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Diabetes, a common chronic disease worldwide, can induce vascular complications, such as coronary heart disease (CHD), which is also one of the main causes of human death. It is of great significance to study the factors of diabetic patients complicated with CHD for understanding the occurrence of diabetes/CHD comorbidity. In this study, by analyzing the risk of CHD in more than 300,000 diabetes patients in southwest China, an artificial intelligence (AI) model was proposed to predict the risk of diabetes/CHD comorbidity. Firstly, we statistically analyzed the distribution of four types of features (basic demographic information, laboratory indicators, medical examination, and questionnaire) in comorbidities, and evaluated the predictive performance of three traditional machine learning methods (eXtreme Gradient Boosting, Random Forest, and Logistic regression). In addition, we have identified nine important features, including age, WHtR, BMI, stroke, smoking, chronic lung disease, drinking and MSP. Finally, the model produced an area under the receiver operating characteristic curve (AUC) of 0.701 on the test samples. These findings can provide personalized guidance for early CHD warning for diabetic populations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aneurysmal subarachnoid hemorrhage (aSAH) develops quickly once it occurs and threatens the life of patients. We aimed to use machine learning to predict mortality for SAH patients at an early stage which can help doctors make clinical decisions. In our study, we applied different machine learning methods to an aSAH cohort extracted from a national EHR database, the Cerner Health Facts EHR database (2000-2018). The outcome of interest was in-hospital mortality, as either passing away while still in the hospital or being discharged to hospice care. Machine learning-based models were primarily evaluated by the area under the receiver operating characteristic curve (AUC). The population size of the SAH cohort was 6728. The machine learning methods achieved an average of AUCs of 0.805 for predicting mortality with only the initial 24 hours' EHR data. Without losing the prediction power, we used the logistic regression to identify 42 risk factors, -examples include age and serum glucose-that exhibit a significant correlation with the mortality of aSAH patients. Our study illustrates the potential of utilizing machine learning techniques as a practical prognostic tool for predicting aSAH mortality at the bedside., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zhu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Non-coding RNAs (ncRNAs) are a class of RNA molecules that do not have the potential to encode proteins. Meanwhile, they can occupy a significant portion of the human genome and participate in gene expression regulation through various mechanisms. Gestational diabetes mellitus (GDM) is a pathologic condition of carbohydrate intolerance that begins or is first detected during pregnancy, making it one of the most common pregnancy complications. Although the exact pathogenesis of GDM remains unclear, several recent studies have shown that ncRNAs play a crucial regulatory role in GDM. Herein, we present a comprehensive review on the multiple mechanisms of ncRNAs in GDM along with their potential role as biomarkers. In addition, we investigate the contribution of deep learning-based models in discovering disease-specific ncRNA biomarkers and elucidate the underlying mechanisms of ncRNA. This might assist community-wide efforts to obtain insights into the regulatory mechanisms of ncRNAs in disease and guide a novel approach for early diagnosis and treatment of disease., (© The Author(s) 2024. Published by Oxford University Press.)

Microplastic pollution in the water environment is becoming increasingly serious, impacting the growth and development of aquatic organisms. There are limited studies on the mechanisms of microplastic effects on biofilm formation. Therefore, in this study, the effects of polystyrene microplastics (PS-MPs) were investigated on the biofilm formation and development of Pseudomonas aeruginosa . Different concentrations and particle sizes of PS-MPs were selected for exposure tests to explore the effects on biofilm biomass, oxidative stress levels, biofilm structure, and population sensing system. The results showed that PS-MPs induced severe oxidative stress and inhibited biofilm formation and development, and the smaller the particle size, the stronger the inhibitory effect was. The inhibition effect was 0.1 μm>0.5 μm≈1 μm>5 μm. PS-MPs caused severe physical damage through contact with bacteria. The thickness of the biofilm was significantly reduced, damaging the structural stability. The bacteria in the biofilm secreted extracellular polymers to resist the stress of PS-MPs. Meanwhile, PS-MPs interfered with the QS system of P. aeruginosa ; down-regulated the expression levels of key genes lasI, lasR, rhlI , and rhlR ; inhibited the synthesis and secretion of signal molecules and related virulence factors; and ultimately affected the formation and structural stability of biofilms.

