Component analysis using UPLC-Q-TOF/MS and quality evaluation using fingerprinting and chemometrics for hops.

Hops, extensively cultivated in China for their food and medicinal applications, currently lack well-defined chemical markers to evaluate variations in their quality. The study aimed to explore variations in the quality of Chinese hops by the chemical characteristics of hops, employing UPLC-Q-TOF/MS, integrated with chemical fingerprinting and chemometrics. The results indicated that Chinese hops are abundant in polyphenols and bitter acids. The integration of UPLC-Q-TOF/MS, Chemical fingerprinting, and chemometrics revealed to be an accurate and effective approach for assessing the quality of Chinese hops. In this study, ten important chemical markers were found to be useful in differentiating various hop varieties. Moreover, the support vector machine showed a prediction accuracy of 92.3077% in identifying Chinese hop varieties. The strategy of the study lays the groundwork for classifying Chinese hop varieties and serves as a prerequisite for future quality control studies, particularly focusing on chemical compositions.

Focus on negatively regulated NLRs in inflammation and cancer.

Nucleotide-binding and oligomerization structural domain (NOD)-like receptors (NLRs) play an important role in innate immunity as cytoplasmic pattern recognition receptors (PRRs). Over the past decade, considerable progress has been made in understanding the mechanisms by which NLR family members regulate immune system function, particularly the formation of inflammasome and downstream inflammatory signals. However, recent studies have shown that some members of the NLRs, including Nlrp12, NLRX1, and NLRC3, are important in the negative regulation of inflammatory signaling and are involved in the development of various diseases, including inflammatory diseases and cancer. Based on this, in this review, we first summarize the interactions between canonical and non-canonical nuclear factor-κB (NF-κB) signaling pathways that are mainly involved in NLRs, then highlight the mechanisms by which the above NLRs negatively regulate inflammatory signaling responses as well as their roles in tumor progression, and finally summarize the synthetic and natural derivatives with therapeutic effects on these NLRs, which are considered as potential therapeutic agents for overcoming inflammatory diseases.

The prognostic value of LAYN in HPV-related head and neck squamous cell carcinoma and its influence on immune cell infiltration.

BACKGROUND: HPV-positive head and neck squamous cell carcinoma (HNSCC) exhibits different characteristics from HPV-negative tumors in terms of tumor development, clinical features, treatment response, and prognosis. Layilin (LAYN), which contains homology with C-type lectins, plays a critical role in tumorigenesis and cancer progression. However, the prognostic value of LAYN and the relationship between LAYN and immune infiltration levels in HPV-related HNSCC patients still require a comprehensive understanding. Herein, we aimed to assess the prognostic value of LAYN and to investigate its underlying immunological function in HPV-related HNSCC. METHODS: Through various bioinformatics methods, we analyzed the data from The Cancer Genome Atlas (TCGA), Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA) databases to explore the potential underlying oncogenic impression of LAYN, including the relevance of LAYN to survival outcomes, clinicopathological factors, immune cell infiltration, and immune marker sets in HPV-related HNSCC. The expression levels of LAYN and HPV were also verified in HNSCC patient tissues. RESULTS: LAYN was differentially expressed in a variety of tumors. The expression of LAYN in HNSCC was significantly higher than that in adjacent normal tissues (P < 0.0001), and high expression of LAYN was correlated with poor overall survival (OS) in HNSCC patients (Hazard Ratio (HR) = 1.3, P = 0.035). Moreover, LAYN expression level in HPV-positive HNSCC patients was significantly lower than that in HPV-negative patients, with HPV-positive HNSCC patients displaying a trend of favorable prognosis. In addition, the relationship between LAYN expression and immune infiltration levels in HPV-positive HNSCC group was less tightly correlated than that in HPV-negative HNSCC group, and there was a strong relationship between LAYN expression and markers of M2 macrophage (P < 0.001) and exhausted T cells (P < 0.05) in HPV-negative HNSCC. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis suggested that LAYN potentially influenced tumor progression through HPV infection and other cancer-related pathways. CONCLUSIONS: LAYN might contribute to tumorigenesis via its positive correlation with immune checkpoint molecules and tumor-associated macrophages (TAMs). Our study might provide a novel prognostic biomarker and latent therapeutic target for the treatment of HPV-related HNSCC.

