Transcription factor EHF drives cholangiocarcinoma development through transcriptional activation of glioma-associated oncogene homolog 1 and chemokine CCL2.

Cholangiocarcinoma (CCA) is characterized by rapid onset and high chance of metastasis. Therefore, identification of novel therapeutic targets is imperative. E26 transformation-specific homologous factor (EHF), a member of the E26 transformation-specific transcription factor family, plays a pivotal role in epithelial cell differentiation and cancer progression. However, its precise role in CCA remains unclear. In this study, through in vitro and in vivo experiments, we demonstrated that EHF plays a profound role in promoting CCA by transcriptional activation of glioma-associated oncogene homolog 1 (GLI1). Moreover, EHF significantly recruited and activated tumor-associated macrophages (TAMs) through the C-C motif chemokine 2/C-C chemokine receptor type 2 (CCL2/CCR2) axis, thereby remodeling the tumor microenvironment. In human CCA tissues, EHF expression was positively correlated with GLI1 and CCL2 expression, and patients with co-expression of EHF/GLI1 or EHF/CCL2 had the most adverse prognosis. Furthermore, the combination of the GLI1 inhibitor, GANT58, and CCR2 inhibitor, INCB3344, substantially reduced the occurrence of EHF-mediated CCA. In summary, our findings suggest that EHF is a potential prognostic biomarker for patients with CCA, while also advocating the therapeutic approach of combined targeting of GLI1 and CCL2/CCR2-TAMs to inhibit EHF-driven CCA development.

In Silico Design of Heterogeneous Microvascular Trees Using Generative Adversarial Networks and Constrained Constructive Optimization.

OBJECTIVE: Designing physiologically adequate microvascular trees is of crucial relevance for bioengineering functional tissues and organs. Yet, currently available methods are poorly suited to replicate the morphological and topological heterogeneity of real microvascular trees because the parameters used to control tree generation are too simplistic to mimic results of the complex angiogenetic and structural adaptation processes in vivo. METHODS: We propose a method to overcome this limitation by integrating a conditional deep convolutional generative adversarial network (cDCGAN) with a local fractal dimension-oriented constrained constructive optimization (LFDO-CCO) strategy. The cDCGAN learns the patterns of real microvascular bifurcations allowing for their artificial replication. The LFDO-CCO strategy connects the generated bifurcations hierarchically to form microvascular trees with a vessel density corresponding to that observed in healthy tissues. RESULTS: The generated artificial microvascular trees are consistent with real microvascular trees regarding characteristics such as fractal dimension, vascular density, and coefficient of variation of diameter, length, and tortuosity. CONCLUSIONS: These results support the adoption of the proposed strategy for the generation of artificial microvascular trees in tissue engineering as well as for computational modeling and simulations of microcirculatory physiology.

Industrial-scale Hard Carbon Designed to Regulate Electrochemical Polarization for Fast Sodium Storage.

Given the merits of abundant resource, low cost and high electrochemical activity, hard carbons have been regarded as one of the most commercializable anode material for sodium-ion batteries (SIBs). However, poor rate capability is one of the main obstacles that severely hinder its further development. In addition, the relationships between preparation method, material structure and electrochemical performance have not been clearly elaborated. Herein, a simple but effective strategy is proposed to accurately construct the multiple structural features in hard carbon via adjusting the components of precursors. Through detailed physical characterization of the hard carbons derived from different regulation steps, and further combined with in-situ Raman and galvanostatic intermittent titration technique (GITT) analysis, the network of multiple relationships between preparation method, microstructure, sodium storage behavior and electrochemical performance have been successfully established. Simultaneously, exceptional rate capability about 108.8 mAh g-1 at 8 A g-1 have been achieved from RHC sample with high reversible capacity and desirable initial Coulombic efficiency (ICE). Additionally, the practical applications can be extended to cylindrical battery with excellent cycle behaviors. Such facile approach can provide guidance for large-scale production of high-performance hard carbons and provides the possibility of building practical SIBs with high energy density and durability.

Association between atherogenic index of plasma and depressive symptoms in US adults: Results from the National Health and Nutrition Examination Survey 2005 to 2018.

