Advances on Senescence-associated secretory phenotype regulated by circular RNAs in tumors.

The components that comprise the senescence-associated secretory phenotype (SASP) include growth factors, proteases, chemokines, cytokines, and bioactive lipids. It drives secondary aging and disrupts tissue homeostasis, ultimately leading to tissue repair and regeneration loss. It has a two-way regulatory effect on tumor cells, resisting cancer occurrence and promoting its progression. A category of single-stranded circular non-coding RNA molecules known as circular RNAs (circRNAs) carries out a series of cellular activities, including sequestering miRNAs and modulating gene editing and expression. Research has demonstrated that a large number of circRNAs exhibit aberrant expression in pathological settings, and play a part in the onset and progress of cancer via modulating SASP factors. However, the research related to SASP and circRNAs in tumors is still in its infancy at this stage. This review centers on the bidirectional modulation of SASP and the role of circRNAs in regulating SASP factors across different types of tumors. The aim is to present novel perspectives for the diagnosis and therapeutic management of malignancies.

Organizing Photosensitive and Photothermal Single-Sites Uniformly in a Trimetallic Metal-Organic Framework for Efficient Photocatalytic Hydrogen Evolution.

Effective combination of the photosensitivity and photothermal property in photocatalyst is vital to achieve the maximum light utilization for superior photocatalytic efficiency. Herein, this work successfully organizes photosensitive Cd-NS single-sites and photothermal Ni-NS single-sites uniformly at a molecular level within a tailored trimetallic metal-organic framework. The optimized Ho6-Cd0.76Ni0.24-NS exhibits a superior photocatalytic hydrogen evolution rate of 40.06 mmol g-1 h-1 under visible-light irradiation and an apparent quantum efficiency of 29.37% at 420 nm without using cocatalysts or photosensitizers. A systematical mechanism study reveals that the uniformly organized photosensitive and photothermal single-sites have synergistic effect, which form ultrashort pathways for efficient transport of photoinduced electrons, suppress the recombination of photogenerated charge carriers, hence promote the hydrogen evolution activity. This work provides a promising approach for organizing dual-functional single-sites uniformly in photocatalyst for high-performance photocatalytic activity.

Breath metabolomics for diagnosis of acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) poses challenges in early identification. Exhaled breath contains metabolites reflective of pulmonary inflammation. AIM: To evaluate the diagnostic accuracy of breath metabolites for ARDS in invasively ventilated intensive care unit (ICU) patients. METHODS: This two-center observational study included critically ill patients receiving invasive ventilation. Gas chromatography and mass spectrometry (GC-MS) was used to quantify the exhaled metabolites. The Berlin definition of ARDS was assessed by three experts to categorize all patients into "certain ARDS", "certain no ARDS" and "uncertain ARDS" groups. The patients with "certain" labels from one hospital formed the derivation cohort used to train a classifier built based on the five most significant breath metabolites. The diagnostic accuracy of the classifier was assessed in all patients from the second hospital and combined with the lung injury prediction score (LIPS). RESULTS: A total of 499 patients were included in this study. Three hundred fifty-seven patients were included in the derivation cohort (60 with certain ARDS; 17%), and 142 patients in the validation cohort (47 with certain ARDS; 33%). The metabolites 1-methylpyrrole, 1,3,5-trifluorobenzene, methoxyacetic acid, 2-methylfuran and 2-methyl-1-propanol were included in the classifier. The classifier had an area under the receiver operating characteristics curve (AUROCC) of 0.71 (CI 0.63-0.78) in the derivation cohort and 0.63 (CI 0.52-0.74) in the validation cohort. Combining the breath test with the LIPS does not significantly enhance the diagnostic performance. CONCLUSION: An exhaled breath metabolomics-based classifier has moderate diagnostic accuracy for ARDS but was not sufficiently accurate for clinical use, even after combination with a clinical prediction score.

Plasma and serum metabolic analysis of healthy adults shows characteristic profiles by subjects' sex and age.