Experiences and Outcomes of Indigenous Patients Undergoing Bariatric Surgery: a Mixed-Method Scoping Review.

Obesity and type 2 diabetes (T2D) are growing global health concerns. Evidence suggests that Indigenous peoples are at higher lifetime risk of obesity and its associated conditions. Obesity increases the risk of T2D, cardiovascular disease, and all-cause mortality. Bariatric surgery is the most sustained and effective intervention for treating obesity-associated medical problems. This review aims to explore the experiences and outcomes of Indigenous peoples undergoing bariatric surgery in Canada, the USA, Australia, and New Zealand (CANZUS). Analysis of quantitative data revealed that Indigenous patients had fewer bariatric procedures, poorer clinic attendance, similar weight loss outcomes and slightly higher post-operative complication rates. Qualitative data analysis revealed that Indigenous patients living with obesity have a desire to improve their health and quality of life.

The emerging role of ectodermal neural cortex 1 in cancer.

Ectodermal neural cortex 1 (ENC1) is a protein that plays a crucial role in the regulation of various cellular processes such as cell proliferation, differentiation, and apoptosis. Numerous studies have shown that ENC1 is overexpressed in various types of cancers, including breast, lung, pancreatic, and colorectal cancer, and its upregulation is correlated with a poorer prognosis. In addition to its role in cancer growth and spreading, ENC1 has also been linked to neuronal process development and neural crest cell differentiation. In this review, we provide an overview of the current knowledge on the relationship between ENC1 and cancer. We discuss the molecular mechanisms by which ENC1 contributes to tumorigenesis, including its involvement in multiple oncogenic signaling pathways. We also summarize the potential of targeting ENC1 for cancer therapy, as its inhibition has been shown to significantly reduce cancer cell invasion, growth, and metastasis. Finally, we highlight the remaining gaps in our understanding of ENC1's role in cancer and propose potential directions for future research.

Let-7c-5p Down Regulates the Proliferation of Colorectal Cancer Through the MAPK-ERK-Signaling Pathway.

Colorectal cancer (CRC) is one of the most prevalent and life-threatening cancers. Rapid cell proliferation is the leading cause of cancer-related death in CRC. MicroRNAs (miRNAs) have been identified to play essential roles in the proliferation of CRC. Differential expression of let-7c-5p in CRC was assessed using a GEO dataset, and confirmed through RT-qPCR using CRC subject tissues. Let-7c-5p-overexpressing HCT8 cell line was constructed by transfecting let-7c-5p. Bioinformatics analysis identified that DUSP7 is the target gene of let-7c-5p. Further experimental assays, including Cell Counting Kit-8 (CCK8), EdU staining, cell colony, and Western Blot assays, confirmed the target genes and pathway of let-7c-5p. Receiver operator characteristic curve (ROC) analysis was performed to evaluate the diagnostic value of let-7c-5p for CRC. Finally, survival analysis was performed to determine the effect of DUSP7 and let-7c-5p on the prognosis of CRC patients. RT-qPCR analysis showed that the expression level of let-7c-5p was significantly increased in CRC subject tissues compared to the adjacent tissue. Overexpression of let-7c-5p promoted cell proliferation in HCT8 cell line. Furthermore, the MAPK-ERK pathway's protein expression of p-ERK1/2 was downregulated, while the ratio of Bcl-2/Bax was increased by let-7c-5p transfection in HCT 8. ROC analysis demonstrated that the expressive level of let-7c-5p had higher diagnostic value for CRC. Survival curve analysis indicated that high expression of DUSP7 and low expression of let-7c-5p were associated with poor prognosis in CRC patients. The findings suggest that let-7c-5p exerts an antitumor function by inhibiting the DUSP7-mediated MAPK-ERK pathway. Both DUSP7 and let-7c-5p have the potential to serve as prognostic biomarkers in CRC patients.