Objectives: The present study aimed to examine the psychometric properties of the Chinese version of the Career Adapt-Abilities Scale-Short Form (CAAS-SF) among a sample of Chinese elite athletes., Methods: A sample of Chinese elite athletes ( n = 770) was invited to participate in this study. First, the factor structure of the Chinese version of the CAAS-SF was examined, and six measurement models (CFA, H-CFA, B-CFA, ESEM, H-ESEM, and B-ESEM) were constructed and compared. Second, the internal consistency reliability of the Chinese version of the CAAS-SF was examined. Finally, structural equation modeling (SEM) was employed to assess the nomological validity of the Chinese version of the CAAS-SF., Results: The results showed that the hierarchical ESEM (H-ESEM) model best represented the factor structure of the CAAS-SF among Chinese elite athletes. It suggests that the higher-order factor of career adaptability explains the four distinctive but interrelated specific factors of concern, control, curiosity, and confidence. Cronbach's alpha coefficients (0.84-0.90), composite reliability (0.81-0.96), and coefficient omega hierarchical (0.855-0.94) of the Chinese version of the CAAS-SF were larger than the cutoff values, which suggest satisfactory reliability. The results of the SEM revealed that the higher-order factor of career adaptability was positively associated with career decision self-efficacy (β = 0.676, p < 0.001). This result is consistent with previous findings (r = 0.65, p < 0.01) and provided support for the nomological validity of the CAAS-SF among Chinese elite athletes., Conclusion: The findings of the present study indicated that the Chinese version of the CAAS-SF displayed satisfactory reliability and validity and could be used to assess the career adaptability of Chinese elite athletes. In addition, the total score of the CAAS-SF is suggested to be used in future research and practical works., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hu, Su, Huang, Zou, Liu and Liu.)

Glioblastoma (GBM) is a highly aggressive primary brain tumor that shows intratumoral heterogeneity at the cellular and molecular level. Activation of programmed death receptor 1 (PD-1) interaction with its ligand PD-L1 is a well-known mechanism requisite for immune evasion deployed by malignant tumors including GBM. Herein, we set out to dissect the mechanism explaining the regulation of PD-L1 gene expression in GBM. The clinical samples consisted of 37 GBM tissues and 18 normal brain tissues. GBM cell model was treated by microRNA (miRNA) inhibitor, DNA constructs, and siRNAs. Assays of CCK-8 and Transwell insert were employed to assess the survival, migratory and invasive ability of GBM cell model. The immunosuppressive factor production, T cell apoptosis, and T cell cytotoxicity to GBM cells were evaluated in the co-culture system. GBM exhibited more miR-10b-5p abundance than normal at both tissue and cellular level. Suppression of miR-10b-5p weakened the ability of GBM cell model to survive, migrate, and invade, decreased the release of immunosuppressive factors, reduced T cell apoptosis, and strengthened the T cell cytotoxicity to GBM cell model. MiR-10b-5p conferred a negative control of Ten-eleven translocation 2 (TET2) that was downregulated in GBM. The functions of miR-10b-5p on GBM cell aggressiveness and immune evasion were mediated by TET2. TET2 recruited histone deacetylases HDAC1 and HDAC2 into the PD-L1 promoter region thus inhibiting its transcription. The study demonstrated the importance of miR-10b-5p-mediated repression of TET2 in PD-L1-driven immune evasion and their potential for immunotherapeutic targeting in GBM.

Background: The activation of YAP/TAZ transcriptional co-activators, downstream effectors of the Hippo/YAP pathway, is commonly observed in human cancers, promoting tumor growth and invasion. The aim of this study was to use machine learning models and molecular map based on the Hippo/YAP pathway to explore the prognosis, immune microenvironment and therapeutic regimen of patients with lower grade glioma (LGG)., Methods: SW1783 and SW1088 cell lines were used as in vitro models for LGG, and the cell viability of the XMU-MP-1 (a small molecule inhibitor of the Hippo signaling pathway) treated group was evaluated using a Cell Counting Kit-8 (CCK-8). Univariate Cox analysis on 19 Hippo/YAP pathway related genes (HPRGs) was performed to identify 16 HPRGs that exhibited significant prognostic value in meta cohort. Consensus clustering algorithm was used to classify the meta cohort into three molecular subtypes associated with Hippo/YAP Pathway activation profiles. The Hippo/YAP pathway's potential for guiding therapeutic interventions was also investigated by evaluating the efficacy of small molecule inhibitors. Finally, a composite machine learning models was used to predict individual patients' survival risk profiles and the Hippo/YAP pathway status., Results: The findings showed that XMU-MP-1 significantly enhanced the proliferation of LGG cells. Different Hippo/YAP Pathway activation profiles were associated with different prognostic and clinical features. The immune scores of subtype B were dominated by MDSC and Treg cells, which are known to have immunosuppressive effects. Gene Set Variation Analysis (GSVA) indicated that subtypes B with a poor prognosis exhibited decreased propanoate metabolic activity and suppressed Hippo pathway signaling. Subtype B had the lowest IC50 value, indicating sensitivity to drugs that target the Hippo/YAP pathway. Finally, the random forest tree model predicted the Hippo/YAP pathway status in patients with different survival risk profiles., Conclusions: This study demonstrates the significance of the Hippo/YAP pathway in predicting the prognosis of patients with LGG. The different Hippo/YAP Pathway activation profiles associated with different prognostic and clinical features suggest the potential for personalized treatments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Guo, Sun, Zhao, Han, Yu and Zhang.)

