Extralobar pulmonary sequestration in children with abdominal pain: Four case reports.

BACKGROUND: Extralobar pulmonary sequestration (ELS) with torsion is extremely rare, consequently, the diagnosis of ELS with torsion in children presents a challenge for clinicians. Herein, we report four cases of ELS with torsion that presented with abdominal pain, and further review the relevant literature to summarize the clinical features. CASE SUMMARY: Four children presented to our department with abdominal pain. All underwent chest computed tomography, which revealed an intrathoracic soft tissue mass with pleural effusion. All four children underwent thoracoscopic resection of the identified pulmonary sequestration, and the vascular pedicle was clipped and excised. None of the patients experienced any postoperative complications. CONCLUSION: Clinicians should consider the possibility of ELS with torsion in children presenting with abdominal pain as the chief complaint.

Multiomics analysis reveal the impact of 17α-Ethinylestradiol on mortality in juvenile zebrafish.

17α-Ethinylestradiol (EE2) is known for its endocrine-disrupting effects on embryonic and adult fish. However, its impact on juvenile zebrafish has not been well established. In this study, juvenile zebrafish were exposed to EE2 at concentrations of 5 ng/L (low dose, L), 10 ng/L (medium dose, M), and 50 ng/L (high dose, H) from 21 days post-fertilization (dpf) to 49 dpf. We assessed their growth, development, behavior, transcriptome, and metabolome. The findings showed that the survival rate in the EE2-H group was 66.8 %, with all surviving fish displaying stunted growth and swollen, transparent abdomens by 49 dpf. Moreover, severe organ deformities were observed in the gills, kidneys, intestines, and heart of fish in both the EE2-H and EE2-M groups. Co-expression analysis of mRNA and lncRNA revealed that EE2 downregulated the transcription of key genes involved in the cell cycle, DNA replication, and Fanconi anemia signaling pathways. Additionally, metabolomic analysis indicated that EE2 influenced metabolism and development-related signaling pathways. These pathways were also significantly identified based on the genes regulated by lncRNA. Consequently, EE2 induced organ deformities and mortality in juvenile zebrafish by disrupting signaling pathways associated with development and metabolism. The results of this study offer new mechanistic insights into the adverse effects of EE2 on juvenile zebrafish based on multiomics analysis. The juvenile zebrafish are highly sensitive to EE2 exposure, which is not limited to adult and embryonic stages. It is a potential model for studying developmental toxicity.

Manganese(III) dominants the mobilization of phosphorus in reducing sediments: Evidence from Aha reservoir, Southwest China.

Eutrophication has become one of the greatest threats to aquatic ecosystems. The release of phosphorus (P) from sediments exerts a critical role on eutrophication level. Both manganese (Mn) and iron (Fe), sensitive to redox conditions, own strong affinity for P. Numerous works have demonstrated that Fe was a key factor to drive P cycle in sediments. However, the role of Mn on P mobilization remains largely unexplored. Herein, the mechanism of P mobilization driven by Mn were investigated in a seasonal anoxic reservoir. Diffusive gradients in thin films (DGT) results, from both field investigations and laboratory incubations, showed P was synchronously distributed and significantly positive correlated (r2 ≥ 0.40, p < 0.01) with Mn, suggested that P cycle was associated with Mn. X-ray photoelectron spectroscopy (XPS) results showed that in the outer layers at the top 1 cm sediment pellet the contents of Mn and P occurred significantly synchronize changed, while that of Fe remains virtually unchanged when oxygen conditions changed. This demonstrated that Mn is likely to be the key factor affect P cycle. Most importantly, the relative content of Mn(III) changed the most (≈20 %) interpreted that Mn(III) is the key Mn species dominants the P mobilization. Furthermore, Dual-Beam scanning electron microscope (DB-SEM) maps clearly showed the co-enrichment of P and Mn in oxic sediments, confirmed P was mainly hosted by Mn minerals. In contrast, the random distributions and weak or negative correlations between P and Fe implied that P cycle was decouple with Fe, this resulted from that Fe was almost deposited as inert Fe fractions (>99.2 %) in reducing sediments. This study significantly expanded our knowledge on the geochemical behavior of P influenced by Mn in aquatic sediments.

OligoFormer: An accurate and robust prediction method for siRNA design.

