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Telomere length plays a crucial role in cellular aging and the risk of diseases. Unlike normal cells, cancer cells can extend their own survival by maintaining telomere stability through telomere maintenance mechanism. Therefore, regulating the lengths of telomeres have emerged as a promising approach for anti-cancer treatment. In this study, we introduce a nanoscale octopus-like structure designed to induce physical entangling of telomere, thereby efficiently triggering telomere dysfunction. The nanoscale octopus, composed of eight-armed PEG (8-arm-PEG), are functionalized with cell penetrating peptide (TAT) to facilitate nuclear entry and are covalently bound to N-Methyl Mesoporphyrin IX (NMM) to target G-quadruplexes (G4s) present in telomeres. The multi-armed configuration of the nanoscale octopus enables targeted binding to multiple G4s, physically disrupting and entangling numerous telomeres, thereby triggering telomere dysfunction. Both in vitro and in vivo experiments indicate that the nanoscale octopus significantly inhibits cancer cell proliferation, induces apoptosis through telomere entanglement, and ultimately suppresses tumor growth. This research offers a novel perspective for the development of innovative anti-cancer interventions and provides potential therapeutic options for targeting telomeres.

Asunto(s)

Apoptosis , Telómero , Telómero/metabolismo , Apoptosis/efectos de los fármacos , Humanos , Animales , Línea Celular Tumoral , Ratones , G-Cuádruplex/efectos de los fármacos , Ratones Desnudos , Polietilenglicoles/química , Proliferación Celular/efectos de los fármacos , Ratones Endogámicos BALB C , Neoplasias/patología , Neoplasias/tratamiento farmacológico , Femenino , Péptidos de Penetración Celular/química , Péptidos de Penetración Celular/farmacología , Nanoestructuras/química

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Precise monitoring of biomolecular radiation damage is crucial for understanding X-ray-induced cell injury and improving the accuracy of clinical radiotherapy. We present the design and performance of lanthanide-DNA-origami nanodosimeters for directly visualizing radiation damage at the single-particle level. Lanthanide ions (Tb3+ or Eu3+) coordinated with DNA origami nanosensors enhance the sensitivity of X-ray irradiation. Atomic force microscopy (AFM) revealed morphological changes in Eu3+-sensitized DNA origami upon X-ray irradiation, indicating damage caused by ionization-generated electrons and free radicals. We further demonstrated the practical applicability of Eu3+-DNA-origami integrated chips in precisely monitoring radiation-mediated cancer radiotherapy. Quantitative results showed consistent trends with flow cytometry and histological examination under comparable X-ray irradiation doses, providing an affordable and user-friendly visualization tool for preclinical applications. These findings provide new insights into the impact of heavy metals on radiation-induced biomolecular damage and pave the way for future research in developing nanoscale radiation sensors for precise clinical radiography.

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Background: Collecting and standardizing clinical research data is a very tedious task. This study is to develop an intelligent data collection tool, named CHB-EDC, for real-world cohort studies of chronic hepatitis B (CHB), which can assist in standardized and efficient data collection. Methods: CHB_EDC is capable of automatically processing various formats of data, including raw data in image format, using internationally recognized data standards, OCR, and NLP models. It can automatically populate the data into eCRFs designed in the REDCap system, supporting the integration of patient data from electronic medical record systems through commonly used web application interfaces. This tool enables intelligent extraction and aggregation of data, as well as secure and anonymous data sharing. Results: For non-electronic data collection, the average accuracy of manual collection was 98.65 %, with an average time of 63.64 min to collect information for one patient. The average accuracy CHB-EDC was 98.66 %, with an average time of 3.57 min to collect information for one patient. In the same data collection task, CHB-EDC achieved a comparable average accuracy to manual collection. However, in terms of time, CHB-EDC significantly outperformed manual collection (p < 0.05). Our research has significantly reduced the required collection time and lowered the cost of data collection while ensuring accuracy. Conclusion: The tool has significantly improved the efficiency of data collection while ensuring accuracy, enabling standardized collection of real-world data.