Objective: To investigate the changes and roles of reactive oxygen species (ROS) and nuclear factor erythroid 2-related factor 2 (Nrf2) related antioxidases during erythroid development., Methods: Flow cytometry was used to detect the sensibility of peripheral red blood cells of wild-type mice to a strong oxidant hydrogen peroxide (H 2 O 2 ). Erythroid cells from different developmental stages in bone marrow (BM) were obtained using fluorescence-activated cell sorter and the ROS levels were detected by flow cytometry. RT-qPCR was used to detect the changes of expression levels of Nrf2 and related antioxidases in erythroid cells from different developmental stages in BM. The ROS levels of the peripheral blood and BM nucleated erythrocytes in Nrf2 knockout mice were further examined. The expression level of Nrf2 in erythroid precursors isolated from 14.5 d embryonic liver of wild-type mice during differentiation and culture in vitro was detected., Results: In the peripheral blood of wild-type mice, the ROS level of reticulocytes and mature erythrocytes treated with H 2 O 2 increased about 4 times and 7 times, respectively ( P <0.01). In BM erythrocytes, the ROS level gradually decreased as the cells matured ( r =0.85), while the expression level of Nrf2 and its related anti-oxidative genes increased ( r =0.99). The ROS levels in peripheral blood erythrocytes and BM nucleated erythrocytes of Nrf2 knockout mice were significantly increased compared with wild-type mice ( P <0.01). The expression of Nrf2 increased during the early erythroid development after embryonic liver cell sorting ( P <0.01)., Conclusion: The expression levels of Nrf2 and its related factors vary during erythropoiesis. Nrf2 at physiological level plays an important antioxidant role during the erythroid development.

The interpretability of machine learning models, even though with an excellent prediction performance, remains a challenge in practical applications. The model interpretability and variable importance for well-performed supervised machine learning models are investigated in this study. With the commonly accepted concept of odds ratio (OR), we propose a novel and computationally efficient Variable Importance evaluation framework based on the Personalized Odds Ratio (VIPOR). It is a model-agnostic interpretation method that can be used to evaluate variable importance both locally and globally. Locally, the variable importance is quantified by the personalized odds ratio (POR), which can account for subject heterogeneity in machine learning. Globally, we utilize a hierarchical tree to group the predictors into five groups: completely positive, completely negative, positive dominated, negative dominated, and neutral groups. The relative importance of predictors within each group is ranked based on different statistics of PORs across subjects for different application purposes. For illustration, we apply the proposed VIPOR method to interpreting a multilayer perceptron (MLP) model, which aims to predict the mortality of subarachnoid hemorrhage (SAH) patients using real-world electronic health records (EHR) data. We compare the important variables derived from MLP with other machine learning models, including tree-based models and the L1-regularized logistic regression model. The top importance variables are consistently identified by VIPOR across different prediction models. Comparisons with existing interpretation methods are also conducted and discussed based on publicly available data sets., (© 2023 John Wiley & Sons Ltd.)