Design, synthesis and anticancer evaluation of polymethoxy aurones as potential cell cycle inhibitors.

Background: Cancer is the most fatal disease in humans and the aberrant activity of various cell cycle proteins results in uncontrolled tumor cell proliferation, thus, regulating the cell cycle is an attractive target in cancer therapy. Objectives: Aurone is a naturally occurring active compound with a wide range of biological activities, of which 3, 4, 5-trimethoxyphenyl (TMP) is an important microtubule targeting pharmacophore. Based on the pharmacophore combination principle, we incorporate the TMP pharmacophore into the aurone structure and design a novel polymethoxy derivative that is expected to inhibit tumor cell proliferation through regulating the cell cycle. Methods: By introducing different substituents on C-4' and C-3', a series of new 4, 5, 6-trimethoxy aurone derivatives have been designed and synthesized. DU145, MCF-7 and H1299 cell lines were selected to evaluate their anticancer activity. The compound with the best cytotoxicity was then selected and the anticancer mechanisms were investigated by network pharmacology, flow cytometry, Western blot, and cell heat transfer assay. ADMET prediction evaluated the draggability of aurone derivatives. Results: Aurones 1b and 1c have selective anti-proliferative activity against DU145 cells. Among them, the compound 1c have better cytotoxicity against DU145. Compound 1c could bind the active cavity of CyclinB1/CDK1/CKS complex protein and induced G2/M phase arrest of DU145 cells by regulating the expression of CyclinB1 and p21. Compound 1c satisfies the Lipinski rule, is suitable for the absorption and metabolism index, and has a lower risk of cardiac toxicity. Conclusions: Polymethoxy aurones 1c might function as a CyclinB1/CDK1 inhibitor that deserved to be further developed for the treatment of prostate cancer.

Prescription drug usage as measure of comorbidity resolution after bariatric surgery: a population-based cohort study.

BACKGROUND: Obesity is a chronic and progressive disease associated with significant morbidity, mortality, and health-care costs. Bariatric surgery is the most effective intervention for sustainable weight loss and resolution of obesity-related comorbidities. Studies examining comorbidity resolution largely rely on individual self-reported outcomes and electronic record reviews. We present a population-based study looking at prescription medication utilization before and after bariatric surgery as a measure of comorbidity resolution. METHODS: All patients enrolled in the Center for Metabolic and Bariatric Surgery who underwent either gastric bypass or sleeve gastrectomy between 2013 and 2019 in Manitoba were included. Demographic information, follow up, and outpatient prescription dispensation data were obtained from the Manitoba Population Research Data Repository housed at the Manitoba Centre for Health Policy for 5 years pre- and post-surgery. RESULTS: A total of 1184 patients were included. Antidepressants and selective serotonin reuptake inhibitors were the most commonly prescribed classes, and along with thyroid medication, utilization remained stable after bariatric surgery. Proton pump inhibitors and opioid class drugs increased at 1 year after surgery then returned to baseline. Glucose and lipid-lowering medications, including statins, biguanides, sulfonylureas, and insulin, were decreased. Antihypertensives, including ACE inhibitors, calcium channel blockers, angiotensin receptors blockers, thiazides, and beta blockers, similarly decreased. CONCLUSION: This is the first Canadian study employing a provincial-wide prescription database to measure long-term comorbidity resolution after bariatric surgery. The use of administrative data eliminates potential biases and inaccuracies in follow up and self-reported outcomes. Consistent with the literature, prescriptions for the treatment of metabolic syndrome all decreased and were sustained at long-term follow up. Further studies are needed to delineate the effects of altered pharmaceutical utilization on patient quality of life and health-care expenditures.

