Multi-omics analysis of the prognostic and biological role of cuproptosis-related gene in gastric cancer.

Background: A considerable number of gastric cancer (GC) patients cannot receive benefits from current treatments. We aimed to identify possible biomarkers of cuproptosis-related genes (CRGs) in GC patients, which may help guide precision medicine-based decision-making. Methods: RNA sequencing data, copy number variations (CNVs) data, and single nucleotide variant (SNV) data were obtained from The Cancer Genome Atlas (TCGA) database and Gene Set Cancer Analysis (GSCA) database. Chi-squared test was adopted to screen differentially expressed CRGs (DE-CRGs) between samples from 14 kinds of carcinoma and adjacent tissue samples. Then, GC samples were divided into high- and low-expressed groups based on DE-CRGs for further survival analyses and the selection of biomarkers. Methylation sites related with biomarkers were acquired. The correlation between immune cells and biomarkers was verified. Finally, miRNA-mRNA, TFs-mRNA, and co-expression networks were established to detect factors with regulating effects on biomarkers. Results: Three CRGs including LIAS, GLS, and CDKN2A were identified as biomarkers in GC patients. Three methylation sites with a significant survival effect including cg13601799, 07562918, and 07253264 were acquired. Then, we found that B cells native was significantly correlated with CDKN2A, four immune cells such as T cells regulatory are significantly correlated with GLS, and two immune cells such as T cells CD4 memory activated were significantly correlated with LIAS. Moreover, 10 miRNAs in the miRNA-mRNA network and three transcription factors (TFs) in the TFs-mRNA network had a significant correlation with overall survival (OS). Finally, 20 enrichment functions were obtained on the basis of the co-expression network. Conclusions: Three biomarkers with a prognosis prediction value of GC were found, and multi-factor regulatory networks were constructed to screen out 13 factors with regulating influences of biomarkers.

TMEM52B Isoforms P18 and P20 Differentially Promote the Oncogenesis and Metastasis of Nasopharyngeal Carcinoma.

Transmembrane protein 52B (TMEM52B), a newly identified tumor-related gene, has been reported to regulate various tumors, yet its role in nasopharyngeal carcinoma (NPC) remains unclear. Transcriptomic analysis of NPC cell lines reveals frequent overexpression of TMEM52B, and immunohistochemical results show that TMEM52B is associated with advanced tumor stage, recurrence, and decreased survival time. Depleting TMEM52B inhibits the proliferation, migration, invasion, and oncogenesis of NPC cells in vivo. TMEM52B encodes two isoforms, TMEM52B-P18 and TMEM52B-P20, differing in their N-terminals. While both isoforms exhibit similar pro-oncogenic roles and contribute to drug resistance in NPC, TMEM52B-P20 differentially promotes metastasis. This functional discrepancy may be attributed to their distinct subcellular localization; TMEM52B-P18 is confined to the cytoplasm, while TMEM52B-P20 is found both at the cell membrane and in the cytoplasm. Mechanistically, cytoplasmic TMEM52B enhances AKT phosphorylation by interacting with phosphoglycerate kinase 1 (PGK1), fostering NPC growth and metastasis. Meanwhile, membrane-localized TMEM52B-P20 promotes E-cadherin ubiquitination and degradation by facilitating its interaction with the E3 ubiquitin ligase NEDD4, further driving NPC metastasis. In conclusion, the TMEM52B-P18 and TMEM52B-P20 isoforms promote the metastasis of NPC cells through different mechanisms. Drugs targeting these TMEM52B isoforms may offer therapeutic benefits to cancer patients with varying degrees of metastasis.

Multimodal data integration for predicting progression risk in castration-resistant prostate cancer using deep learning: a multicenter retrospective study.