Objective: To investigate the expression of miR-451 during erythroid differentiation and its correlation with hematological diseases., Methods: The expression of miR-451 in erythroid differentiation of mouse hematopoietic stem cells (derived from fetal liver) was analyzed by cell culture, flow cytometry, magnetic bead sorting and qRT-PCR. The expression of miR-451 during erythroid differentiation of mouse erythroid leukemia cells (MEL) was analyzed by cell culture and qRT-PCR. The expression of miR-451 in peripheral blood of mice was detected by qRT-PCR, and the expression of miR-451 in fetal liver (14.5 days) was analyzed by microarray. The nucleated erythroid cells from bone marrow of wild type (WT) mice and β-thalassemia (β-thal) mice were sorted by flow cytometry, and the levels of miR-451 and erythroid genes were detected by qRT-PCR. The expression of miR-451 in peripheral blood of patients with clinical hematological diseases was detected by qRT-PCR., Results: During the differentiation of mouse hematopoietic stem cells (derived from fetal liver) and MEL cells, the expression levels of miR-451 increased gradually. Compared with WT mice, the expression levels of miR-451 in peripheral blood, 14.5-day fetal liver cells and nucleated erythroid cells (sorted from bone marrow) of β-thal mice were significantly increased( P <0.05). Many erythroid differentiation genes in nucleated erythroid cells (sorted from bone marrow) of β-thal mice decreased. Compared with healthy controls, the expression levels of miR-451 was increased in peripheral blood of patients with β-thalassemia and iron deficiency anemia, while the expression levels of miR-451 was decreased in patients with aplastic anemia and myelodysplastic syndrome., Conclusion: During erythroid differentiation, the expression levels of miR-451 increases gradually. In hematological diseases, the expression levels of miR-451 is different from that of normal controls, which is expected to become an auxiliary diagnostic index for clinical hematological diseases.

Lung adenocarcinoma is a malignancy with a low overall survival and a poor prognosis. Studies have shown that lung adenocarcinoma progression relates to locus-specific/global changes in histone modifications. To explore the relationship between histone modification and gene expression changes, we focused on 11 histone modifications and quantitatively analyzed their influences on gene expression. We found that, among the studied histone modifications, H3K79me2 displayed the greatest impact on gene expression regulation. Based on the Shannon entropy, 867 genes with differential H3K79me2 levels during tumorigenesis were identified. Enrichment analyses showed that these genes were involved in 16 common cancer pathways and 11 tumors and were target-regulated by trans -regulatory elements, such as Tp53 and WT1. Then, an open-source computational framework was presented (https://github.com/zlq-imu/Identification-of-potential-LUND-driver-genes). Twelve potential driver genes were extracted from the genes with differential H3K79me2 levels during tumorigenesis. The expression levels of these potential driver genes were significantly increased/decreased in tumor cells, as assayed by RT-qPCR. A risk score model comprising these driver genes was further constructed, and this model was strongly negatively associated with the overall survival of patients in different datasets. The proportional hazards assumption and outlier test indicated that this model could robustly distinguish patients with different survival rates. Immune analyses and responses to immunotherapeutic and chemotherapeutic agents showed that patients in the high and low-risk groups may have distinct tendencies for clinical selection. Finally, the regions with clear H3K79me2 signal changes on these driver genes were accurately identified. Our research may offer potential molecular biomarkers for lung adenocarcinoma treatment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Pulmonary drug delivery has gained great attention in local or systemic diseases therapy, however it is still difficult to scale-up DPI production due to the complexity of interactions taking place in DPI systems and limited understanding between flowability and inter-particle interactions in DPI formulations. Therefore, finding some quantitative parameters related to DPI delivery performance for predicting the in vitro drug deposition behavior is essential. Therefore, this study introduces a potential model for predicting aerodynamic performance of carrier-based DPIs, as well to find more relevant fine powder size and optimal shape to improve aerodynamic performance. Using salbutamol sulfate as a model drug, Lactohale®206 as coarse carrier, Lactohale®300, Lactohale®230, and Lactohale®210 as third fine components individually, the mixtures were prepared at 1% (w/w) drug content accompanied with carriers and the third component (ranging from 3% to 7%), influence of lactose fines size on DPI formulation's rheological and aerodynamic properties was investigated. The optimum drug particle shape was also confirmed by computer fluid dynamics model. This study proved that pulmonary deposition efficiency could be improved by decreasing lactose fines size. Only fines in the size range of 0-11 μm have a good linear relationship with FPF, attributed to the fluidization energy enhancement and aggregates mechanism. Once exceeding 11 μm, fine lactose would act as a second carrier, with increased drug adhesion. Computational fluid dynamics (CFD) models indicated fibrous drug particles were beneficial to transfer to the deep lung. Furthermore, good correlations between rheological parameters and FPF of ternary mixtures with different lactose fines were established, and it was disclosed that the FPF was more dependent on interaction parameters than that of flowability., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The purpose of the study was to translate the athlete burnout questionnaire (ABQ) into Simplified Chinese and examine its psychometric properties in Chinese collegiate athletes and elite athletes. Firstly, the factor structure, internal consistency reliability and nomological validity of the Chinese translated ABQ was examined in a sample of Chinese collegiate athletes ( n = 214, 58.9% females). Secondly, abovementioned psychometric properties were examined in a sample of Chinese elite athletes ( n = 505, 52.7% females). Finally, measurement invariance of the Chinese translated ABQ was examined across the two samples. It was found that the 12-item three-correlated-factors model outperformed the one factor model and bi-factor model in collegiate athlete sample whereas the 12-item bi-factor model best represented the factor structure of the Chinese translated ABQ in elite athlete sample. Satisfactory internal consistency reliabilities of the Chinese translated ABQ were evidenced in the two samples. Nomological validity was also supported by the results of the two samples that the three subscales of the ABQ were significantly associated with its theoretically related variables. Results of multiple-group confirmatory factor analysis revealed that weak measurement invariance of the Chinese translated ABQ (three-correlated-factors model) was evidenced across the two samples. Collectively, results of this study indicated that the 12-item Chinese translated ABQ could be used for measuring burnout of Chinese collegiate and elite athletes. Significance and implication of the current study as well as recommendations for future study were discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Wang, Wu, Zou, Jiang, Gao, You, Hu and Liu.)