AI diagnostic performance based on multiple imaging modalities for ovarian tumor: A systematic review and meta-analysis.

Background: In recent years, AI has been applied to disease diagnosis in many medical and engineering researches. We aimed to explore the diagnostic performance of the models based on different imaging modalities for ovarian cancer. Methods: PubMed, EMBASE, Web of Science, and Wanfang Database were searched. The search scope was all published Chinese and English literatures about AI diagnosis of benign and malignant ovarian tumors. The literature was screened and data extracted according to inclusion and exclusion criteria. Quadas-2 was used to evaluate the quality of the included literature, STATA 17.0. was used for statistical analysis, and forest plots and funnel plots were drawn to visualize the study results. Results: A total of 11 studies were included, 3 of them were modeled based on ultrasound, 6 based on MRI, and 2 based on CT. The pooled AUROCs of studies based on ultrasound, MRI and CT were 0.94 (95% CI 0.88-1.00), 0.82 (95% CI 0.71-0.93) and 0.82 (95% Cl 0.78-0.86), respectively. The values of I2 were 99.92%, 99.91% and 92.64% based on ultrasound, MRI and CT. Funnel plot suggested no publication bias. Conclusion: The models based on ultrasound have the best performance in diagnostic of ovarian cancer.

Early prediction of acute pancreatitis severity based on changes in pancreatic and peripancreatic computed tomography radiomics nomogram.

Background: Early identification of severe acute pancreatitis (SAP) is key to reducing mortality and improving prognosis. We aimed to establish a radiomics model and nomogram for early prediction of acute pancreatitis (AP) severity based on contrast-enhanced computed tomography (CT) images. Methods: We retrospectively analyzed 215 patients with first-episode AP, including 141 in the training cohort (87 men and 54 women, mean age 51.37±16.09 years) and 74 in the test cohort (40 men and 34 women, mean age 55.49±17.83 years). Radiomics features were extracted from portal venous phase images based on pancreatic and peripancreatic regions. The light gradient boosting machine (LightGBM) algorithm was used for feature selection, a logistic regression (LR) model was established and trained by 10-fold cross-validation, and a nomogram was established based on the best features. The model's predictive performance was evaluated according to the area under the curve (AUC) of the receiver operating characteristic (ROC) curve, sensitivity, specificity, and accuracy. Results: A total of 13 optimal radiomics features were selected by LightGBM for LR model building. The AUC of the radiomics (LR) model was 0.992 [95% confidence interval (CI): 0.963-0.996] in the training cohort, 0.965 (95% CI: 0.924-0.981) in the validation cohort, and 0.894 (95% CI: 0.789-0.966) in the test cohort. The sensitivity was 0.862 (95% CI: 0.674-0.954), the specificity was 0.800 (95% CI: 0.649-0.899), and the accuracy was 0.824 (95% CI: 0.720-0.919). The nomogram based on the 13 radiomics features showed that SAP would be predicted when the total score was greater than 124. Conclusions: The radiomics model based on enhanced-CT images of pancreatic and peripancreatic regions performed well in the early prediction of AP severity. The nomogram based on selected radiomics features could provide a reference for AP clinical assessment.

Dysregulation of innate cell types in the hepatic immune microenvironment of alcoholic liver cirrhosis.