Purpose: Patients with advanced prostate cancer (PCa) often develop castration-resistant PCa (CRPC) with poor prognosis. Prognostic information obtained from multiparametric magnetic resonance imaging (mpMRI) and histopathology specimens can be effectively utilized through artificial intelligence (AI) techniques. The objective of this study is to construct an AI-based CRPC progress prediction model by integrating multimodal data. Methods and materials: Data from 399 patients diagnosed with PCa at three medical centers between January 2018 and January 2021 were collected retrospectively. We delineated regions of interest (ROIs) from 3 MRI sequences viz, T2WI, DWI, and ADC and utilized a cropping tool to extract the largest section of each ROI. We selected representative pathological hematoxylin and eosin (H&E) slides for deep-learning model training. A joint combined model nomogram was constructed. ROC curves and calibration curves were plotted to assess the predictive performance and goodness of fit of the model. We generated decision curve analysis (DCA) curves and Kaplan-Meier (KM) survival curves to evaluate the clinical net benefit of the model and its association with progression-free survival (PFS). Results: The AUC of the machine learning (ML) model was 0.755. The best deep learning (DL) model for radiomics and pathomics was the ResNet-50 model, with an AUC of 0.768 and 0.752, respectively. The nomogram graph showed that DL model contributed the most, and the AUC for the combined model was 0.86. The calibration curves and DCA indicate that the combined model had a good calibration ability and net clinical benefit. The KM curve indicated that the model integrating multimodal data can guide patient prognosis and management strategies. Conclusion: The integration of multimodal data effectively improves the prediction of risk for the progression of PCa to CRPC.

Application of conventional ultrasound coupled with shear wave elastography in the assessment of muscle strength in patients with type 2 diabetes.

Background: In patients with type 2 diabetes mellitus (T2DM), a decrease in muscle function may be related to changes in the biomechanical properties of skeletal muscles. However, the correlations between muscle function and the characteristics of muscle size and stiffness as measured by ultrasound in patients with T2DM are unclear. The aim of this study was to investigate the abilities of conventional ultrasound and shear wave elastography (SWE) to assess muscle properties in patients with T2DM and to correlate the findings with isokinetic muscle testing and functional tests. Methods: Sixty patients from the Department of Endocrinology in The Third Affiliated Hospital of Southern Medical University diagnosed with T2DM were recruited in this cross-sectional study from September 2021 to September 2022. T2DM was defined based on the American Diabetes Association criteria. The exclusion criteria were a history of injury or operation of the lower limb or clinical signs of neuromuscular disorders, any muscle-induced disease, and the presence of other types of diabetes mellitus. Thirty-five matched healthy volunteers were continuously included in the control group. SWE was used to measure the muscle stiffness of the quadriceps femoris [vastus lateralis (VL), rectus femoris (RF), vastus medialis (VM), vastus intermedius (VI)] and the biceps brachii (BB) in a relaxed position, and the shear wave velocity (SWV) values were recorded. Muscle size was measured using conventional ultrasound. The participants underwent isokinetic knee extension/flexion (60°/sec) to assess muscle strength and functional tests of physical performance, including the short physical performance battery, 30-s chair stand test, timed up-and-go test, and 6-meter walk test. All demographics and measured variables were compared using the independent samples t-test. Interclass correlation coefficient analysis was performed on the measurement data obtained by the two operators, and Pearson correlation coefficients were used to determine the relationships between variables. Results: Patients with T2DM exhibited worse physical performance (P<0.05) and weaker lower limb muscle strength (P<0.05) than did healthy controls, but their handgrip strength was comparable (P=0.102). Patients with T2DM had significantly decreased muscle thickness [RF thickness: 10.69±3.21 vs. 13.09±2.41 mm, mean difference =-2.40, 95% confidence interval (CI): -3.56 to -1.24, P<0.001; anterior quadriceps thickness: 23.45±7.11 vs. 27.25±5.25 mm, mean difference =-3.80, 95% CI: -6.33 to -1.26, P=0.004] and RF cross-sectional area (3.04±1.10 vs. 4.11±0.95 cm2, mean difference =-1.07, 95% CI: -1.49 to -0.64; P<0.001) compared to healthy controls. Smaller muscle size was associated with decreased muscle strength (r=0.44-0.69, all P values <0.001). Except for the BB (3.48±0.38 vs. 3.61±0.61 m/s, mean difference =-0.12, 95% CI: -0.35 to 0.11; P=0.257) and VI (2.59±0.34 vs. 2.52±0.23 m/s, mean difference =0.03, 95% CI: -0.06 to 0.18; P=0.299), the muscle stiffness in patients with T2DM was significantly decreased. For the patients with T2DM and healthy participants, the SWV of the RF was 1.66±0.23 and 1.83±0.18 m/s (mean difference =-0.17, 95% CI: -0.25 to -0.08; P<0.001), respectively; that of the VM was 1.34±0.15 and 1.51±0.16 m/s (mean difference =-0.17, 95% CI: -0.24 to -0.10; P<0.001), respectively; and that of VL was 1.38±0.19 and 1.53±0.19 m/s (mean difference =-0.15, 95% CI: -0.23 to -0.07; P<0.001), respectively. Excellent interobserver reliability of the SWV measurements on the muscle of T2DM patients was observed (all intraclass correlation coefficients >0.75; P<0.001). The SWV showed moderate correlations with muscle strength in the RF, VM, and VL (r=0.30-0.61; all P values <0.05). Conclusions: Ultrasound technology exhibits good reliability for repeated measurements of muscle size and stiffness. Reduced muscle stiffness as detected by SWE was demonstrated in patients with diabetes and was associated with decreased muscle strength and impaired functional activity.

