Core-shell Ru@Co2P synergistic catalyst as polysulfides adsorption-catalytic conversion mediator with enhanced redox kinetics in lithium-sulfur batteries.

Lithium-sulfur batteries (LSBs) have emerged as the research hotspot due to their compelling merits, including high specific capacity (1675 mAh g-1), theoretical energy density (2600 Wh kg-1), environmental friendliness, and economic advantages. However, challenges still exist for further application due to their inherent issues such as the natural insulation, shuttle effect, and volume expansion of sulfur cathode during the continuous cycle processes. These factors obstruct the lithium ions (Li+) transfer process and sulfur utilization, resulting in significant impedance and inducing inferior battery performance. Herein, the core-shell nanocube anchoring ruthenium atoms and dicobalt phosphate (Ru@Co2P@NC) were fabricated as the effective catalyst and inhibited barrier for LSBs. On the one hand, the core-shell structure offers numerous channels to expedite Li+ diffusion. On the other hand, ruthenium (Ru) and dicobalt phosphate (Co2P) active sites facilitate the chemical capture of lithium polysulfides (LiPSs), accelerating sluggish kinetics. Ru@Co2P@NC modified cells not only exhibited a high initial specific capacity (1609.35 mAh g-1) at 0.5C and enduring stability with high specific capacity retention of 906.60 mAh g-1 at 0.5C after 400 cycles but also possessed low capacity attenuation rate of 0.07 % per cycle after 600 cycles (1C, Sulfur loading: 1.2 mg). Interestingly, the modified cells demonstrated a high specific capacity and long-cycle stability with high sulfur loading (from 1.984 to 3.137 mg), which provides a promising research approach for high-performance LSBs.

Multi-omics analysis reveals that agaro-oligosaccharides with different degrees of polymerization alleviate colitis in mice by regulating intestinal flora and arginine synthesis.

Inflammatory bowel disease (IBD) is a common chronic disease with a complex etiology, characterized by body weight loss, intestinal barrier damage, and an imbalance of intestinal flora, posing a significant threat to people's health. In this work, we studied whether safer natural active agaro-oligosaccharides (AOSs) benefit mice with IBD and elucidated their underlying mechanisms. The findings indicated that oral administration of agarobiose (A2), agarotriose (A3), and agarotetraose (A4) contributed to alleviating body weight loss and colon shortening, as well as enhancing IL-10 levels while reducing IL-6, IL-1ß, and TNF-α. AOSs improved colon disruption, reduced the number of goblet cells caused by DSS, and enhanced the expression of Muc2, ZO-1, and occludin-1 to repair the intestinal barrier. It is noteworthy that A3 demonstrated superior outcomes in the evaluated AOSs relative to A2 and A4. This was evidenced by an increase in Bacteroidota and reduced Firmicutes at the phylum level, which corrected DSS-induced intestinal dysbiosis and significantly restored disrupted metabolic pathways, including amino acid and lipid metabolism. The differential metabolites between the AOS treatment groups and the model group were mainly enriched in arginine synthesis with co-regulated critical substances N-acetyl-L-citrulline and N2-acetylornithine, which alleviated colitis. This evidence offers a fresh perspective on the potential application of AOSs as functional foods to improve intestinal inflammation and metabolism.

Viruses Identified in Shrews (Soricidae) and Their Biomedical Significance.

Shrews (Soricidae) are common small wild mammals. Some species of shrews, such as Asian house shrews (Suncus murinus), have a significant overlap in their habitats with humans and domestic animals. Currently, over 190 species of viruses in 32 families, including Adenoviridae, Arenaviridae, Arteriviridae, Astroviridae, Anelloviridae, Bornaviridae, Caliciviridae, Chuviridae, Coronaviridae, Filoviridae, Flaviviridae, Hantaviridae, Hepadnaviridae, Hepeviridae, Nairoviridae, Nodaviridae, Orthoherpesviridae, Orthomyxoviridae, Paramyxoviridae, Parvoviridae, Phenuiviridae, Picobirnaviridae, Picornaviridae, Polyomaviridae, Poxviridae, Rhabdoviridae, Sedoreoviridae, Spinareoviridae, and three unclassified families, have been identified in shrews. Diverse shrew viruses, such as Borna disease virus 1, Langya virus, and severe fever with thrombocytopenia syndrome virus, cause diseases in humans and/or domestic animals, posing significant threats to public health and animal health. This review compiled fundamental information about shrews and provided a comprehensive summary of the viruses that have been detected in shrews, with the aim of facilitating a deep understanding of shrews and the diversity, epidemiology, and risks of their viruses.