OBJECTIVE: This study, utilizing data from the U.S. National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018, investigates the association between the atherogenic index of plasma (AIP), a lipid biomarker, and symptoms of depression in American adults. METHODS: In this cross-sectional study of 12,534 adults aged 20 years and older, depressive symptoms were measured utilizing the Patient Health Questionnaire-9 (PHQ-9) scale. Weighted logistic regression models were employed to scrutinize the independent relationship between AIP levels and the likelihood of developing such symptoms. Moreover, a series of subgroup analyses were conducted to delve deeper into these relationships. RESULTS: Following adjustment for confounders, logistic regression by grouping AIP into quartiles revealed a significant association between AIP and an augmented likelihood of self-reported depression. Participants in the fourth quartile (Q4) exhibited a higher odds ratio (OR = 1.34, 95 % CI: 1.02-1.75, p < 0.05) compared to those in the first quartile (Q1). Notably, subgroup analysis unveiled significant interactions involving the smoking and diabetes subgroups, indicating that smoking status and diabetes may modify the relationship between AIP and depression incidence. CONCLUSION: This study reveals a positive correlation between AIP and the self-reported likelihood of depression among US adults, thereby underscoring AIP's potential clinical utility as a biomarker for depressive disorders. Our findings emphasize the necessity to consider and optimize cardiovascular health factors within depression management strategies and offer fresh insights into the development of risk stratification and intervention methods for psychiatric conditions.

Myeloid-derived suppressor cells in cancer: therapeutic targets to overcome tumor immune evasion.

Paradoxically, tumor development and progression can be inhibited and promoted by the immune system. After three stages of immune editing, namely, elimination, homeostasis and escape, tumor cells are no longer restricted by immune surveillance and thus develop into clinical tumors. The mechanisms of immune escape include abnormalities in antitumor-associated immune cells, selection for immune resistance to tumor cells, impaired transport of T cells, and the formation of an immunosuppressive tumor microenvironment. A population of distinct immature myeloid cells, myeloid-derived suppressor cells (MDSCs), mediate immune escape primarily by exerting immunosuppressive effects and participating in the constitution of an immunosuppressive microtumor environment. Clinical trials have found that the levels of MDSCs in the peripheral blood of cancer patients are strongly correlated with tumor stage, metastasis and prognosis. Moreover, animal experiments have confirmed that elimination of MDSCs inhibits tumor growth and metastasis to some extent. Therefore, MDSCs may become the target of immunotherapy for many cancers, and eliminating MDSCs can help improve the response rate to cancer treatment and patient survival. However, a clear definition of MDSCs and the specific mechanism involved in immune escape are lacking. In this paper, we review the role of the MDSCs population in tumor development and the mechanisms involved in immune escape in different tumor contexts. In addition, we discuss the use of these cells as targets for tumor immunotherapy. This review not only contributes to a systematic and comprehensive understanding of the essential role of MDSCs in immune system reactions against tumors but also provides information to guide the development of cancer therapies targeting MDSCs.

Enhancing removal of air contaminants in existing aircraft cabins by optimizing supply air direction based on Re-field synergy and Bayesian optimization.

There are a large number of airplanes currently being operated, in which the ventilation system needs to be improved to more effectively remove air contaminants. A potential approach is to adjust the supply air directions with the use of simple airflow deflectors. This study proposed a method for optimizing the supply air direction of ventilation in aircraft cabins based on the Re-field synergy index and Bayesian optimization. A validated numerical model was used to calculate the air distribution and air contaminant transport in a single-row single-aisle aircraft cabin to obtain the Re-field synergy values. The Bayesian optimization approach was used to identify the supply air direction which maximizes the Re-field synergy, namely, maximizes the mass transfer effectiveness. Finally, the air contaminant transport in a 7-row single-aisle aircraft cabin with the optimized supply air direction was evaluated to demonstrate the enhancement of ventilation performance. The results show that the proposed method based on the Re-field synergy index and Bayesian optimization can efficiently optimize the supply air direction in order to enhance the air contaminant removal in aircraft cabins. In the 7-row single-aisle aircraft cabin, the optimized supply air direction can reduce the average air contaminant concentration in the breathing zone of the passengers by up to 23 %.

TRIM29 facilitates gemcitabine resistance via MEK/ERK pathway and is modulated by circRPS29/miR-770-5p axis in PDAC.