INTRODUCTION: Pre-analytical factors like sex, age, and blood processing methods introduce variability and bias, compromising data integrity, and thus deserve close attention. OBJECTIVES: This study aimed to explore the influence of participant characteristics (age and sex) and blood processing methods on the metabolic profile. METHOD: A Thermo UPLC-TSQ-Quantiva-QQQ Mass Spectrometer was used to analyze 175 metabolites across 9 classes in 208 paired serum and lithium heparin plasma samples from 51 females and 53 males. RESULTS: Comparing paired serum and plasma samples from the same cohort, out of the 13 metabolites that showed significant changes, 4 compounds related to amino acids and derivatives had lower levels in plasma, and 5 other compounds had higher levels in plasma. Sex-based analysis revealed 12 significantly different metabolites, among which most amino acids and derivatives and nitrogen-containing compounds were higher in males, and other compounds were elevated in females. Interestingly, the volcano plot also confirms the similar patterns of amino acids and derivatives higher in males. The age-based analysis suggested that metabolites may undergo substantial alterations during the 25-35-year age range, indicating a potential metabolic turning point associated with the age group. Moreover, a more distinct difference between the 25-35 and above 35 age groups compared to the below 25 and 25-35 age groups was observed, with the most significant compound decreased in the above 35 age groups. CONCLUSION: These findings may contribute to the development of comprehensive metabolomics analyses with confounding factor-based adjustment and enhance the reliability and interpretability of future large-scale investigations.

Chitosan-Rapamycin Carbon Dots Alleviate Glaucomatous Retinal Injury by Inducing Autophagy to Promote M2 Microglial Polarization.

Introduction: Glaucoma is a prevalent cause of irreversible vision impairment, characterized by progressive retinal ganglion cells (RGCs) loss, with no currently available effective treatment. Rapamycin (RAPA), an autophagy inducer, has been reported to treat glaucoma in rodent models by promoting RGC survival, but its limited water solubility, systemic toxicity, and pre-treatment requirements hinder its potential clinical applications. Methods: Chitosan (CS)-RAPA carbon dot (CRCD) was synthesized via hydrothermal carbonization of CS and RAPA and characterized by transmission electron microscopy, Fourier transform infrared spectra, and proton nuclear magnetic resonance. In vitro assays on human umbilical cord vein endothelial and rat retinal cell line examined its biocompatibility and anti-oxidative capabilities, while lipopolysaccharide-stimulated murine microglia (BV2) assays measured its effects on microglial polarization. In vivo, using a mouse retinal ischemia/reperfusion (I/R) model by acute intraocular pressure elevation, the effects of CRCD on visual function, RGC apoptosis, oxidative stress, and M2 microglial polarization were examined. Results: CRCD exhibited good water solubility and anti-oxidative capabilities, in the form of free radical scavenging. In vitro, CRCD was bio-compatible and lowered oxidative stress, which was also found in vivo in the retinal I/R model. Additionally, both in vitro with lipopolysaccharide-stimulated BV2 cells and in vivo with the I/R model, CRCD was able to promote M2 microglial polarization by activating autophagy, which, in turn, down-regulated pro-inflammatory cytokines, such as IL-1ß and TNF-α, as well as up-regulated anti-inflammatory cytokines, such as IL-4 and TGF-ß. All these anti-oxidative and anti-inflammatory effects ultimately aided in preserving RGCs, and subsequently, improved visual function. Discussion: CRCD could serve as a potential novel treatment strategy for glaucoma, via incorporating RAPA into CDs, in turn not only mitigating its toxic side effects but also enhancing its therapeutic efficacy.

Dynamic Cytoophidia during Late-Stage Drosophila Oogenesis.

CTP synthase (CTPS) catalyzes the final step of de novo synthesis of CTP. CTPS was first discovered to form filamentous structures termed cytoophidia in Drosophila ovarian cells. Subsequent studies have shown that cytoophidia are widely present in cells of three life domains. In the Drosophila ovary model, our previous studies mainly focused on the early and middle stages, with less involvement in the later stages. In this work, we focus on the later stages of female germline cells in Drosophila. We use live-cell imaging to capture the continuous dynamics of cytoophidia in Stages 10-12. We notice the heterogeneity of cytoophidia in the two types of germline cells (nurse cells and oocytes), manifested in significant differences in morphology, distribution, and dynamics. Surprisingly, we also find that neighboring nurse cells in the same egg chamber exhibit multiple dynamic patterns of cytoophidia over time. Although the described dynamics may be influenced by the in vitro incubation conditions, our observation provides an initial understanding of the dynamics of cytoophidia during late-stage Drosophila oogenesis.

