DiSMVC: a multi-view graph collaborative learning framework for measuring disease similarity.

MOTIVATION: Exploring potential associations between diseases can help in understanding pathological mechanisms of diseases and facilitating the discovery of candidate biomarkers and drug targets, thereby promoting disease diagnosis and treatment. Some computational methods have been proposed for measuring disease similarity. However, these methods describe diseases without considering their latent multi-molecule regulation and valuable supervision signal, resulting in limited biological interpretability and efficiency to capture association patterns. RESULTS: In this study, we propose a new computational method named DiSMVC. Different from existing predictors, DiSMVC designs a supervised graph collaborative framework to measure disease similarity. Multiple bio-entity associations related to genes and miRNAs are integrated via cross-view graph contrastive learning to extract informative disease representation, and then association pattern joint learning is implemented to compute disease similarity by incorporating phenotype-annotated disease associations. The experimental results show that DiSMVC can draw discriminative characteristics for disease pairs, and outperform other state-of-the-art methods. As a result, DiSMVC is a promising method for predicting disease associations with molecular interpretability. AVAILABILITY AND IMPLEMENTATION: Datasets and source codes are available at https://github.com/Biohang/DiSMVC.

Multicentric intelligent cardiotocography signal interpretation using deep semi-supervised domain adaptation via minimax entropy and domain invariance.

BACKGROUND AND OBJECTIVE: Obstetricians use Cardiotocography (CTG), which is the continuous recording of fetal heart rate and uterine contraction, to assess fetal health status. Deep learning models for intelligent fetal monitoring trained on extensively labeled and identically distributed CTG records have achieved excellent performance. However, creation of these training sets requires excessive time and specialist labor for the collection and annotation of CTG signals. Previous research has demonstrated that multicenter studies can improve model performance. However, models trained on cross-domain data may not generalize well to target domains due to variance in distribution among datasets. Hence, this paper conducted a multicenter study with Deep Semi-Supervised Domain Adaptation (DSSDA) for intelligent interpretation of antenatal CTG signals. This approach helps to align cross-domain distribution and transfer knowledge from a label-rich source domain to a label-scarce target domain. METHODS: We proposed a DSSDA framework that integrated Minimax Entropy and Domain Invariance (DSSDA-MMEDI) to reduce inter-domain gaps and thus achieve domain invariance. The networks were developed using GoogLeNet to extract features from CTG signals, with fully connected, softmax layers for classification. We designed a Dynamic Gradient-driven strategy based on Mutual Information (DGMI) to unify the losses from Minimax Entropy (MME), Domain Invariance (DI), and supervised cross-entropy during iterative learning. RESULTS: We validated our DSSDA model on two datasets collected from collaborating healthcare institutions and mobile terminals as the source and target domains, which contained 16,355 and 3,351 CTG signals, respectively. Compared to the results achieved with deep learning networks without DSSDA, DSSDA-MMEDI significantly improved sensitivity and F1-score by over 6%. DSSDA-MMEDI also outperformed other state-of-the-art DSSDA approaches for CTG signal interpretation. Ablation studies were performed to determine the unique contribution of each component in our DSSDA mechanism. CONCLUSIONS: The proposed DSSDA-MMEDI is feasible and effective for alignment of cross-domain data and automated interpretation of multicentric antenatal CTG signals with minimal annotation cost.

Hematochezia due to rectal invasion by an internal iliac artery aneurysm: A case report.

BACKGROUND: This case report presents the rare occurrence of hematochezia due to an internal iliac artery aneurysm leading to an arterioenteric fistula, expanding the differential diagnosis for gastrointestinal bleeding. It emphasizes the importance of considering vascular origins in cases of atypical hematochezia, particularly in the absence of common gastrointestinal causes, and highlights the role of imaging and multidisciplinary management in diagnosing and treating such unusual presentations. CASE SUMMARY: A 75-year-old man with a history of hypertension presented with 12 d of hematochezia, experiencing bloody stools 7-8 times per day. Initial computed tomography (CT) scans revealed an aneurysmal rupture near the right internal iliac artery with suspected hematoma development. Hemoglobin levels progressively decreased to 7 g/dL. Emergency arterial angiography and iliac artery-covered stent placement were performed, followed by balloon angioplasty. Despite initial stabilization, minor rectal bleeding and abdominal pain persisted, leading to further diagnostic colonoscopy. This identified a neoplasm and potential perforation at the proximal rectum. An exploratory laparotomy confirmed the presence of a hematoma and an aneurysm invading the rectal wall, necessitating partial rectal resection, intestinal anastomosis, and ileostomy. Postoperative recovery was successful, with no further bleeding incidents and normal follow-up CT and colonoscopy results after six months. CONCLUSION: In cases of unusual gastrointestinal bleeding, it is necessary to consider vascular causes for effective diagnosis and intervention.