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Biochemical recurrence (BCR) is common in prostate cancer (PCa), and patients with BCR usually have a poor prognosis. Cuproptosis is a unique type of cell death, and copper homeostasis is crucial to the occurrence and development of malignancies. The present study aimed to explore the prognostic value of cuproptosis-related long non-coding RNAs (lncRNAs; CRLs) in PCa and to develop a predictive signature for forecasting BCR in patients with PCa. Using The Cancer Genome Atlas database, transcriptomic, mutation and clinical data were collected from patients with PCa. A total of 121 CRLs were identified using Pearson's correlation coefficient. Subsequently, a 6-CRL signature consisting of AC087276.2, CNNM3-DT, AC090198.1, AC138207.5, METTL14-DT and LINC01515 was created to predict the BCR of patients with PCa through Cox and least absolute shrinkage and selection operator regression analyses. Kaplan-Meier curve analysis demonstrated that high-risk patients had a low BCR-free survival rate. In addition, there was a substantial difference between the high- and low-risk groups in the immune microenvironment, immune therapy, drug sensitivity and tumor mutational burden. A nomogram integrating the Gleason score, 6-CRL signature and clinical T-stage was established and evaluated. Finally, the expression of signature lncRNAs in PCa cells was verified through reverse transcription-quantitative PCR. In conclusion, the 6-CRL signature may be a potential tool for making predictions regarding BCR in patients with PCa, and the prognostic nomogram may be considered a practical tool for clinical decision-making.

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Inhibitor of ß-catenin and T-cell factor (ICAT) is a classical inhibitor of the Wnt signaling pathway. Nonetheless, our previous work found that ICAT is overexpressed in cervical cancer (CC), resulting in the augmentation of migration and invasion capabilities of CC cells. It remains unclear what molecular mechanism underlies this phenomenon. The interaction between cancer cells and the tumor microenvironment (TME) promotes the outgrowth and metastasis of tumors. Tumor-associated macrophages (TAMs) are a major constituent of the TME and have a significant impact on the advancement of CC. Consequently, our inquiry pertains to the potential of ICAT to facilitate tumor development through its modulation of the cervical TME. In this study, we first verified that ICAT regulated the secretion of cytokines interleukin-10 (IL-10) and transforming growth factor-ß (TGF-ß) in CC cells, leading to M2-like macrophage polarization and enhancement of the migration and invasion of CC cells. Furthermore, the system of co-culturing human umbilical vein endothelial cells (HUVECs) with macrophages revealed that depending on the CC cells' overexpression or inhibition of ICAT, the vascular tube formation by HUVECs can be either increased or decreased. Overall, our study indicates that ICAT stimulates M2-like polarization of TAMs via upregulating IL-10 and TGF-ß, which results in increased neovascularization, tumor metastasis, and immunosuppression in CC. In upcoming times, inhibiting crosstalk between CC cells and TAMs may be a possible strategy for CC therapy.

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The aim of this study was to construct the sixth in a series of guidelines on the treatment of urolithiasis by the International Alliance of Urolithiasis (IAU) that by providing a clinical framework for the management of pediatric patients with urolithiasis based on the best available published literature. All recommendations were summarized following a systematic review and assessment of literature in the PubMed database from January 1952 to December 2023. Each generated recommendation was graded using a modified GRADE methodology. Recommendations are agreed upon by Panel Members following review and discussion of the evidence. Guideline recommendations were developed that addressed the following topics: etiology, risk factors, clinical presentation and symptoms, diagnosis, conservative management, surgical interventions, prevention, and follow-up. Similarities in the treatment of primary stone episodes between children and adults, incorporating conservative management and advancements in technology for less invasive stone removal, are evident. Additionally, preventive strategies aiming to reduce recurrence rates, such as ensuring sufficient fluid intake, establishing well-planned dietary adjustments, and selective use pharmacologic therapies will also result in highly successful outcomes in pediatric stone patients. Depending on the severity of metabolic disorders and also anatomical abnormalities, a careful and close follow-up program should inevitably be planned in each pediatric patient to limit the risk of future recurrence rates.