Cells in the liver microenvironment regulate the process of liver metastasis.

The research of liver metastasis is a developing field. The ability of tumor cells to invade the liver depends on the complicated interactions between metastatic cells and local subpopulations in the liver (including Kupffer cells, hepatic stellate cells, liver sinusoidal endothelial cells, and immune-related cells). These interactions are mainly mediated by intercellular adhesion and the release of cytokines. Cell populations in the liver microenvironment can play a dual role in the progression of liver metastasis through different mechanisms. At the same time, we can see the participation of liver parenchymal cells and nonparenchymal cells in the process of liver metastasis of different tumors. Therefore, the purpose of this article is to summarize the relationship between cellular components of liver microenvironment and metastasis and emphasize the importance of different cells in the occurrence or potential regression of liver metastasis.

Enrichment of milk antioxidant activity by dietary supplementation of red clover isoflavone in cows and its improvement on mice intestinal health.

Red clover (Trifolium pratense) isoflavone was supplemented to dairy cows, and antioxidant capacity of milk was assessed. Treated cows increased the activities of antioxidant enzymes, reduced production of oxidation products, and enhanced the concentrations of vitamin E and vitamin C. Moreover, milk fatty acid profile was positive influenced by 8 g/kg red clover isoflavone, with changes in the lower saturated and higher unsaturated fatty acids. We further demonstrated the efficacy of antioxidant capacity of milk in mice, found that milk from cows feeding red clover isoflavone increased the expressions of antioxidant enzymes, and alleviated lipopolysaccharide (LPS)-stimulated tissue damage of duodenum and jejunum, which was related to upregulated metabolism pathways of carbohydrate, lipid, and amino acid, as well as downregulated inflammatory related pathways. Together, dietary supplementation of red clover isoflavone is an effective way to improve milk antioxidant capacity, providing a natural strategy for developing functional foods.

Insights into a functional model of key deubiquitinases UBP12/13 in plants.

Understanding the complexities of protein ubiquitination is crucial, as it plays a multifaceted role in controlling protein stability, activity, subcellular localization, and interaction, which are central to diverse biological processes. Deubiquitinases (DUBs) serve to reverse ubiquitination, but research progress in plant DUBs is noticeably limited. Among existing studies, UBIQUITIN-SPECIFIC PROTEASE 12 (UBP12) and UBP13 have garnered attention for their extensive role in diverse biological processes in plants. This review systematically summarizes the recent advancements in UBP12/13 studies, emphasizing their function, and their substrate specificity, their relationship with E3 ubiquitin ligases, and the similarities and differences with their mammalian orthologue, USP7. By unraveling the molecular mechanisms of UBP12/13, this review offers in-depth insights into the ubiquitin-proteasome system (UPS) in plants and aims to catalyze further explorations and comprehensive understanding in this field.

The XCL1-Mediated DNA Vaccine Targeting Type 1 Conventional Dendritic Cells Combined with Gemcitabine and Anti-PD1 Antibody Induces Potent Antitumor Immunity in a Mouse Lung Cancer Model.

With the advent of cancer immunotherapy, there is a growing interest in vaccine development as a means to activate the cellular immune system against cancer. Despite the promise of DNA vaccines in this regard, their effectiveness is hindered by poor immunogenicity, leading to modest therapeutic outcomes across various cancers. The role of Type 1 conventional dendritic cells (cDC1), capable of cross-presenting vaccine antigens to activate CD8+T cells, emerges as crucial for the antitumor function of DNA vaccines. To address the limitations of DNA vaccines, a promising approach involves targeting antigens to cDC1 through the fusion of XCL1, a ligand specific to the receptor XCR1 on the surface of cDC1. Here, female C57BL/6 mice were selected for tumor inoculation and immunotherapy. Additionally, recognizing the complexity of cancer, this study explored the use of combination therapies, particularly the combination of cDC1-targeted DNA vaccine with the chemotherapy drug Gemcitabine (Gem) and the anti-PD1 antibody in a mouse lung cancer model. The study's findings indicate that fusion antigens with XCL1 effectively enhance both the immunogenicity and antitumor effects of DNA vaccines. Moreover, the combination of the cDC1-targeted DNA vaccine with Gemcitabine and anti-PD1 antibody in the mouse lung cancer model demonstrates an improved antitumor effect, leading to the prolonged survival of mice. In conclusion, this research provides important support for the clinical investigation of cDC1-targeting DNA vaccines in combination with other therapies.