MOTIVATION: RNA interference (RNAi) has become a widely used experimental approach for post-transcriptional regulation and is increasingly showing its potential as future targeted drugs. However, the prediction of highly efficient siRNAs (small interfering RNA) is still hindered by dataset biases, the inadequacy of prediction methods, and the presence of off-target effects. To overcome these limitations, we propose an accurate and robust prediction method, OligoFormer, for siRNA design. RESULTS: OligoFormer comprises three different modules including thermodynamic calculation, RNA-FM module, and Oligo encoder. Oligo encoder is the core module based on the transformer encoder. Taking siRNA and mRNA sequences as input, OligoFormer can obtain thermodynamic parameters, RNA-FM embedding, and Oligo embedding through these three modules, respectively. We carefully benchmarked OligoFormer against 6 comparable methods on siRNA efficacy datasets. OligoFormer outperforms all the other methods, with an average improvement of 9% in AUC, 6.6% in PRC, 9.8% in F1 score, and 5.1% in PCC compared to the best method among them in our inter-dataset validation. We also provide a comprehensive pipeline with prediction of siRNA efficacy and off-target effects using PITA score and TargetScan score. The ablation study shows RNA-FM module and thermodynamic parameters improved the performance and accelerated convergence of OligoFormer. The saliency maps by gradient backpropagation and base preference maps show certain base preferences in initial and terminal region of siRNAs. AVAILABILITY AND IMPLEMENTATION: The source code of OligoFormer is freely available on GitHub at: Https://github.com/lulab/OligoFormer. Docker image of OligoFormer is freely available on the docker hub at https://hub.docker.com/r/yilanbai/oligoformer. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Engineering an Epoxide Hydrolase for Chemoenzymatic Asymmetric Synthesis of Chiral Triazole Fungicide (S)- and (R)-Flutriafol.

Flutriafol, a globally utilized triazole fungicide in agriculture, is typically applied as a racemic mixture, but its enantiomers differ in bioactivity and environmental impact. The synthesis of flutriafol enantiomers is critically dependent on chiral precursors: 2,2-bisaryl-substituted oxirane [(2-fluorophenyl)-2-(4-fluorophenyl)oxirane, 1a] and 1,2-diol [1-(2-fluorophenyl)-1-(4-fluorophenyl)ethane-1,2-diol, 1b]. Here, we engineered a Rhodotorula paludigensis epoxide hydrolase (RpEH), obtaining mutant Escherichia coli/RpehH336W/L360F with a 6.4-fold enhanced enantiomeric ratio (E) from 5.5 to 35.4. This enabled a gram-scale resolution of rac-1a by E. coli/RpehH336W/L360F, producing (S)-1a (98.2% ees) and (R)-1b (75.0% eep) with 44.3 and 55.7% analytical yields, respectively. As follows, chiral (S)-flutriafol (98.2% ee) and (R)-flutriafol (75.0% ee) were easily synthesized by a one-step chemocatalytic process from (S)-1a and a two-step chemocatalytic process from (R)-1b, respectively. This chemoenzymatic approach offers a superior alternative for the asymmetric synthesis of flutriafol enantiomers. Furthermore, molecular dynamics simulations revealed insight into the enantioselectivity improvement of RpEH toward bulky 2,2-bisaryl-substituted oxirane 1a.

Protective effect of ferulic acid-hyaluronic acid copolymer against UVB irradiation in a human HaCaT cell line.

Excessive UVB exposure increased the production of reactive oxygen species (ROS), leading to oxidative damage and epidermal inflammation. To enhance UVB protection effect, a strong phenolic antioxidant, ferulic acid (FA) was designed onto HA via a free radical mediated method. Our previous work has confirmed its structural characterization and in vitro antioxidant. The aim of this study was to evaluate its protective effects against UVB-induced damage in human HaCaT cells. We observed a significant reduction in cell viability to 57.43 % following UVB exposure at a dose of 80 mJ/cm2. However, pretreatment with FA-HA (250 to 2000 µg·mL-1) significantly attenuated cytotoxicity in a dose-dependent manner. Furthermore, FA-HA was found to suppress the intracellular generation of ROS and up-regulated the expression of the antioxidant enzyme superoxide dismutase (SOD). The elevated levels of pro-inflammatory cytokines, including interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) as well as the mRNA expression of matrix metalloproteinase-1/9 (MMP-1/9) induced by UVB irradiation, were also effectively reduced by FA-HA. Additionally, FA-HA treatment decreases the phosphorylation of mitogen-activated protein kinase (MAPK) and activator protein-1 (AP-1), ultimately preventing apoptosis. These findings suggest that FA-HA is a promising candidate for UVB protection in skincare formulations.

