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Background Gastric cancer is a highly aggressive malignancy characterized by a complex tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs), which are a key component of the TME, exhibit significant heterogeneity and play crucial roles in tumor progression. Therefore, a comprehensive understanding of CAFs is essential for developing novel therapeutic strategies for gastric cancer. Methods This study investigates the characteristics and functional information of CAF subtypes and explores the intercellular communication between CAFs and malignant epithelial cells (ECs) in gastric cancer by analyzing single-cell sequencing data from 24 gastric cancer samples. CellChat was employed to map intercellular communication, and Seurat was used to integrate single-cell sequencing data with spatial transcriptome data to reconstruct a comprehensive single-cell spatial map. The spatial relationship between apCAFs and cancer cells was analyzed using multicolor immunohistochemistry. Results Cells were categorized into nine distinct categories, revealing a positive correlation between the proportions of epithelial cells (ECs) and fibroblasts. Furthermore, six fibroblast subpopulations were identified: inflammatory (iCAFs), pericytes, matrix (mCAFs), antigen-presenting (apCAFs), smooth muscle cells (SMCs), and proliferative CAFs (pCAFs). Each of these subpopulations was linked to various biological processes and immune responses. Malignant ECs exhibited heightened intercellular communication, particularly with CAF subpopulations, through specific ligand-receptor interactions. High-density regions of CAF subpopulations displayed spatial exclusivity, with pericytes serving as a source for iCAFs, mCAFs, and apCAFs. Notably, malignant ECs and apCAFs showed increased interactions, with certain ligand-receptor pairs potentially impacting the prognosis of gastric cancer. Multiplex immunohistochemistry (mIHC) confirmed the close spatial proximity of apCAFs to cancer cells in gastric cancer. Conclusion Our study provided a comprehensive characterization of CAF heterogeneity in gastric cancer and revealed the intricate intercellular networks within the TME. The identified CAF subpopulations and their interactions with malignant cells could serve as potential therapeutic targets. Highlights Six distinct fibroblast subpopulations with unique roles in tumor progression and immune response were identified in gastric cancer. Increased interactions between malignant epithelial cells and CAFs, highlighted the importance of specific ligand-receptor pairs in gastric cancer. ApCAFs were in close spatial proximity to cancer cells in gastric cancer.

Background Postoperative radiotherapy (RT) is increasingly used in hepatocellular carcinoma (HCC) patients with high-risk pathological features to reduce recurrence. However, RT may compromise liver regeneration (LR), particularly in patients with underlying hepatic dysfunction. Accurate evaluation of LR potential is therefore critical for individualized treatment planning. Methods In this retrospective, multicenter study, 315 HCC patients were enrolled—139 in the training cohort and 85 and 91 in two external validation cohorts. All patients underwent postoperative intensity-modulated radiotherapy (IMRT), and pre-RT portal-venous phase contrast-enhanced computed tomography (CE-CT) scans were analyzed to extract whole-liver histogram features. Patients with a ≥ 10% increase in remnant liver volume within 1 year were classified as effective liver regeneration (ELR), and the remainder as impaired liver regeneration (ILR). Independent predictors of ELR were identified using logistic regression, and a nomogram was developed and evaluated with ROC, calibration, and decision-curve analyses. Results Among the 315 patients, 187 (59.4%) achieved ELR and 128 (40.6%) showed ILR. Multivariate analysis identified kurtosis, mean liver dose (Liver-Dmean), standardized remnant liver volume (SRLV), and fibrosis stage as independent predictors of ELR. The nomogram demonstrated robust performance with AUCs of 0.866 (95% CI: 0.804–0.928) in the training cohort and 0.794 (95% CI: 0.698–0.889) and 0.733 (95% CI: 0.617–0.848) in the validation cohorts. Conclusion We established and externally validated a CE-CT histogram-based nomogram that accurately predicts LR following adjuvant IMRT in high-risk HCC patients. This model offers a clinically applicable tool to optimize postoperative management by balancing oncologic control with preservation of hepatic function. Trial registration This is a study that follows the Declaration of Helsinki and good clinical practice guidelines, and was approved by the Ethics Committee of Lanzhou University Second Hospital, the second affiliated hospital of shandong first medical university and the Affiliated Hospital of Qingdao University(approval no. 2025 A-539). As a retrospective analysis without any intervention in patient treatment, the Ethics Committees waived the requirement for individual informed consent. Graphical Abstract