Asunto(s)

Urolitiasis , Humanos , Urolitiasis/terapia , Urolitiasis/diagnóstico , Niño

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Multistate nonadiabatic dynamics combined with Mixed-Reference Spin-Flip Time-Dependent Density Functional Theory (MRSF-TDDFT) were performed to investigate the chemoexcitation dynamics of firefly dioxetanone (FDO- in S0) to oxyluciferin (OxyLH- in S1) and its subsequent decay dynamics. The formation of oxyluciferin occurs within approximately 100 fs and is primarily controlled by oscillatory CO2 decarboxylation. Unexpected radiationless decay from oxyluciferin was also observed, facilitated by intramolecular rotation. Simulations under three thermal conditions reveal that higher initial thermal energy not only enhances the formation of oxyluciferin but also increases radiationless decay by surpassing barriers to the ground state. Conversely, lower thermal energy conditions reduce oxyluciferin formation but suppress radiationless decay. These findings suggest that optimal conditions for higher chemiluminescence quantum yield involve initial high thermal energy to accelerate CO2 decarboxylation and gradual thermal dissipation to prevent intramolecular rotation of oxyluciferin. This approach could enhance the chemiluminescence quantum yield beyond the current limit of 40%, offering significant potential for applications in biological imaging and analytical chemistry.

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BACKGROUND: Gene therapy in bladder cancer (BLCA) remains an area ripe for exploration. Recent studies have highlighted the crucial role of SHTN1 in the initiation and progression of various cancers and SHTN1 may have interacted with the FGFR gene. However, its specific function in BLCA remains unclear. MATERIALS AND METHODS: We investigated the association between SHTN1 expression and prognosis, immune infiltration, and the tumor microenvironment (TME) across multiple malignancies using 433 BLCA samples from The Cancer Genome Atlas (TCGA). Differential gene expression analysis, functional annotation via Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were performed for SHTN1-related genes by using R packages. Immune response and TME scores, along with drug sensitivity profiles of SHTN1, were analyzed using R packages. Immunohistochemistry (IHC) and western blotting were conducted to assess SHTN1 expression in surgical specimens from BLCA patients.CCK8 assay and cells wound healing assay were performed.The bioinformatics was analyzed by R software. Significant differences were evaluated using unpaired t test. RESULTS: SHTN1 expression levels were significantly elevated in BLCA associated with poor prognosis (p < 0.01). Receiver operating characteristic (ROC) curves and nomograms demonstrated the diagnostic and prognostic efficacy of SHTN1 in BLCA. Notably, SHTN1 expression was higher in high-grade BLCA compared to lower-grade (p = 5.6e-10), a finding corroborated by IHC and western blotting. Pathway enrichment analysis revealed significant involvement of the Neuroactive ligand-receptor interaction and Chemical carcinogenesis - DNA adducts signaling pathways among SHTN1 differentially expressed genes. In terms of immune infiltration, T cells CD8, T cells follicular helper, and dendritic cells were predominant in the SHTN1 low-expression group, whereas macrophages M0 and M2, and mast cells were predominant in the high-expression group. Multivariate Cox regression analysis identified SHTN1 as an independent prognostic factor for overall survival (HR = 2.93; 95 % CI = 1.40-6.13; p = 0.004).CCK8 and wound healing experiments showed that SHTN1 knockdown reduced the cell proliferation and migration. Western blot showed that the EMT pathway was clearly associated with SHTN1. CONCLUSIONS: Our findings suggest that SHTN1 holds promise as a prognostic and diagnostic biomarker for BLCA. Moreover, it is closely associated with elevated immune infiltration and distinct characteristics of the tumor microenvironment in BLCA.