Currently, research on the effects of microplastics (MPs) in biofilms has mainly been focused on the mature biofilm communities, with a lack of sufficient details on the influence on different development stages of biofilms. Proteus and 1 μm polystyrene microplastics (PS-MPs), which are widely found in the environment, were selected as the research objects to explore the effects of microplastics on biofilms at different developmental stages. In our study, the effects of PS-MPs on biofilm biomass, extracellular polymer composition(EPS), and extracellular enzyme activity were investigated using an exposure test. Our results showed that the effect of PS-MPs on biofilms at different stages was similar, but the effect was significantly reduced with the development of biofilms. Biofilms at different development stages had different sensitivities to microplastics. In the reversible attachment stage, the no observed effect concentration (NOEC) of EPS composition, reactive oxygen species (ROS) production, and extracellular enzyme activity were significantly lower than those in other stages; however, the NOEC of total antioxidant capacity (T-AOC) and lactate dehydrogenase (LDH) activity were similar. This may be the result of ROS-mediated protein oxidation, which can be reduced but not completely eliminated by EPS in other stages of biofilm. This indicates that PS-MPs has a low toxic effect on biofilm.

Acute myeloid leukemia（AML）is a myelopoietic stem/progenitor malignant disease. The exact etiology of this leukemia remains unclear, thus it is important to explore the pathogenesis of AML and to discover the new diagnostic markers and therapeutic targets. The long non coding RNA (lnc RNA) is a class of RNA molecules with transcripts over 200 nucleotides in eukaryotic cells which almost don't possess the ability to code proteins, but can regulate the expression of other genes at transcriptional and post-transcriptional levels, thereby participate in occurrence and development of varied tumors. Of late years, along with the deepening of study, the lncRNA roles played in the AML have been reported and confirmed. In this review, the relationships between the IncRNA (UCA1, ANRIL, H19, HOTAIR, CCAT1, ZFAS1, LINC00152, HOXA-A52, NEAT1, TUG1, IRAIN1, PANDAR, LINC00899, SNHG5, and KCNQ1OT1) and AML is summarized briefly, so as to provide the potential basis for the clinical diagnosis and therapy of AML.

Pediatric medulloblastoma is the leading cause of cancer-related death in children. However, few studies have reported gene expression profiles of pediatric medulloblastoma and the molecular mechanism underlying this disease is unclear. To identify essential genes in pediatric medulloblastoma, we analyzed three microarray data sets from the Gene Expression Omnibus (GEO). We identified 1798 differentially expressed genes (DEGs) using the limma package. Gene set enrichment analysis demonstrated that "entrainment of circadian clock by photoperiod," "regulation of triglyceride biosynthetic process," and "snare complex" pathway were significantly enriched gene sets that correlated with pediatric medulloblastoma. Enriched Gene Ontology annotations of DEGs mostly included "ion-gated channel activity," "gated channel activity," and "channel activity." Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that DEGs were enriched in "glutamatergic synapse," "synaptic vesicle cycle," and "GABAergic synapse." Protein-protein interaction (PPI) network analysis showed that RAB5C, VAMP2, AP2M1, FNBP1, AP2A1, SYT1, SYNJ2, SYT2, HIP1R, UBB, WNT5A, SH3GL2, SYNJ1, EPN1, and DNM1 were hub genes. In conclusion, the identification of the above hub genes and pathways will help to reveal the pathogenesis of pediatric medulloblastoma and will also provide prognostic markers and therapeutic targets for pediatric medulloblastoma.

