Predicting the potentially exacerbation of severe viral pneumonia in hospital by MuLBSTA score joint CD4 + and CD8 +T cell counts: construction and verification of risk warning model.

PURPOSE: This study mainly focuses on the immune function and introduces CD4+, CD8+ T cells and their ratios based on the MuLBSTA score, a previous viral pneumonia mortality risk warning model, to construct an early warning model of severe viral pneumonia risk. METHODS: A retrospective single-center observational study was operated from January 2021 to December 2022 at the People's Hospital of Liangjiang New Area, Chongqing, China. A total of 138 patients who met the criteria for viral pneumonia in hospital were selected and their data, including demographic data, comorbidities, laboratory results, CT scans, immunologic and pathogenic tests, treatment regimens, and clinical outcomes, were collected and statistically analyzed. RESULTS: Forty-one patients (29.7%) developed severe or critical illness. A viral pneumonia severe risk warning model was successfully constructed, including eight parameters: age, bacterial coinfection, CD4+, CD4+/CD8+, multiple lung lobe infiltrations, smoking, hypertension, and hospital admission days. The risk score for severe illness in patients was set at 600 points. The model had good predictive performance (AUROC = 0.94397), better than the original MuLBSTA score (AUROC = 0.8241). CONCLUSION: A warning system constructed based on immune function has a good warning effect on the risk of severe conversion in patients with viral pneumonia.

Comprehensive analysis of the miRNA-mRNA regulatory network involved in spontaneous recovery of an H2O2-induced zebrafish cataract model.

OBJECTIVE: To identify the hub miRNAs and mRNAs contributing to the spontaneous recovery of an H2O2-induced zebrafish cataract model. METHODS: Zebrafishes were divided into three groups, i.e., Group A, which included normal control fish (day 0), and Groups B and C, where fish were injected with 2.5% hydrogen peroxide into the anterior chamber and reared for 14 and 30 days, respectively. Fish eyes were examined by stereomicroscope photography and optical coherence tomography (OCT). RNA profiles of fish lenses were detected by RNA sequencing. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEmiRs) were identified among three groups. The DEGs and DEmiRs, which changed in opposite positions between "B vs. A" and "C vs. B" were defined as ODGs (opposite positions changed DEGs) and ODmiRs (opposite positions changed DEmiRs). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) analysis were carried out by R language. The protein-protein interaction network (PPI) was constructed using STRING. Potential targets of miRNAs were obtained using miRanda. miRNA-mRNA networks were constructed by Cytoscape. RESULTS: The fish lens opacity formed on day 14 and recovered to transparent on day 30 after injection. Compared to group B, 1366 DEGs and 54 DEmiRs were identified in group C. "C vs. B" DEGs were enriched in gene clusters related to development and oxidative phosphorylation. Target genes of DEmiRs were enriched in clusters such as development and cysteine metabolism. Among three groups, 786 ODGs and 27 ODmiRs were identified, and 480 ODGs were predicted as targets of ODmiRs. Target ODGs were enriched in pathways related to methionine metabolism, ubiquitin, sensory system development, and structural constituents of the eye lens. In addition, we established an ODmiRs-ODGs regulation network. CONCLUSION: We identified several hub mRNAs and altered miRNAs in the formation and reversal of zebrafish cataracts. These hub miRNAs/mRNAs could be potential targets for the non-surgical treatment of ARC.

Biological signatures of the International Prognostic Index in diffuse large B-cell lymphoma.