Tunable High-Performance Electromagnetic Interference Shielding of VO2 Nanowires-Based Composite.

The unique metal-insulator transition of VO2 is very suitable for dynamic electromagnetic (EM) regulation materials due to its sharp change in electrical conductivity. Here, we have developed an off/on switchable electromagnetic interference (EMI) shielding composite by interconnecting VO2 nanowires (NWs) in poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) to form conductive networks, resulting in outstanding performance at the X and Ku bands with maximum change values of 44.8 and 59.4 dB, respectively. The unique insulator-to-metal transition (IMT) of VO2 NWs has dominated the variation of polarization loss (εp″) and conductivity loss (εσ″) for the composites, which is the mechanism of EMI shielding switching between off and on states. Furthermore, the composite exhibits good cycling stability of the off/on switchable EMI shielding performance and has excellent mechanical properties, especially with 200 times abrasion resistance without obvious weight loss. This study provides a unique approach for dynamic switching of EM response with the potential to construct practical intelligent EM response systems for next-generation smart electromagnetic devices in various scenarios.

Angiostrongylus cantonensis induces energy imbalance and dyskinesia in mice by reducing the expression of melanin-concentrating hormone.

BACKGROUND: Infection with Angiostrongylus cantonensis (AC) in humans or mice can lead to severe eosinophilic meningitis or encephalitis, resulting in various neurological impairments. Developing effective neuroprotective drugs to improve the quality of life in affected individuals is critical. METHODS: We conducted a Gene Ontology enrichment analysis on microarray gene expression (GSE159486) in the brains of AC-infected mice. The expression levels of melanin-concentrating hormone (MCH) were confirmed through real-time quantitative PCR (RT-qPCR) and immunofluorescence. Metabolic parameters were assessed using indirect calorimetry, and mice's energy metabolism was evaluated via pathological hematoxylin and eosin (H&E) staining, serum biochemical assays, and immunohistochemistry. Behavioral tests assessed cognitive and motor functions. Western blotting was used to measure the expression of synapse-related proteins. Mice were supplemented with MCH via nasal administration. RESULTS: Postinfection, a marked decrease in Pmch expression and the encoded MCH was observed. Infected mice exhibited significant weight loss, extensive consumption of sugar and white fat tissue, reduced movement distance, and decreased speed, compared with the control group. Notably, nasal administration of MCH countered the energy imbalance and dyskinesia caused by AC infection, enhancing survival rates. MCH treatment also increased the expression level of postsynaptic density protein 95 (PSD95) and microtubule-associated protein-2 (MAP2), as well as upregulated transcription level of B cell leukemia/lymphoma 2 (Bcl2) in the cortex. CONCLUSIONS: Our findings suggest that MCH improves dyskinesia by reducing loss of synaptic proteins, indicating its potential as a therapeutic agent for AC infection.

Highly-dispersed 2D NiFeP/CoP heterojunction trifunctional catalyst for efficient electrolysis of water and urea.

The electrocatalytic production of "green hydrogen", such as through the electrolysis of water or urea has been vigorously advocated to alleviate the energy crisis. However, their electrode reactions including oxygen evolution reaction (OER), urea oxidation reaction (UOR), and hydrogen evolution reaction (HER) all suffer from sluggish kinetics, which urgently need catalysts to accelerate the processes. Herein, we design and prepare an OER/UOR/HER trifunctional catalyst by transforming the homemade CoO nanorod into a two-dimensional (2D) ultrathin heterojunction nickel-iron-cobalt hybrid phosphides nanosheet (NiFeP/CoP) via a hydrothermal-phosphorization method. Consequently, a strong electronic interaction was found among the Ni2P/FeP4/CoP heterogeneous interfaces, which regulates the electronic structure. Besides the high mass transfer property of 2D nanosheet, Ni2P/FeP4/CoP displays improved OER/UOR/HER performance. At 10 mA cm-2, the OER overpotential reaches 274 mV in 1.0 M KOH, and the potential of UOR is only 1.389 V in 1.0 M KOH and 0.33 M urea. More strikingly, the two-electrode systems for electrolysis water and urea-assisted electrolysis water assembled by NiFeP/CoP could maintain long-term stability for 35 h and 12 h, respectively. This work may help to pave the way for upcoming research horizons of multifunctional electrocatalysts.