A homogeneous fluorescence quenching immunoassay is described for simultaneous separation and detection of aflatoxin M 1 (AFM 1 ) in milk. The novel assay relies on monoclonal antibody (mAb) functionalized Fe 3 O 4 decorated reduced-graphene oxide (rGO-Fe 3 O 4 -mAb) as both capture probe and energy acceptor, combined with tetramethylrhodamine cadaverine-labeled aflatoxin B 1 (AFB 1 -TRCA) as the energy donor. In the assay, AFB 1 -TRCA binds to rGO-Fe 3 O 4 -mAb in the absence of AFM 1 , quenching the fluorescence of TRCA by resonance energy transfer. Significantly, the immunoassay integrates sample preparation and detection into a single step, by using magnetic graphene composites to avoid washing and centrifugation steps, and the assay can be completed within 10 min. Under optimized conditions, the visual and quantitative detection limits of the assay for AFM 1 were 50 and 3.8 ng L −1 , respectively, which were significantly lower than those obtained by fluorescence polarization immunoassay using the same immunoreagents. Owing to its operation and highly sensitivity, the proposed assay provides a powerful tool for the detection of AFM 1 . Graphical abstract

Accurate evaluation of inflammation severity in ulcerative colitis (UC) can guide treatment strategy selection. The potential value of the pericolic fat attenuation index (FAI) on CT as an indicator of disease severity remains unknown. This study aimed to assess the diagnostic accuracy of pericolic FAI in predicting UC severity. This retrospective study enrolled 148 patients (mean age 48 years; 87 males). The fat attenuation on CT was measured in four different locations: the mesocolic vascular side (MS) and opposite side of MS (OMS) around the most severe bowel lesion, the retroperitoneal space (RS), and the subcutaneous area. The fat attenuation indices (FAI , FAI , and FAI ) were calculated as the fat attenuation measured in MS, OMS, and RS, respectively, minus that of the subcutaneous area, and were obtained in the non-enhanced, arterial, and delayed phases. Correlations between the FAI and UC Endoscopic Index of Severity (UCEIS) were assessed using Spearman's correlation. Predictors of severe UC (UCEIS ≥7) were selected by univariable analysis. The performance of FAI in predicting severe UC was evaluated using the area under the receiver operating characteristic curve (AUC). The FAI and FAI scores were significantly higher than FAI in three phases (all < 0.001). The FAI and FAI scores moderately correlated with the UCEIS score ( = 0.474-0.649 among the three phases). Additionally, FAI and FAI identified severe UC, with AUC varying from 0.77 to 0.85. Increased CT attenuation of pericolic adipose tissue could serve as a noninvasive marker for evaluating UC severity. FAI and FAI of three phases showed similar prediction accuracies for severe UC identification.

Proline and its synthesis enzyme pyrroline-5-carboxylate reductase 1 (PYCR1) are implicated in epithelial-mesenchymal transition (EMT), yet how proline and PYCR1 function in allergic asthmatic airway remodeling via EMT has not yet been addressed. In the present study, increased levels of plasma proline and PYCR1 were observed in asthmatic patients. Similarly, proline and PYCR1 in lung tissues were higher in a murine allergic asthma model induced by house dust mites (HDMs). Pycr1 knockout (KO) decreased proline in lung tissues, with reduced airway remodeling and EMT. Mechanistically, loss of Pycr1 restrained HDM-induced EMT by modulating mitochondrial fission, metabolic reprogramming, and the AKT/mTOR1 and WNT3a/β-catenin signaling pathways in airway epithelial cells. Therapeutic inhibition of PYCR1 in wild-type mice disrupted HDM-induced airway inflammation and remodeling. Deprivation of exogeneous proline partially relieved HDM-induced airway remodeling to some extent. Collectively, this study illuminates that proline and PYCR1 involved with airway remodeling in allergic asthma could be viable targets for asthma treatment.

Purpose This study aimed to explore the feasibility and safety of the tunnel approach in laparoscopic radical right hemicolectomy for colon cancer. Methods From July 2016 to October 2018, a total of 106 consecutive patients with colon cancer who underwent laparoscopic radical right hemicolectomy at the Affiliated Cancer Hospital of Zhengzhou University were enrolled. The patients were stratified into either a tunnel approach (TA) (n = 56) group or traditional medial approach (MA) (n = 50) group according to the surgical technique performed. The baseline demographics, perioperative outcomes and oncologic outcomes were compared between the two groups. Results The baseline characteristics did not differ between groups. The TA group had significantly less blood loss [20.0 (10.0–40.0) vs. 100 (100.0–150.0) ml, p < 0.001] and a shorter operation time [128.4 ± 16.7 vs. 145.6 ± 20.3 min, p < 0.001] than the MA group. The time to first flatus and postoperative hospital stay were similar [3.0 (2.0–4.0) vs. 3.0 (3–4.0) days, p = 0.329; 10.4 ± 2.6 vs. 10.7 ± 3.0 days, p = 0.506] between the two groups. The conversion to laparotomy and complication rates were similar between groups (0 vs. 6.0%, p = 0.203; 14.3% vs. 18.0%, p = 0.603, respectively). No treatment-related deaths occurred in either group. The TA group did not have significantly better survival outcomes than the MA group (p = 0.372). Conclusions The TA seems to allow for more favourable results in terms of blood loss and operative time than the MA, with similar results regarding time to first flatus, hospital stay, postoperative complication rate, conversion rate and oncologic outcomes; moreover, the TA is easier for beginners to master.