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BACKGROUND: Lung adenocarcinoma (LUAD) is a fatal disease with metabolic abnormalities. The dysregulation of S100 calcium-binding protein A2 (S100A2), a member of the S100 protein family, is connected to the development of various cancers. The impact of S100A2 on the LUAD occurrence and metastasis, however, has not yet been reported. The functional mechanism of S100A2 on LUAD cell metastasis was examined in this article. METHODS: The expression of TFAP2A and S100A2 in LUAD tissues and cells was analyzed by bioinformatics and qRT-PCR, respectively. The enrichment pathway analysis was performed on S100A2. Bioinformatics analysis determined the binding relationship between TFAP2A and S100A2, and their interaction was validated through dual-luciferase and chromatin immunoprecipitation experiments. Cell viability was determined using cell counting kit-8 (CCK-8). A transwell assay was performed to analyze the invasion and migration of cells. Immunofluorescence was conducted to obtain vimentin and E-cadherin expression, and a western blot was used to detect the expression of MMP-2, MMP-9, GLS, and GLUD1. The kits measured the NADPH/NADP ratio, glutathione (GSH)/glutathione disulfide (GSSG) levels, and the contents of glutamine, α-KG, and glutamate. RESULTS: S100A2 was upregulated in LUAD tissues and cells, and S100A2 mediated glutamine metabolism to induce LUAD metastasis. Additionally, the transcriptional regulator TFAP2A was discovered upstream of S100A2, and TFAP2A expression was upregulated in LUAD, which indicated that TFAP2A promoted the S100A2 expression. The rescue experiment found that upregulation of S100A2 could reverse the inhibitory effects of silencing TFAP2A on glutamine metabolism and cell metastasis. CONCLUSION: In conclusion, by regulating glutamine metabolism, the TFAP2A/S100A2 axis facilitated LUAD metastasis. This suggested that targeting S100A2 could be beneficial for LUAD treatment.

Asunto(s)

Adenocarcinoma del Pulmón , Glutamina , Neoplasias Pulmonares , Proteínas S100 , Factor de Transcripción AP-2 , Humanos , Factor de Transcripción AP-2/metabolismo , Factor de Transcripción AP-2/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundario , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/secundario , Glutamina/metabolismo , Proteínas S100/metabolismo , Proteínas S100/genética , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral , Movimiento Celular , Metástasis de la Neoplasia , Masculino , Regulación hacia Arriba , Femenino , Proliferación Celular , Factores Quimiotácticos

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The traditional formulation Hanchuan zupa granules (HCZPs) have been widely used for controlling coronavirus disease 2019 (COVID-19). However, its active components remain unknown. Here, HCZP components targeting the spike receptor-binding domain (S-RBD) of SARS-CoV-2 were investigated using a surface plasmon resonance (SPR) biosensor-based active ingredient recognition system (SPR-AIRS). Recombinant S-RBD proteins were immobilized on the SPR chip by amine coupling for the prescreening of nine HCZP medicinal herbs. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) identified gallic acid (GA) and methyl gallate (MG) from Rosa rugosa as S-RBD ligands, with KD values of 2.69 and 0.95 µM, respectively, as shown by SPR. Molecular dynamics indicated that GA formed hydrogen bonds with G496, N501, and Y505 of S-RBD, and MG with G496 and Y505, inhibiting S-RBD binding to angiotensin-converting enzyme 2 (ACE2). SPR-based competition analysis verified that both compounds blocked S-RBD and ACE2 binding, and SPR demonstrated that GA and MG bound to ACE2 (KD = 5.10 and 4.05 µM, respectively), suggesting that they blocked the receptor and neutralized SARS-CoV-2. Infection with SARS-CoV-2 pseudovirus showed that GA and MG suppressed viral entry into 293T-ACE2 cells. These S-RBD inhibitors have potential for drug design, while the findings provide a reference on HCZP composition and its use for treating COVID-19.