Predicting tissue distribution and tumor delivery of nanoparticles in mice using machine learning models.

Nanoparticles (NPs) can be designed for targeted delivery in cancer nanomedicine, but the challenge is a low delivery efficiency (DE) to the tumor site. Understanding the impact of NPs' physicochemical properties on target tissue distribution and tumor DE can help improve the design of nanomedicines. Multiple machine learning and artificial intelligence models, including linear regression, support vector machine, random forest, gradient boosting, and deep neural networks (DNN), were trained and validated to predict tissue distribution and tumor delivery based on NPs' physicochemical properties and tumor therapeutic strategies with the dataset from Nano-Tumor Database. Compared to other machine learning models, the DNN model had superior predictions of DE to tumors and major tissues. The determination coefficients (R2) for the test datasets were 0.41, 0.42, 0.45, 0.79, 0.87, and 0.83 for DE in tumor, heart, liver, spleen, lung, and kidney, respectively. All the R2 and root mean squared error (RMSE) results of the test datasets were similar to the 5-fold cross validation results. Feature importance analysis showed that the core material of NPs played an important role in output predictions among all physicochemical properties. Furthermore, multiple NP formulations with greater DE to the tumor were determined by the DNN model. To facilitate model applications, the final model was converted to a web dashboard. This model could serve as a high-throughput pre-screening tool to support the design of new and efficient nanomedicines with greater tumor DE and serve as an alternative tool to reduce, refine, and partially replace animal experimentation in cancer nanomedicine research.

EXPRESS: Exploring the association between hemoglobin, albumin, lymphocyte, and platelet score and all-cause mortality among middle-aged and older patients with osteoarthritis.

Integrating hemoglobin, albumin, lymphocyte, and platelets (HALP) score can simultaneously reflect systemic inflammation and nutritional status. Some evidence suggests its prognostic value in certain malignancies, however, the impact of HALP on individuals with osteoarthritis (OA) who were middle-aged and older remains unknown.This retrospective cohort study included 3,566 individuals from National Health and Nutrition Examination Survey (NHANES) 2003-2018. The study endpoint was the all-cause mortality of OA patients. Weighted Cox models were used to assess the relationship between HALP score and all-cause mortality. Subgroup analyses stratified by age, gender, diabetes, dyslipidemia, cardiovascular disease (CVD) was conducted. After the follow-up is terminated, 920 participants experienced all-cause mortality, and 2,646 participants survived. After adjusting for covariates, the continuous analysis revealed an inverse association between HALP score and all-cause mortality [hazard ratio (HR)=0.89, 95% confidence interval (CI): 0.83-0.95]. The categorical analysis indicated that the lowest quartile of HALP score was related to higher all-cause mortality by using the highest quartile of HALP score as a reference (HR=1.46, 95%CI: 1.18-1.81). The association between HALP score with lowest quartile and all-cause mortality remained significant across different subgroups.This study suggested that HALP score was linked with all-cause mortality among middle-aged and older individuals diagnosed with OA, thereby indicating its potential as a reliable prognostic indicator for this patient population.

A green extraction method for agar with improved thermal stability and water holding capacity.

The conventional agar extraction method has drawbacks such as high energy consumption, low yield, poor quality, and possible residual harmful factors, which greatly limit its application in high-end fields such as biomedicine and high-end materials. This work explored a new freezing-thawing-high-temperature coupling technique for agar extraction. It increased the yield and the strength of agar by 10.6 % and 13.7 %, respectively, as compared to direct high-temperature extraction of agar (HA). The greater molecular weight and lower sulfate content of agar obtained from freeze-thaw cycles combined with high temperature extraction (FA) may be attributed to the desulfurization effect caused by freeze-thaw cycles and the preservation of the molecular chain structure. The reduction in sulfate content decreases the steric hindrance resistance of the polysaccharide chains, enhances their interactions, and promotes the regularity and density of the agar structure, while also improving its water retention and thermal stability. In conclusion, this research can offer a theoretical basis and guidance for the eco-friendly extraction of agar with improved agar characteristics and expended its applications.