Metformin improves nonalcoholic fatty liver disease in db/db mice by inhibiting ferroptosis.

Nonalcoholic fatty liver disease (NAFLD) is the primary complication of type 2 diabetes (T2DM)-related liver disease, lacking effective treatment options. Metformin (Met), a widely prescribed anti-hyperglycemic medication, has been found to protect against NAFLD. Ferroptosis, a newly discovered form of cell death, is associated with the development of NAFLD. Despite this association, the extent of Met's protective effects on NAFLD through the modulation of ferroptosis has yet to be thoroughly investigated. In the present study, the administration of erastin or Ras-selective lethal 3 (RSL3), both known ferroptosis inducers, resulted in elevated cell mortality and reduced cell viability in AML12 hepatocytes. Notably, Met treatment demonstrated the capacity to mitigate these effects. Furthermore, we observed increased ferroptosis levels in both AML12 hepatocytes treated with palmitate and oleate (PA/OA) and in the liver tissue of db/db mice. Met treatment demonstrated significant reductions in iron accumulation and lipid-related reactive oxygen species production, simultaneously elevating the glutathione/glutathione disulfide ratio in both PA/OA-treated AML12 hepatocytes and the liver tissue of db/db mice. Interestingly, the anti-ferroptosis effects of Met were significantly reversed with the administration of RSL3, both in vitro and in vivo. Mechanistically, Met treatment regulated the glutathione peroxidase 4/solute carrier family 7 member 11/acyl-CoA synthetase long-chain family member 4 axis to alleviate ferroptosis in NAFLD hepatocytes. Overall, our findings highlight the crucial role of ferroptosis in the development of T2DM-related NAFLD and underscore the potential of Met in modulating key factors associated with ferroptosis in the context of NAFLD.

Adipocyte-derived extracellular vesicles: bridging the communications between obesity and tumor microenvironment.

By the year 2035 more than 4 billion people might be affected by obesity and being overweight. Adipocyte-derived Extracellular Vesicles (ADEVs/ADEV-singular) are essential for communication between the tumor microenvironment (TME) and obesity, emerging as a prominent mechanism of tumor progression. Adipose tissue (AT) becomes hypertrophic and hyperplastic in an obese state resulting in insulin resistance in the body. This modifies the energy supply to tumor cells and simultaneously stimulates the production of pro-inflammatory adipokines. In addition, obese AT has a dysregulated cargo content of discharged ADEVs, leading to elevated amounts of pro-inflammatory proteins, fatty acids, and carcinogenic microRNAs. ADEVs are strongly associated with hallmarks of cancer (proliferation and resistance to cell death, angiogenesis, invasion, metastasis, immunological response) and may be useful as biomarkers and antitumor therapy strategy. Given the present developments in obesity and cancer-related research, we conclude by outlining significant challenges and significant advances that must be addressed expeditiously to promote ADEVs research and clinical applications.

Label-free plasmonic metasensing of PSA and exosomes in serum for rapid high-sensitivity diagnosis of early prostate cancer.

Prostate-specific antigen (PSA) test is widely used to diagnose early prostate cancer (PCa). Its low sensitivity, especially in the gray zone, usually incurs overtreatment or missed diagnosis. As an emerging tumor marker, exosomes have attracted great interest in non-invasive diagnosis of PCa. However, the quick direct detection of exosomes in serum is still a big challenge for convenient screening of early PCa due to their high-degree heterogeneity and complexity. Here we develop the label-free biosensors based on wafer-scale plasmonic metasurfaces, and establish a flexible spectral methodology of exosomes profiling, which facilitates their identification and quantification in serum. We combine the metasurfaces functionalized by anti-PSA and anti-CD63, respectively, and build a portable immunoassay system to detect serum PSA and exosomes simultaneously within 20 min. Our scheme can discriminate early PCa from benign prostatic hyperplasia with a diagnostic sensitivity of 92.3%, which is much higher that of 58.3% for conventional PSA tests. The receiver operating characteristic analysis in clinical trials demonstrates significant PCa distinguishing capability with an area under the curve up to 99.4%. Our work provides a rapid and powerful approach for precise diagnosis of early PCa, and will inspire more exosomes metasensing studies for other early cancer screening.