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Bladder cancer (BC), the predominant urological malignancy in men, exhibits complex molecular underpinnings contributing to its progression. This investigation aims to elucidate the expression dynamics of calcium-binding protein 39 (CAB39) in both healthy and cancerous tissues and to explore its functional role in the epithelial-mesenchymal transition (EMT) within human bladder cancer contexts. Utilizing immunohistochemistry and quantitative reverse transcription analyses, we assessed CAB39 expression across BC specimens and cell lines. Further, we implemented wound healing, cell invasion, and CCK-8 proliferation assays in CAB39-knockdown cell lines, alongside a nude mouse xenograft model, to gauge the impact of diminished CAB39 expression on the invasive, migratory, and proliferative capacities of BC cells. Our gene set enrichment analysis probed into the repertoire of genes augmented by increased CAB39 expression in BC cells, with subsequent validation via western blotting. Our findings reveal a pronounced overexpression of CAB39 in both BC tissues and cellular models, inversely correlated with disease prognosis. Remarkably, the oncogenic trajectory of bladder cancer was mitigated upon the establishment of shRNA-mediated CAB39 knockdown in vitro and in vivo, effectively reversing the cancer's invasive and metastatic behaviors and curbing tumorigenesis in xenograft models. Hence, CAB39 emerges as a critical biomarker for bladder cancer progression, significantly implicated in facilitating EMT via the upregulation of neural cadherin (N-cadherin) and the suppression of epithelial cadherin through NF-κB signaling pathways. CU-T12-9 effectively overturned the downregulation of p65-NF-kB and N-cadherin, key elements involved in EMT and cell motility, induced by CAB39 knockdown. This study underscores CAB39's pivotal role in bladder cancer pathophysiology and its potential as a therapeutic target.

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Purpose: This retrospective study was to investigate the efficacy of Gasserian ganglion pulsed radiofrequency therapy (PRF) combined with low-dose morphine injection in the treatment of refractory ophthalmic herpetic neuralgia. Patients and methods: A total of 40 intractable ophthalmic herpetic neuralgia patients who received Gasserian ganglion PRF therapy in Pain Department of Nanjing Drum Tower Hospital were retrospectively analysed, with an average age of 70.2 ± 8.5 years and an average disease course of 30 (30, 60) days. According to different interventions, they were divided into two groups: Group A, 19 patients who received Gasserian ganglion PRF therapy combined with 0.2 mg morphine injection via puncture needle; Group B, 21 patients who received only Gasserian ganglion PRF therapy. Data related to the length of hospital stay and associated costs, numerical rating scale scores (NRS), intravenous morphine and oral oxycodone doses during hospitalization, Short form McGill pain questionnaire and Pittsburgh sleep quality index (PSI), and conditions of opioid use and postherpetic neuralgia after discharge were collected in the two groups. SPSS 25.0 was used to perform statistical analysis on data. Results: The hospital stay, hospitalization costs, and oxycodone dosages for Group A were lower than those for Group B (p = 0.02, p = 0.015 and p = 0.023, respectively). The proportion of patients in group A still taking oral opioids 1 month after discharge and experiencing postherpetic neuralgia 6 months after the onset was lower than that in group B (p = 0.004 and p = 0.049). The NRS upon discharge, as well as the McGill and PSQI scores at the time of discharge and at 1, 3, 6 and 12 months post-discharge, were all significantly reduced compared to those measured upon admission in two groups (p = 0.000). Conclusion: Gasserian ganglion PRF therapy combined with low-dose morphine injection offers an alternative option for managing intractable herpetic neuralgia and prevention of postherpetic neuralgia in ocular branches. Clinical Trial Registration: ChiCTR2300073281.