AIMS: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease. Chemotherapy based on gemcitabine (GEM) remains the first-line drug for patients with advanced PDAC. However, GEM resistance impairs its therapeutic effectiveness. Therefore, identifying effective therapeutic targets are urgently needed to overcome GEM resistance. METHODS: The clinical significance of Tripartite Motif Containing 29 (TRIM29) was identified by exploring GEO datasets and TCGA database and its potential biological functions were predicted by GSEA analysis. The regulatory axis was established by bioinformatics analysis and validated by mechanical experiments. Then, in vitro and in vivo assays were performed to validate the roles of TRIM29 in PDAC GEM resistance. RESULTS: High TRIM29 expression was associated with poor prognosis of PDAC and functional experiments demonstrated that TRIM29 promoted GEM resistance in PDAC GEM-resistant (GR) cells. Furthermore, we revealed that circRPS29 promoted TRIM29 expression via competitive interaction with miR-770-5p and then activated MEK/ERK signaling pathway. Additionally, both in vitro and in vivo functional experiments demonstrated that circRPS29/miR-770-5p/TRIM29 axis promoted PDAC GEM resistance via activating MEK/ERK signaling pathway. CONCLUSION: Our results identify the significance of the signaling axis, circRPS29/miR-770-5p/TRIM29-MEK/ERK, in PDAC GEM resistance, which will provide novel therapeutic targets for PDAC treatment.

Radiomics-based nomogram guides adaptive de-intensification in locoregionally advanced nasopharyngeal carcinoma following induction chemotherapy.

OBJECTIVES: This study aimed to construct a radiomics-based model for prognosis and benefit prediction of concurrent chemoradiotherapy (CCRT) versus intensity-modulated radiotherapy (IMRT) in locoregionally advanced nasopharyngeal carcinoma (LANPC) following induction chemotherapy (IC). MATERIALS AND METHODS: A cohort of 718 LANPC patients treated with IC + IMRT or IC + CCRT were retrospectively enrolled and assigned to a training set (n = 503) and a validation set (n = 215). Radiomic features were extracted from pre-IC and post-IC MRI. After feature selection, a delta-radiomics signature was built with LASSO-Cox regression. A nomogram incorporating independent clinical indicators and the delta-radiomics signature was then developed and evaluated for calibration and discrimination. Risk stratification by the nomogram was evaluated with Kaplan-Meier methods. RESULTS: The delta-radiomics signature, which comprised 19 selected features, was independently associated with prognosis. The nomogram, composed of the delta-radiomics signature, age, T category, N category, treatment, and pre-treatment EBV DNA, showed great calibration and discrimination with an area under the receiver operator characteristic curve of 0.80 (95% CI 0.75-0.85) and 0.75 (95% CI 0.64-0.85) in the training and validation sets. Risk stratification by the nomogram, excluding the treatment factor, resulted in two groups with distinct overall survival. Significantly better outcomes were observed in the high-risk patients with IC + CCRT compared to those with IC + IMRT, while comparable outcomes between IC + IMRT and IC + CCRT were shown for low-risk patients. CONCLUSION: The radiomics-based nomogram can predict prognosis and survival benefits from concurrent chemotherapy for LANPC following IC. Low-risk patients determined by the nomogram may be potential candidates for omitting concurrent chemotherapy during IMRT. CLINICAL RELEVANCE STATEMENT: The radiomics-based nomogram was constructed for risk stratification and patient selection. It can help guide clinical decision-making for patients with locoregionally advanced nasopharyngeal carcinoma following induction chemotherapy, and avoid unnecessary toxicity caused by overtreatment. KEY POINTS: • The benefits from concurrent chemotherapy remained controversial for locoregionally advanced nasopharyngeal carcinoma following induction chemotherapy. • Radiomics-based nomogram achieved prognosis and benefits prediction of concurrent chemotherapy. • Low-risk patients defined by the nomogram were candidates for de-intensification.

Potential locus W and candidate gene McPRR2 associated with pericarp pigment accumulation in bitter gourd (Momordica charantia L.) revealed via BSA-seq analysis.