Effect of red clover isoflavones on hormone, immune, inflammatory, and plasma biochemistry in lactating dairy cows.

This study was to conducted to investigate the effect of red clover isoflavones on the health indicated by immune status and blood biochemistry in dairy cows. Sixty-eight healthy Holstein lactating cows were randomly divided into four treatments (n = 17 per treatment) from 5 blocks according to milk yield using a randomized complete block design. No initial differences in parity (2.13 ± 1.21), days in milk (165 ± 21 d), and milk yield (33.93 ± 3.81 kg/d) between groups. Cows were fed the basal diet supplemented with 0, 2, 4, or 8 g/kg red clover extract (RCE) in diet (dry matter based). Feeding, refusal feed weights, and milk yield were recorded three consecutive days in weeks 0, 4, 8, and 12. Blood was collected from the tail vein of the cows on the last day of weeks 4, 8 and 12, 1 h after the morning feeding, and analyzed for hormones, immunoglobulins, inflammatory markers, and markers of liver and kidney activities. The dry matter intake was significantly decreased by 3.7% in the 8 g/kg group (P < 0.05). The fat-corrected milk yield was significantly higher in both of the 2 and 4 g/kg groups (P < 0.01). Plasma estradiol and prolactin showed a quadratic effect with increasing RCE levels, with the highest in the 4 g/kg group (P < 0.05). Plasma tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß levels decreased linearly with increasing dietary RCE levels. Plasma IL-18 levels showed a quadratic effect with increasing dietary RCE levels, with significantly lower levels in both of the 2 and 4 g/kg groups (P < 0.05). Plasma immunoglobulin A and D-lactic acid levels showed a quadratic effect with increasing dietary RCE levels, with significantly higher level in the 4 g/kg group (P < 0.05). The liver function and kidney activity makers were similar (P > 0.05). These results recommend the supplementation of RCE at a level from 2 to 4 g/kg DM.

Integrating Network Pharmacology and Experimental Verification to Explore the Pharmacological Mechanisms of Radix Paeoniae Rubra Against Glioma.

Glioma has a high mortality and can hardly be completely cured. Radix Paeoniae Rubra (RPR) is a prevalent component in traditional Chinese medicine used for tumor treatments. We explored the mechanism of RPR in treating glioma using network pharmacology and experiments. A network pharmacology approach was used to screen active ingredients, targets of RPR and glioma. We then constructed a herb-active ingredient-target-pathway network and conducted protein-protein interaction (PPI) network analysis, as well as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecular docking was also performed. Using CCK-8, colony formation, and xenograft experiments, we evaluated the effect of RPR on glioma. The involved pathway and proteins were identified by Western blot. From public databases, we identified nine active RPR ingredients and 40 overlapping targets among 109 RPR targets and 1360 glioma-associated targets. The PPI analysis revealed ten targets, such as AKT1, TP53, and VEGFA, which were identified as hub genes. The results from GO and KEGG analysis highlighted the involvement of the PI3K/AKT pathway. A herb-active ingredient-target-pathway network was constructed. By docking molecular structures, six suitable conformations have been identified. The RPR extract demonstrated anti-tumor properties by inhibiting glioma cell proliferation in vitro and in vivo, likely achieved by suppressing the phosphorylation of the PI3K/AKT signaling pathway. RPR concurrently downregulated the phosphorylation level of AKT1 and the protein expression level of VEGFA, while upregulating the expression of P53 in the U251 cell line. Utilizing network pharmacology and molecular docking, our study not only predicted the impact of RPR on glioma but also delineated the herb-active ingredient-target-pathway network. Experimentally, we confirmed that RPR may exert its anti-tumor properties by inhibiting the phosphorylation of the PI3K/AKT pathway, including AKT1, and by regulating the expression levels of VEGFA and P53.