A temperature-adjustable in situ infrared diffuse reflectance spectroscopy system for catalysts.

We introduce an innovative in situ infrared diffuse reflection rapid detection system, endowed with a temperature regulation function. This system is adept at conducting rapid infrared spectra scanning as well as simulating the catalytic environment of diverse reaction systems. The infrared absorption spectra of four kinds of Pt-based catalysts under vacuum conditions across a wide temperature spectrum ranging from -180 to 300 °C are obtained and analysed through IR correlation spectroscopy. A key finding is the notable variance in peak intensity within Pt/CeO2/CNT catalysts, highlighting a robust adsorption capacity for oxygen-containing groups at lower temperatures and a marked desorption at higher temperatures. By enabling rapid and accurate assessments of catalyst behavior under varying temperatures, it not only accelerates the evaluation process but also provides valuable insights that can guide the synthesis of more efficient catalysts.

Wearable and interactive multicolored photochromic fiber display.

Endowing flexible and adaptable fiber devices with light-emitting capabilities has the potential to revolutionize the current design philosophy of intelligent, wearable interactive devices. However, significant challenges remain in developing fiber devices when it comes to achieving uniform and customizable light effects while utilizing lightweight hardware. Here, we introduce a mass-produced, wearable, and interactive photochromic fiber that provides uniform multicolored light control. We designed independent waveguides inside the fiber to maintain total internal reflection of light as it traverses the fiber. The impact of excessive light leakage on the overall illuminance can be reduced by utilizing the saturable absorption effect of fluorescent materials to ensure light emission uniformity along the transmission direction. In addition, we coupled various fluorescent composite materials inside the fiber to achieve artificially controllable spectral radiation of multiple color systems in a single fiber. We prepared fibers on mass-produced kilometer-long using the thermal drawing method. The fibers can be directly integrated into daily wearable devices or clothing in various patterns and combined with other signal input components to control and display patterns as needed. This work provides a new perspective and inspiration to the existing field of fiber display interaction, paving the way for future human-machine integration.

Tunable VO2 cavity enables multispectral manipulation from visible to microwave frequencies.

Optical materials capable of dynamically manipulating electromagnetic waves are an emerging field in memories, optical modulators, and thermal management. Recently, their multispectral design preliminarily attracts much attention, aiming to enhance their efficiency and integration of functionalities. However, the multispectral manipulation based on these materials is challenging due to their ubiquitous wavelength dependence restricting their capacity to narrow wavelengths. In this article, we cascade multiple tunable optical cavities with selective-transparent layers, enabling a universal approach to overcoming wavelength dependence and establishing a multispectral platform with highly integrated functions. Based on it, we demonstrate the multispectral (ranging from 400 nm to 3 cm), fast response speed (0.9 s), and reversible manipulation based on a typical phase change material, vanadium dioxide. Our platform involves tandem VO2-based Fabry-Pérot (F-P) cavities enabling the customization of optical responses at target bands independently. It can achieve broadband color-changing capacity in the visible region (a shift of ~60 nm in resonant wavelength) and is capable of freely switching between three typical optical models (transmittance, reflectance, and absorptance) in the infrared to microwave regions with drastic amplitude tunability exceeding 0.7. This work represents a state-of-art advance in multispectral optics and material science, providing a critical approach for expanding the multispectral manipulation ability of optical systems.

Unprecedented Spatial Manipulation and Transformation of Dynamic Thermal Radiation Based on Vanadium Dioxide.

Reconfigurable infrared (IR) materials have widespread applications in thermal management and smart IR concealment. Although various reconfigurable IR materials can be customized by positive or negative differential VO2-based resonators, their insightful mechanism remains unknown. Here, we comprehensively investigate the fundamental design rule of reconfigurable thermal radiation between positive and negative differential thermal radiation properties for the first time. Importantly, the skin depth of VO2 film in the metal state is investigated to clarify the transformation from positive to negative differential thermal radiation properties, and the critical thickness is further derived, providing important guidance in designing the reconfigurable thermal radiation regulator. Furthermore, the reconfigurable multistate thermal images had been presented into one plate. The resulting emittance variation (△ε8-14 µm) of the VO2-based resonator can change from 0.61 to -0.53, which consummates the ability for diverse demands such as infrared concealment, thermal illusion, and thermal management. This work constitutes a promising and universal route toward designing whole smart devices and may create new scientific and technological opportunities for platforms that can benefit from reconfigurable electromagnetic manipulation.