Analytical Methods to Evaluate RNA Circularization Efficiency.

Circular RNAs (circRNAs) have emerged as pivotal players in RNA therapeutics. Unlike linear counterparts, circRNAs possess a closed-loop structure, conferring them with enhanced stability and resistance to degradation. Ribozyme-based strategy stands out as the predominant method for synthetic circRNA production, by precisely cleaving and promoting the formation of a covalent circular structure. However, there is still a lack of analytical methods that can provide high-throughput and quantitative analysis to facilitate the circRNA vector engineering process. In the report, we detail analytical methods to characterize and evaluate ribozyme-based RNA circularization efficiency. Our approach will capture the attention of researchers interested in optimizing RNA circularization efficiency, as well as those focused on exploring key elements for ribozyme catalytic activity.

Epigenetic modifications of inflammation in spinal cord injury.

Spinal cord injury (SCI) is a central nervous system injury that leads to neurological dysfunction or paralysis, which seriously affects patients' quality of life and causes a heavy social and economic burden. The pathological mechanism of SCI has not been fully revealed, resulting in unsatisfactory clinical treatment. Therefore, more research is urgently needed to reveal its precise pathological mechanism. Numerous studies have shown that inflammation is closely related to various pathological processes in SCI. Inflammatory response is an important pathological process leading to secondary injury, and sustained inflammatory response can exacerbate the injury and hinder the recovery of neurological function after injury. Epigenetic modification is considered to be an important regulatory mechanism in the pathological process of many diseases. Epigenetic modification mainly affects the function and characteristics of genes through the reversibility of mechanisms such as DNA methylation, histone modification, and regulation of non-coding RNA, thus having a significant impact on the pathological process of diseases and the survival state of the body. Recently, the role of epigenetic modification in the inflammatory response of SCI has gradually entered the field of view of researchers, and epigenetic modification may be a potential means to treat SCI. In this paper, we review the effects and mechanisms of different types of epigenetic modifications (including histone modifications, DNA methylation, and non-coding RNAs) on post-SCI inflammation and their potential therapeutic effects on inflammation to improve our understanding of the secondary SCI stage. This review aims to help identify new markers, signaling pathways and targeted drugs, and provide theoretical basis and new strategies for the diagnosis and treatment of SCI.

Nickel-Molybdenum-Based Three-Dimensional Nanoarrays for Oxygen Evolution Reaction in Water Splitting.

Water splitting is an important approach to hydrogen production. But the efficiency of the process is always controlled by the oxygen evolution reaction process. In this study, a three-dimensional nickel-molybdenum binary nanoarray microstructure electrocatalyst is successfully synthesized. It is grown uniformly on Ni foam using a hydrothermal method. Attributed to their unique nanostructure and controllable nature, the Ni-Mo-based nanoarray samples show superior reactivity and durability in oxygen evolution reactions. The series of Ni-Mo-based electrocatalysts presents a competitive overpotential of 296 mV at 10 mA·cm-2 for an OER in 1.0 M KOH, corresponding with a low Tafel slope of 121 mV dec-1. The three-dimensional nanostructure has a large double-layer capacitance and plenty of channels for ion transfer, which demonstrates more active sites and improved charge transmission. This study provides a valuable reference for the development of non-precious catalysts for water splitting.

Enhanced tooth bleaching with a hydrogen peroxide/titanium dioxide gel.