Value of T2-weighted-based radiomics model in distinguishing Warthin tumor from pleomorphic adenoma of the parotid.

OBJECTIVES: The differentiation of Warthin tumor and pleomorphic adenoma before treatment is crucial for clinical strategies. The aim of this study was to develop and test a T2-weighted-based radiomics model for differentiating pleomorphic adenoma from Warthin tumor of the parotid gland. METHODS: A total of 117 patients, including 61 cases of Warthin tumor and 56 cases of pleomorphic adenoma, were retrospectively enrolled from two centers between January 2010 and June 2022. The training set included 82 cases, and the validation set included 35 cases. From T2-weighted images, 971 radiomics features were extracted. Seven radiomics features remained after a two-step selection process. We used the seven radiomics features and clinical factors through multivariable logistic regression to build radiomics and clinical models, respectively. A radiomics-clinical model was also built that combined the independent clinical predictors with the radiomics features. Through ROC curves, the three models were evaluated and compared. RESULTS: In the radiomics model, AUCs were 0.826 and 0.796 in training and validation sets, respectively. In the clinical model, the AUCs were 0.923 and 0.926 in the training and validation sets, respectively. Decision curve analysis revealed that the radiomics-clinical model had the best diagnostic performance for distinguishing Warthin tumor from pleomorphic adenoma of the parotid gland (AUC = 0.962 and 0.934 for the training and validation sets, respectively). CONCLUSION: The radiomics-clinical model performed well in differentiating pleomorphic adenoma from Warthin tumor of the parotid gland. KEY POINTS: • The clinical model outperformed the radiomics model in distinguishing pleomorphic adenoma from Warthin tumor of the parotid gland. • The radiomics features extracted from T2-weighted images could help differentiate pleomorphic adenoma from Warthin tumor of the parotid gland. • The radiomics-clinical model was superior to the radiomics and the clinical models for differentiating pleomorphic adenoma from Warthin tumor of the parotid gland.

Fraxinellone inhibits progression of glioblastoma via regulating the SIRT3 signaling pathway.

Glioblastoma (GBM) is the most prevalent type of adult primary brain tumor and chemotherapy of GBM was limited by drug-resistance. Fraxinellone is a tetrahydro-benzofuranone derivative with various pharmacological activities. However, the pharmacological effects of fraxinellone on GBM remains largely unknown. Here, we found that fraxinellone inhibited the proliferation and growth of GBM cells in a dose-dependent manner in vitro. Subsequently, we found that fraxinellone suppressed the migration and induced apoptosis of GBM cells in vitro. Using western blot and immunostaining, we further found that fraxinellone downregulated the expressions of sirtuin 3 (SIRT3), and superoxide dismutase 2 (SOD2), a downstream of SIRT3 in GBM cells. Meanwhile, reactive oxygen species (ROS) were increased in these fraxinellone-treated GBM cells. Interestingly, overexpression of SIRT3 (SIRT3-OE) indeed partially restored the inhibition of both cell proliferation and migration of GBM cells induced by fraxinellone. Finally, we found that fraxinellone could inhibit the growth of GBM in xenograft model through the inactivation of SIRT3 signaling pathway. Taken together, these results suggest that fraxinellone suppressed the growth and migration of GBM cells by downregulating SIRT3 signaling in vitro, and inhibited the tumorigenesis of GBMs in vivo.

Atractylon inhibits the tumorigenesis of glioblastoma through SIRT3 signaling.