Pericarp color is a prominent agronomic trait that exerts a significant impact on consumer and breeder preferences. Genetic analysis has revealed that the pericarp color of bitter gourd is a quantitative trait. However, the underlying mechanism for this trait in bitter gourd remains largely unknown. In the present study, we employed bulked segregant analysis (BSA) to identify the candidate genes responsible for bitter gourd pericarp color (specifically, dark green versus white) within F2 segregation populations resulting from the crossing of B07 (dark green pericarp) and A06 (white pericarp). Through genomic variation, genetic mapping, and expression analysis, we identified a candidate gene named McPRR2, which was a homolog of Arabidopsis pseudo response regulator 2 (APRR2) encoded by LOC111023472. Sequence alignment of the candidate gene between the two parental lines revealed a 15-bp nucleotide insertion in the coding region of LOC111023472, leading to a premature stop codon and potentially causing a loss-of-function mutation. qRT-PCR analysis demonstrated that the expression of McPRR2 was significantly higher in B07 compared to A06, and it was primarily expressed in the immature fruit pericarp. Moreover, overexpression of McPRR2 in tomato could enhance the green color of immature fruit pericarp by increasing the chlorophyll content. Consequently, McPRR2 emerged as a strong candidate gene regulating the bitter gourd pericarp color by influencing chlorophyll accumulation. Finally, we developed a molecular marker linked to pericarp color, enabling the identification of genotypes in breeding populations. These findings provided valuable insights into the genetic improvement of bitter gourd pericarp color.

Optimal cut-off value for identifying objective response in patients with nasopharyngeal carcinoma after induction chemotherapy.

BACKGROUND: We aimed to establish the most suitable threshold for objective response (OR) in the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in patients with nasopharyngeal carcinoma (NPC). METHODS: According to RECIST 1.1, we retrospectively evaluated MR images of NPC lesions in patients before and after induction chemotherapy (IC). Restricted cubic spline and maximally selected rank statistics were used to determine the cut-off value. Survival rates and differences between groups were compared with Kaplan-Meier curves and log-rank tests. RESULTS: Of 1126 patients, 365 cases who received IC treatment were suitable for RECIST 1.1 evaluation. The 20% cut-off value maximized between-group differences according to maximally selected rank statistics. No difference in distant metastasis-free survival between OR and non-response groups was shown using the primary threshold of OR (30%), while it differed when 20% was employed. CONCLUSIONS: With an optimal cut-off value of 20%, RECIST may assist clinicians to accurately evaluate disease response in NPC patients.

Versatile Triblock Peptide Self-Assembly System to Mimic Collagen Structure and Function.

The construction of collagen mimetic peptides has been a hot topic in tissue engineering due to their attractive advantages, such as virus-free nature and low immunogenicity. However, all of the reported self-assembled peptides rely on the inclusion of risky elements of potential safety concerns or lack the capability of incorporating critical functional motifs. A versatile self-assembly design of pure synthetic peptides that can mimic the collagen structure and function remains an insurmountably challenging target. We have herein created a type of triblock peptide consisting of a central triple helical block and N-terminal/C-terminal blocks with oppositely charged amino acids. Favorable electrostatic interactions between the two terminal blocks have been demonstrated to trigger the triblock peptides to form collagen-like nanofibers with a distinct D-banding pattern. A length of 3 or above charged amino acid pairs as well as the maintenance of the triple helical conformation are required for the self-assembly of triblock peptides. Notably, integrin and discoidin domain receptor (DDR) binding sequences GFOGER and GVMGFO have been well demonstrated as vivid examples of convenient incorporation of functional motifs into the triblock peptides without interfering with their self-assembly. These triblock peptides provide a robust and versatile strategy to create next-generation peptide-based biomaterials that can recapitulate the structure and function of collagen, which have promising applications in the fields of tissue engineering and regenerative medicine.

TGF-ß1-Induced SOX18 Elevation Promotes Hepatocellular Carcinoma Progression and Metastasis Through Transcriptionally Upregulating PD-L1 and CXCL12.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is characterized by an immune-suppressive microenvironment, which contributes to tumor progression, metastasis, and immunotherapy resistance. Identification of HCC-intrinsic factors regulating the immunosuppressive microenvironment is urgently needed. Here, we aimed to elucidate the role of SYR-Related High-Mobility Group Box 18 (SOX18) in inducing immunosuppression and to validate novel combination strategies for SOX18-mediated HCC progression and metastasis. METHODS: The role of SOX18 in HCC was investigated in orthotopic allografts and diethylinitrosamine/carbon tetrachloride-induced spontaneous models by using murine cell lines, adeno-associated virus 8, and hepatocyte-specific knockin and knockout mice. The immune cellular composition in the HCC microenvironment was evaluated by flow cytometry and immunofluorescence. RESULTS: SOX18 overexpression promoted the infiltration of tumor-associated macrophages (TAMs) and regulatory T cells (Tregs) while diminishing cytotoxic T cells to facilitate HCC progression and metastasis in cell-derived allografts and chemically induced HCC models. Mechanistically, transforming growth factor-beta 1 (TGF-ß1) upregulated SOX18 expression by activating the Smad2/3 complex. SOX18 transactivated chemokine (C-X-C motif) ligand 12 (CXCL12) and programmed death ligand 1 (PD-L1) to induce the immunosuppressive microenvironment. CXCL12 knockdown significantly attenuated SOX18-induced TAMs and Tregs accumulation and HCC dissemination. Antagonism of chemokine receptor 4 (CXCR4), the cognate receptor of CXCL12, or selective knockout of CXCR4 in TAMs or Tregs likewise abolished SOX18-mediated effects. TGFßR1 inhibitor Vactosertib or CXCR4 inhibitor AMD3100 in combination with anti-PD-L1 dramatically inhibited SOX18-mediated HCC progression and metastasis. CONCLUSIONS: SOX18 promoted the accumulation of immunosuppressive TAMs and Tregs in the microenvironment by transactivating CXCL12 and PD-L1. CXCR4 inhibitor or TGFßR1 inhibitor in synergy with anti-PD-L1 represented a promising combination strategy to suppress HCC progression and metastasis.