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BACKGROUND: Evidence from various cohort studies indicate a potential association between depressive disorder and benign prostatic hyperplasia (BPH), yet findings are inconsistent. This study employs bidirectional two-sample Mendelian randomisation (MR) analysis to explore the causal relationship between BPH and major depressive disorder (MDD). METHODS: Genetic variants strongly associated with MDD were extracted as instrumental variables conducted by the Psychiatric Genomics Consortium (PGC). Two sets of genetic variants associated with BPH were extracted from the recent FinnGen and Medical Research Council-Integrative Epidemiology Unit Consortium of BPH as the discovery and replication stages, respectively. Bidirectional MR analysis employed methods such as inverse variance weighted, MR-Egger, weighted median, maximum likelihood, and weighted mode. The inverse variance weighted method was primarily used to evaluate the causal relationship. RESULTS: MR analysis in both the discovery and replication stages showed a significant causal relationship between MDD and the risk of BPH (discovery stages, odds ratio (OR) = 1.1146, 95% CI 1.0058-1.2353, P = 0.03852; replication stage, OR: 1.0042, 95% CI 1.0019-1.0065, P = 0.0004). No causal relationship was found between BPH and MDD risk in the reverse MR analysis. CONCLUSIONS: Our findings highlight a significant association between MDD and an increased risk of BPH development. Further investigation is needed to elucidate the underlying mechanisms linking depression and BPH.

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OBJECTIVE: This study aimed to verify if intraoperative radiotherapy (IORT) can achieve the same survival outcome as whole-breast external beam radiotherapy (EBRT) in early breast cancer after breast-conserving surgery (BCS), and to explore the suitable candidates that can safely receive IORT after BCS. METHODS: Eligible post-BCS patients who received IORT or EBRT were included in the Surveillance, Epidemiology and End Results (SEER) database from 2010 to 2018. Risk factors that affected 5-year overall survival (OS) or breast cancer specific survival (BCSS) were identified by Cox proportional hazards regression analysis. Clinical characteristics, OS, and BCSS were comparatively analyzed between the two treatment modalities. RESULTS: The survival analysis after propensity score matching confirmed that patients who received IORT (n = 2200) had a better 5-year OS than those who received EBRT (n = 2200) (p = 0.015). However, the two groups did not differ significantly in 5-year BCSS (p = 0.381). This feature persisted even after multivariate analyses that took into account numerous clinical characteristics. Although there was no significant difference in BCSS between different subgroups of patients treated with IORT or EBRT, patients over 55 years of age, with T1, N0, non-triple negative breast cancers, hormone receptor-positive, and histologic grade II showed a better OS after receiving IORT. CONCLUSION: In low-risk, early-stage breast cancer, IORT was not inferior to EBRT considering 5-year BCSS and OS. Considering the equivalent clinical outcome but less radiotoxicity, IORT might be a reasonable alternative to EBRT in highly selective patients undergoing BCS.

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Neoplasias de la Mama , Mastectomía Segmentaria , Programa de VERF , Humanos , Femenino , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Persona de Mediana Edad , Anciano , Radioterapia Adyuvante/métodos , Cuidados Intraoperatorios/métodos , Adulto , Puntaje de Propensión , Estudios Retrospectivos , Resultado del Tratamiento

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Childhood asthma is one of the most common respiratory diseases with rising mortality and morbidity. The multi-omics data is providing a new chance to explore collaborative biomarkers and corresponding diagnostic models of childhood asthma. To capture the nonlinear association of multi-omics data and improve interpretability of diagnostic model, we proposed a novel deep association model (DAM) and corresponding efficient analysis framework. First, the Deep Subspace Reconstruction was used to fuse the omics data and diagnostic information, thereby correcting the distribution of the original omics data and reducing the influence of unnecessary data noises. Second, the Joint Deep Semi-Negative Matrix Factorization was applied to identify different latent sample patterns and extract biomarkers from different omics data levels. Third, our newly proposed Deep Orthogonal Canonical Correlation Analysis can rank features in the collaborative module, which are able to construct the diagnostic model considering nonlinear correlation between different omics data levels. Using DAM, we deeply analyzed the transcriptome and methylation data of childhood asthma. The effectiveness of DAM is verified from the perspectives of algorithm performance and biological significance on the independent test dataset, by ablation experiment and comparison with many baseline methods from clinical and biological studies. The DAM-induced diagnostic model can achieve a prediction AUC of 0.912, which is higher than that of many other alternative methods. Meanwhile, relevant pathways and biomarkers of childhood asthma are also recognized to be collectively altered on the gene expression and methylation levels. As an interpretable machine learning approach, DAM simultaneously considers the non-linear associations among samples and those among biological features, which should help explore interpretative biomarker candidates and efficient diagnostic models from multi-omics data analysis for human complex diseases.