Glioblastoma (GBM) is the most common primary malignant brain tumor. Although there are various treatments for glioblastoma including surgery, radiotherapy, systemic therapy (chemotherapy and targeted therapy) and supportive therapy, the overall prognosis remains poor and the long-term survival rate is very low. Atractylon, a bioactive compound extracted from the Chinese herb Atractylodes lancea (Thunb.) DC. or Atractylodes chinensis (DC.) Koidz., has been reported to induce apoptosis and suppress metastasis in hepatic cancer cells. However, the roles and mechanisms of atractylon in GBM cells remain unknown. In the present study, we aimed to evaluate the effects of atractylon on the anti-tumorigenesis properties of GBM. Firstly, results of CCK8, colony formation, cell proliferation, and flow cytometry assays showed that atractylon inhibited the proliferation of GBM cells by arresting cells at the G1 phase of cell cycle. In addition, atractylon suppressed the migration and induced apoptosis of GBM cells. Mechanistically, atractylon treatment caused a significant up-regulation of sirtuin 3 (SIRT3, a tumor suppressor) mRNA and protein in GBM cells. Furthermore, inhibition of SIRT3 by the selective SIRT3 inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP) partially restored the anti-proliferation and migration effects of atractylon in GBM cells. Finally, atractylon treatment also inhibited the in vivo growth of GBM cells in xenograft models through SIRT3 activation. Taken together, these results reveal a previously unknown role of atractylon in inhibiting GBM in vitro and in vivo through up-regulating SIRT3, which suggests novel strategies for the treatment of GBM.

Evaluation of crossing-linking sites of egg white protein-polyphenol conjugates: Fabricated using a conventional and ultrasound-assisted free radical technique.

There has been strong interest in developing effective strategies to inhibit lipid oxidation in emulsified food products such as ω-3 fatty acids, carotenoids, or carotenoids. Dual-functional protein emulsifiers with antioxidant and emulsifying properties are in the spotlight. Our aim was to investigate the influence of caffeic acid (CF), chlorogenic acid (CA) with a C3-C6 structure, epigallocatechin gallate (EGCG), catechin (CT), and quercetin (QE) with a C6-C3-C6 structure on the cross-linking sites and structure of egg white protein (EWP)-polyphenol conjugates fabricated by the free radical method under conventional water bath (WB) and ultrasound assisted (US) conditions. Results of structural analysis and liquid chromatography-tandem mass spectrometry indicated that the structure of EWP-polyphenol conjugates and the cross-linking sites of the two are influenced by the polyphenol structure and the free radical system. Our study provides important information about the mechanism of research into proteins and polyphenols using the free radical method.

Development of a TCR-like antibody and chimeric antigen receptor against NY-ESO-1/HLA-A2 for cancer immunotherapy.

BACKGROUND: The current therapeutic antibodies and chimeric antigen receptor (CAR) T cells are capable of recognizing surface antigens, but not of intracellular proteins, thus limiting the target coverage for drug development. To mimic the feature of T-cell receptor (TCR) that recognizes the complex of major histocompatibility class I and peptide on the cell surface derived from the processed intracellular antigen, we used NY-ESO-1, a cancer-testis antigen, to develop a TCR-like fully human IgG1 antibody and its derivative, CAR-T cells, for cancer immunotherapy. METHODS: Human single-chain variable antibody fragment (scFv) phage library (~10∧11) was screened against HLA-A2/NY-ESO-1 (peptide 157-165) complex to obtain target-specific antibodies. The specificity and affinity of those antibodies were characterized by flow cytometry, ELISA, biolayer interferometry, and confocal imaging. The biological functions of CAR-T cells were evaluated against target tumor cells in vitro. In vivo antitumor activity was investigated in a triple-negative breast cancer (TNBC) model and primary melanoma tumor model in immunocompromised mice. RESULTS: Monoclonal antibody 2D2 identified from phage-displayed library specifically bound to NY-ESO-1157-165 in the context of human leukocyte antigen HLA-A*02:01 but not to non-A2 or NY-ESO-1 negative cells. The second-generation CAR-T cells engineered from 2D2 specifically recognized and eliminated A2+/NY-ESO-1+tumor cells in vitro, inhibited tumor growth, and prolonged the overall survival of mice in TNBC and primary melanoma tumor model in vivo. CONCLUSIONS: This study showed the specificity of the antibody identified from human scFv phage library and demonstrated the potential antitumor activity by TCR-like CAR-T cells both in vitro and in vivo, warranting further preclinical and clinical evaluation of the TCR-like antibody in patients. The generation of TCR-like antibody and its CAR-T cells provides the state-of-the-art platform and proof-of-concept validation to broaden the scope of target antigen recognition and sheds light on the development of novel therapeutics for cancer immunotherapy.

Dynamic Tumor-Specific MHC-II Immuno-PET Predicts the Efficacy of Checkpoint Inhibitor Immunotherapy in Melanoma.

