant-garde technologies such as synthetic biology and single-cell omics and discuss their pivotal role in tailoring personalized medicine, enhancing high-throughput drug screening, and constructing physiologically pertinent disease models. Our comprehensive analysis and reflective discourse provide a deep dive into the existing landscape and emerging trends in organoid technology. We spotlight technological innovations, methodological evolution, and the broadening spectrum of applications, emphasizing the revolutionary influence of organoids in personalized medicine, oncology, drug discovery, and other fields. Looking ahead, we cautiously anticipate future developments in the field of organoid research, especially its potential implications for personalized patient care, new avenues of drug discovery, and clinical research. We trust that our comprehensive review will be an asset for researchers, clinicians, and patients with keen interest in personalized medical strategies. We offer a broad view of the present and prospective capabilities of organoid technology, encompassing a wide range of current and future applications. In summary, in this review we attempt a comprehensive exploration of the organoid field. We offer reflections, summaries, and projections that might be useful for current researchers and clinicians, and we hope to contribute to shaping the evolving trajectory of this dynamic and rapidly advancing field.

3.
Comput Struct Biotechnol J ; 23: 1877-1885, 2024 Dec.
Article En | MEDLINE | ID: mdl-38707542

Transcription factors (TFs) are major contributors to gene transcription, especially in controlling cell-specific gene expression and disease occurrence and development. Uncovering the relationship between TFs and their target genes is critical to understanding the mechanism of action of TFs. With the development of high-throughput sequencing techniques, a large amount of TF-related data has accumulated, which can be used to identify their target genes. In this study, we developed TFTG (Transcription Factor and Target Genes) database (http://tf.liclab.net/TFTG), which aimed to provide a large number of available human TF-target gene resources by multiple strategies, besides performing a comprehensive functional and epigenetic annotations and regulatory analyses of TFs. We identified extensive available TF-target genes by collecting and processing TF-associated ChIP-seq datasets, perturbation RNA-seq datasets and motifs. We also obtained experimentally confirmed relationships between TF and target genes from available resources. Overall, the target genes of TFs were obtained through integrating the relevant data of various TFs as well as fourteen identification strategies. Meanwhile, TFTG was embedded with user-friendly search, analysis, browsing, downloading and visualization functions. TFTG is designed to be a convenient resource for exploring human TF-target gene regulations, which will be useful for most users in the TF and gene expression regulation research.

4.
Article En | MEDLINE | ID: mdl-38724231

BACKGROUND: Sleep fragmentation is a persistent problem throughout the course of Parkinson's disease (PD). However, the related neurophysiological patterns and the underlying mechanisms remained unclear. METHOD: We recorded subthalamic nucleus (STN) local field potentials (LFPs) using deep brain stimulation (DBS) with real-time wireless recording capacity from 13 patients with PD undergoing a one-night polysomnography recording, 1 month after DBS surgery before initial programming and when the patients were off-medication. The STN LFP features that characterised different sleep stages, correlated with arousal and sleep fragmentation index, and preceded stage transitions during N2 and REM sleep were analysed. RESULTS: Both beta and low gamma oscillations in non-rapid eye movement (NREM) sleep increased with the severity of sleep disturbance (arousal index (ArI)-betaNREM: r=0.9, p=0.0001, sleep fragmentation index (SFI)-betaNREM: r=0.6, p=0.0301; SFI-gammaNREM: r=0.6, p=0.0324). We next examined the low-to-high power ratio (LHPR), which was the power ratio of theta oscillations to beta and low gamma oscillations, and found it to be an indicator of sleep fragmentation (ArI-LHPRNREM: r=-0.8, p=0.0053; ArI-LHPRREM: r=-0.6, p=0.0373; SFI-LHPRNREM: r=-0.7, p=0.0204; SFI-LHPRREM: r=-0.6, p=0.0428). In addition, long beta bursts (>0.25 s) during NREM stage 2 were found preceding the completion of transition to stages with more cortical activities (towards Wake/N1/REM compared with towards N3 (p<0.01)) and negatively correlated with STN spindles, which were detected in STN LFPs with peak frequency distinguishable from long beta bursts (STN spindle: 11.5 Hz, STN long beta bursts: 23.8 Hz), in occupation during NREM sleep (ß=-0.24, p<0.001). CONCLUSION: Features of STN LFPs help explain neurophysiological mechanisms underlying sleep fragmentations in PD, which can inform new intervention for sleep dysfunction. TRIAL REGISTRATION NUMBER: NCT02937727.