Introduction: The risk of alcoholic cirrhosis increases in a dose- and time-dependent manner with alcohol consumption and ethanol metabolism in the liver. Currently, no effective antifibrotic therapies are available. We aimed to obtain a better understanding of the cellular and molecular mechanisms involved in the pathogenesis of liver cirrhosis. Methods: We performed single-cell RNA-sequencing to analyze immune cells from the liver tissue and peripheral blood form patients with alcoholic cirrhosis and healthy controls to profile the transcriptomes of more than 100,000 single human cells and yield molecular definitions for non-parenchymal cell types. In addition, we performed single-cell RNA-sequencing analysis to reveal the immune microenvironment related to alcoholic liver cirrhosis. Hematoxylin and eosin, Immunofluorescence staining and Flow cytometric analysis were employed to study the difference between tissues and cells with or without alcoholic cirrhosis. Results: We identified a fibrosis-associated M1 subpopulation of macrophages that expands in liver fibrosis, differentiates from circulating monocytes, and is pro-fibrogenic. We also define mucosal-associated invariant T (MAIT) cells that expand in alcoholic cirrhosis and are topographically restricted to the fibrotic niche. Multilineage modeling of ligand and receptor interactions between the fibrosis-associated macrophages, MAIT, and NK cells revealed the intra-fibrotic activity of several pro-fibrogenic pathways, including responses to cytokines and antigen processing and presentation, natural killer cell-mediated cytotoxicity, cell adhesion molecules, Th1/Th2/Th17 cell differentiation, IL-17 signaling pathway, and Toll-like receptor signaling pathway. Discussion: Our work dissects unanticipated aspects of the cellular and molecular basis of human organ alcoholic fibrosis at the single-cell level and provides a conceptual framework for the discovery of rational therapeutic targets in liver alcoholic cirrhosis.

Utilizing Grasp Monitoring to Predict Microsurgical Expertise.

INTRODUCTION: Most microsurgical procedures require the surgeon to use tools to grasp and hold fragile objects in the surgical site. Prior research on grasping in surgery has mostly either been in other surgical techniques or used grasping as an auxiliary metric. We focus on microsurgery and investigate what grasping can tell about microsurgical skill and suturing performance. This study lays groundwork for using automatic detection of grasps to evaluate surgical skill. METHODS: Five expert surgeons and six novices completed sutures on a microsurgical training board. Video recordings of the performance were annotated for the number of grasps, while an eye tracker recorded the participants' pupil dilations for cognitive workload assessment. Performance was measured with suturing duration and the University of Western Ontario Microsurgical Skills Assessment instrument (UWOMSA). Differences in skill, suturing performance and cognitive workload were compared with grasping behavior. RESULTS: Novices needed significantly more grasps to complete sutures and failed to grasp more often than the experts. The number of grasps affected the suturing duration more in novices. Decreasing suturing efficiency as measured by UWOMSA instrument was associated with increase in grasps, even when we controlled for overall skill differences. Novices displayed larger pupil dilations when averaged over a sufficiently large sample, and the difference increased after the grasp. CONCLUSIONS: Grasping action during microsurgical procedures can be used as a conceptually simple yet objective proxy in microsurgical performance assessment. If the grasps could be detected automatically, they could be used to aid in computational evaluation of surgical trainees' performance.

Upregulated ENC1 predicts unfavorable prognosis and correlates with immune infiltration in endometrial cancer.

A better knowledge of the molecular process behind uterine corpus endometrial carcinoma (UCEC) is important for prognosis prediction and the development of innovative targeted gene therapies. The purpose of this research is to discover critical genes associated with UCEC. We analyzed the gene expression profiles of TCGA-UCEC and GSE17025, respectively, using Weighted Gene Co-expression Network Analysis (WGCNA) and differential gene expression analysis. From four sets of findings, a total of 95 overlapping genes were retrieved. On the 95 overlapping genes, KEGG pathway and GO enrichment analysis were conducted. Then, we mapped the PPI network of 95 overlapping genes using the STRING database. Twenty hub genes were evaluated using the Cytohubba plugin, including NR3C1, ATF3, KLF15, THRA, NR4A1, FOSB, PER3, HLF, NTRK3, EGR3, MAPK13, ARNTL2, PKM2, SCD, EIF5A, ADHFE1, RERGL, TUB, and ENC1. The expression levels of NR3C1, PKM2, and ENC1 were shown to be adversely linked with the survival time of UCEC patients using univariate Cox regression analysis and Kaplan-Meier survival calculation. ENC1 were also overexpressed in UCEC tumor tissues or cell lines, as shown by quantitative real-time PCR and Western blotting. Then we looked into it further and discovered that ENC1 expression was linked to tumor microenvironment and predicted various immunological checkpoints. In conclusion, our data indicate that ENC1 may be required for the development of UCEC and may serve as a future biomarker for diagnosis and therapy.