BACKGROUND: This study aimed to explore the effects of the titanium dioxide (TiO2) concentration and particle size in hydrogen peroxide (HP) on tooth bleaching effectiveness and enamel surface properties. METHODS: TiO2 at different concentrations and particle sizes was incorporated into 40% HP gel to form an HP/TiO2 gel. The specimens were randomly divided into 8 groups: C1P20: HP + 1% TiO2 (20 nm); C3P20: HP + 3% TiO2 (20 nm); C5P20: HP + 5% TiO2 (20 nm); C1P100: HP + 1% TiO2 (100 nm); C3P100: HP + 3% TiO2 (100 nm); C5P100: HP + 5% TiO2 (100 nm); C0: HP with LED; and C0-woL: HP without LED. Bleaching was conducted over 2 sessions, each lasting 40 min with a 7-day interval. The color differences (ΔE00), whiteness index for dentistry (WID), surface microhardness, roughness, microstructure, and composition were assessed. RESULTS: The concentration and particle size of TiO2 significantly affected ΔE00 and ΔWID values, with the C1P100 group showing the greatest ΔE00 values and C1P100, C3P100, and C5P100 groups showing the greatest ΔWID values (p < 0.05). No significant changes were observed in surface microhardness, roughness, microstructure or composition (p > 0.05). CONCLUSIONS: Incorporating 1% TiO2 with a particle size of 100 nm into HP constitutes an effective bleaching strategy to achieve desirable outcomes.

APOE ε4-associated downregulation of the IL-7/IL-7R pathway in effector memory T cells: Implications for Alzheimer's disease.

INTRODUCTION: The apolipoprotein E (APOE) ε4 allele exerts a significant influence on peripheral inflammation and neuroinflammation, yet the underlying mechanisms remain elusive. METHODS: The present study enrolled 54 patients diagnosed with late-onset Alzheimer's disease (AD; including 28 APOE ε4 carriers and 26 non-carriers). Plasma inflammatory cytokine concentration was assessed, alongside bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) analysis of peripheral blood mononuclear cells (PBMCs). RESULTS: Plasma tumor necrosis factor α, interferon γ, and interleukin (IL)-33 levels increased in the APOE ε4 carriers but IL-7 expression notably decreased. A negative correlation was observed between plasma IL-7 level and the hippocampal atrophy degree. Additionally, the expression of IL-7R and CD28 also decreased in PBMCs of APOE ε4 carriers. ScRNA-seq data results indicated that the changes were mainly related to the CD4+ Tem (effector memory) and CD8+ Tem T cells. DISCUSSION: These findings shed light on the role of the downregulated IL-7/IL-7R pathway associated with the APOE ε4 allele in modulating neuroinflammation and hippocampal atrophy. HIGHLIGHTS: The apolipoprotein E (APOE) ε4 allele decreases plasma interleukin (IL)-7 and aggravates hippocampal atrophy in Alzheimer's disease. Plasma IL-7 level is negatively associated with the degree of hippocampal atrophy. The expression of IL-7R signaling decreased in peripheral blood mononuclear cells of APOE ε4 carriers Dysregulation of the IL-7/IL-7R signal pathways enriches T cells.

Development and Validation of a Carbohydrate Metabolism-Related Model for Predicting Prognosis and Immune Landscape in Hepatocellular Carcinoma Patients.

OBJECTIVE: The activities and products of carbohydrate metabolism are involved in key processes of cancer. However, its relationship with hepatocellular carcinoma (HCC) is unclear. METHODS: The cancer genome atlas (TCGA)-HCC and ICGC-LIRI-JP datasets were acquired via public databases. Differentially expressed genes (DEGs) between HCC and control samples in the TCGA-HCC dataset were identified and overlapped with 355 carbohydrate metabolism-related genes (CRGs) to obtain differentially expressed CRGs (DE-CRGs). Then, univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses were applied to identify risk model genes, and HCC samples were divided into high/low-risk groups according to the median risk score. Next, gene set enrichment analysis (GSEA) was performed on the risk model genes. The sensitivity of the risk model to immunotherapy and chemotherapy was also explored. RESULTS: A total of 8 risk model genes, namely, G6PD, PFKFB4, ACAT1, ALDH2, ACYP1, OGDHL, ACADS, and TKTL1, were identified. Moreover, the risk score, cancer status, age, and pathologic T stage were strongly associated with the prognosis of HCC patients. Both the stromal score and immune score had significant negative/positive correlations with the risk score, reflecting the important role of the risk model in immunotherapy sensitivity. Furthermore, the stromal and immune scores had significant negative/positive correlations with risk scores, reflecting the important role of the risk model in immunotherapy sensitivity. Eventually, we found that high-/low-risk patients were more sensitive to 102 drugs, suggesting that the risk model exhibited sensitivity to chemotherapy drugs. The results of the experiments in HCC tissue samples validated the expression of the risk model genes. CONCLUSION: Through bioinformatic analysis, we constructed a carbohydrate metabolism-related risk model for HCC, contributing to the prognosis prediction and treatment of HCC patients.