A novel ferroptosis-related gene signature for overall survival prediction in patients with gastric cancer.

The global diagnosis rate and mortality of gastric cancer (GC) are among the highest. Ferroptosis and iron-metabolism have a profound impact on tumor development and are closely linked to cancer treatment and patient's prognosis. In this study, we identified six PRDEGs (prognostic ferroptosis- and iron metabolism-related differentially expressed genes) using LASSO-penalized Cox regression analysis. The TCGA cohort was used to establish a prognostic risk model, which allowed us to categorize GC patients into the high- and the low-risk groups based on the median value of the risk scores. Our study demonstrated that patients in the low-risk group had a higher probability of survival compared to those in the high-risk group. Furthermore, the low-risk group exhibited a higher tumor mutation burden (TMB) and a longer 5-year survival period when compared to the high-risk group. In summary, the prognostic risk model, based on the six genes associated with ferroptosis and iron-metabolism, performs well in predicting the prognosis of GC patients.

Transcription factor BACH1 in cancer: roles, mechanisms, and prospects for targeted therapy.

Transcription factor BTB domain and CNC homology 1 (BACH1) belongs to the Cap 'n' Collar and basic region Leucine Zipper (CNC-bZIP) family. BACH1 is widely expressed in mammalian tissues, where it regulates epigenetic modifications, heme homeostasis, and oxidative stress. Additionally, it is involved in immune system development. More importantly, BACH1 is highly expressed in and plays a key role in numerous malignant tumors, affecting cellular metabolism, tumor invasion and metastasis, proliferation, different cell death pathways, drug resistance, and the tumor microenvironment. However, few articles systematically summarized the roles of BACH1 in cancer. This review aims to highlight the research status of BACH1 in malignant tumor behaviors, and summarize its role in immune regulation in cancer. Moreover, this review focuses on the potential of BACH1 as a novel therapeutic target and prognostic biomarker. Notably, the mechanisms underlying the roles of BACH1 in ferroptosis, oxidative stress and tumor microenvironment remain to be explored. BACH1 has a dual impact on cancer, which affects the accuracy and efficiency of targeted drug delivery. Finally, the promising directions of future BACH1 research are prospected. A systematical and clear understanding of BACH1 would undoubtedly take us one step closer to facilitating its translation from basic research into the clinic.

SOX on tumors, a comfort or a constraint?

The sex-determining region Y (SRY)-related high-mobility group (HMG) box (SOX) family, composed of 20 transcription factors, is a conserved family with a highly homologous HMG domain. Due to their crucial role in determining cell fate, the dysregulation of SOX family members is closely associated with tumorigenesis, including tumor invasion, metastasis, proliferation, apoptosis, epithelial-mesenchymal transition, stemness and drug resistance. Despite considerable research to investigate the mechanisms and functions of the SOX family, confusion remains regarding aspects such as the role of the SOX family in tumor immune microenvironment (TIME) and contradictory impacts the SOX family exerts on tumors. This review summarizes the physiological function of the SOX family and their multiple roles in tumors, with a focus on the relationship between the SOX family and TIME, aiming to propose their potential role in cancer and promising methods for treatment.

Relationship between semen parameters, serum InhB, and INSL-3 levels, and the degree of varicocele.