Donor Electrocardiogram Associations With Cardiac Dysfunction, Heart Transplant Use, and Survival: The Donor Heart Study.

BACKGROUND: Potential organ donors often exhibit abnormalities on electrocardiograms (ECGs) after brain death, but the physiological and prognostic significance of such abnormalities is unknown. OBJECTIVES: This study sought to characterize the prevalence of ECG abnormalities in a nationwide cohort of potential cardiac donors and their associations with cardiac dysfunction, use for heart transplantation (HT), and recipient outcomes. METHODS: The Donor Heart Study enrolled 4,333 potential cardiac organ donors at 8 organ procurement organizations across the United States from 2015 to 2020. A blinded expert reviewer interpreted all ECGs, which were obtained once hemodynamic stability was achieved after brain death and were repeated 24 ± 6 hours later. ECG findings were summarized, and their associations with other cardiac diagnostic findings, use for HT, and graft survival were assessed using univariable and multivariable regression. RESULTS: Initial ECGs were interpretable for 4,136 potential donors. Overall, 64% of ECGs were deemed clinically abnormal, most commonly as a result of a nonspecific St-T-wave abnormality (39%), T-wave inversion (19%), and/or QTc interval >500 ms (17%). Conduction abnormalities, ectopy, pathologic Q waves, and ST-segment elevations were less common (each present in ≤5% of donors) and resolved on repeat ECGs in most cases. Only pathological Q waves were significant predictors of donor heart nonuse (adjusted OR: 0.39; 95% CI: 0.29-0.53), and none were associated with graft survival at 1 year post-HT. CONCLUSIONS: ECG abnormalities are common in potential heart donors but often resolve on serial testing. Pathologic Q waves are associated with a lower likelihood of use for HT, but they do not portend worse graft survival.

Metformin improved a heterologous prime-boost of dual-targeting cancer vaccines to inhibit tumor growth in a melanoma mouse model.

Therapeutic cancer vaccines, which induce anti-tumor immunity by targeting specific antigens, constitute a promising approach to cancer therapy. Our previous work proposed an optimized heterologous immunization strategy using cancer gene vaccines co-targeting MUC1 and survivin. Administration of a DNA vaccine three times within a week followed by a single recombinant MVA (rMVA) boost was able to efficiently induce anti-tumor immunity and inhibit tumor growth in tumor-bearing mouse models However, the complex immunosuppressive tumor microenvironment always limits infiltration by vaccine-induced T cells. Modifying the immunosuppressive microenvironment of tumors would be a breakthrough in enhancing the therapeutic effects of a cancer vaccine. Recent studies have reported that metformin, a type 2 diabetes drug, may ameliorate the tumor microenvironment, thereby enhancing anti-tumor immunity. Here, we tested whether the combinational therapeutic strategy of cancer vaccines administered with a heterologous prime-boost strategy with metformin enhanced anti-tumor effects in a melanoma mouse model. The results showed that metformin promoted the transition of M2-tumor-associated macrophages (M2-TAM) to M1-TAM, induced more tumor-infiltrating proliferative CD4 and CD8 T cells, and decreased exhausted T cells. This combinational treatment induced anti-tumor immunity from cancer vaccines, ameliorating the tumor microenvironment, showing improved tumor inhibition, and prolonging survival in tumor-bearing mice compared with either a cancer vaccine or metformin alone.

A novel synchronous fluorescence spectrometry combined with fluorescence sensitization for the highly sensitive and simultaneous detection of enoxacin, ofloxacin and tetracycline hydrochloride residues in wastewater.