Inclusion complex of turmeric essential oil with hydroxypropyl-ß-cyclodextrin: Preparation, characterization and release kinetics.

The application of turmeric essential oil (TEO), a natural effective antibacterial agent, in food preservation is limited due to high volatility and low stability. This study aimed to improve its stability and release behavior by synthesizing TEO/hydroxypropyl-ß-cyclodextrin (HP-ß-CD) inclusion complex (IC) in a saturated aqueous solution. An orthogonal experimental design was used to determine the optimal process conditions (HP-ß-CD to TEO, g/mL), 16:1; stirring speed, 850 r/min; encapsulation time, 2 h), achieving a comprehensive score value of 85.62% for TEO/HP-ß-CD-IC. Through comprehensive characterization, the results showed that TEO was completely embedded in HP-ß-CD with increased stability. Free TEO exhibited a weight loss of 67.64% between 30 and 300 °C, while TEO/HP-ß-CD-IC had a mass loss of only 9.33%. HP-ß-CD and TEO/HP-ß-CD-IC showed positive ZP values that were 124.76 mV and 132.16 mV, respectively. The release behavior and release kinetics of TEO/HP-ß-CD-ICs were also studied, and the results showed that TEO/HP-ß-CD-IC release rate increased under higher temperature and relative humidity-consistent with Fick's diffusion.

Temperature-Tunable Operando Nondestructive Detection of Electronic and Geometrical Structures in Battery Electrodes.

Real-time monitoring of the structural evolution of battery materials is crucial for understanding their underlying reaction mechanisms, which cannot be satisfied by the typically used post-mortem analysis. While more and more operando techniques were constructed and employed, they are all based on ambient working conditions that are not generally the case for real-world applications. Indeed, batteries work in an environment where self-heat dissipation increases the surrounding temperature, and extreme temperature applications (<-20 °C or >60 °C) are also frequently proposed. Operando characterization techniques under variable temperatures are therefore highly desired for tracking battery reactions under real-working conditions. Here, we develop a methodology to operando monitor the electronic and geometrical structures of battery materials over a wide range of temperatures based on X-ray spectroscopies. It is substantiated with data collected on a model LiNi0.90Co0.05Mn0.05O2/Si@C pouch cell under operando quick X-ray absorption fine structure spectroscopy, by which we found a temperature-dependent structure evolution behavior that is highly correlated with the electrochemical performance. Our work establishes an exemplary protocol for analyzing battery materials under temperature-variable environments that can be widely used in other related fields.

DNMT3a-mediated methylation of PPARγ promote intervertebral disc degeneration by regulating the NF-κB pathway.

Intervertebral disc degeneration (IVDD) is a common chronic musculoskeletal disease that causes chronic low back pain and imposes an immense financial strain on patients. The pathological mechanisms underlying IVDD have not been fully elucidated. The development of IVDD is closely associated with abnormal epigenetic changes, suggesting that IVDD progression may be controlled by epigenetic mechanisms. Consequently, this study aimed to investigate the role of epigenetic regulation, including DNA methyltransferase 3a (DNMT3a)-mediated methylation and peroxisome proliferator-activated receptor γ (PPARγ) inhibition, in IVDD development. The expression of DNMT3a and PPARγ in early and late IVDD of nucleus pulposus (NP) tissues was detected using immunohistochemistry and western blotting analyses. Cellularly, DNMT3a inhibition significantly inhibited IL-1ß-induced apoptosis and extracellular matrix (ECM) degradation in rat NP cells. Pretreatment with T0070907, a specific inhibitor of PPARγ, significantly reversed the anti-apoptotic and ECM degradation effects of DNMT3a inhibition. Mechanistically, DNMT3a modified PPARγ promoter hypermethylation to activate the nuclear factor-κB (NF-κB) pathway. DNMT3a inhibition alleviated IVDD progression. Conclusively, the results of this study show that DNMT3a activates the NF-κB pathway by modifying PPARγ promoter hypermethylation to promote apoptosis and ECM degradation. Therefore, we believe that the ability of DNMT3a to mediate the PPARγ/NF-κB axis may provide new ideas for the potential pathogenesis of IVDD and may become an attractive target for the treatment of IVDD.