Recent Advances in the Enzyme-Activatable Organic Fluorescent Probes for Tumor Imaging and Therapy.

The exploration of advanced probes for cancer diagnosis and treatment is of high importance in fundamental research and clinical practice. In comparison with the traditional "always-on" probes, the emerging activatable probes enjoy advantages in promoted accuracy for tumor theranostics by specifically releasing or activating fluorophores at the targeting sites. The main designing principle for these probes is to incorporate responsive groups that can specifically react with the biomarkers (e. g., enzymes) involved in tumorigenesis and progression, realizing the controlled activation in tumors. In this review, we summarize the latest advances in the molecular design and biomedical application of enzyme-responsive organic fluorescent probes. Particularly, the fluorophores can be endowed with ability of generating reactive oxygen species (ROS) to afford the photosensitizers, highlighting the potential of these probes in simultaneous tumor imaging and therapy with rational design. We hope that this review could inspire more research interests in the development of tumor-targeting theranostic probes for advanced biological studies.

Diagnostic Accuracy of Deep Learning and Radiomics in Lung Cancer Staging: A Systematic Review and Meta-Analysis.

Background: Artificial intelligence has far surpassed previous related technologies in image recognition and is increasingly used in medical image analysis. We aimed to explore the diagnostic accuracy of the models based on deep learning or radiomics for lung cancer staging. Methods: Studies were systematically reviewed using literature searches from PubMed, EMBASE, Web of Science, and Wanfang Database, according to PRISMA guidelines. Studies about the diagnostic accuracy of radiomics and deep learning, including the identifications of lung cancer, tumor types, malignant lung nodules and lymph node metastase, were included. After identifying the articles, the methodological quality was assessed using the QUADAS-2 checklist. We extracted the characteristic of each study; the sensitivity, specificity, and AUROC for lung cancer diagnosis were summarized for subgroup analysis. Results: The systematic review identified 19 eligible studies, of which 14 used radiomics models and 5 used deep learning models. The pooled AUROC of 7 studies to determine whether patients had lung cancer was 0.83 (95% CI 0.78-0.88). The pooled AUROC of 9 studies to determine whether patients had NSCLC was 0.78 (95% CI 0.73-0.83). The pooled AUROC of the 6 studies that determined patients had malignant lung nodules was 0.79 (95% CI 0.77-0.82). The pooled AUROC of the other 6 studies that determined whether patients had lymph node metastases was 0.74 (95% CI 0.66-0.82). Conclusion: The models based on deep learning or radiomics have the potential to improve diagnostic accuracy for lung cancer staging. Systematic Review Registration: https://inplasy.com/inplasy-2022-3-0167/, identifier: INPLASY202230167.