ABSTRACT: Diffuse large B-cell lymphoma (DLBCL) is a highly aggressive subtype of lymphoma with clinical and biological heterogeneity. The International Prognostic Index (IPI) shows great prognostic capability in the era of rituximab, but the biological signatures of IPI remain to be discovered. In this study, we analyzed the clinical data in a large cohort of 2592 patients with newly diagnosed DLBCL. Among them, 1233 underwent DNA sequencing for oncogenic mutations, and 487 patients underwent RNA sequencing for lymphoma microenvironment (LME) alterations. Based on IPI scores, patients were categorized into 4 distinct groups, with 5-year overall survival of 41.6%, 55.3%, 71.7%, and 89.7%, respectively. MCD-like subtype was associated with age of >60 years, multiple extranodal involvement, elevated serum lactate dehydrogenase (LDH), and IPI scores ranging from 2 to 5, whereas ST2-like subtype showed an opposite trend. Patients with EZB-like MYC+ and TP53Mut subtypes exhibited poor clinical outcome independent of the IPI; integrating TP53Mut into IPI could better distinguish patients with dismal survival. The EZB-like MYC-, BN2-like, N1-like, and MCD-like subtypes had inferior prognosis in patients with IPI scores of ≥2, indicating necessity for enhanced treatment. Regarding LME categories, the germinal center-like LME was more prevalent in patients with normal LDH and IPI scores of 0 to 1. The mesenchymal LME served as an independent protective factor, whereas the germinal center-like, inflammatory, and depleted LME categories correlated with inferior prognosis for IPI scores of 2 to 5. In summary, our work explored the biological signatures of IPI, thus providing useful rationale for future optimization of the IPI-based treatment strategies with multi-omics information in DLBCL.

A fusion of VGG-16 and ViT models for improving bone tumor classification in computed tomography.

Background and Objective: Bone tumors present significant challenges in orthopedic medicine due to variations in clinical treatment approaches for different tumor types, which includes benign, malignant, and intermediate cases. Convolutional Neural Networks (CNNs) have emerged as prominent models for tumor classification. However, their limited perception ability hinders the acquisition of global structural information, potentially affecting classification accuracy. To address this limitation, we propose an optimized deep learning algorithm for precise classification of diverse bone tumors. Materials and Methods: Our dataset comprises 786 computed tomography (CT) images of bone tumors, featuring sections from two distinct bone species, namely the tibia and femur. Sourced from The Second Affiliated Hospital of Fujian Medical University, the dataset was meticulously preprocessed with noise reduction techniques. We introduce a novel fusion model, VGG16-ViT, leveraging the advantages of the VGG-16 network and the Vision Transformer (ViT) model. Specifically, we select 27 features from the third layer of VGG-16 and input them into the Vision Transformer encoder for comprehensive training. Furthermore, we evaluate the impact of secondary migration using CT images from Xiangya Hospital for validation. Results: The proposed fusion model demonstrates notable improvements in classification performance. It effectively reduces the training time while achieving an impressive classification accuracy rate of 97.6%, marking a significant enhancement of 8% in sensitivity and specificity optimization. Furthermore, the investigation into secondary migration's effects on experimental outcomes across the three models reveals its potential to enhance system performance. Conclusion: Our novel VGG-16 and Vision Transformer joint network exhibits robust classification performance on bone tumor datasets. The integration of these models enables precise and efficient classification, accommodating the diverse characteristics of different bone tumor types. This advancement holds great significance for the early detection and prognosis of bone tumor patients in the future.

Human endogenous retroviruses as epigenetic therapeutic targets in TP53-mutated diffuse large B-cell lymphoma.

TP53 mutation (TP53mut) occurs in 10-20% of diffuse large B-cell lymphoma (DLBCL) cases and serves as an unfavorable biomarker of DLBCL progression. It confers resistance to immunochemotherapy, high-dose chemotherapy, autologous stem cell transplantation, and anti-CD19 chimeric antigen receptor T-cell therapy. Therapeutic targeting of TP53mut remains a significant challenge in DLBCL treatment. Here we assessed TP53mut in 667 patients with newly diagnosed DLBCL, including 576 patients treated with immunochemotherapy rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and 91 patients with decitabine plus R-CHOP (DR-CHOP, NCT02951728 and NCT04025593). TP53mut independently predicted an inferior prognosis in R-CHOP-treated DLBCL, although this could be mitigated by DR-CHOP treatment. In TP53mut patients, multiple viral regulation pathways were repressed, resulting in the inhibition of immune modulation, as revealed by gene set enrichment analysis. TP53mut DLBCL exhibited increased methyltransferase SUV39H1 expression and H3K9 trimethylation (H3K9me3), contributing to repression of endogenous retroviruses (ERVs) and immunosuppressive tumor microenvironment. In TP53mut DLBCL cell lines, decitabine down-regulated SUV39H1, inhibited H3K9me3 occupancy on ERVs, and triggered ERV expression, thereby unleashing interferons program and CD4+T/CD8+T cell activation. Molecular silencing of SUV39H1 significantly abrogated decitabine-induced H3K9me3 inhibition and ERV expression. In TP53mut patient-derived xenograft models and TP53mut patients, the anti-tumor effect was improved upon the use of combined treatment of decitabine and doxorubicin via SUV39H1-H3K9me3-ERVs axis. Collectively, our findings highlight an ERV regulatory circuitry in TP53mut DLBCL and the crucial roles ERVs for epigenetically reprogramming tumor microenvironment for treating TP53mut-driven cancers.