Despite the advance of immunotherapy, only a small subset of patients gains long-term survival benefit. This fact represents a compelling rationale to develop immuno-PET imaging that can predict tumor response to immunotherapy. An increasing number of studies have shown that tumor-specific major histocompatibility complex II (tsMHC-II) is associated with improved responses to targeted immunotherapy. The aim of this study was to investigate the potential of tsMHC-II protein expression and its dynamic change on treatment with interferon γ (IFNγ) as a new target for immuno-PET to predict response to immunotherapy. Methods: Major histocompatibility complex II (MHC-II) antibody was radiolabeled with DOTA-chelated 64Cu to derive an MHC-II immuno-PET tracer. Two melanoma models (B16SIY, B16F10) that are respondent and nonrespondent, respectively, to PD1/PD-L1 checkpoint inhibitor were used. Both tumor models were treated with anti-PD1 and IFNγ, enabling observation of dynamic changes in tsMHC-II. Small-animal PET imaging, biodistribution, and histologic studies were performed to validate the correlation of tsMHC-II with the tumor response to the immunotherapy. Results: Fluorescence-activated cell sorting analysis of the 2 tumors supported the consensual recognition of tsMHC-II correlated with the tumor response to the immunotherapy. The in vivo PET imaging revealed higher basal levels of tsMHC-II in the responder, B16SIY, than in the nonresponder, B16F10. When treated with anti-PD1 antibody in animals, B16SIY tumors displayed a sensitive increase in tsMHC-II compared with B16F10 tumors. In IFNγ stimulation groups, the greater magnitude of tsMHC-II was further amplified when the IFNγ signaling was activated in the B16SIY tumors, as IFNγ signaling positively upregulates tsMHC-II in the tumor immunity. Subsequent histopathologic analysis supported the correlative characteristics of tsMHC-II with tumor immunity and response to cancer immunotherapy. Conclusion: Collectively, the predictive value of tsMHC-II immuno-PET was validated for stratifying tumor immunotherapy responders versus nonresponders. Monitoring sensitivity of tsMHC-II to IFNγ stimulation may provide an effective strategy to predict the tumor response to immunotherapy.

64Cu/177Lu-DOTA-diZD, a Small-Molecule-Based Theranostic Pair for Triple-Negative Breast Cancer.

Despite advances in targeted therapies, the prognosis for patients with triple-negative breast cancer (TNBC) is poor because there are few actionable molecular targets. The dependence of solid tumor growth on angiogenesis prompted our development of angiogenic-receptor-targeted radionuclide therapy (TRT) to treat TNBC by targeted delivery of therapeutic doses of ionizing radiation to tumors. A high-affinity vascular endothelial growth factor receptor (VEGFR)-targeted agent, diZD, was synthesized and labeled with 177Lu and 64Cu by 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator giving the TRT agent, 177Lu-DOTA-diZD, and PET imaging agent, 64Cu-DOTA-diZD. We showed that "64Cu/177Lu"-DOTA-diZD radiotracers are a promising theranostic pair for TNBC. 4T1-bearing mice treated with 177Lu-DOTA-diZD-based TRT survived with a median of 28 days, which was significantly longer than that of control mice as 18 days. Anti-PD1 immunotherapy resulted in a shorter median survival of 16 days. This work presents for the first time that small-molecule VEGFR-oriented TRT is a promising therapeutic option to treat "immunogenic cold" TNBC.

The speciation and adaptation of the polyploids: a case study of the Chinese Isoetes L. diploid-polyploid complex.

BACKGROUND: The Chinese Isoetes L. are distributed in a stairway pattern: diploids in the high altitude and polyploids in the low altitude. The allopolyploid I. sinensis and its diploid parents I. yunguiensis and I. taiwanensis is an ideal system with which to investigate the relationships between polyploid speciation and the ecological niches preferences. RESULTS: There were two major clades in the nuclear phylogenetic tree, all of the populations of polyploid were simultaneously located in both clades. The chloroplast phylogenetic tree included two clades with different populations of the polyploid clustered with the diploids separately: I. yunguiensis with partial populations of the I. sinensis and I. taiwanensis with the rest populations of the I. sinensis. The crow node of the I. sinensis allopolyploid system was 4.43 Ma (95% HPD: 2.77-6.97 Ma). The divergence time between I. sinensis and I. taiwanensis was estimated to 0.65 Ma (95% HPD: 0.26-1.91 Ma). The narrower niche breadth in I.sinensis than those of its diploid progenitors and less niche overlap in the pairwise comparisons between the polyploid and its progenitors. CONCLUSIONS: Our results elucidate that I. yunguinensis and I. taiwanensis contribute to the speciation of I. sinensis, the diploid parents are the female parents of different populations. The change of altitude might have played an important role in allopolyploid speciation and the pattern of distribution of I. sinensis. Additionally, niche novelty of the allopolyploid population of I. sinensis has been detected, in accordance with the hypothesis that niche shift between the polyploids and its diploid progenitors is important for the establishment and persistence of the polyploids.