The synergistic effect of sodium dodecyl sulfate (SDS) and Mg2+ could significantly enhance the fluorescence intensity of enoxacin (ENO) at λex/λem = 269.2 nm/385.6 nm, ofloxacin (OFL) at λex/λem = 290.8 nm/466.2 nm and tetracycline hydrochloride (TCH) at λex/λem = 372.6 nm/514.8 nm. Moreover, when the wavelength difference (Δλ) was chosen 135 nm, the synchronous fluorescence spectra of the three antibiotic complexes could be well separated and the interference of the samples matrix were eliminated primely. Therefore, only one synchronous fluorescence scan was needed to simultaneously determine the three antibiotics. Based on these facts, a synchronous fluorescence spectrometry combining fluorescence sensitization for highly sensitive and selective determination of ENO, OFL and TCH residues in wastewater was developed for the first time. The experimental results showed that the concentrations of ENO, OFL and TCH in the range of 0.5-550 ng mL-1, 1-1500 ng mL-1 and 10-5500 ng mL-1 showed a good linear relationship with fluorescence intensity. The limits of detection were 0.0599 ng mL-1, 0.115 ng mL-1 and 0.151 ng mL-1, respectively. The recoveries of the actual sample were 87.50%-99.99 %, 93.00%-98.50 % and 85.70%-98.42 %, respectively. Overall, the novel synchronous fluorescence spectrometry established in the experiment has the advantages of high sensitivity, good selectivity, fast detection speed and high accuracy. It has been successfully applied to the detection of residual amounts of ENO, OFL and TCH in wastewater with satisfactory results.

Cracking the code of health security: unveiling the balanced indices through rank-ordered effect analysis.

BACKGROUND: Health security is a critical issue which involves multiple dimensions. It has received increasing attention in recent years, especially in China. In order to improve the national health level, China has made many efforts, such as the "Healthy China 2030" plan proposed several years ago. However, due to the complexity of its national conditions and the difficulty of index design, the results of these efforts are not significant. Therefore, it is necessary to construct a new measurement index system. METHODS: Based on the questionnaire of "Health China 2030", we have collected a total of 3,000 participants from all 31 provinces, autonomous regions, and municipalities in China. We used statistical methods such as multiple correspondence analysis and rank-ordered effect analysis to process the data. The balance index is constructed by a series of actions such as weight division, order calculation and ranking. RESULTS: Through multiple correspondence analysis, we can find that there was a close relation in the correspondence space between the satisfaction degrees 1, 2, and 3, while a far distance from satisfaction degrees 4 and 5. There were four positive and four negative indices separately based on the average expected level and four clusters after ordinal rank cluster analysis. Generally speaking, there are no prominent discrepancies across gender and residential areas. CONCLUSIONS: We created and examined balanced indicators for health security in China based on the "Health China 2030" questionnaire. The findings of this study give insight into the overall situation of health security in China and indicate opportunities for improvement.

Identification of a Branch Number Locus in Soybean Using BSA-Seq and GWAS Approaches.

The determination of the soybean branch number plays a pivotal role in plant morphogenesis and yield components. This polygenic trait is subject to environmental influences, and despite its significance, the genetic mechanisms governing the soybean branching number remain incompletely understood. To unravel these mechanisms, we conducted a comprehensive investigation employing a genome-wide association study (GWAS) and bulked sample analysis (BSA). The GWAS revealed 18 SNPs associated with the soybean branch number, among which qGBN3 on chromosome 2 emerged as a consistently detected locus across two years, utilizing different models. In parallel, a BSA was executed using an F2 population derived from contrasting cultivars, Wandou35 (low branching number) and Ruidou1 (high branching number). The BSA results pinpointed a significant quantitative trait locus (QTL), designated as qBBN1, located on chromosome 2 by four distinct methods. Importantly, both the GWAS and BSA methods concurred in co-locating qGBN3 and qBBN1. In the co-located region, 15 candidate genes were identified. Through gene annotation and RT-qPCR analysis, we predicted that Glyma.02G125200 and Glyma.02G125600 are candidate genes regulating the soybean branch number. These findings significantly enhance our comprehension of the genetic intricacies regulating the branch number in soybeans, offering promising candidate genes and materials for subsequent investigations aimed at augmenting the soybean yield. This research represents a crucial step toward unlocking the full potential of soybean cultivation through targeted genetic interventions.

Distinct plasma molecular profiles between early-onset and late-onset colorectal cancer patients revealed by metabolic and lipidomic analyses.