Bioanalysis of free antisense oligonucleotide payload from antibody-oligonucleotide conjugate by hybridization LC-MS/MS.

Background: Antisense oligonucleotides (ASOs) have been conjugated to various moieties, such as peptides, antibodies or Fab regions of antibodies, to enhance their delivery to target tissues. The quantitation of free ASO (ASO payload) is critical to characterize its pharmacokinetics/pharmacodynamics (PK/PD) properties and biodistribution after delivery of the peptide/antibody/Fab ASO conjugates.Results: We developed a hybridization-based LC-MS/MS methodology for quantification of free ASO in tissues in the presence of Fab-ASO and ASO with linker (ASO-linker).Conclusion: The developed method was applied to measure accurately the free ASO concentrations in liver and gastrocnemius in mice that were dosed with Fab-ASO. This methodology has also been applied to free ASO bioanalysis for other antibody-ASO and Fab-ASO conjugates in various tissues and plasma/serum samples.

[Box: see text].

Human umbilical cord mesenchymal stem cells derived-exosomes on VEGF-A in hypoxic-induced mice retinal astrocytes and mice model of retinopathy of prematurity.

AIM: To observe the effect of human umbilical cord mesenchymal stem cells (hUCMSCs) secretions on the relevant factors in mouse retinal astrocytes, and to investigate the effect of hUCMSCs on the expression of vascular endothelial growth factor-A (VEGF-A) and to observe the therapeutic effect on the mouse model of retinopathy of prematurity (ROP). METHODS: Cultured hUCMSCs and extracted exosomes from them and then retinal astrocytes were divided into control group and hypoxia group. MTT assay, flow cytometry, reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect related indicators. Possible mechanisms by which hUCMSCs exosomes affect VEGF-A expression in hypoxia-induced mouse retinal astrocytes were explored. At last, the efficacy of exosomes of UCMSCs in a mouse ROP model was explored. Graphpad6 was used to comprehensively process data information. RESULTS: The secretion was successfully extracted from the culture supernatant of hUCMSCs by gradient ultracentrifugation. Reactive oxygen species (ROS) and hypoxia inducible factor-1α (HIF-1α) of mice retinal astrocytes under different hypoxia time and the expression level of VEGF-A protein and VEGF-A mRNA increased, and the ROP cell model was established after 6h of hypoxia. The secretions of medium and high concentrations of hUCMSCs can reduce ROS and HIF-1α, the expression levels of VEGF-A protein and VEGF-A mRNA are statistically significant and concentration dependent. Compared with the ROP cell model group, the expression of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signal pathway related factors in the hUCMSCs exocrine group is significantly decreased. The intravitreal injection of the secretions of medium and high concentrations of hUCMSCs can reduce VEGF-A and HIF-1α in ROP model tissues. HE staining shows that the number of retinal neovascularization in ROP mice decreases with the increase of the dose of hUCMSCs secretion. CONCLUSION: In a hypoxia induced mouse retinal astrocyte model, hUCMSCs exosomes are found to effectively reduce the expression of HIF-1α and VEGF-A, which are positively correlated with the concentration of hUCMSCs exosomes. HUCMSCs exosomes can effectively reduce the number of retinal neovascularization and the expression of HIF-1α and VEGF-A proteins in ROP mice, and are positively correlated with drug dosage. Besides, they can reduce the related factors on the PI3K/AKT/mTOR signaling pathway.

Taxane combined with lobaplatin or anthracycline for neoadjuvant chemotherapy of triple-negative breast cancer: a randomized, controlled, phase II study.