Type 2 and Type 17 Invariant Natural Killer T Cells Contribute to Local Eosinophilic and Neutrophilic Inflammation and Their Function Is Regulated by Mucosal Microenvironment in Nasal Polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by heterogeneous inflammatory endotypes of unknown etiology. Invariant natural killer T (iNKT) cells are multifunctional innate T cells that exhibit Th1-, Th2-, and Th17-like characteristics. We investigated functional relationships between iNKT cells and inflammatory subtypes of CRSwNP. Eighty patients with CRSwNP and thirty-two control subjects were recruited in this study. Flow cytometry was used to analyze the frequencies and functions of iNKT cells and their subsets in peripheral blood mononuclear cells (PBMCs) and tissues. Polyp tissue homogenates were used to study the multifunctionality of iNKT cells. iNKT cells were significantly increased in polyps (0.41%) than in control mucosa (0.12%). iNKT cells were determined in the paucigranunlocytic (n=20), eosinophilic (n=22), neutrophilic (n=23), and mixed granulocytic (n=13) phenotypes of CRSwNP. The percentages of iNKT cells and HLA-DR+PD-1+ subsets were lower in eosinophilic or mixed granulocytic polyps than those of other phenotypes. iNKT cells and subsets were enriched in polyp tissues than in matched PBMCs. The evaluation of surface markers, transcription factors, and signature cytokines indicated that the frequencies of iNKT2 and iNKT17 subsets were significantly increased in eosinophilic and neutrophilic polyps, respectively, than in the paucigranulocytic group. Moreover, the production of type 2 (partially dependent on IL-7) and type 17 (partially dependent on IL-23) iNKT cells could be stimulated by eosinophilic and neutrophilic homogenates, respectively. Our study revealed that type 2 and type 17 iNKT cells were involved in eosinophilic and neutrophilic inflammation, respectively, in CRSwNP, while different inflammatory microenvironments could modulate the functions of iNKT cells, suggesting a role of iNKT cells in feedback mechanisms and local inflammation.

Gliadin interacted with tea polyphenols: potential application and action mechanism.

The effect of tea polyphenols (TPs) on noodles quality was investigated, and the interaction mechanism between catechins and gliadins was explored. With TPs addition, noodles showed the significant changes in physicochemical and sensory properties. The water absorption, tensile strength and elasticity increased by 1.35%, 4.98%, 28.51% with 0.5% of TPs, and then decreased with the increasing of TPs. According to the determinations of surface hydrophobicity, spatial structure, thermal properties, amidogen and sulfhydryl content, the structure and properties of gliadin were affected by catechins. Esterified catechins tended to disrupt gliadin structures and non-esterified catechins polymerised gliadin molecules. Furthermore, molecular docking results indicated that catechins interacted with gliadin mainly by hydrogen bonds and hydrophobic action. The reactivity of catechins with gliadin was in the sequence as: epigallocatechin gallate > epicatechin gallate > epigallocatechin > epicatechin, which was based on the account of gallate and B-ring hydroxyl number discrepancy. All results suggested that catechins affected greatly on gliadin, and TPs were potentially used to improve the quality of flour products.

Hepatocellular carcinoma-infiltrating γδ T cells are functionally defected and allogenic Vδ2+ γδ T cell can be a promising complement.

In hepatocellular carcinoma (HCC), γδ T cells participate in mediating the anti-tumour response and are linked with a positive prognosis. However, these cells can become pro-tumoural in the tumour microenvironment (TME). We aimed to decipher the immune landscape and functional states of HCC-infiltrating γδ T cells to provide fundamental evidence for the adoptive transfer of allogeneic Vδ2+ γδ T cells in HCC immunotherapy. We performed single-cell RNA sequencing (scRNA-seq) on γδ T cells derived from HCC tumours and healthy donor livers. Confocal microscopy, flow cytometry and a Luminex assay were applied to validate the scRNA-seq findings. The γδ T cells in the HCC TME entered G2/M cell cycle arrest, and expressed cytotoxic molecules such as interferon-gamma and granzyme B, but were functionally exhausted as indicated by upregulated gene and protein LAG3 expression. The γδ T cells in the HCC TME were dominated by the LAG3+ Vδ1+ population, whereas the Vδ2+ γδ T population was greatly depleted. Moreover, glutamine metabolism of γδ T cells was markedly upregulated in the glutamine-deficient TME. Both in vitro and in vivo experiments showed that glutamine deficiency upregulated LAG3 expression. Finally, our results indicated that ex vivo-expanded Vδ2+ γδ T cells from healthy donor could complement the loss of T cell receptor clonality and effector functions of HCC-derived γδ T cells. This work deciphered the dysfunctional signatures of HCC-infiltrating γδ T cells in the HCC TME, providing scientific support for the use of allogeneic Vδ2+ γδ T cells in HCC cellular therapy.