5.
Genetica ; 2024 May 10.
Article En | MEDLINE | ID: mdl-38724749

DnaJs/Hsp40s/JPDs are obligate co-chaperones of heat shock proteins (Hsp70), performing crucial biological functions within organisms. A comparative genome analysis of four genomes (Vitis vinifera, Eucalyptus grandis, Lagerstroemia indica, and Punica granatum) revealed that the DnaJ gene family in L. indica has undergone expansion, although not to the extent observed in P. granatum. Inter-genome collinearity analysis of four plants indicates that members belonging to Class A and B are more conserved during evolution. In L. indica, the expanded members primarily belong to Class-C. Tissue expression patterns and the biochemical characterization of LiDnaJs further suggested that DnaJs may be involved in numerous biological processes in L. indica. Transcriptome and qPCR analyses of salt stressed leaves identified at least ten LiDnaJs that responded to salt stress. In summary, we have elucidated the expansion mechanism of the LiDnaJs, which is attributed to a recent whole-genome triplication. This research laid the foundation for functional analysis of LiDnaJs and provides gene resources for breeding salt-tolerant varieties of L. indica.

6.
Environ Toxicol ; 2024 May 10.
Article En | MEDLINE | ID: mdl-38727095

Osteoporosis (OP) can result in slower bone regeneration than the normal condition due to abnormal oxidative stress and high levels of reactive oxygen species (ROS), a condition detrimental for bone formation, making the OP-related bone healing a significant clinical challenge. As the osteogenic differentiation ability of bone marrow mesenchymal stem cells (BMSCs) is closely related to bone regeneration; currently, this study assessed the effects of Picein on BMSCs in vitro and bone regeneration in osteoporotic bone defect in vivo. Cell viability was determined by CCK-8 assay. The production of (ROS), malonaldehyde, superoxide dismutase activities, and glutathione was evaluated by using commercially available kits, and a flow cytometry analysis was adopted to detect macrophage polarization. Osteogenic capacity of BMSCs was evaluated by alkaline phosphatase (ALP) activity, ALP staining, and Alizarin red S staining. The expression of osteogenic-related proteins (OPN, Runx-2, OCN) and osteogenic-related genes (ALP, BMP-4, COL-1, and Osterix) were evaluated by Western blotting and real-time PCR (RT-PCR). In addition, proliferation, migration ability, and angiogenic capacity of human umbilical vein endothelial cells (HUVECs) were evaluated by EdU staining, scratch test, transwell assay, and tube formation assay, respectively. Angiogenic-related genes (VEGF, vWF, CD31) were also evaluated by RT-PCR. Results showed that Picein alleviated erastin-induced oxidative stress, enhanced osteogenic differentiation capacity of BMSCs, angiogenesis of HUVECs, and protects cells against ferroptosis through Nrf2/HO-1/GPX4 axis. Moreover, Picein regulate immune microenvironment by promoting the polarization of M2 macrophages in vitro. In addition, Picein also reduce the inflammation levels and promotes bone regeneration in osteoporotic bone defect in OP rat models in vivo. Altogether, these results suggested that Picein can promote bone regeneration and alleviate oxidative stress via Nrf2/HO-1/GPX4 pathway, offering Picein as a novel antioxidant agent for treating osteoporotic bone defect.