Adjuvant radiotherapy and chemotherapy in early-stage diffuse large B cell lymphoma of head and neck with extranodal involvement.

Objectives: Diffuse large B cell lymphoma (DLBCL) is a heterogeneous lymphoma with a variety of presentations and treatment modalities. With the introduction of immunotherapy as an addition to chemotherapy (CT), there is ongoing debate about the role of radiotherapy (RT) in treatment and a need to clarify differences by specific anatomic locations.Methods: We identified a cohort of 1929 individuals with limited stage (stage I and II) head and neck DLBCL with extranodal involvement from the National Cancer Data Base. Overall survival (OS) was evaluated by Kaplan-Meier analysis, multivariable Cox proportional hazard regression, and propensity score-matched analysis.Results: Multi-agent CT plus RT was associated with longer OS (HR, 0.763; 95% CI, 0.614 to 0.948; p = 0.015) when compared with multi-agent CT alone on multivariate analysis. After propensity score matching to account for confounding variables, multi-agent CT plus RT was associated with longer OS than those who received multi-agent CT alone (HR = 0.769; 95% CI, 0.609-0.971; p = 0.027). The survival benefit persisted in patients over the age of 60 years and those who received RT within 180 days of CT. However, there was no significant difference in OS between the two groups in subgroup analysis of patients who received immunotherapy.Conclusion: The addition of RT to CT resulted in longer OS in patients with limited stage head and neck DLBCL with extranodal involvement.

Prognostic values of preoperative platelet-to-lymphocyte ratio, albumin and hemoglobin in patients with non-metastatic colon cancer.

Purpose: Preoperative platelet-to-monocyte ratio (PLR), albumin and hemoglobin are suggested prognostic indicators in various malignancies. However, the prognostic values of PLR, albumin and hemoglobin remain elusive. The objective of the present study was to evaluate the prognostic values of PLR, albumin and hemoglobin in stage I-III colon cancer. Patients and methods: A total of 312 patients with non-metastatic colon cancer undergoing curative resection were enrolled in this study. The prognostic values of PLR, albumin and hemoglobin were identified by receiver operating characteristics, and univariate and multivariate analyses. Results: Univariate analysis revealed that preoperative PLR, albumin and hemoglobin were significantly associated with overall survival (OS) and that preoperative PLR and albumin were significantly associated with progression-free survival (PFS). Multivariate analysis revealed that preoperative PLR was significantly associated with OS. Conclusion: Reduced preoperative PLR was significantly associated with better OS in patients with stage I-III colon cancer. Preoperative PLR was an independent prognostic indictor for OS in patients with colon cancer undergoing curative resection.

NDNF inhibits the migration and invasion of human renal cancer cells through epithelial-mesenchymal transition.

Neuron-derived neurotrophic factor (NDNF) is a glycosylated, disulfide-bonded secretory protein that contains a fibronectin type III domain. NDNF has been identified as a neurotrophic factor; however, its role in carcinogenesis has not yet been identified. To investigate the expression and role of NDNF in carcinogenesis, the expression of NDNF in human Renal cell carcinoma (RCC) cell lines and tissues was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. Cell proliferation was investigated using CCK-8 and colony formation assays, and the cell invasion and immigration capacity was evaluated using the transwell assay. The results demonstrated that NDNF expression was downregulated in RCC cell lines and RCC tissues. Restoring NDNF expression significantly inhibited the proliferation, migration and invasion of RCC cells. The study also demonstrated that the inhibitory effect of NDNF on invasive ability was mediated by suppressing the epithelial-mesenchymal transition (EMT) in RCC cells. NDNF may therefore be considered an important regulator of EMT in RCC progression and may represent a novel promising target for antimetastatic therapy.