BACKGROUND: Previous studies have shown that the addition of platinum to neoadjuvant chemotherapy (NAC) improved outcomes for patients with triple-negative breast cancer (TNBC). However, no studies have assessed the efficacy and safety of the combination of taxane and lobaplatin. In this study, we conducted a randomized controlled phase II clinical study to compare the efficacy and safety of taxane combined with lobaplatin or anthracycline. METHODS: We randomly allocated patients with stage I-III TNBC into Arm A and Arm B. Arm A received six cycles of taxane combined with lobaplatin (TL). Arm B received six cycles of taxane combined with anthracycline and cyclophosphamide (TEC) or eight cycles of anthracycline combined with cyclophosphamide and sequential use of taxane (EC-T). Both Arms underwent surgery after NAC. The primary endpoint was the pathologic complete response (pCR). Secondary endpoints were event-free survival (EFS), overall survival (OS), and safety. RESULTS: A total of 103 patients (51 in Arm A and 52 in Arm B) were assessed. The pCR rate of Arm A was significantly higher than that of Arm B (41.2% vs. 21.2%, P = 0.028). Patients with positive lymph nodes and low neutrophil-to-lymphocyte ratio (NLR) benefited significantly more from Arm A than those with negative lymph nodes and high NLR (Pinteraction = 0.001, Pinteraction = 0.012, respectively). There was no significant difference in EFS (P = 0.895) or OS (P = 0.633) between the two arms. The prevalence of grade-3/4 anemia was higher in Arm A (P = 0.015), and the prevalence of grade-3/4 neutropenia was higher in Arm B (P = 0.044). CONCLUSIONS: Neoadjuvant taxane plus lobaplatin has shown better efficacy than taxane plus anthracycline, and both regimens have similar toxicity profiles. This trial may provide a reference for a better combination strategy of immunotherapy in NAC for TNBC in the future.

2023 White Paper on Recent Issues in Bioanalysis: Deuterated Drugs; LNP; Tumor/FFPE Biopsy; Targeted Proteomics; Small Molecule Covalent Inhibitors; Chiral Bioanalysis; Remote Regulatory Assessments; Sample Reconciliation/Chain of Custody (PART 1A - Recommendations on Mass Spectrometry, Chromatography, Sample Preparation Latest Developments, Challenges, and Solutions and BMV/Regulated Bioanalysis PART 1B - Regulatory Agencies' Inputs on Regulated Bioanalysis/BMV, Biomarkers/IVD/CDx/BAV, Immunogenicity, Gene & Cell Therapy and Vaccine).

The 17th Workshop on Recent Issues in Bioanalysis (17th WRIB) took place in Orlando, FL, USA on June 19-23, 2023. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 17th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.Moreover, in-depth workshops on "EU IVDR 2017/746 Implementation and impact for the Global Biomarker Community: How to Comply with this NEW Regulation" and on "US FDA/OSIS Remote Regulatory Assessments (RRAs)" were the special features of the 17th edition.As in previous years, WRIB continued to gather a wide diversity of international, industry opinion leaders and regulatory authority experts working on both small and large molecules as well as gene, cell therapies and vaccines to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance, and achieving scientific excellence on bioanalytical issues.This 2023 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2023 edition of this comprehensive White Paper has been divided into three parts for editorial reasons.This publication covers the recommendations on Mass Spectrometry Assays, Regulated Bioanalysis/BMV (Part 1A) and Regulatory Inputs (Part 1B). Part 2 (Biomarkers, IVD/CDx, LBA and Cell-Based Assays) and Part 3 (Gene Therapy, Cell therapy, Vaccines and Biotherapeutics Immunogenicity) are published in volume 16 of Bioanalysis, issues 7 and 8 (2024), respectively.

Chinese herbal medicine Shufeng Jiedu capsule for mild to moderate COVID-19: a multicenter, randomized, double-blind, placebo-controlled phase II trial.