BACKGROUND: Varicocele is an abnormal expansion of the pampininias venous plexus in the scrotum, resulting in impaired sperm production and reduced sperm quality. The exact pathophysiological mechanism leading to varicocele-related infertility has not been fully elucidated. Although treatable, varicocele may lead to male infertility. OBJECTIVE: To investigate the relationship between semen parameters, serum InhB and INSL-3 levels, and the degree of varicocele in male patients. METHODS: Serum InhB and INSL-3 were detected. To evaluate the relationship between semen parameters and serum InhB and INSL-3 levels. To evaluate the value of semen parameters and serum InhB and INSL-3 levels in distinguishing disease severity in patients with varicocele. RESULTS: Serum INSL-3 in patients with varicocele decreased with the severity of the disease. Serum INSL-3 was positively correlated with total sperm count and frequency of normal sperm morphology. There was a weak correlation between serum InhB and semen volume, concentration, and total sperm. Patients with different disease severity were similar within the groups, with partial overlap or similarity between varicocele Grade I and Grade II, and significant differences between Grade III and Grade I and II. Semen volume, concentration, total sperm, normal sperm morphology, and serum InhB and INSL-3 levels could distinguish the degree of varicocele. CONCLUSION: Semen parameters and the combination of serum InhB and INSL-3 levels in patients with varicocele are closely related to the severity of the disease. Serum INSL-3 is expected to be a potential biomarker for early clinical intervention.

Identification and Characterization of a ceRNA Regulatory Network Involving LINC00482 and PRRC2B in Peripheral Blood Mononuclear Cells: Implications for COPD Pathogenesis and Diagnosis.

Purpose: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide, characterized by intense lung infiltrations of immune cells (macrophages and monocytes). While existing studies have highlighted the crucial role of the competitive endogenous RNA (ceRNA) regulatory network in COPD development, the complexity and characteristics of the ceRNA network in monocytes remain unexplored. Methods: We downloaded messenger RNA (mRNA), microRNA (miRNA), and long noncoding RNA (lncRNA) microarray data from GSE146560, GSE102915, and GSE71220 in the Gene Expression Omnibus (GEO) database. This data was used to identify differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs), and lncRNAs (DElncRNAs). Predicted miRNAs that bind to DElncRNAs were intersected with DEmiRNAs, forming a set of intersecting miRNAs. This set was then used to predict potential binding mRNAs, intersected with DEmRNAs, and underwent functional enrichment analysis using R software and the STRING database. The resulting triple regulatory network and hub genes were constructed using Cytoscape. Comparative Toxicomics Database (CTD) was utilized for disease correlation predictions, and ROC curve analysis assessed diagnostic accuracy. Results: Our study identified 5 lncRNAs, 4 miRNAs, and 149 mRNAs as differentially expressed. A lncRNA-miRNA-mRNA regulatory network was constructed, and hub genes were selected through hub analysis. Enrichment analysis highlighted terms related to cell movement and gene expression regulation. We established a LINC00482-has-miR-6088-PRRC2B ceRNA network with diagnostic relevance for COPD. ROC analysis demonstrated the diagnostic value of these genes. Moreover, a positive correlation between LINC00482 and PRRC2B expression was observed in COPD PBMCs. The CTD database indicated their involvement in inflammatory responses. Conclusion: In summary, our study not only identified pivotal hub genes in peripheral blood mononuclear cells (PBMCs) of COPD but also constructed a ceRNA regulatory network. This contributes to understanding the pathophysiological processes of COPD through bioinformatics analysis, expanding our knowledge of COPD, and providing a foundation for potential diagnostic and therapeutic targets for COPD.

Value of radiological depth of invasion in non-pT4 Oral tongue squamous cell carcinoma: implication for preoperative MR T-staging.