Analysis of the relationship between drug susceptibility of Cryptococcus neoformans isolates and mortality in HIV-negative cryptococcal meningitis.

OBJECTIVES: The relationship between antifungal susceptibility and mortality of cryptococcal meningitis (CM) in HIV-negative patients is poorly understood. METHODS: We conducted a retrospective analysis of 1-year follow-up of 200 HIV-negative CM patients with an initial cerebrospinal fluid (CSF) culture for Cryptococcus neoformans. According to the cut-off values of minimum inhibitory concentration (MIC), two groups of five antifungal agents were classified: amphotericin B (AmB), ≤0.5 µg/mL, >0.5 µg/mL; 5-flucytosine (5-FC), ≤4 µg/mL, >4 µg/mL; fluconazole (FLU), ≤4 µg/mL, >4 µg/mL; itraconazole (ITR), ≤0.125 µg/mL, >0.125 µg/mL; and voriconazole (VOR), <0.25 µg/mL, ≥0.25 µg/mL. Comparisons were performed to analyse clinical features, laboratory, modified Rankin Scale (mRS) scores, and CSF findings under different prognosis outcomes in 1-year. RESULTS: All of Cryptococcus neoformans isolates were sensitive to AmB and VOR, most of them were sensitive to 5-FC and FLU (95.5% and 90.5%, respectively) while only 55.0% of them were susceptible to ITR. Minimum inhibitory concentrations of ITR and VOR were significantly related to baseline mRS scores. All-cause mortality was not significantly related to MICs in Cryptococcus neoformans strains. The combination of actual antifungal agents and two groups of the MICs values for antifungal agents had no significant effects on all-cause mortality. CONCLUSION: Most Cryptococcus neoformans isolates were sensitive to AmB, VOR, 5-FC, and FLU. Because of the small number of deaths, we are not able to comment on whether MIC is associated with mortality of CM in HIV-negative patients.

Momordica anti-HIV protein MAP30 abrogates the Epstein-Barr virus nuclear antigen 1 dependent functions in host cells.

Originally extracted from Momordica charantia seeds, the antiviral and anti-tumor activities of Momordica anti-HIV protein MAP30 have become well known. Although MAP30 has been reported to possess antiviral activity against several human viruses, the current understanding of the MAP30-mediated antiviral response is mainly derived from the previous research work on anti-HIV herbal medicines; the mechanistic insight of its effects on other viruses remains largely unknown. In this study, we showed that both ectopically expressed and purified recombinant MAP30 (rMAP30) impeded Epstein-Barr virus Nuclear Antigen 1 (EBNA1)-mediated transcription from the viral latent replication origin. Mechanistically, in vivo and in vitro studies revealed that MAP30 caused EBNA1 to dissociate from the cognate binding sites, which disrupted downstream EBNA1-dependent viral epigenome accumulation and cell maintenance of Epstein-Barr virus (EBV)-associated neoplastic cells. Finally, mutational analysis indicated that the N-terminal ricin A homologous domain shared by ricin-like proteins was implicated in the anti-EBV response. Our study provides evidence to support that MAP30 has a unique property to combat EBV latent infection, suggesting a potential to develop this herbal protein to be an alternative medicine for EBV associated diseases.

A hybrid stacked ensemble and Kernel SHAP-based model for intelligent cardiotocography classification and interpretability.