Genetic subtype-guided immunochemotherapy in diffuse large B cell lymphoma: The randomized GUIDANCE-01 trial.

We report the results of GUIDANCE-01 (NCT04025593), a randomized, phase II trial of R-CHOP alone or combined with targeted agents (R-CHOP-X) guided by genetic subtyping of newly diagnosed, intermediate-risk, or high-risk diffuse large B cell lymphoma (DLBCL). A total of 128 patients were randomized 1:1 to receive R-CHOP-X or R-CHOP. The study achieved the primary endpoint, showing significantly higher complete response rate with R-CHOP-X than R-CHOP (88% vs. 66%, p = 0.003), with overall response rate of 92% vs. 73% (p = 0.005). Two-year progression-free survival rates were 88% vs. 63% (p < 0.001), and 2-year overall survival rates were 94% vs. 77% (p = 0.001). Meanwhile, post hoc RNA-sequencing validated our simplified genetic subtyping algorithm and previously established lymphoma microenvironment subtypes. Our findings highlight the efficacy and safety of R-CHOP-X, a mechanism-based tailored therapy, which dually targeted genetic and microenvironmental alterations in patients with newly diagnosed DLBCL.

The microRNA-4766/VEGFA axis mediates macrophage M2-type polarization to inhibit colorectal cancer proliferation and migration.

OBJECTIVE: To investigate the miR-4766/VEGFA axis in regulating M2-type macrophage polarization under hypoxia and its effect on the proliferation and migration of colorectal cancer (CRC) cells. METHODS: The differentially expressed genes (DEGs) in macrophages before and after hypoxia treatment in the dataset GSE154427 were analyzed. microRNA (miR)-4766 and VEGFA were selected as the research objects and then detected for mRNA expression and protein level using qRT-PCR and Western blot, respectively. The expression levels of M2 macrophage markers such as CD206, CD163, and ARG1 were detected to determine the M2-type macrophage polarization. The targeted binding of miR-4766 to VEGFA was verified using Dual-luciferase reporter gene assay. CCK-8 and Transwell assays were performed, respectively, to detect the capacity of cells to proliferate and migrate. IL-10 and TGF-ß levels in the conditioned medium were detected using ELISA. RESULTS: miR-4766 was upregulated, and VEGFA was downregulated in hypoxia-treated macrophages. miR-4766 inhibited, while VEGFA promoted the polarization of M2-type macrophages. miR-4766 targeted and negatively regulated VEGFA. miR-4766 inhibited the polarization of M2-type macrophages and then suppressed CRC cell proliferation and migration via targeting VEGFA. CONCLUSION: Restoring miR-4766 expression to inhibit VEGFA expression promised to be a potential strategy to suppress CRC development.

Simplified algorithm for genetic subtyping in diffuse large B-cell lymphoma.