Diffuse large B-cell lymphoma (DLBCL) accounts for approximately 30% of the non-Hodgkin's lymphoma patients. The underlying molecular mechanism of its pathogenesis is not well defined and the survival rate of DLBCL patients is very low. Moreover, the annual incidence and mortality of DLBCL is still rising. Accordingly, identification and characterization of new molecular pathways of DLBCL will lead to the development of novel diagnostic markers and molecular therapeutic targets. Long non-coding RNAs (LncRNA) are non-coding RNAs with a length greater than 200 bp in eukaryotic cells, which can regulate the expression of their target genes at the transcriptional and post transcriptional levels. The function of LncRNAs is involved in the initiation, progression, invasion and metastasis of many cancers. Recently, the role of LncRNAs in DLBCL has been identified and intensely studied. This review summarizes the recent discoveries in the expression and function of LncRNAs including HULC,PEG10,LincRNA-p21,HOTAIR,LUNAR1,MALAT1 and SubSigLnc-17 in DLBCL, so as to find potential diagnostic biomarkers and therapeutic targets for DLBCL.

Objective: To determine whether B lymphocyte-specific transcription factor Pax5 regulates B-lympho-magenesis without direct binding to promoter., Methods: Mouse B-lymphoma cell line myc3 and 38B9 were infected with GFP - tagged retrovirus that encodes wide type or various mutant pax5 genes. After viral infection for 48 hours, the percentage of GFP positive lymphoma cells was determined by flow cytomety. The percentage of GFP positive tumor cells was further monitored every 3 days in vitro or once the tumor was formed in vivo. Both cell cycle and apoptic cell number of GFP positive lymphoma cells were analyzed using flow cytometry., Results: Similar to the infection with wild type Pax5 retrovirus, infection with Pax5 mt 1-357 and Pax5 mt 304-358 that lacks of DNA binding motif can strongly increase the percentage of GFP + B-lymphoma cells both in vitro and in vivo (P<0.01), while infection with empty viral vector migR-GFP and Pax5 mt 1-143 containing only DNA binding motif failed to increase the percentage of GFP positive tumor cells (P>0.05). Moreover, the analysis of flow cytometry demonstrated that more B-lymphoma cells infected with wild type Pax5, Pax5 mt 1-357 and Pax5 mt 304-358 retroviruses entered S and G 2 /M phases in comparison with those infected with empty viral vector migR-GFP and Pax5 mt 1-143. Apoptotic rates among different groups were not significantly changed., Conclusion: Pax5 can promote B-lymphoma cell growth both in vitro and in vivo in a promoter-independent manner. This is mainly due to the accelerating of cell cycle rather than decreasing apoptosis. Our studies provide potential theory for restraing B-lymphomagenesis by targeting the specific Pax5 domains.

β-thalassemia is a chronic hemolytic anemia characterized by the reduction or absence of synthesis of β-globin chains because of the β-globin gene mutations. β-thalassemia belongs to the inherited hemoglobin disease, and occurs in some provinces of China, such as in Guangdong, Guangxi, Fujian, its prevalence is about 2%. The treatment of this disease include transfusion, iron chelating agent, hematopoietic stem cell transplantation, splenectomy, induced expression of Fetal Hemoglobin (HbF) and gene therapies. However, the mortality rate of this disease is still higher, thus some new treatments are urgently needed. In recent years, the study was mainly concentrated in 2 aspects: the normal β-globin gene transfer and endogenous γ-globin re-activation. Some studies showed that the expression of miRNAs was dysregulated in β-thalassemia. Some miRNAs could regulate γ-globin at posttranscriptional level, thus, the clarification of relationship between miRNAs and β-thalassemia is expected to provide experimental bases to β-thalassemia therapy. In this review, the induced therapy of γ-globin for β-thalassemia and its relationship with the miRNA are summarized.