BACKGROUND: Intelligent cardiotocography (CTG) classification can assist obstetricians in evaluating fetal health. However, high classification performance is often achieved by complex machine learning (ML)-based models, which causes interpretability concerns. The trade-off between accuracy and interpretability makes it challenging for most existing ML-based CTG classification models to popularize in prenatal clinical applications. METHODS: Aiming to improve CTG classification performance and prediction interpretability, a hybrid model was proposed using a stacked ensemble strategy with mixed features and Kernel SHapley Additive exPlanations (SHAP) framework. Firstly, the stacked ensemble classifier was established by employing support vector machines (SVM), extreme gradient boosting (XGB), and random forests (RF) as base learners, and backpropagation (BP) as a meta learner whose input was mixed with the CTG features and the probability value of each category output by base learners. Then, the public and private CTG datasets were used to verify the discriminative performance. Furthermore, Kernel SHAP was applied to estimate the contribution values of features and their relationships to the fetal states. RESULTS: For intelligent CTG classification using 10-fold cross-validation, the accuracy and average F1 score were 0.9539 and 0.9249 in the public dataset, respectively; and those were 0.9201 and 0.8926 in the private dataset, respectively. For interpretability, the explanation results indicated that accelerations (AC) and the percentage of time with abnormal short-term variability (ASTV) were the key determinants. Specifically, the probability of abnormality increased and that of the normal state decreased as the value of ASTV grew. In addition, the likelihood of the normal status rose with the increase of AC. CONCLUSIONS: The proposed model has high classification performance and reasonable interpretability for intelligent fetal monitoring.

Chromosome-scale genome of the human blood fluke Schistosoma mekongi and its implications for public health.

BACKGROUND: Schistosoma mekongi is a human blood fluke causing schistosomiasis that threatens approximately 1.5 million humans in the world. Nonetheless, the limited available S. mekongi genomic resources have hindered understanding of its biology and parasite-host interactions for disease management and pathogen control. The aim of our study was to integrate multiple technologies to construct a high-quality chromosome-level assembly of the S. mekongi genome. METHODS: The reference genome for S. mekongi was generated through integrating Illumina, PacBio sequencing, 10 × Genomics linked-read sequencing, and high-throughput chromosome conformation capture (Hi-C) methods. In this study, we conducted de novo assembly, alignment, and gene prediction to assemble and annotate the genome. Comparative genomics allowed us to compare genomes across different species, shedding light on conserved regions and evolutionary relationships. Additionally, our transcriptomic analysis focused on genes associated with parasite-snail interactions in S. mekongi infection. We employed gene ontology (GO) enrichment analysis for functional annotation of these genes. RESULTS: In the present study, the S. mekongi genome was both assembled into 8 pseudochromosomes with a length of 404 Mb, with contig N50 and scaffold N50 lengths of 1168 kb and 46,759 kb, respectively. We detected that 43% of the genome consists of repeat sequences and predicted 9103 protein-coding genes. We also focused on proteases, particularly leishmanolysin-like metalloproteases (M8), which are crucial in the invasion of hosts by 12 flatworm species. Through phylogenetic analysis, it was discovered that the M8 gene exhibits lineage-specific amplification among the genus Schistosoma. Lineage-specific expansion of M8 was observed in blood flukes. Additionally, the results of the RNA-seq revealed that a mass of genes related to metabolic and biosynthetic processes were up-regulated, which might be beneficial for cercaria production. CONCLUSIONS: This study delivers a high-quality, chromosome-scale reference genome of S. mekongi, enhancing our understanding of the divergence and evolution of Schistosoma. The molecular research conducted here also plays a pivotal role in drug discovery and vaccine development. Furthermore, our work greatly advances the understanding of host-parasite interactions, providing crucial insights for schistosomiasis intervention strategies.

CD45- erythroid progenitor cells promote lymph node metastasis in gastric cancer by inducing a hybrid epithelial/mesenchymal state in lymphatic endothelial cells.

BACKGROUND AND AIMS: Specific mechanisms of lymph node (LN) metastasis in early-stage gastric cancer (GC) have not been elucidated. The role of anemia, a vital clinical feature of GC, in LN metastasis is also unclear. Since the number of erythroid progenitor cells (EPCs) is increased in chronic anemia, we investigated its association with LN metastasis in GC. METHODS: Flow cytometry and immunofluorescence analyses were performed to sort and study EPCs from the circulation and tumors of patients with stage I-III GC. The effect of these EPCs on the activation of T and B cells and on the functions of lymphatic endothelial cells (LECs) was determined, and their ability to promote LN metastasis was evaluated using a footpad-popliteal LN metastasis model based on two human adenocarcinoma GC cell lines in nude mice. The prognostic value of EPCs was also analyzed. RESULTS: The proportion of CD45- EPCs was higher in the mononuclear cells in the circulation, tumors, and LNs of GC patients with LN metastasis (N+) than in those of GC patients without LN metastasis (N0). In N+ patients, CD45- EPCs were more abundant in metastatic LNs than in non-metastatic LNs. Lymphatic vessel endothelial hyaluronan receptor 1 immunoreactivity in tumors revealed that CD45- EPCs were positively associated with nodal stages and lymph vessel density. Furthermore, CD45- EPCs increased LEC proliferation and migration through their S100A8/A9 heterodimer-induced hybrid epithelial/mesenchymal (E/M) state; however, they did not influence the invasion and tubulogenesis of LECs or T and B cell proliferation. CD45- EPCs promoted LN metastasis in vivo; the S100A8/A9 heterodimer mimicked this phenomenon. Finally, CD45- EPCs predicted the overall and disease-free survival of stage I-III GC patients after radical resection. CONCLUSIONS: The CD45- EPCs accumulated in GC tissues and metastatic LNs and promoted LN metastasis via the S100A8/9-induced hybrid E/M state of LECs, which was the specific mechanism of LN metastasis in the early stages of GC.