7.
Front Plant Sci ; 15: 1371252, 2024.
Article En | MEDLINE | ID: mdl-38711601

Stem diameter is a critical phenotypic parameter for maize, integral to yield prediction and lodging resistance assessment. Traditionally, the quantification of this parameter through manual measurement has been the norm, notwithstanding its tedious and laborious nature. To address these challenges, this study introduces a non-invasive field-based system utilizing depth information from RGB-D cameras to measure maize stem diameter. This technology offers a practical solution for conducting rapid and non-destructive phenotyping. Firstly, RGB images, depth images, and 3D point clouds of maize stems were captured using an RGB-D camera, and precise alignment between the RGB and depth images was achieved. Subsequently, the contours of maize stems were delineated using 2D image processing techniques, followed by the extraction of the stem's skeletal structure employing a thinning-based skeletonization algorithm. Furthermore, within the areas of interest on the maize stems, horizontal lines were constructed using points on the skeletal structure, resulting in 2D pixel coordinates at the intersections of these horizontal lines with the maize stem contours. Subsequently, a back-projection transformation from 2D pixel coordinates to 3D world coordinates was achieved by combining the depth data with the camera's intrinsic parameters. The 3D world coordinates were then precisely mapped onto the 3D point cloud using rigid transformation techniques. Finally, the maize stem diameter was sensed and determined by calculating the Euclidean distance between pairs of 3D world coordinate points. The method demonstrated a Mean Absolute Percentage Error (MAPE) of 3.01%, a Mean Absolute Error (MAE) of 0.75 mm, a Root Mean Square Error (RMSE) of 1.07 mm, and a coefficient of determination (R²) of 0.96, ensuring accurate measurement of maize stem diameter. This research not only provides a new method of precise and efficient crop phenotypic analysis but also offers theoretical knowledge for the advancement of precision agriculture.

8.
Front Hum Neurosci ; 18: 1380739, 2024.
Article En | MEDLINE | ID: mdl-38715702

Objective: This study aims to investigate the influence of the cerebellum on visual selective attention function and its neuromodulatory mechanism in patients with multiple lacunar cerebral infarction (MLCI). Methods: A retrospective analysis was conducted on 210 patients admitted with MLCI from January 2016 to May 2022. Analyzed the electrophysiological characteristics of the P3a and P3b components of vision in both groups, as well as source reconstruction simulations of dipole activation in the brains of the two groups, and analyzed the brain regions with differences in activation strength between the two groups. Results: This study found that there was no significant difference in peak amplitude between the two groups, but compared with the control group, the peak latency of the case group was significantly prolonged. Specifically, the P3a peak latency induced by the novel stimulus was longer than that induced by the target stimulus P3b peak latency. Source reconstruction results showed decreased and increased activation in several brain regions in the case group compared to the control group. Conclusion: The study suggests that the impairment of distracted attention capture is more pronounced in patients with MLCI. The cerebellum indirectly influences the ventral and dorsal frontoparietal attention networks by modulating the levels of excitation and inhibition within the cerebral cortex of the attention network. This may represent a potential mechanism through which the cerebellum regulates visual selective attention information in MLCI patients.