Background: The COVID-19 pandemic has had a profound global impact, although the majority of recently infected cases have presented with mild to moderate symptoms. Previous clinical studies have demonstrated that Shufeng Jiedu (SFJD) capsule, a Chinese herbal patent medicine, effectively alleviates symptoms associated with the common cold, H1N1 influenza, and COVID-19. This study aimed to assess the efficacy and safety of SFJD capsules in managing symptoms of mild to moderate COVID-19 infection. Methods: A randomized, double-blind, placebo-controlled trial was conducted from May to December 2022 at two hospitals in China. Mild and moderate COVID-19-infected patients presenting respiratory symptoms within 3 days from onset were randomly assigned to either the SFJD or placebo groups in a 1:1 ratio. Individuals received SFJD capsules or a placebo three times daily for five consecutive days. Participants were followed up for more than 14 days after their RT-PCR nucleoid acid test for SARS-CoV-2 turned negative. The primary outcome measure was time to alleviate COVID-19 symptoms from baseline until the end of follow-up. Results: A total of 478 participants were screened; ultimately, 407 completed the trial after randomization (SFJD, n = 203; placebo, n = 204). No statistically significant difference in baseline parameters was observed between the two groups. The median time to alleviate all symptoms was 7 days in the SFJD group compared to 8 days in the placebo group (p = 0.037). Notably, the SFJD group significantly attenuated fever/chills (p = 0.04) and headache (p = 0.016) compared to the placebo group. Furthermore, the median time taken to reach normal body temperature within 24 h was reduced by 7 hours in the SFJD group compared to the placebo group (p = 0.033). No deaths or instances of serious or critical conditions occurred during this trial period; moreover, no serious adverse events were reported. Conclusion: The trial was conducted in a unique controlled hospital setting, and the 5-day treatment with SFJD capsules resulted in a 1-day reduction in overall symptoms, particularly headache and fever/chills, among COVID-19-infected participants with mild or moderate symptoms. Compared to placebo, SFJD capsules were found to be safe with fewer side effects. SFJD capsules could potentially serve as an effective treatment for alleviating mild to moderate symptoms of COVID-19. Clinical Trial Registration: https://www.isrctn.com/, identifier ISRCTN14236594.

[Effects of water level on soil seed bank in the floodplain wetland of Juzhang River, China]. / 水位变化对沮漳河河漫滩湿地土壤种子库的影响.

Aiming to understand the responses of soil seed bank to different water levels, we investigated vegetation and soil seed bank along a water level gradient (frequently flooded area, unflooded area) on the floodplain wetland of Juzhang River. We used the structural equation model to explore the direct and indirect effects of water level on soil seed bank, and used non-metric multidimensional scaling (NMDS) to assess the role of soil seed bank for vegetation regeneration. The results showed that the density of transient and persistent seed banks at unflooded area was 36.9% and 7.8% higher than that of frequently flooded area, respectively. Shannon index and Pielou index of seed bank and vegetation were significantly affected by water level and sampling location. Water level significantly affected the similarity between seed bank and aboveground vegetation, and the similarity of persistent seed bank with aboveground vegetation was significantly higher than that with transient seed bank. Structural equation model showed that water level had a direct effect on seed bank density, and indirect effects on density and richness of seed bank via affecting soil pH and NH4+-N content. NMDS results showed that there was no significant difference in the composition of the persistent seed bank and vegetation community in autumn under different water levels, but water level significantly changed the community composition of transient seed bank. Transient seed bank was affected by the vegetation and soil property, while persistent seed bank was determined by aboveground vegetation and water level. Although soil seed bank had low regeneration potential for the vegetation communities in floodplain wetlands, soil seed bank could not be neglected during the restoration of propagule diversity after disturbance in wetlands. Persistent seed bank would be an importance source of diversity of propagules for floodplain wetlands restoration following disturbance.

Raman spectroscopy study on terephthalamide crystal at high pressures.

In this study, we have investigated the structural stability of terephthalamide (TPA) crystal at pressure from ambient to 15 GPa in the diamond anvil cell at room temperature by Raman spectroscopy. Assignment for the Raman vibration modes of TPA crystal at ambient conditions has been performed based on the density functional theory (DFT) calculations. Pressure-induced structural transition was monitored using in-situ Raman spectroscopy. Remarkable changes (including the appearance of new Raman peaks, disappearance of original Raman bands, discontinuous changes in the pressure dependence of some Raman wavenumbers at different pressures) in Raman spectra were observed at approximately 1.3 and 5.2 GPa, provided clear evidences for two pressure-induced phase transitions: phase I to phase II at ∼1.3 GPa, phase II to phase III at ∼5.2 GPa.