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The duck gastrointestinal tract (GIT) harbors an abundance of microorganisms that play an important role in duck health and production. Here, we constructed the first relatively comprehensive duck gut microbial gene catalog (24 million genes) and 4437 metagenome-assembled genomes using 375 GIT metagenomic samples from four different duck breeds across five intestinal segments under two distinct rearing conditions. We further characterized the intestinal region-specific microbial taxonomy and their assigned functions, as well as the temporal development and maturation of the duck gut microbiome. Our metagenomic analysis revealed the similarity within the microbiota of the foregut and hindgut compartments, but distinctive taxonomic and functional differences between distinct intestinal segments. In addition, we found a significant shift in the microbiota composition of newly hatched ducks (3 days), followed by increased diversity and enhanced stability across growth stages (14, 42, and 70 days), indicating that the intestinal microbiota develops into a relatively mature and stable community as the host duck matures. Comparing the impact of different rearing conditions (with and without water) on duck cecal microbiota communities and functions, we found that the bacterial capacity for lipopolysaccharide biosynthesis was significantly increased in ducks that had free access to water, leading to the accumulation of pathogenic bacteria and antibiotic-resistance genes. Taken together, our findings expand the understanding of the microbiome signatures linked to intestinal regional, temporal development, and rearing conditions in ducks, which highlight the significant impact of microbiota on poultry health and production.

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Egg production is an important economic trait in layer ducks and understanding the genetics basis is important for their breeding. In this study, a genome-wide association study (GWAS) for egg production traits in 303 female Longyan Shan-ma ducks was performed based on a genotyping-by-sequencing strategy. Sixty-two single nucleotide polymorphisms (SNPs) associated with egg weight traits were identified (P < 9.48 × 10-5), including 8 SNPs at 5% linkage disequilibrium (LD)-based Bonferroni-corrected genome-wide significance level (P < 4.74 × 10-6). One hundred and nineteen SNPs were associated with egg number traits (P < 9.48 × 10-5), including 13 SNPs with 5% LD-based Bonferroni-corrected genome-wide significance (P < 4.74 × 10-6). These SNPs annotated 146 target genes which contained known candidate genes for egg production traits, such as prolactin and prolactin releasing hormone receptor. This study identified that these associated genes were significantly enriched in egg production-related pathways (P < 0.05), such as the oxytocin signaling, MAPK signaling, and calcium signaling pathways. It was notable that 18 genes were differentially expressed in ovarian tissues between higher and lower egg production in Shan-ma ducks. The identified potential candidate genes and pathways provide insight into the genetic basis underlying the egg production trait of layer ducks.