Colorectal cancer (CRC) incidence in younger adults has been steadily rising, warranting an in-depth investigation into the distinctions between early-onset CRC (EOCRC, < 50 years) and late-onset CRC (LOCRC, ≥ 50 years). Despite extensive study of clinical, pathological, and molecular traits, differentiating EOCRC from LOCRC and identifying potential biomarkers remain elusive. We analyzed plasma samples from healthy individuals, EOCRC, and LOCRC patients using liquid-chromatography mass spectrometry (LC/MS)-based metabolomics and lipidomics. Distinct polar metabolite and lipid profiles with significant metabolites altered in CRC group (e.g., choline and DG 40:4) were identified. Notably, EOCRC exhibited distinct polar metabolomic and differential lipidomic profiles compared to LOCRC, with polar metabolites like aminoadipate and uridine contributing significantly to the difference, and originating from pathways such as lysine biosynthesis and nucleotide metabolism. Furthermore, gene set enrichment analysis (GSEA) using independent TCGA gene expression data identified pathways significantly enriched in either EOCRC or LOCRC. Integrating gene expression and metabolomics data revealed numerous associations differentiating EOCRC and LOCRC. Our multi-omics integration underscores critical molecular distinctions, offers insights into the EOCRC development mechanisms and potential plasma biomarkers for diagnosis.

A Bioinformatics Tool for Identifying Intratumoral Microbes from the ORIEN Dataset.

Evidence supports significant interactions among microbes, immune cells, and tumor cells in at least 10%-20% of human cancers, emphasizing the importance of further investigating these complex relationships. However, the implications and significance of tumor-related microbes remain largely unknown. Studies have demonstrated the critical roles of host microbes in cancer prevention and treatment responses. Understanding interactions between host microbes and cancer can drive cancer diagnosis and microbial therapeutics (bugs as drugs). Computational identification of cancer-specific microbes and their associations is still challenging due to the high dimensionality and high sparsity of intratumoral microbiome data, which requires large datasets containing sufficient event observations to identify relationships, and the interactions within microbial communities, the heterogeneity in microbial composition, and other confounding effects that can lead to spurious associations. To solve these issues, we present a bioinformatics tool, microbial graph attention (MEGA), to identify the microbes most strongly associated with 12 cancer types. We demonstrate its utility on a dataset from a consortium of nine cancer centers in the Oncology Research Information Exchange Network. This package has three unique features: species-sample relations are represented in a heterogeneous graph and learned by a graph attention network; it incorporates metabolic and phylogenetic information to reflect intricate relationships within microbial communities; and it provides multiple functionalities for association interpretations and visualizations. We analyzed 2,704 tumor RNA sequencing samples and MEGA interpreted the tissue-resident microbial signatures of each of 12 cancer types. MEGA can effectively identify cancer-associated microbial signatures and refine their interactions with tumors. SIGNIFICANCE: Studying the tumor microbiome in high-throughput sequencing data is challenging because of the extremely sparse data matrices, heterogeneity, and high likelihood of contamination. We present a new deep learning tool, MEGA, to refine the organisms that interact with tumors.

Association of C-reactive protein level with adverse outcomes in patients with atrial fibrillation: A meta-analysis.

BACKGROUND: Studies on the association between C-reactive protein (CRP) level and poor outcomes have been yielded controversial results in patients with atrial fibrillation (AF). This meta-analysis sought to investigate the utility of elevated CRP level in predicting adverse outcomes in AF patients. METHODS: Two authors systematically searched PubMed and Embase databases (until December 10, 2022) for studies evaluating the value of elevated CRP level in predicting all-cause mortality, cardiovascular death, stroke, or major adverse cardiovascular events (MACEs) in AF patients. The predictive value of CRP was expressed by pooling adjusted hazard ratio (HR) with 95% confidence intervals (CI) for the highest versus the lowest level or per unit of log-transformed increase. RESULTS: Ten studies including 30,345 AF patients satisfied our inclusion criteria. For the highest versus the lowest CRP level, the pooled adjusted HR was 1.57 (95% CI 1.34-1.85) for all-cause mortality, 1.18 (95% CI 0.92-1.50) for cardiovascular death, and 1.57 (95% CI 1.10-2.24) for stroke, respectively. When analyzed the CRP level as continuous data, per unit of log-transformed increase was associated with a 27% higher risk of all-cause mortality (HR 1.27; 95% CI 1.23-1.32) and 16% higher risk of MACEs (HR 1.16; 95% CI 1.05-1.28). CONCLUSIONS: Elevated CRP level may be an independent predictor of all-cause mortality, stroke, and MACEs in patients with AF. CRP level at baseline can provide important prognostic information in risk classification of AF patients.