Integration of Clinical Trial Spatial Multiomics Analysis and Virtual Clinical Trials Enables Immunotherapy Response Prediction and Biomarker Discovery.

Due to the lack of treatment options, there remains a need to advance new therapeutics in hepatocellular carcinoma (HCC). The traditional approach moves from initial molecular discovery through animal models to human trials to advance novel systemic therapies that improve treatment outcomes for patients with cancer. Computational methods that simulate tumors mathematically to describe cellular and molecular interactions are emerging as promising tools to simulate the impact of therapy entirely in silico, potentially greatly accelerating delivery of new therapeutics to patients. To facilitate the design of dosing regimens and identification of potential biomarkers for immunotherapy, we developed a new computational model to track tumor progression at the organ scale while capturing the spatial heterogeneity of the tumor in HCC. This computational model of spatial quantitative systems pharmacology was designed to simulate the effects of combination immunotherapy. The model was initiated using literature-derived parameter values and fitted to the specifics of HCC. Model validation was done through comparison with spatial multiomics data from a neoadjuvant HCC clinical trial combining anti-PD1 immunotherapy and a multitargeted tyrosine kinase inhibitor cabozantinib. Validation using spatial proteomics data from imaging mass cytometry demonstrated that closer proximity between CD8 T cells and macrophages correlated with nonresponse. We also compared the model output with Visium spatial transcriptomics profiling of samples from posttreatment tumor resections in the clinical trial and from another independent study of anti-PD1 monotherapy. Spatial transcriptomics data confirmed simulation results, suggesting the importance of spatial patterns of tumor vasculature and TGFß in tumor and immune cell interactions. Our findings demonstrate that incorporating mathematical modeling and computer simulations with high-throughput spatial multiomics data provides a novel approach for patient outcome prediction and biomarker discovery. Significance: Incorporating mathematical modeling and computer simulations with high-throughput spatial multiomics data provides an effective approach for patient outcome prediction and biomarker discovery.

Subclone from CT26 resistant to anti-PD-1 therapy associated with increased expression of genes related to glucocorticoids.

BACKGROUND: Although the use of anti-PD-1 antibodies has fundamentally changed traditional cancer treatment, most patients are resistant to anti-PD-1 treatment. Glucocorticoids (GCs) play an important role in tumorigenesis and tumor progression, but the role of endogenous GCs in resistance to anti-PD-1 antibody therapy remains unclear. METHODS: Single cell-derived cell lines (SCDCLs) were generated from a colorectal cancer cell line (CT26) using limiting dilution. We analyzed tumor tissues from anti-PD-1 antibody-treated and untreated mice inoculated with SCDCLs via transcriptome sequencing and flow cytometry to detect pathway activity and immune cell composition changes in the tumor microenvironment. RESULTS: Five SCDCLs were inoculated into wild-type BALB/c mice (all tumorigenic). Single-cell clone (SCC)-2 exhibited the slowest growth rates both in vivo and in vitro compared to other single-cell clones, and better long-term survival than SCC1 and CT26. Flow cytometry showed that SCC2 tumor-bearing mice exhibited significantly higher infiltration of T cells within the tumor tissue, and higher expression of PD-1 on these T cells than the other groups in vivo. However, the SCC2 group showed no response to anti-PD-1 therapy. Transcriptome analysis revealed that the SCC2 group exhibited increased expression of genes related to GC (Hsd11b1, Sgk3, Tgfbr2, and Il7r) compared to SCC2-anti-PD-1 treated tumors. CONCLUSIONS: GC pathway activation is related to resistance to anti-PD-1 therapy.

The biomedical knowledge graph of symptom phenotype in coronary artery plaque: machine learning-based analysis of real-world clinical data.