EBF1-COX4I2 signaling axis promotes a myofibroblast-like phenotype in cancer-associated fibroblasts (CAFs) and is associated with an immunosuppressive microenvironment.

Immunotherapy has limited response rates in colorectal cancer (CRC) due to an immunosuppressive tumor microenvironment (TME). Combining transcriptome sequencing, clinical specimens, and functional experiments, we identified a unique group of CAF subpopulations (COX4I2 + ) with inhibited mitochondrial respiration and enhanced glycolysis. Through bioinformatics predictions and luciferase reporter assays, we determined that EBF1 can upstreamly regulate COX4I2 transcription. COX4I2 + CAFs functionally and phenotypically resemble myofibroblasts, are important for the formation of the fibrotic TME, and are capable of activating the M2 phenotype of macrophages. In vitro experiments demonstrated that COX4I2 + CAFs promote immunosuppressive TME by blocking CD8 + T cell infiltration and inducing CD8 + T cell dysfunction. Using multiple independent cohorts, we also found a strong correlation between the immunotherapy response rate of CRC patients and COX4I2 expression in their tumors. Our results identify a CAF subpopulation characterized by activation of the EBF1-COX4I2 axis, and this group of CAFs can be targeted to improve cancer immunotherapy outcomes.

Unmasking Spatial Heterogeneity in Phytotoxicology Mechanisms Induced by Carbamazepine by Mass Spectrometry Imaging and Multiomics Analyses.

Previous studies have highlighted the toxicity of pharmaceuticals and personal care products (PPCPs) in plants, yet understanding their spatial distribution within plant tissues and specific toxic effects remains limited. This study investigates the spatial-specific toxic effects of carbamazepine (CBZ), a prevalent PPCP, in plants. Utilizing desorption electrospray ionization mass spectrometry imaging (DESI-MSI), CBZ and its transformation products were observed predominantly at the leaf edges, with 2.3-fold higher concentrations than inner regions, which was confirmed by LC-MS. Transcriptomic and metabolic analyses revealed significant differences in gene expression and metabolite levels between the inner and outer leaf regions, emphasizing the spatial location's role in CBZ response. Notably, photosynthesis-related genes were markedly downregulated, and photosynthetic efficiency was reduced at leaf edges. Additionally, elevated oxidative stress at leaf edges was indicated by higher antioxidant enzyme activity, cell membrane impairment, and increased free fatty acids. Given the increased oxidative stress at the leaf margins, the study suggests using in situ Raman spectroscopy for early detection of CBZ-induced damage by monitoring reactive oxygen species levels. These findings provide crucial insights into the spatial toxicological mechanisms of CBZ in plants, forming a basis for future spatial toxicology research of PPCPs.

Bonding affinity and durability of recycled zirconia.

STATEMENT OF PROBLEM: While repurposing waste materials into zirconia blocks presents a promising avenue, uncertainty remains regarding whether the bonding properties of recycled zirconia align with those of commercially available zirconia. PURPOSE: The purpose of this in vitro study was to evaluate the bonding affinity and durability of composite resin to recycled zirconia. MATERIAL AND METHODS: A series of processing steps were performed with recycled zirconia residuals (Lava Plus; 3M Oral Care), including pulverization, sieving, heating, compaction, isostatic pressing, and presintering. The presintered blocks of recycled zirconia (Group R) and commercially available zirconia (Group C) were sectioned and sintered to create test specimens (10×10×1.5 mm). After polishing and airborne-particle abrasion, specimens within each group were bonded to composite resin cylinders using a resin cement (Multilink Speed; Ivoclar AG). The specimens were then divided into 3 subgroups for shear bond strength (SBS) testing: no further treatment, 10 000 thermocycles, and 30 000 thermocycles (n=10). X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectrometry (EDS), surface roughness, and contact angle were used to analyze the surface physicochemical differences between Groups C and R. Data were analyzed with 2-way ANOVA followed by the Tukey post hoc test for SBS values, Pearson chi-squared test for failure modes, and independent t test for grain size, surface roughness, and wettability (α=.05). RESULTS: No significant difference was found in the SBS values between Group R and Group C (P=.403), while thermocycling significantly affected the SBS values (P<.05). Group R showed significantly greater Ra, Rz, and Rq values (P<.05) than did Group C. SEM analysis revealed that Group R exhibited more prominent grooves than Group C, while the XRD and EDS patterns exhibited similarities in both the crystalline phase and elemental composition. No significant difference was observed in the water contact angle between the 2 groups (P=.196). CONCLUSIONS: The bonding protocol established for commercially available zirconia was comparable with that of recycled zirconia, but both decreased after thermocycling. The recycling process did not affect the crystalline phase or elemental composition of the zirconia, but it induced alterations in the surface roughness.