Genetic classification helps to disclose molecular heterogeneity and therapeutic implications in diffuse large B-cell lymphoma (DLBCL). Using whole exome/genome sequencing, RNA-sequencing, and fluorescence in situ hybridization in 337 newly diagnosed DLBCL patients, we established a simplified 38-gene algorithm (termed 'LymphPlex') based on the information on mutations of 35 genes and rearrangements of three genes (BCL2, BCL6, and MYC), identifying seven distinct genetic subtypes: TP53Mut (TP53 mutations), MCD-like (MYD88, CD79B, PIM1, MPEG1, BTG1, TBL1XR1, PRDM1, IRF4 mutations), BN2-like (BCL6 fusion, NOTCH2, CD70, DTX1, BTG2, TNFAIP3, CCND3 mutations), N1-like (NOTCH1 mutations), EZB-like (BCL2 fusion, EZH2, TNFRSF14, KMT2D, B2M, FAS, CREBBP, ARID1A, EP300, CIITA, STAT6, GNA13 mutations, with or without MYC rearrangement), and ST2-like (SGK1, TET2, SOCS1, DDX3X, ZFP36L1, DUSP2, STAT3, IRF8 mutations). Extended validation of 1001 DLBCL patients revealed clinical relevance and biological signature of each genetic subtype. TP53Mut subtype showed poor prognosis, characterized by p53 signaling dysregulation, immune deficiency, and PI3K activation. MCD-like subtype was associated with poor prognosis, activated B-cell (ABC) origin, BCL2/MYC double-expression, and NF-κB activation. BN2-like subtype showed favorable outcome within ABC-DLBCL and featured with NF-κB activation. N1-like and EZB-like subtypes were predominated by ABC-DLBCL and germinal center B-cell (GCB)-DLBCL, respectively. EZB-like-MYC+ subtype was characterized by an immunosuppressive tumor microenvironment, while EZB-like-MYC- subtype by NOTCH activation. ST2-like subtype showed favorable outcome within GCB-DLBCL and featured with stromal-1 modulation. Genetic subtype-guided targeted agents achieved encouraging clinical response when combined with immunochemotherapy. Collectively, LymphPlex provided high efficacy and feasibility, representing a step forward to the mechanism-based targeted therapy in DLBCL.

Acetylation of MLH1 by CBP increases cellular DNA mismatch repair activity.

The DNA mismatch repair (MMR) proteins recognize and repair DNA base pair mismatches and insertions/deletions of DNA that have occurred during DNA replication. Additionally, they are involved in regulation of the DNA damage response, including cell cycle checkpoints and apoptosis. Therefore, regulation of these proteins is essential for maintaining genomic integrity. It has been recognized that post-translational modifications, such as phosphorylation, ubiquitination, and acetylation, are being used as an important means to regulate the functions and stability of MMR proteins. Here, we report that a histone acetyltransferase CREB binding protein (CBP) interacts with and acetylates MLH1, a component of the MutLα complex (MLH1-PMS2). Moreover, CBP stabilizes MLH1 by preventing it from degradation via the ubiquitin-proteasome degradation pathway. Consistently, acetylation induced by a pan-histone deacetylase inhibitor, Trichostatin A, promotes the assembly between the MutSα (MSH2-MSH6) and MutLα complexes. Furthermore, overexpression of CBP enhances MMR activities in cells. Overall, our results suggest a novel role of CBP in prolonging MLH1 stability and enhancing MutSα-MutLα complex formation, leading to increased cellular MMR activity.

Bone marrow-derived mesenchymal stem cells accelerate angiogenesis in pregnant experimentally induced deep venous thrombosis rat model via up-regulation of pro-angiogenic secretogranin II.

The present study investigated whether bone marrow-derived mesenchymal stem cells (BMMSCs) facilitate angiogenesis and improve outcomes of pregnancy with obstetric deep venous thrombosis (DVT) and explored the underlying mechanism. A pregnant DVT rat model was established using a "stenosis" method on the lower segment of the inferior vena cava (IVC). The extent of vascularization in thrombosed IVC was examined by immunohistochemistry. In addition, the effect of BMMSCs on DVT pregnancy outcomes was evaluated. We also characterized the effect of BMMSC-derived conditioned medium (BM-CM) on the impaired human umbilical vein endothelial cells (HUVECs). Thereafter, transcriptome sequencing was employed to identify the differentially expressed genes in thrombosed IVC tissues of DVT and DVT plus BMMSCs (thrice) groups. Lastly, the candidate gene's role in the promotion of angiogenesis was demonstrated in vitro and in vivo. The DVT model was successfully established using IVC stenosis. The injection of three consecutive BMMSC doses into pregnant SD rats with DVT was demonstrated to be the most effective treatment, which significantly reduced the length and weight of the thrombus, induced the highest level of angiogenesis, and ameliorated the embryo absorption rate. In vitro, BM-CM efficiently increased the abilities of impaired endothelial cells to proliferate, migrate, invade, and form vessel-like tubes, while inhibiting their apoptosis. Transcriptome sequencing revealed that BMMSCs induced a prominent upregulation of a variety of pro-angiogenic genes, including secretogranin II (SCG2). When SCG2 expression was knocked down by lentivirus, the BMMSCs' and BM-CM-induced pro-angiogenic effects on pregnant DVT rats and HUVECs were markedly attenuated. In conclusion, the study results suggest that BMMSCs enhance angiogenesis via up-regulation of SCG2, providing an effective alternative regenerative agent and novel target for the therapy of obstetric DVT.