The paper applies modern industrial economic theories to give an overview of the emerging phenomenon of digital personal assistants (DPAs). A DPA is an automated system that serves personal usage only and interacts with the user in natural language, meanwhile applying original and third-party services to obtain information and perform various actions. We analyze the economic benefits of increasing usage of DPAs, such as reduction of transaction costs, procompetitive effects, and boosting the e-commerce economy. Besides benefits, however, adopting DPA in life may also contain some risks and downsides, which may reduce the positive welfare effects or even lead to decreasing welfare: biased services, market power on the DPA market and economic dependence on a dominant DPA, potential leveraging of DPA suppliers’ market power into neighboring markets, personalized data (ab)use and privacy, media bias and manipulation of public opinion, and loss of autonomy. We identify the degree of effective competition and the degree of rationality of consumer behavior as the most relevant factors for either the advantages or the disadvantages to prevail and derive first regulatory implications.

Gastric cancer is one of the most prevalent malignant tumors worldwide, characterized by high incidence and mortality rates. At present, comprehensive surgical treatment has enhanced the prognosis of locally advanced gastric cancer patients significantly. However, the postoperative recurrence rate remains high, and the long-term survival for patients is sub-optimal. In recent years, immunotherapy has garnered extensive attention as an innovative approach to the treatment of gastric cancer. Indeed, multiple studies have validated its therapeutic effects in advanced gastric cancer patients, leading to its incorporation into treatment guidelines. Currently, researchers are exploring the application of immunotherapy in the neoadjuvant setting globally in order to further adjust and refine neoadjuvant immunotherapy regimens for gastric cancer. This article summarizes the research progress and controversies associated with neoadjuvant immunotherapy in gastric cancer, aiming to optimize clinical benefits for gastric cancer patients undergoing this treatment approach. The retrieval methods of this study encompassed databases such as PubMed, Google Scholar, Web of Science, clinicaltrials.gov, etc. The retrieved articles included guidelines, consensus, meta-analyses, clinical trials, and reviews related to locally advanced gastric cancer published up to January 2024.

Cryptococcus neoformans (C. neoformans) is an important opportunistic fungal pathogen for pulmonary cryptococcosis. Previously, we demonstrated that CD146 mediated the adhesion of C. neoformans to the airway epithelium. CD146 is more than an adhesion molecule. In the present study, we aimed to explore the roles of CD146 in the inflammatory response in pulmonary cryptococcosis. CD146 was decreased in lung tissues from patients with pulmonary cryptococcosis. Similarly, C. neoformans reduced pulmonary CD146 expression in mice following intratracheal inoculation. To explore the pathological roles of CD146 reduction in pulmonary cryptococcosis, CD146 knockout (KO) mice were inoculated with C. neoformans via intratracheal instillation. CD146 deficiency aggravated C. neoformans infection, as evidenced by a shortened survival time and increased fungal burdens in the lung. Inflammatory type 2 cytokines (IL-4, IL-5, and TNF-α) and alternatively activated macrophages were increased in the pulmonary tissues of CD146 KO-infected mice. CD146 is expressed in immune cells (macrophages, etc.) and nonimmune cells, i.e., epithelial cells and endothelial cells. Bone marrow chimeric mice were established and infected with C. neoformans. CD146 deficiency in immune cells but not in nonimmune cells increased fungal burdens in the lung. Mechanistically, upon C. neoformans challenge, CD146 KO macrophages produced more neutrophil chemokine KC and inflammatory cytokine TNF-α. Meanwhile, CD146 KO macrophages decreased the fungicidity and production of reactive oxygen species. Collectively, C. neoformans infection decreased CD146 in pulmonary tissues, leading to inflammatory type 2 responses, while CD146 deficiency worsened pulmonary cryptococcosis.

A homogeneous fluorescence quenching immunoassay is described for simultaneous separation and detection of aflatoxin M.sub.1 (AFM.sub.1) in milk. The novel assay relies on monoclonal antibody (mAb) functionalized Fe.sub.3O.sub.4 decorated reduced-graphene oxide (rGO-Fe.sub.3O.sub.4-mAb) as both capture probe and energy acceptor, combined with tetramethylrhodamine cadaverine-labeled aflatoxin B.sub.1 (AFB.sub.1-TRCA) as the energy donor. In the assay, AFB.sub.1-TRCA binds to rGO-Fe.sub.3O.sub.4-mAb in the absence of AFM.sub.1, quenching the fluorescence of TRCA by resonance energy transfer. Significantly, the immunoassay integrates sample preparation and detection into a single step, by using magnetic graphene composites to avoid washing and centrifugation steps, and the assay can be completed within 10 min. Under optimized conditions, the visual and quantitative detection limits of the assay for AFM.sub.1 were 50 and 3.8 ng L.sup.-1, respectively, which were significantly lower than those obtained by fluorescence polarization immunoassay using the same immunoreagents. Owing to its operation and highly sensitivity, the proposed assay provides a powerful tool for the detection of AFM.sub.1. Graphical abstract