A knowledge graph can effectively showcase the essential characteristics of data and is increasingly emerging as a significant means of integrating information in the field of artificial intelligence. Coronary artery plaque represents a significant etiology of cardiovascular events, posing a diagnostic challenge for clinicians who are confronted with a multitude of nonspecific symptoms. To visualize the hierarchical relationship network graph of the molecular mechanisms underlying plaque properties and symptom phenotypes, patient symptomatology was extracted from electronic health record data from real-world clinical settings. Phenotypic networks were constructed utilizing clinical data and protein‒protein interaction networks. Machine learning techniques, including convolutional neural networks, Dijkstra's algorithm, and gene ontology semantic similarity, were employed to quantify clinical and biological features within the network. The resulting features were then utilized to train a K-nearest neighbor model, yielding 23 symptoms, 41 association rules, and 61 hub genes across the three types of plaques studied, achieving an area under the curve of 92.5%. Weighted correlation network analysis and pathway enrichment were subsequently utilized to identify lipid status-related genes and inflammation-associated pathways that could help explain the differences in plaque properties. To confirm the validity of the network graph model, we conducted coexpression analysis of the hub genes to evaluate their potential diagnostic value. Additionally, we investigated immune cell infiltration, examined the correlations between hub genes and immune cells, and validated the reliability of the identified biological pathways. By integrating clinical data and molecular network information, this biomedical knowledge graph model effectively elucidated the potential molecular mechanisms that collude symptoms, diseases, and molecules.

Expressions of CXCR3 and PD-1 on T cells and their clinical relevance in colorectal cancer.

PURPOSE: Clinical application of immunotherapy represented by Programmed Death-1 (PD-1) monoclonal antibody has changed the treatment paradigm for colorectal cancer (CRC), and tumor-infiltrating T lymphocytes are critical for anti-PD-1 therapy in CRC. However, there are few studies on the relationship between the expression CXCR3 on T lymphocytes and the clinical aspects of CRC. In this study, we analyzed the expression levels of CXCR3 and PD-1 in CD8+ and CD4+ T lymphocytes in healthy donors (HDs) and patients with CRC. METHODS: We detected the expressions of CXCR3 and PD-1 on T lymphocytes in peripheral blood of healthy donors as well as peripheral blood, tumor tissue and para-cancerous tissues of patients with CRC using flow cytometry. We also analyzed the relationship between the expressions of CXCR3 and PD-1 on T lymphocytes and the pathological characteristics of CRC using t test. RESULTS: Expression of CXCR3 on tumor-infiltrating T lymphocytes was lower, whereas the expression of PD-1 was higher than that on para-cancerous tissues and PB in patients with CRC. In patients with lymph node metastasis of CRC, the expressions levels of CXCR3+ PD-1+ on tumor-infiltrating CD8+ and CD4+ T lymphocytes were higher than those in patients without lymph node metastasis. The levels of CXCR3+ PD-1+ expressions differed depending on the primary tumor site. CONCLUSION: Expressions of CXCR3 and PD-1 on tumor-infiltrating T lymphocytes are related to the development of CRC and metastasis, providing clues for exploring the pathogenesis of CRC and developing new strategies for tumor immunotherapy.

Correlation of CT parameters and PD-L1 expression status in gastric cancer.

OBJECTIVE: We aimed to explore the correlation between routine computed tomography (CT) imaging features and programmed cell death ligand-1(PD-L1) expression status in gastric cancer and evaluate the predictive value of imaging parameters for this immunotherapy biomarker. MATERIALS AND METHODS: Patients with gastric adenocarcinoma who underwent abdominal CT three-stage enhanced scan and PD-L1 immunohistochemical testing before treatment were retrospectively examined. All diagnoses were confirmed through pathology. According to the expression status of PD-L1, they were divided into the positive (CPS ≥ 5) or negative group (CPS < 5). Baseline CT imaging features were collected. Diagnostic performances of the different variables were evaluated using receiver operating characteristic (ROC) curve. RESULTS: In total, 67 patients (17 women and 50 men; mean age: 59.55 ± 10.22 years) with gastric adenocarcinoma were included in the study. The overall stages, probability of maximum lymph node short diameter > 1 cm and peak of lesion enhancement occurring in the arterial phase were statistically significant between the two groups (p < 0.05). Moreover, the arterial enhancement fraction (AEF) was significantly higher in the positive group than that in the negative group (p < 0.05), and ROC curve analysis showed that the AEF exhibited a high evaluation efficacy (area under the curve [AUC] = 0.724 [95% confidence interval (CI): 0.602-0.826]). The combined parameters had the best diagnostic efficacy (AUC = 0.825 [95%CI: 0.716-0.933]), sensitivity (75.00%), and specificity (81.40%). CONCLUSIONS: These findings confirm a correlation between CT imaging features and PD-L1 expression status in gastric cancer, and AEF may help evaluate high PD-L1 expression and select patients suitable for immunotherapy.