Comparison of S-Detect and thyroid imaging reporting and data system classifications in the diagnosis of cytologically indeterminate thyroid nodules.

Purpose: The aim of this study was to investigate the value of S-Detect for predicting the malignant risk of cytologically indeterminate thyroid nodules (CITNs). Methods: The preoperative prediction of 159 CITNs (Bethesda III, IV and V) were performed using S-Detect, Thyroid Imaging Reporting and Data System of American College of Radiology (ACR TI-RADS) and Chinese TI-RADS (C-TIRADS). First, Linear-by-Linear Association test and chi-square test were used to analyze the malignant risk of CITNs. McNemar's test and receiver operating characteristic curve were used to compare the diagnostic efficacy of S-Detect and the two TI-RADS classifications for CITNs. In addition, the McNemar's test was used to compare the diagnostic accuracy of the above three methods for different pathological types of nodules. Results: The maximum diameter of the benign nodules was significantly larger than that of malignant nodules [0.88(0.57-1.42) vs 0.57(0.46-0.81), P=0.002]. The risk of malignant CITNs in Bethesda system and the two TI-RADS classifications increased with grade (all P for trend<0.001). In all the enrolled CITNs, the diagnostic results of S-Detect were significantly different from those of ACR TI-RADS and C-TIRADS, respectively (P=0.021 and P=0.007). The sensitivity and accuracy of S-Detect [95.9%(90.1%-98.5%) and 88.1%(81.7%-92.5%)] were higher than those of ACR TI-RADS [87.6%(80.1%-92.7%) and 81.8%(74.7%-87.3%)] (P=0.006 and P=0.021) and C-TIRADS [84.3%(76.3%-90.0%) and 78.6%(71.3%-84.5%)] (P=0.001 and P=0.001). Moreover, the negative predictive value and the area under curve value of S-Detect [82.8% (63.5%-93.5%) and 0.795%(0.724%-0.855%)] was higher than that of C-TIRADS [54.8%(38.8%-69.8%) and 0.724%(0.648%-0.792%] (P=0.024 and P=0.035). However, the specificity and positive predictive value of S-Detect were similar to those of ACR TI-RADS (P=1.000 and P=0.154) and C-TIRADS (P=1.000 and P=0.072). There was no significant difference in all the evaluated indicators between ACR TI-RADS and C-TIRADS (all P>0.05). The diagnostic accuracy of S-Detect (97.4%) for papillary thyroid carcinoma (PTC) was higher than that of ACR TI-RADS (90.4%) and C-TIRADS (87.8%) (P=0.021 and P=0.003). Conclusion: The diagnostic performance of S-Detect in differentiating CITNs was similar to ACR TI-RADS and superior to C-TIRADS, especially for PTC.

Identification of HOXB9 to predict prognosis of endometrial cancer based on comprehensive bioinformatics analysis.