9.
Acta Pharmacol Sin ; 2024 May 08.
Article En | MEDLINE | ID: mdl-38719955

Pulmonary hypertension (PH) is a progressive fatal disease with no cure. Canagliflozin (CANA), a novel medication for diabetes, has been found to have remarkable cardiovascular benefits. However, few studies have addressed the effect and pharmacological mechanism of CANA in the treatment of PH. Therefore, our study aimed to investigate the effect and pharmacological mechanism of CANA in treating PH. First, CANA suppressed increased pulmonary artery pressure, right ventricular hypertrophy, and vascular remodeling in both mouse and rat PH models. Network pharmacology, transcriptomics, and biological results suggested that CANA could ameliorate PH by suppressing excessive oxidative stress and pulmonary artery smooth muscle cell proliferation partially through the activation of PPARγ. Further studies demonstrated that CANA inhibited phosphorylation of PPARγ at Ser225 (a novel serine phosphorylation site in PPARγ), thereby promoting the nuclear translocation of PPARγ and increasing its ability to resist oxidative stress and proliferation. Taken together, our study not only highlighted the potential pharmacological effect of CANA on PH but also revealed that CANA-induced inhibition of PPARγ Ser225 phosphorylation increases its capacity to counteract oxidative stress and inhibits proliferation. These findings may stimulate further research and encourage future clinical trials exploring the therapeutic potential of CANA in PH treatment.

10.
Environ Res ; 252(Pt 3): 119052, 2024 Apr 30.
Article En | MEDLINE | ID: mdl-38697596

Biochar has emerged as a versatile and efficient multi-functional material, serving as both an adsorbent and catalyst in removing emerging pollutants (EPs) from aquatic matrices. However, pristine biochar's catalytic and adsorption capabilities are hindered by its poor surface functionality and small pore size. Addressing these limitations involves the development of functionalized biochar, a strategic approach aimed at enhancing its physicochemical properties and improving adsorption and catalytic efficiencies. Despite a growing interest in this field, there is a notable gap in existing literature, with no review explicitly concentrating on the efficacy of biochar-based functional materials (BCFMs) for removing EPs in aquatic environments. This comprehensive review aims to fill this void by delving into the engineering considerations essential for designing BCFMs with enhanced physiochemical properties. The focus extends to understanding the treatment efficiency of EPs through mechanisms such as adsorption or catalytic degradation. The review systematically outlines the underlying mechanisms involved in the adsorption and catalytic degradation of EPs by BCFMs. By shedding light on the prospects of BCFMs as a promising multi-functional material, the review underscores the imperative for sustained research efforts. It emphasizes the need for continued exploration into the practical implications of BCFMs, especially under environmentally relevant pollutant concentrations. This holistic approach seeks to contribute to advancing knowledge and applying biochar-based solutions in addressing the challenges posed by emerging pollutants in aquatic ecosystems.

11.
Int J Biol Sci ; 20(7): 2403-2421, 2024.
Article En | MEDLINE | ID: mdl-38725848

Ciliogenesis-associated kinase 1 (CILK1) plays a key role in the ciliogenesis and ciliopathies. It remains totally unclear whether CILK1 is involved in tumor progression and therapy resistance. Here, we report that the aberrant high-expression of CILK1 in breast cancer is required for tumor cell proliferation and chemoresistance. Two compounds, CILK1-C30 and CILK1-C28, were identified with selective inhibitory effects towards the Tyr-159/Thr-157 dual-phosphorylation of CILK1, pharmacological inhibition of CILK1 significantly suppressed tumor cell proliferation and overcame chemoresistance in multiple experimental models. Large-scale screen of CILK1 substrates confirmed that the kinase directly phosphorylates ERK1, which is responsible for CILK1-mediated oncogenic function. CILK1 is also indicated to be responsible for the chemoresistance of small-cell lung cancer cells. Our data highlight the importance of CILK1 in cancer, implicating that targeting CILK1/ERK1 might offer therapeutic benefit to cancer patients.


Breast Neoplasms , Cell Proliferation , Drug Resistance, Neoplasm , Humans , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Drug Resistance, Neoplasm/genetics , Female , Phosphorylation , Cell Line, Tumor , Mitogen-Activated Protein Kinase 3/metabolism , Animals , Proto-Oncogene Proteins , MAP Kinase Kinase Kinases
12.
Anal Chem ; 2024 May 10.
Article En | MEDLINE | ID: mdl-38730304