Extracellular volume fraction can predict the treatment response and survival outcome of colorectal cancer liver metastases.

OBJECTIVE: To assess the prognostic value of pre- and post-therapeutic changes in extracellular volume (ECV) fraction of liver metastases (LMs) for treatment response (TR) and survival outcomes in colorectal cancer liver metastases (CRLM). METHODS: 186 LMs were confirmed by pathology or follow-up (Training: 130; Test: 56). We analyzed the changes in ECV fraction of LMs before and after 2 cycles of chemotherapy combined with bevacizumab. After 12 cycles, we evaluated the TR on LMs based on the RECIST v1.1. Relative changes in ECV fraction and Hounsfield Units (HU), defined as ΔECV and ΔHU, were associated with progression-free survival (PFS), overall survival (OS), and TR. We identified TR predictors with multivariate logistic regression and PFS, OS risk factors with COX analysis. RESULTS: 186 LMs were classified as TR lesions (TR+: 84) and non-TR lesions (TR-:102). ΔECV, ΔHUA-E, and texture could distinguish the TR of LMs in training and test set (P < 0.05). ΔECV [Odds ratio (OR): 1.03; 95% Confidence interval (CI): 1.02-1.05, P < 0.01] was an independent predictor of TR-. Area under the curve (AUC), sensitivity and specificity of TR model in training and test set were 0.87, 0.84, 90.14%, 90.32%, 72.88%, 64.00%, respectively. High CRD_score indicates that patients have shorter PFS [Hazard ratio (HR): 2.01; 95%CI: 1.02-3.98, P = 0.045)] and OS (HR: 1.89, 95%CI: 1.04-3.42, P = 0.038). CONCLUSION: ΔECV can be used as an independent predictor of TR of CRLM chemotherapy combined with bevacizumab.

Two Hematological Markers Predicting the Efficacy and Prognosis of Neoadjuvant Chemotherapy Using Lobaplatin Against Triple-Negative Breast Cancer.

BACKGROUND: Our previous work indicated that the addition of lobaplatin to combined therapy with taxane and anthracycline can improve the pathological complete response rate of neoadjuvant therapy for triple-negative breast cancer (TNBC) and lengthen long-term survival significantly, but the therapeutic markers of this regimen are unclear. METHODS: Eighty-three patients who met the inclusion criteria were included in this post hoc analysis. We analyzed the association between platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) before neoadjuvant chemotherapy with the efficacy and prognosis after treatment with docetaxel, epirubicin, and lobaplatin neoadjuvant chemotherapy regimen. χ2 test and Cox regression were used to analyze the association between PLR and NLR with total pathologic complete response (tpCR), as well as the association between PLR and NLR with event-free survival (EFS) and overall survival (OS), respectively. RESULTS: The tpCR rate in the PLR- group was 49.0% (25/51), which was significantly higher than that in the PLR+ group (25.0% [8/32], P = .032). The tpCR rate in the NLR- group was 49.1% (26/53), which was significantly higher than that in the NLR+ group (23.3% [7/30], P = .024). The tpCR rate of the PLR-NLR- (PLR- and NLR-) group was 53.7% (22/41), which was significantly higher than that of the PLR+/NLR+ (PLR+ or/and NLR+) group (26.1% [11/42]; P = .012). EFS and OS in the NLR+ group were significantly shorter than those in the NLR- group (P = .028 for EFS; P = .047 for OS). Patients in the PLR-NLR- group had a longer EFS than those in the PLR+/NLR+ group (P = .002). CONCLUSION: PLR and NLR could be used to predict the efficacy of neoadjuvant therapy with the taxane, anthracycline, and lobaplatin regimen for patients with TNBC, as patients who had lower PLR and NLR values had a higher tpCR rate and a better long-term prognosis.