BACKGROUND: The HOXB9 gene, which plays a key role in embryonic development, is also involved in the regulation of various human cancers. However, the potential relationship between HOXB9 and endometrial cancer (EC) has not yet been comprehensively analyzed and fully understood. METHODS: We used multiple bioinformatics tools to explore the role of HOXB9 in EC. RESULTS: The expression of HOXB9 was significantly upregulated in pan-cancer, including EC (P < 0.05). Quantitative real time polymerase chain reaction (qRT-PCR) experiment confirmed the high expression of HOXB9 in EC from clinical samples (P < 0.001). Double validated by Enrichr and Metascape, HOXB9 showed a strong correlation with HOX family, suggesting that HOX family may also involve in the development of EC (P < 0.05). Enrichment analysis revealed HOXB9 is mainly associated with cellular process, developmental process, P53 signaling pathway, etc. At the single-cell level, the clusters of cells ranked were glandular and luminal cells c-24, glandular and luminal cells c-9, endothelial cells c-15, compared with the other cells. At the genetic level, promoter methylation levels of HOXB9 were significantly higher in tumors than in normal tissues. Furthermore, variations of HOXB9 were closely associated with overall survival (OS) and recurrence free survival (RFS) in EC patients (P < 0.05). The agreement between univariate and multivariate Cox regression indicated that the results were more reliable. Stages III and IV, G2 and G3, tumor invasion ≥ 50%, mixed or serous histological type, age > 60 years, and high expression of HOXB9 were risk factors strongly associated with OS in EC patients (P < 0.05). Therefore, six factors were incorporated to construct a nomogram for survival prediction. Finally, we used the Kaplan-Meier (KM) curve, receiver operating characteristic (ROC) curve, and time-dependent ROC to assess predictive power of HOXB9. KM curve showed EC patients overexpressing HOXB9 had a worse OS. AUC of diagnostic ROC was 0.880. AUCs of time-dependent ROC were 0.602, 0.591, and 0.706 for 1-year, 5-year, and 10-year survival probabilities (P < 0.001). CONCLUSIONS: Our study provids new insights into the diagnosis and prognosis of HOXB9 in EC and constructs a model that can accurately predict the prognosis of EC.

Combined Synthesis of Cerium Oxide Particles for Effective Anti-Bacterial and Anti-Cancer Nanotherapeutics.

Introduction: Kochiae Fructus has been widely used in Chinese Herbal medicine to treat various diseases. We report a rapid and eco-friendly approach for cerium oxide (CeO2) nanoparticles (NPs) synthesis using the extract of medicinally important plant "Kochiae Fructus", and the synthesized NPs were named KF-CeO2 NPs. Methods: Various spectroscopic approaches such as transmission electron microscope (TEM), powder X-ray diffraction (XRD), and energy-dispersive X-Ray (EDX) were used to characterize the KF-CeO2 NPs effectively. The antibacterial and biofilm inhibition activity of KF-CeO2 NPs against Gram-positive and Gram-negative multi-drug resistant (MDR) bacteria was determined using the serial dilution method and XTT assay. KF-CeO2 NPs were assessed for anticancer activity against HeLa cancer cells using an MTT assay. Cytobiocompatibility was determined in two normal cell lines (3T3 and hMSC). Results and Discussion: The average size of the KF-CeO2 NPs was 11.3 ± 3.9 nm with spherical morphology. KF-CeO2 NPs demonstrated a greater than 95% bactericidal efficacy against MDR microorganisms. In addition, KF-CeO2 NPs strongly suppressed (more than 79%) the biofilms of MDR bacteria, indicating their potential for addressing antibiotic resistance issues. Compared to Kochiae Fructus extract and CH-CeO2 NPs, they exhibited significant cytotoxic effects (35.60% cell viability) on HeLa cancer cells. In addition, the KF-CeO2 NPs were shown to be highly biocompatible with hMSC and 3T3 cell lines (85.13% and 81.17% cell viability, respectively), suggesting that they may be employed in biological systems. Conclusion: These data indicate that KF-CeO2 NPs synthesized using Kochiae Fructus extract are promising alternative treatments for MDR. In addition, this study will give the potential for the sustained development of biocompatible NPs with enhanced biological capabilities derived from vital pharmaceutical plants.

Impact of repeated intravenous infusions of umbilical cord-derived versus bone marrow-derived mesenchymal stem cells on angiogenesis in a pregnant experimentally induced deep venous thrombosis rat model.

Deep venous thrombosis (DVT) therapy during pregnancy warrants special consideration for the woman and the fetus. This study aimed to evaluate the impact of umbilical cord-derived mesenchymal stem cells (UC-MSCs) and bone marrow-derived mesenchymal stem cells (BM-MSCs) in terms of pro-angiogenic capacity and amelioration of pregnancy outcomes. The pregnant DVT rat model was successfully established by the "stenosis" method. Three consecutive injections of both UC-MSCs and BM-MSCs improved angiogenesis and ameliorated the embryo absorption rate in pregnant SD rats with DVT, in which UC-MSCs promoted angiogenesis more significantly. Furthermore, the levels of serum vascular endothelial growth factor-A (VEGF-A) and epidermal growth factor (EGF) were significantly higher in the UC-MSC group compared to those of the BM-MSC group. Thereafter, differentially expressed genes (DEGs) in thrombosed inferior vena cava tissues in the UC-MSC and BM-MSC groups were identified using transcriptome sequencing and further assessed by RT-qPCR and western blotting. The bioinformatics analysis indicated that the enriched DEG terms occurred in the cytokine activity, and the DEG pathways were significantly enriched in the cytokine-cytokine receptor interaction. In addition, both the mRNA and protein levels of angiogenic genes and their receptors, including VEGF-A, VEGF receptor-1, EGF, and EGF receptor, were significantly higher in the UC-MSC group. In conclusion, the BM-MSCs and UC-MSCs both significantly stimulate angiogenesis and ameliorate the embryo absorption rate in pregnant SD rats with DVT, but the difference in cytokine secretion causes UC-MSCs to have more potent angiogenic effects than BM-MSCs.