Rapidly identifying and quantifying Gram-positive bacteria are crucial to diagnosing and treating bacterial lower respiratory tract infections (LRTIs). This work presents a field-deployable biosensor for detecting Gram-positive bacteria from exhaled breath condensates (EBCs) based on peptidoglycan recognition using an aptamer. Dielectrophoretic force is employed to enrich the bacteria in 10 s without additional equipment or steps. Concurrently, the measurement of the sensor's interfacial capacitance is coupled to quantify the bacteria during the enrichment process. By incorporation of a semiconductor condenser, the whole detection process, including EBC collection, takes about 3 min. This biosensor has a detection limit of 10 CFU/mL, a linear range of up to 105 CFU/mL and a selectivity of 1479:1. It is cost-effective and disposable due to its low cost. The sensor provides a nonstaining, culture-free and PCR-independent solution for noninvasive and real-time diagnosis of Gram-positive bacterial LRTIs.

13.
Adv Mater ; : e2401585, 2024 May 02.
Article En | MEDLINE | ID: mdl-38696723

The processing of visual information occurs mainly in the retina, and the retinal preprocessing function greatly improves the transmission quality and efficiency of visual information. The artificial retina system provides a promising path to efficient image processing. Here, graphene/InSe/h-BN heterogeneous structure is proposed, which exhibits negative and positive photoconductance (NPC and PPC) effects by altering the strength of a single wavelength laser. Moreover, a modified theoretical model is presented based on the power-dependent photoconductivity effect of laser: I ph = - mP α 1 + nP α 2 ${\rm I}_{\rm ph}\,=\,-{\rm mP}^{\alpha _{1}} + {\rm nP}^{\alpha _{2}}$ , which can reveal the internal physical mechanism of negative/positive photoconductance effects. The present 2D structure design allows the field effect transistor (FET) to exhibit excellent photoelectric performance (RNPC = 1.1× 104 AW-1, RPPC = 13 AW-1) and performance stability. Especially, the retinal pretreatment process is successfully simulated based on the negative and positive photoconductive effects. Moreover, the pulse signal input improves the device responsivity by 167%, and the transmission quality and efficiency of the visual signal can also be enhanced. This work provides a new design idea and direction for the construction of artificial vision, and lay a foundation for the integration of the next generation of optoelectronic devices.

14.
PLoS Comput Biol ; 20(5): e1012024, 2024 May.
Article En | MEDLINE | ID: mdl-38717988

The activation levels of biologically significant gene sets are emerging tumor molecular markers and play an irreplaceable role in the tumor research field; however, web-based tools for prognostic analyses using it as a tumor molecular marker remain scarce. We developed a web-based tool PESSA for survival analysis using gene set activation levels. All data analyses were implemented via R. Activation levels of The Molecular Signatures Database (MSigDB) gene sets were assessed using the single sample gene set enrichment analysis (ssGSEA) method based on data from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), The European Genome-phenome Archive (EGA) and supplementary tables of articles. PESSA was used to perform median and optimal cut-off dichotomous grouping of ssGSEA scores for each dataset, relying on the survival and survminer packages for survival analysis and visualisation. PESSA is an open-access web tool for visualizing the results of tumor prognostic analyses using gene set activation levels. A total of 238 datasets from the GEO, TCGA, EGA, and supplementary tables of articles; covering 51 cancer types and 13 survival outcome types; and 13,434 tumor-related gene sets are obtained from MSigDB for pre-grouping. Users can obtain the results, including Kaplan-Meier analyses based on the median and optimal cut-off values and accompanying visualization plots and the Cox regression analyses of dichotomous and continuous variables, by selecting the gene set markers of interest. PESSA (https://smuonco.shinyapps.io/PESSA/ OR http://robinl-lab.com/PESSA) is a large-scale web-based tumor survival analysis tool covering a large amount of data that creatively uses predefined gene set activation levels as molecular markers of tumors.