Development and Validation of an Interpretable Machine Learning Model for Early Prognosis Prediction in ICU Patients with Malignant Tumors and Hyperkalemia.

This study aims to develop and validate a machine learning (ML) predictive model for assessing mortality in patients with malignant tumors and hyperkalemia (MTH). We extracted data on patients with MTH from the Medical Information Mart for Intensive Care-IV, version 2.2 (MIMIC-IV v2.2) database. The dataset was split into a training set (75%) and a validation set (25%). We used the Least Absolute Shrinkage and Selection Operator (LASSO) regression to identify potential predictors, which included clinical laboratory indicators and vital signs. Pearson correlation analysis tested the correlation between predictors. In-hospital death was the prediction target. The Area Under the Curve (AUC) and accuracy of the training and validation sets of 7 ML algorithms were compared, and the optimal 1 was selected to develop the model. The calibration curve was used to evaluate the prediction accuracy of the model further. SHapley Additive exPlanations (SHAP) and Local Interpretable Model-agnostic Explanations (LIME) enhanced model interpretability. 496 patients with MTH in the Intensive Care Unit (ICU) were included. After screening, 17 clinical features were included in the construction of the ML model, and the Pearson correlation coefficient was <0.8, indicating that the correlation between the clinical features was small. eXtreme Gradient Boosting (XGBoost) outperformed other algorithms, achieving perfect scores in the training set (accuracy: 1.000, AUC: 1.000) and high scores in the validation set (accuracy: 0.734, AUC: 0.733). The calibration curves indicated good predictive calibration of the model. SHAP analysis identified the top 8 predictive factors: urine output, mean heart rate, maximum urea nitrogen, minimum oxygen saturation, minimum mean blood pressure, maximum total bilirubin, mean respiratory rate, and minimum pH. In addition, SHAP and LIME performed in-depth individual case analyses. This study demonstrates the effectiveness of ML methods in predicting mortality risk in ICU patients with MTH. It highlights the importance of predictors like urine output and mean heart rate. SHAP and LIME significantly enhanced the model's interpretability.

Depletion-assisted multiplexed cell-free RNA sequencing reveals distinct human and microbial signatures in plasma versus extracellular vesicles.

BACKGROUND: Cell-free long RNAs in human plasma and extracellular vesicles (EVs) have shown promise as biomarkers in liquid biopsy, despite their fragmented nature. METHODS: To investigate these fragmented cell-free RNAs (cfRNAs), we developed a cost-effective cfRNA sequencing method called DETECTOR-seq (depletion-assisted multiplexed cell-free total RNA sequencing). DETECTOR-seq utilised a meticulously tailored set of customised guide RNAs to remove large amounts of unwanted RNAs (i.e., fragmented ribosomal and mitochondrial RNAs) in human plasma. Early barcoding strategy was implemented to reduce costs and minimise plasma requirements. RESULTS: Using DETECTOR-seq, we conducted a comprehensive analysis of cell-free transcriptomes in both whole human plasma and EVs. Our analysis revealed discernible distributions of RNA types in plasma and EVs. Plasma exhibited pronounced enrichment in structured circular RNAs, tRNAs, Y RNAs and viral RNAs, while EVs showed enrichment in messenger RNAs (mRNAs) and signal recognition particle RNAs (srpRNAs). Functional pathway analysis highlighted RNA splicing-related ribonucleoproteins (RNPs) and antimicrobial humoral response genes in plasma, while EVs demonstrated enrichment in transcriptional activity, cell migration and antigen receptor-mediated immune signals. Our study indicates the comparable potential of cfRNAs from whole plasma and EVs in distinguishing cancer patients (i.e., colorectal and lung cancer) from healthy donors. And microbial cfRNAs in plasma showed potential in classifying specific cancer types. CONCLUSIONS: Our comprehensive analysis of total and EV cfRNAs in paired plasma samples provides valuable insights for determining the need for EV purification in cfRNA-based studies. We envision the cost effectiveness and efficiency of DETECTOR-seq will empower transcriptome-wide investigations in the fields of cfRNAs and liquid biopsy. KEYPOINTS: DETECTOR-seq (depletion-assisted multiplexed cell-free total RNA sequencing) enabled efficient and specific depletion of sequences derived from fragmented ribosomal and mitochondrial RNAs in plasma. Distinct human and microbial cell-free RNA (cfRNA) signatures in whole Plasma versus extracellular vesicles (EVs) were revealed. Both Plasma and EV cfRNAs were capable of distinguishing cancer patients from normal individuals, while microbial RNAs in Plasma cfRNAs enabled better classification of cancer types than EV cfRNAs.