FOXQ1 recruits the MLL complex to activate transcription of EMT and promote breast cancer metastasis.

Aberrant expression of the Forkhead box transcription factor, FOXQ1, is a prevalent mechanism of epithelial-mesenchymal transition (EMT) and metastasis in multiple carcinoma types. However, it remains unknown how FOXQ1 regulates gene expression. Here, we report that FOXQ1 initiates EMT by recruiting the MLL/KMT2 histone methyltransferase complex as a transcriptional coactivator. We first establish that FOXQ1 promoter recognition precedes MLL complex assembly and histone-3 lysine-4 trimethylation within the promoter regions of critical genes in the EMT program. Mechanistically, we identify that the Forkhead box in FOXQ1 functions as a transactivation domain directly binding the MLL core complex subunit RbBP5 without interrupting FOXQ1 DNA binding activity. Moreover, genetic disruption of the FOXQ1-RbBP5 interaction or pharmacologic targeting of KMT2/MLL recruitment inhibits FOXQ1-dependent gene expression, EMT, and in vivo tumor progression. Our study suggests that targeting the FOXQ1-MLL epigenetic axis could be a promising strategy to combat triple-negative breast cancer metastatic progression.

Croceicoccus hydrothermalis sp. nov., isolated from shallow-sea hydrothermal system off Kueishantao Island.

A Gram-stain-negative, strictly aerobic, non-motile, ovoid or short-rod shaped, orange-pigmented bacterial strain, designated as strain JLT1T, was isolated from seawater of the shallow-sea hydrothermal system, near Kueishantao Islet. Growth was observed at 5-45°C (optimum, 30 °C) and pH 5.0-11.0 (optimum, pH 7.0). The salinity range for growth was 0-12 % (optimum, 2-4 %) (w/v) NaCl. JLT1T contained ubiquinone-10 as the main respiratory quinone. Iso-C12 : 0, summed feature 3 (C16 : 1ω7c/ω6c) and summed feature 8 (C18 : 1ω6c/ω7c) were identified as the major cellular fatty acids. Polar lipids included diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, three unidentified phospholipids, eight unidentified glycolipids and an unidentified lipid. The 16S rRNA gene of JLT1T shared the greatest similarity (96.31 %) with those of Croceicoccus pelagius Ery9T and Croceicoccus ponticola GM-16T. The draft genome size of JLT1T is 3.56 Mb, with 3578 potential genes and a genomic DNA G+C content of 63.24 mol %. Average nucleotide identity and digital DNA-DNA hybridization values of JLT1T compared with C. pelagius Ery9T, C. ponticola GM-16T, Croceicoccus sediminis S2-4-2T, Croceicoccus mobilis Ery22T and Croceicoccus marinus E4A9T were 74.5, 73.9, 74.4, 74.3 and 74.8 % and 20.6, 19.2, 20.0, 20.5 and 19.8%, respectively. On the basis of these phylogenetic, chemotaxonomic and phenotypic features, JLT1T is concluded to represent a novel species of the genus Croceicoccus, for which the name Croceicoccus hydrothermalis sp. nov. is proposed. The type strain is JLT1T (=CGMCC 1.15786T =JCM 31508T).