Biomarkers, Tumor , Computational Biology , Databases, Genetic , Internet , Neoplasms , Software , Humans , Neoplasms/genetics , Neoplasms/mortality , Survival Analysis , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Computational Biology/methods , Prognosis , Gene Expression Profiling/methods , Gene Expression Regulation, Neoplastic/genetics
16.
Heliyon ; 10(10): e31307, 2024 May 30.
Article En | MEDLINE | ID: mdl-38803884

Objectives: N7-methylguanosine (m7G) plays a crucial role in mRNA metabolism and other biological processes. However, its regulators' function in Primary Sjögren's Syndrome (PSS) remains enigmatic. Methods: We screened five key m7G-related genes across multiple datasets, leveraging statistical and machine learning computations. Based on these genes, we developed a prediction model employing the extreme gradient boosting decision tree (XGBoost) method to assess PSS risk. Immune infiltration in PSS samples was analyzed using the ssGSEA method, revealing the immune landscape of PSS patients. Results: The XGBoost model exhibited high accuracy, AUC, sensitivity, and specificity in both training, test sets and extra-test set. The decision curve confirmed its clinical utility. Our findings suggest that m7G methylation might contribute to PSS pathogenesis through immune modulation. Conclusions: m7G regulators play an important role in the development of PSS. Our study of m7G-realted genes may inform future immunotherapy strategies for PSS.

17.
Heliyon ; 10(10): e31251, 2024 May 30.
Article En | MEDLINE | ID: mdl-38803941

Background and aims: Postoperative atrial fibrillation (POAF) is considered the most prevalent irregular heart rhythm after heart surgery. The cardiac autonomic nervous system significantly affects POAF, and neuropeptide Y (NPY), an abundant neuropeptide in the cardiovascular system, is involved in this autonomic regulation. The current work aimed to examine the potential association of NPY with POAF in individuals administered isolated off-pump coronary artery bypass grafting. Methods: From January 1 to May 31, 2020, we examined consecutive cases administered successful isolated off-pump coronary artery bypass grafting with no previously diagnosed atrial fibrillation (AF). Clinical characteristics and plasma samples were collected before surgery. NPY was quantified by enzyme-linked immunosorbent assay (ELISA) in peripheral blood, and POAF cases were identified through a 7-day Holter monitoring. Results: Among 120 cases with no previously diagnosed AF, 33 (27.5 %) developed POAF during hospitalization. Median NPY levels were markedly elevated in the POAF group in comparison with the sinus rhythm group (31.72 vs. 27.95, P = 0.014). Multivariable logistic regression analysis revealed age (OR = 1.135, 95%CI 1.054-1.223; P = 0.001), left atrial size (OR = 1.136, 95%CI 1.004-1.285; P = 0.043), and NPY levels in peripheral blood (OR = 1.055, 95%CI 1.002-1.111; p = 0.041) independently predicted POAF. Additionally, NPY levels were positively correlated with high-frequency (HF) (r = 0.2774, P = 0.0022) and low-frequency (LF) (r = 0.2095, P = 0.0217) components of heart rate variability. Conclusion: In summary, this study demonstrates an association between elevated NPY levels in peripheral blood before surgery and POAF occurrence.

18.
Dermatology ; 2024 May 24.
Article En | MEDLINE | ID: mdl-38797168

Introduction With the aging of the population in China, the prevalence of atopic dermatitis (AD) is high in the elderly patients. These patients usually have more comorbidities and they need more effective and safer treatments. Dupilumab is an anti-interleukin-4 (IL-4) receptor monoclonal antibody which was approved for the treatment of moderate to severe AD. Objective To investigate the efficacy and safety of dupilumab in elderly patients with moderate to severe AD. Methods A real world retrospective study was conducted. Elderly patients (60 years or older) with moderate-to-severe AD who treated with dupilumab were included. Eczema Area and Severity Index (EASI) score, Peak Pruritus Numerical Rating Scale (PP-NRS), EASI-50, EASI-75 and EASI-50 were evaluated. The efficacy in subgroups was also investigated. Results Fifty-eight patients were enrolled. The EASI score and PP-NRS score were significantly reduced at week 4, 16, 28 and 52 during dupilumab treatments. 91.2% and 79.4% of the patients achieved EASI-50 and EASI-75 at week 16, respectively. This results sustained across 52 weeks. 95.8% and 87.5% patients achieved EASI-50 and EASI-75 at week 52, respectively. Adverse events were reported in 10 (17.2%) patients and no severe adverse event was reported. Male,older age and moderate AD (EASI<21) was related to better efficacy of dupilumab. Conclusions This study demonstrated that dupilumab is an effective and safe treatment in elderly patients with AD.