Asunto(s)

Patos , Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido Simple , Animales , Patos/genética , Patos/fisiología , Femenino , Estudio de Asociación del Genoma Completo/veterinaria , Óvulo/fisiología

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Pekin ducks and Shaoxing ducks are 2 Chinese local duck breeds, both domesticated from mallard, but after domestication and long-term artificial selection, the body weight of Pekin ducks is significantly higher than that of Shaoxing ducks. It is no debate that genetic factors are the main factors responsible for this difference, but whether intestinal microbiota contribute to this difference is yet unknown. Thus, we performed comparative intestinal metagenomics and metabolomics analysis between Pekin ducks and Shaoxing ducks. We found obvious differentiation of intestinal metagenome and metabolome between the 2 breeds. Four cecal microbial genera, including Fusobacterium, Methanobrevibacter, Butyricicoccus, and Anaerotignum showed higher abundance in Pekin ducks. Among them, Methanobrevibacter and Butyricicoccus may positively correlate with fat deposition and body weight. A total of 310 metabolites showed difference between the 2 breeds. Functions of these differential metabolites were mainly enriched in amino acid metabolism, including energy metabolism-related histidine metabolism. Integrated omics analysis showed that microbial changes were closely related to altered metabolites. Especially, Butyricicoccus showing higher abundance in Pekin ducks was significantly negatively correlated with D-glucosamine-6-phosphate, which has been reported to prevent body weight gains. These findings may contribute to further understand the difference in body weight between Pekin ducks and Shaoxing ducks.

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Patos , Microbioma Gastrointestinal , Animales , Metaboloma , Metabolómica , Metagenoma , Metagenómica , Bacterias/clasificación , Bacterias/genética , Bacterias/metabolismo , Bacterias/aislamiento & purificación

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Objective: There is suggestive data indicating a correlation among dietary protein intake and the progression of chronic kidney disease (CKD). Nonetheless, the exact associations between dietary protein intake and the incidence of CKD have remained uncertain. We performed the first meta-analysis to explore the correlation among total protein, plant protein, animal protein intake and CKD risk. Methods: The study conformed the PRISMA statement guidelines. We comprehensively searched PubMed, Web of Science, and Embase until to December 2023. The retrieved studies underwent rigorous evaluation for eligibility, and relevant data were meticulously extracted. The Newcastle-Ottawa Scale (NOS) tool was applied to evaluate the risk of bias. Subsequently, relevant data were extracted and pooled to evaluate the relations among dietary protein intake and CKD incidence. Results: Totally, 6,191 articles were identified, six studies were eligible. A total of 148,051 participants with 8,746 CKD cases were included. All studies had a low overall risk of bias. Higher total, plant and animal protein intake were all correlated with decreased CKD incidence, pooled risk ratios (RRs) and 95% confidence intervals (CIs) were as follows: (RR = 0.82, 95% CI = 0.71-0.94, p = 0.005; I2 = 38%, p = 0.17); (RR = 0.77, 95% CI = 0.61-0.97, p = 0.03; I2 = 77%, p = 0.001); (RR = 0.86, 95% CI = 0.76-0.97, p = 0.02; I2 = 0%, p = 0.59), respectively. For fish and seafood within animal protein: RR = 0.84, 95% CI = 0.74-0.94. Subgroup analysis showed that geographical region, sample size, follow-up time, not assessing protein by food frequency questionnaire, using %energy as the measurement index, not adjusting for several covariates may be the sources of heterogeneity for plant protein. A significant non-linear relation among plant protein and incident CKD was observed by dose-response analysis. Conclusion: The data showed a lower CKD risk significantly associated higher-level dietary total, plant or animal protein (especially for fish and seafood) intake. Further prospective studies demonstrating the correlations of precise sources, intake and duration of dietary protein and incident CKD are warranted.

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BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare genetic disorder stemming from ferrochelatase gene mutations, which leads to abnormal accumulation of protoporphyrin IX primarily in erythrocytes, skin, bone marrow and liver. Although porphyria-related severe liver damage is rare, its consequences can be severe with limited treatment options. CASE SUMMARY: This case study highlights a successful intervention for a 35-year-old male with EPP-related liver impairment, employing a combination of red blood cell (RBC) exchange and therapeutic plasma exchange (TPE). The patient experienced significant symptom relief and a decrease in bilirubin levels following multiple PE sessions and an RBC exchange. CONCLUSION: The findings suggest that this combined approach holds promise for managing severe hepatic impairment in EPP.