Dynamic change of soluble interleukin-2 receptor distinguished molecular heterogeneity and microenvironment alterations in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma with variable clinical outcomes and prediction of prognosis remains important for long-term remission. We performed serial serum soluble interleukin-2 receptor (sIL-2R) measurement pretreatment and before each cycle of the treatment in 599 patients with de novo DLBCL. Genomic and transcriptomic features were analyzed by 223 DNA- and 227 RNA-sequencing, respectively. Applying the cut-off value to sIL-2R pretreatment and cycle 2 (C2) level, patients were classified into FINE subtype (pretreatment low level) with good prognosis, RES subtype (pretreatment high level and C2 low level) with intermediate prognosis, and RET subtype (pretreatment high level and C2 high level) with poor prognosis, independent of International Prognostic Index. In "others" genetic subtype, dynamic change of sIL-2R showed prognostic significance and genetic features. Compared with FINE subtype, RES subtype had increased ARID1A and MYD88 mutations, and RET subtype had increased KMT2D, LYN and SOCS1 mutations. RES and RET subtypes showed significant enrichment in oncogenic pathways, such as ERK, NF-κB, JAK-STAT, and immune-associated pathways. As for tumor microenvironment, RES subtype exhibited increased recruiting activity of CD8 + T, T helper 1, and natural killer cells, and RET subtype with increased recruiting activity of CD4 + T and regulatory T cells in silico. There was a positive correlation between transcripts of IL-2R and immune checkpoint expressions including PD-1 and CTLA-4. Our findings identified that dynamic change of sIL-2R, with this simple and easy detection method in peripheral blood, had long-term prognostic effect and specific relation to microenvironment alterations in DLBCL.

Investigation of clinical application of claudin 18 isoform 2 in pancreatic ductal adenocarcinoma: A retrospective analysis of 302 chinese patients.

The malignancy of pancreatic ductal adenocarcinoma (PDAC) results from high frequency of recurrence and limited effective therapies. Targeted therapy is a promising treatment in multiple solid tumours. A new target, claudin 18 isoform 2 (CLDN18.2) was discovered in gastric and pancreatic adenocarcinoma, but more clinical evaluations of CLDN18.2 are still needed. Several CLDN18.2-targeted drugs have already been in procedure of clinical trials. Therefore, the present study aimed to explore the expression and clinical value of CLDN18.2 in PDAC by immunohistochemistry. A microarray cohort of 302 PDAC specimens and a whole-slide cohort of randomized 84 PDAC specimens were constructed. In total, 56.52% (171/302) of PDAC patients showed diverse positivity for CLDN18.2, especially in highly differentiated PDAC. About eighty-two percent (62/75) highly- and 62.61% (72/115) intermediate-differentiated PDAC showed positive for CLDN18.2, while only 10.16% (6/59) low differentiated PDAC was positive for CLDN18.2. Besides, CLDN18.2 positivity was associated with several clinicopathological characteristics, including sex (P=0.001), smoking (P=0.006), abdominal pain (P=0.021), jaundice (P=0.010), pathological differentiation (P=0.001), common bile duct invasion (P=0.010), and M stage (P=0.003). CLDN18.2-positive expression also predicts an improved survival (P=0.032) but not progression free survival (P=0.460). However, CLDN18.2 is not an independent prognostic predictor. In conclusion, CLDN18.2 may be a potential therapeutic target for PDAC and the study supplies persuasive pathological evidence for CLDN18.2-targeted therapy on PDAC patients.

Individualized Whole Course Nutrition Management for Nasopharyngeal Carcinoma Patients Undergoing Radiotherapy.

BACKGROUND: Radiotherapy-induced oral mucositis (RIOM) is the most common toxicity associated with radiotherapy for nasopharyngeal carcinoma (NPC). Patients with RIOM become malnourished, which can affect the delivery and dose of radiotherapy. The value of personalizing nutrition recommendations for cancer prevention and management is increasingly recognized. To investigate the effect of individualized whole course nutrition management on nutritional status and the incidence and severity of RIOM in NPCs. METHODS: This retrospective study included 77 patients who were provided individualized whole course nutrition management during radiotherapy (RT) and a 1-month follow-up. Seventy-one patients were included in the control group. RESULTS: During radiotherapy, severity of RIOM was significantly lower in the intervention group. There were statistically significant differences in oral mucosa recovery time and nutritional status between the two groups (p < 0.05). CONCLUSIONS: Individualized whole course nutrition management had the potential to maintain nutritional status and decrease the adverse effects of radiotherapy in NPCs.