19.
Clin Exp Pharmacol Physiol ; 51(7): e13875, 2024 Jul.
Article En | MEDLINE | ID: mdl-38797522

N6-methyladenosine (m6A) methylation modification affects the tumorigenesis and metastasis of breast cancer (BC). This study investigated the association between m6A regulator-mediated methylation modification patterns and characterization of the tumour microenvironment in BC, as well as their prognostic importance. Public gene expression data and clinical annotations were collected from The Cancer Genome Atlas (TCGA) database, the Gene Expression Omnibus website and the METABRIC program. We analysed the genetic expression, gene-gene interactions, gene mutations and copy number variations using R software. The data were screened for risk genes using the Cox risk regression model, and we developed an algorithm for risk score and its predictive value. Compared to adjacent normal tissue, we identified 16 differentially expressed m6A regulators in BC, including six writers and 10 readers. Under unsupervised clustering, two distinguished modification patterns were identified, cluster C1 and C2. Compared to m6A cluster C2, cluster C1 was found to be more involved in immune-related pathways, with a relatively higher immune score and stromal score (P < 0.05). Patients were divided into two groups based on their risk scores for survival analysis. The patients in the high-risk score group had significantly worse overall survival than patients in the low-risk score group, (P < 0.0001). The TCGA database validation revealed the same prognostic tendency. In summary, our study showed distinct m6A regulator modification patterns contribute to the immunological heterogeneity and diversity of BC. The development of m6A gene signatures and the m6A score aid in the prognostic prediction of patients with BC.


Adenosine , Breast Neoplasms , Tumor Microenvironment , Humans , Adenosine/analogs & derivatives , Adenosine/metabolism , Adenosine/genetics , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Breast Neoplasms/immunology , Breast Neoplasms/mortality , Female , Tumor Microenvironment/genetics , Tumor Microenvironment/immunology , Gene Expression Regulation, Neoplastic , Methylation , Prognosis , Databases, Genetic
20.
Article En | MEDLINE | ID: mdl-38797757

A simple, low-cost, and highly sensitive method using a modified QuECHERS procedure based on a liquid chromatography-tandem mass spectrometer (LC-MS/MS) was established to simultaneously quantify lufenuron and chlorfenapyr and the corresponding metabolite tralopyril in cabbage for the first time. On the basis of this method, terminal residue and dietary risk of lufenuron and chlorfenapyr in cabbage were investigated. The recoveries of lufenuron, chlorfenapyr, and tralopyril ranged from 88 to 110%, with relative standard deviation of less than 12.4%. The field trial results showed that at the pre-harvest interval (PHI) of 21 days, the terminal residues of lufenuron, chlorfenapyr, and tralopyril in the supervised trials were not higher than 0.02 mg/kg, and the highest detected residue levels of lufenuron, chlorfenapyr, and tralopyril were 0.047, 0.055, and <0.02 mg·kg-1 at 14-day pre-harvest respectively, which were lower than the maximum residue limits (MRLs) for cabbage established in China. For the dietary risk assessment, the national estimated daily intakes (NEDIs) as proportion of acceptable daily intakes (ADIs) were 80.4% and 29.9% for chlorfenapyr and lufenuron respectively indicating an acceptable dietary risk to Chinese population.

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