SOx-modified porous carbon as a highly active electrocatalyst for efficient H2O2 generation.

A SOx-decorated porous carbon electrocatalyst that exhibits excellent 2e- oxygen reduction reaction activity is synthesized using UV-curing technology in combination with a pyrolysis process. The H2O2 selectivity using the SOx-porous C shows 95.1% at 0.4 V and delivers a H2O2 production rate of 604.2 mmol gcat-1 h-1. Density-functional theory calculations reveal the reasons for the improvement of catalytic performance.

Erythroid-transdifferentiated myeloid cells promote portal vein tumor thrombus in hepatocellular carcinoma.

Rationale: Hepatocellular carcinoma (HCC) is primarily characterized by a high incidence of vascular invasion. However, the specific mechanism underlying portal vein tumor thrombus (PVTT) in HCC remains unclear. As a consequence of myeloid cell developmental arrest, CD71+ erythroid progenitor cells (EPCs) and myeloid-derived suppressor cells play important roles in HCC; however, their roles in PVTT remain unclear. Methods: The role of CD71+ EPCs in the HCC tumor microenvironment (TME) was evaluated via morphological, RNA-sequencing, enzyme-linked immunosorbent assay, and flow cytometric analyses. Co-culture techniques were employed to assess the CD45+ EPCs and their vascular compromising effect. Additionally, the PVTT-promoting function of CD45+ EPCs was explored in vivo in a murine model. Results: The CD45+EPCs in HCC tissues exhibited increased myeloid cell features, including morphology, surface markers, transforming growth factor (TGF)-ß generation, and gene expression, compared with those in circulation. Hence, a large proportion of CD45+EPCs, particularly those in TMEs, comprise erythroid-transdifferentiated myeloid cells (EDMCs). Additionally, the expression of C-C chemokine receptor type 2 (CCR2) mRNA was upregulated in CD45+EPCs within the TME. Tumor macrophages from HCC tissues induced substantial migration of CD45+EPCs in a dose-dependent manner. Meanwhile, results from immunofluorescence analyses revealed that these two cell types are positively associated in the TME and circulation. That is, EDMCs are chemoattracted by HCC macrophages mainly via CCR2 from CD45+ EPCs in the circulation. Additionally, the expressions of FX, FVII, FGB, C4b, CFB, and CFH were elevated in CD45+EPCs within the TME compared with those in the spleen. The CD45+EPCs from the HCC TME promoted vessel endothelial cell migration and compromised tube formation through TGF-ß and FGB, respectively. Additionally, CD45+EPCs from the TME induced HCC cell migration. HCC macrophage-induced CD45+EPCs to exhibit higher levels of FX, FVII, FGB, and TGF-ß. Meanwhile, upregulation of CCAAT/enhancer binding protein beta expression induced FGB and TGF-ß generation in CD45+EPCs in the TME. WTAP, a major RNA m6A writer, stabilized FX and FVII mRNA and enhanced their nuclear export in CD45+EPCs from the TME. CD45+EPCs from the TME were positively associated with PVTT and poor prognosis. Splenectomy reduced the level of CD45+EPCs in the circulation and TME, as well as the incidence of microvascular invasion. The incidence of microvascular invasion increased following the transfer of HCC tissue CD45+EPCs to splenectomized HCC-bearing mice. Conclusions: The CD45+EPCs enriched in the HCC microenvironment are EDMCs, which are induced by HCC macrophages to migrate from the circulation to the TME. Subsequently, EDMCs promote PVTT by compromising the blood vessel endothelium, aggravating coagulation, and promoting HCC cell migration.