Copper-Based Composites Nanoparticles Improve Triple-Negative Breast Cancer Treatment with Induction of Apoptosis-Cuproptosis and Immune Activation.

The synergistic effect of apoptosis and cuproptosis, along with the activation of the immune system, presents a promising approach to enhance the efficacy against triple-negative breast cancer (TNBC). Here, two prodrugs are synthesized: a reactive oxygen species (ROS)-responsive prodrug PEG-TK-DOX and a glutathione (GSH)-responsive prodrug PEG-DTPA-SS-CPT. These prodrugs are self-assembled and chelated Cu2+ to prepare nanoparticle PCD@Cu that simultaneously loaded doxorubicin (DOX), camptothecin (CPT), and Cu2+. The elevated levels of ROS and GSH in TNBC cells disrupted the PCD@Cu structure, leading to the release of Cu+, DOX, and CPT and the depletion of GSH. DOX and CPT triggered apoptosis with immunogenic cell death (ICD) in TNBC cells. Simultaneously, PCD@Cu downregulated the expression of copper transporting ATPase 2 (ATP7B), causing a significant accumulation of copper ions in TNBC cells. This further induced the aggregation of lipoylated dihydrolipoamide S-acetyltransferase (DLAT) and downregulation of iron-sulfur (Fe-S) cluster proteins, ultimately leading to cuproptosis and ICD in TNBC. In vitro and in vivo experiments confirmed that PCD@Cu induced apoptosis and cuproptosis in TNBC and activated the immune system, demonstrating strong anti-tumor capabilities. Moreover, PCD@Cu exhibited an excellent biosafety profile. Overall, this study provides a promising strategy for effective TNBC therapy.

New application of intestinal obstruction catheter in enterocutaneous fistula: A case report.

BACKGROUND: Enterocutaneous fistula (ECF) is an abnormal connection between the gastrointestinal tract and the skin. ECF can lead to massive body fluid loss, hypercatabolism, and malnutrition. Therefore, nutritional support plays a crucial role in managing ECFs and promoting the healing of fistulas. For nutritional support, enteral nutrition (EN) is the preferred method when gastrointestinal function is recovering. Currently, various EN approaches have been applied for different anatomical positions of the ECF. However, the effectiveness of administering EN support for treating lower ECFs still needs further exploration and improvement. CASE SUMMARY: We present the case of a 46-year-old male who underwent gastrointestinal stromal tumour resection. Six days after the surgery, the patient presented with fever, fatigue, severe upper abdominal pain, and septic shock. Subsequently, lower ECFs were diagnosed through laboratory and imaging examinations. In addition to symptomatic treatment for homeostasis, total parenteral nutrition support was administered in the first 72 h due to dysfunction of the intestine. After that, we gradually provided EN support through the intestinal obstruction catheter in consideration of the specific anatomic position of the fistula instead of using the nasal jejunal tube. Ultimately, the patient could receive optimal EN support via the catheter, and no complications were found during the treatment. CONCLUSION: Nutritional support is a crucial element in ECF management, and intestinal obstruction catheters could be used for early EN administration.