Background: There is increasing evidence demonstrating the role of human trophoblast cell surface antigen 2 (TROP2) in cancer development and progression. However, their prognostic value in Epstein-Barr virus (EBV) associated nasopharyngeal carcinoma (NPC) remains to be elucidated., Method: The prognostic significances of TROP2 and Ki-67 were determined by immunohistochemistry in 58 NPC samples. TROP2 mRNA expression level and biological functions were evaluated. The presence of EBV was assessed using in situ hybridization. Analyses were conducted on the association between each of these variables as well as clinical outcome., Results: TROP2 was exhibited over expression in 64% of NPC samples and significantly associated with highly proliferative tumor cells (P = 0.05) and lymph node metastases (P = 0.03). Overexpression of TROP2 significantly correlated with worse overall survival (P = 0.026) and poor disease-free survival (P = 0.021). By univariate analysis, high expression of TROP2 significantly correlated with patients with distant metastases, Ki-67 and EBV infection. Multivariate analysis further revealed that TROP2 along with Ki-67 and distant metastasis are independent prognostic predictors for NPC patients., Conclusion: Our findings have demonstrated that overexpression of TROP2 appears to be an independent predictor for poor clinical outcome in NPC. The strong correlation of overexpression of TROP2 with Ki-67 and distant metastases indicates a potentially therapeutic strategies targeting TROP2 for NPC patients.

Purpose: In the present study, we made an attempt to elucidate the role of oversecretion of interleukin-4 (IL-4) in cancer stem cells (CSCs) of head and neck squamous cell carcinoma (HNSCC)., Methods: HNSCC samples were analyzed for the presence of CSCs by flow cytometry. In addition, we have performed drug and apoptosis resistance assays to determine the role of IL-4 in CSCs., Results: HNSCC samples contained 3.3% of CD133+ cancer stem like side population (SP) cells in HNSCC which displayed infinite cell proliferation and they had high self-renewal capacity. These CD133+ cells displayed enhanced expression of IL-4, which promoted multidrug and apoptosis resistance. After neutralizing IL-4, the CD133+ SP cells became more sensitive to drug treatment and apoptosis., Conclusions: Our data suggest that the autocrine secretion of IL-4 is a potential target for the development of novel anticancer drugs to prevent the CSCs-mediated therapy failure and tumorigenesis.

To better understand the effects of Corbicula fluminea bioturbation on the ammonia-oxidizing microorganisms in the surface sediment, sediment-water microcosms with different densities of Corbicula fluminea were constructed. Clone libraries and real-time qPCR were applied to analyze the community composition and abundance of ammonia-oxidizing archaea (AOA) and bacteria (AOB) in the surface sediments. The results obtained indicated that the bioturbation of Corbicula fluminea accelerated the release of nitrogen from the surface sediment. In the amoA gene clone libraries, the identified AOA amoA gene sequences affiliated with the two known clusters (marine and soil clusters). The identified AOB amoA gene sequences mostly belonged to the Nitrosomonas of beta-Proteobacteria. The abundance of the bacterial amoA gene was higher than that of the archaeal amoA gene in all treatments. With increasing density of Corbicula fluminea, decreased abundances of the bacterial amoA gene were observed. At the same time, the diversity of AOA and AOB reduced in the Corbicula fluminea containing microcosms. In conclusion, the bioturbation of Corbicula fluminea could affected the community composition and abundance of ammonia-oxidizing microorganisms in surface sediments.

Objective: To observe the exposure levels of extremely low frequency electromagnetic fields in workplaces and to analyze the effects of extremely low frequency electromagnetic radiation on cardiovascular system of occupationally exposed people., Method: Intensity of electromagnetic fields in two workplaces (control and exposure groups) was detected with EFA-300 frequency electromagnetic field strength tester, and intensity of the noise was detected with AWA5610D integral sound level. The information of health physical indicators of 188 controls and 642 occupationally exposed workers was collected. Data were analyzed by SPSS17.0 statistic software., Results: The intensity of electric fields and the magnetic fields in exposure groups was significantly higher than that in control group (P < 0.05), but there was no significant difference of noise between two workplaces (P > 0.05). The results of physical examination showed that the abnormal rates of HCY, ALT, AST, GGT, ECG in the exposure group were significantly higher than those in control group (P < 0.05). There were no differences of sex, age, height, weight between two groups (P > 0.05)., Conclusion: Exposure to extremely low frequency electromagnetic radiation may have some effects on the cardiovascular system of workers.