OBJECTIVE: The prognostic stratification for oral tongue squamous cell carcinoma (OTSCC) is heavily based on postoperative pathological depth of invasion (pDOI). This study aims to propose a preoperative MR T-staging system based on tumor size for non-pT4 OTSCC. METHODS: Retrospectively, 280 patients with biopsy-confirmed, non-metastatic, pT1-3 OTSCC, treated between January 2010 and December 2017, were evaluated. Multiple MR sequences, including axial T2-weighted imaging (WI), unenhanced T1WI, and axial, fat-suppressed coronal, and sagittal contrast-enhanced (CE) T1WI, were utilized to measure radiological depth of invasion (rDOI), tumor thickness, and largest diameter. Intra-class correlation (ICC) and univariate and multivariate analyses were used to evaluate measurement reproducibility, and factors' significance, respectively. Cutoff values were established using an exhaustive method. RESULTS: Intra-observer (ICC = 0.81-0.94) and inter-observer (ICC = 0.79-0.90) reliability were excellent for rDOI measurements, and all measurements were significantly associated with overall survival (OS) (all p < .001). Measuring the rDOI on axial CE-T1WI with cutoffs of 8 mm and 12 mm yielded an optimal MR T-staging system for rT1-3 disease (5-year OS of rT1 vs rT2 vs rT3: 94.0% vs 72.8% vs 57.5%). Using multivariate analyses, the proposed T-staging exhibited increasingly worse OS (hazard ratio of rT2 and rT3 versus rT1, 3.56 [1.35-9.6], p = .011; 4.33 [1.59-11.74], p = .004; respectively), which outperformed pathological T-staging based on nonoverlapping Kaplan-Meier curves and improved C-index (0.682 vs. 0.639, p < .001). CONCLUSIONS: rDOI is a critical predictor of OTSCC mortality and facilitates preoperative prognostic stratification, which should be considered in future oral subsite MR T-staging. CLINICAL RELEVANCE STATEMENT: Utilizing axial CE-T1WI, an MR T-staging system for non-pT4 OTSCC was developed by employing rDOI measurement with optimal thresholds of 8 mm and 12 mm, which is comparable with pathological staging and merits consideration in future preoperative oral subsite planning. KEY POINTS: • Tumor morphology, measuring sequences, and observers could impact MR-derived measurements and compromise the consistency with histology. • MR-derived measurements, including radiological depth of invasion (rDOI), tumor thickness, and largest diameter, have a prognostic impact on OS (all p < .001). • rDOI with cutoffs of 8 mm and 12 mm on axial CE-T1WI is an optimal predictor of OS and could facilitate risk stratification in non-pT4 OTSCC disease.

Five genes identified as prognostic markers for colorectal cancer through the integration of genome-wide association study and expression quantitative trait loci data.

Background: Colorectal cancer (CRC) is a prominent form of cancer globally, ranking second in terms of prevalence and serving as a leading cause of cancer-related deaths, but the underlying biological interpretation remains largely unknown. Methods: We used the summary data-based Mendelian randomization method to integrate CRC genome-wide association studies (ncase = 7062; ncontrol = 195,745) and expression quantitative trait loci summary data in peripheral whole blood (Consortium for Architecture of Gene Expression: n = 2765; Genotype-Tissue Expression [v8]: n = 755) and colon tissue (colon-transverse: n = 406; colon-sigmoid: n = 373) and identified related genes. Results: Genes ABTB1, CYP21A2, NLRP1, PHKG1 and PIP5K1C have emerged as significant prognostic markers for CRC patient survival. Functional analysis revealed their involvement in cancer cell migration and invasion mechanisms, providing valuable insights for the development of future anti-CRC drugs. Conclusion: We successfully identified five CRC risk genes, providing new insights and research directions for the effective mechanisms of CRC.

The light and hypoxia induced gene ZmPORB1 determines tocopherol content in the maize kernel.

Tocopherol is an important lipid-soluble antioxidant beneficial for both human health and plant growth. Here, we fine mapped a major QTL-qVE1 affecting γ-tocopherol content in maize kernel, positionally cloned and confirmed the underlying gene ZmPORB1 (por1), as a protochlorophyllide oxidoreductase. A 13.7 kb insertion reduced the tocopherol and chlorophyll content, and the photosynthetic activity by repressing ZmPORB1 expression in embryos of NIL-K22, but did not affect the levels of the tocopherol precursors HGA (homogentisic acid) and PMP (phytyl monophosphate). Furthermore, ZmPORB1 is inducible by low oxygen and light, thereby involved in the hypoxia response in developing embryos. Concurrent with natural hypoxia in embryos, the redox state has been changed with NO increasing and H2O2 decreasing, which lowered γ-tocopherol content via scavenging reactive nitrogen species. In conclusion, we proposed that the lower light-harvesting chlorophyll content weakened embryo photosynthesis, leading to fewer oxygen supplies and consequently diverse hypoxic responses including an elevated γ-tocopherol consumption. Our findings shed light on the mechanism for fine-tuning endogenous oxygen concentration in the maize embryo through a novel feedback pathway involving the light and low oxygen regulation of ZmPORB1 expression and chlorophyll content.