The Legionella spp. are ubiquitous in aquatic environment and could cause certain risks on human health. In order to investigate the distribution and diversity of Legionella spp. in Lake Taihu during winter time, water samples were collected from 32 sites of the whole lake in February 2010. The presence of Legionella spp. was screened by nested-PCR and their phylogenetic diversity was determined by denaturing gradient gel electrophorese (DGGE) and sequencing analysis of excised DGGE bands. The Legionella spp. was detected from 21 out of 32 sites in particle-associated bacterial samples and 11 out of 32 sites in free-living bacterial samples, which accounted for 65.63% and 34.38% of each type of bacteria, respectively. In total, 40 and 36 unique bands were identified among those particle-associated and free-living bacterial DGGE profiles, respectively. Community characteristic indices of different euthrophic areas showed that the diversity of Legionella spp. in mild eutrophic areas was higher than that in the moderate eutrophic areas. In total, thirty-four DGGE bands were excised and sequenced, which could be classified into 12 OTUs by 97% similarity. Among all the sequences, three showed a high similarity with two pathogenic Legionella species Legionella feeleii and Legionella longbeachae. This revealed potential healthy risks to the people lived around the Lake Taihu.

After X-ray treatment at 1.82 keV and 40 mA and 4 hours, the cellobiohydrolase II (CBH II) aqueous solution of Trichoderma viride was analysed, and the damage state of the irradiated molecule was detected using some cysteine residue relative parameters in Raman spectroscopic methods. The results show that S-H stretch modes of CBH II exhibited some shift, which means that the hydrogen proton donor state of sulfhydryl groups was stronger and weaker, respectively. The 2 554 cm(-1) peak of irradiated sample was wide. The -S-S- construction of disulfide bonds was not broken, and the geometrical conformation types did not change either, but its bond length was somewhat shortened. Before irradiation, C-S isomer mode content of cysteine residue was Pc type slightly more than both P(N) and P(H) types, while P(N) and P(H) types increased after irradiation. Besides, CH2 rocking mode of cysteine residue was weakened remarkably after the treatement, and the protein molecule structure did not show important damage in sulfhydryl and disulfide bonds, but showed some change because of the X-ray irradiation condition.

Aim: To express, purify, and characterize scdsFv antibody fused with superantigen SEA(D227A)., Methods: The expression plasmid of scdsFv-SEA(D227A) was constructed by standard molecular cloning procedures. The recombinant protein was induced to express in E. coli BL21plusS by IPTG and purified by Q Sepharose HP column and Hiprep 26/60 Sephacryl S-200 HR column. Formation of the intramolecular disulfide bond of the purified protein was analysed by AMS alkylation and PAGE electrophoresis. The binding activity, stability and killing activity of the purified protein were assayed by ELISA and MTS, respectively., Results: The recombinant protein was expressed as inclusion body, accounting for more than 30% of total bacterial protein. After purification by Q Sepharose HP and Hiprep 26/60 Sephacryl S-200 HR, the yield of the purified protein was 60 mg per liter of induced culture. AMS alkylation and PAGE electrophoresis analysis showed that intramolecular disulfide bond formed correctly in the recombinant protein. The purified protein had similar binding affinity as dsFv fused SEA and scFv fused SEA have and similar killing activity as native SEA has to human hepatoma cell line, but more stable, in vitro, as compared with dsFv fused SEA and scFv fused with SEA., Conclusion: The scdsFv fused with SEA, as a novel form of immunotoxin, might be used in cancer treatment.

Hydrogen-bond states on cellobiohydrolase II (CBH II) of Trichoderma viride were analysed by laser Raman spectroscopic method used to reveal molecular normal modes of vibration character. The results indicated that hydrogen-bond ability of carbonyl oxygen-atom of amide I was raised in two types of aqueous solution samples (6.0 and 8.0 of pH value) compared to the solid sample. The variation trend of beta structure modes was similar between amide II and amide I. As far as the ability of hydrogen-bond forming is concerned, tryptophan (Trp) and tyrosine (Typ) residues are strong hydrogen proton donor in pH 6.0 and solid sample, thus proving the results of previously spatial structure analysis. By analysis of free S-H character, the -S-S- construction in Trichoderma viride mature peptide has been proved to be the same as that of Trichoderma reesei.

The circadian clock genes, which generate and control the running of the circadian rhythms, exist in organisms ranging from prokaryotes to mammals. The oscillator genes and its coding proteins compose the feedback loops of circadian system. The kind, number and regulating route of clock genes are characterized by living things at different evolution levels. The molecular mechanism of the run of circadian clock genes in cyanobacteria, neurospore, fruit fly, mouse and human being is introduced in this article.