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In the past decade, more and more attention has been paid to the fire performance of concrete-filled double-skin steel tubular (CFDST) columns. The columns in actual structures are not isolated members and are affected by the adjacent structural members. However, little research has been conducted on the behaviour of restrained CFDST columns under fire. In this paper finite element models were developed to analyse the fire performance of axially and rotationally restrained circular CFDST columns. The predicted temperature–time curves, internal axial force–time curves and fire resistance agreed well with the related test results. Based on the verified models, a parametric study was performed to investigate the effect on the internal axial force–time curves and fire resistance. The parameters included axial load level, axial restraint ratio, diameter of the outer tube, slenderness ratio, diameter-to-thickness ratios of the outer and inner steel tubes, dimension ratio of the inner tube to the outer tube, load eccentricity, yield strengths of the outer and inner tubes, compressive strength of the concrete, fire protection thickness and rotational restraint ratio. Through regression analysis, a design formula was proposed to calculate the fire resistance of restrained circular CFDST columns.

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Additional file 1: Figure S1. Diagram for pathways in the mediation analysis. Figure S2. Flowchart for population selection from the UK Biobank. Figure S3. Sex differences in the incidence of all-cause dementia mediated by individual chronic diseases. Figure S4. Sex differences in the incidence of young-onset dementia mediated by individual chronic diseases. Figure S5. Sex differences in the incidence of late-onset dementia mediated by individual chronic diseases. Figure S6. Mediators of sex differences in the incidence of dementia among individuals by excluding those who were diagnosed with dementia in the first five years of follow-up. Figure S7. Mediators of sex differences in the incidence of dementia among individuals with complete data. Table S1. Codes for international classification disease and self-reported fields for dementia. Table S2. Chronic conditions used to create the multimorbidity score for dementia. Table S3. Potential mediators tested in the analysis. Table S4. Other baseline characteristics in women and men. Table S5. Categorical variables in imputed and non-imputed data. Table S6. Continuous variables in imputed and non-imputed data. Table S7. Risk for incident dementia associated with mediators.

Additional file 1: Figure S1. Bioinformation analysis of TIM. Figure S2. The expression level of TIM in different metastatic sites. Figure S3. The protocol and detection using mouse breast cancer cell line 4T1 co-cultured with their specific CTLs or CD8+ T cells in the siNC group and siTIM group. Figure S4. The correlation between PD-L1 and TIMELESS in different breast cancer subtypes. Table S1. RNA sequences used in this study. Table S2. Stable cell line sequences. Table S3. DNA Oligo Sequences used in this study.

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Floods are one of the most dangerous disasters that affect human beings. Timely and accurate flood forecasting can effectively reduce losses to human life and property as well as improve the utilization rate of flood resources. In this study, an F-K++ real-time flood classification forecasting framework based on k-means++, principal component analysis, and backpropagation (BP) neural network was constructed using the Jingle sub-basin, a tributary of the Yellow River Basin, as the study area. The model parameters of different flood types were obtained, and a flood classification and predictions were made based on the mature M-EIES model applied in the study area. The relationship between the hydrological model parameters and hydrological characteristics of the different flood types was analyzed. The results show that the flood real-time classification framework established in this study can be used for flood classifications and predictions in real time. The parameters of the flood classification and prediction model were consistent with the characteristics of the flood events. Compared with unclassified predictions, the accuracy of the classification and prediction models significantly improved. The Nash coefficient increased by 5%–11.62%, the relative error of the average flood peak was reduced by 6.08%–12.7%, the relative error of average flood volume was reduced by 5.74%–8.07%, and the time difference of the average peak was reduced by 43%–66%. The methodology proposed in this study can identify extreme flood events and provide scientific support for flood classifications and predictions, flood control and disaster reduction in river basins, and the efficient utilization of water resources.

L-shaped concrete-filled steel hollow-section (CFSHS) columns have the potential to be widely used as corner columns, and have the advantage of creating larger usable areas in buildings. However, few experimental tests of this kind of column under diagonal cyclic loading have been reported. Tests on eight L-shaped CFSHS columns with equal legs were conducted to study their hysteretic behaviour; the test variables were: loading angle, concrete compressive strength, axial load level and presence or absence of stiffeners. The failure process and modes, stiffness degradation, ductility and energy dissipation were observed, and lateral load–displacement hysteretic curves and envelope curves were plotted. The results show that L-shaped CFSHS columns have generally good hysteretic behaviour and that the displacement ductility coefficients are in excess of 3 in most cases. Columns with a loading angle of 45° have >10% decrease in ultimate strength but a slightly higher ductility than columns with a loading angle of 0°. The ultimate strength, ductility and energy dissipation of columns all decrease with increasing axial load levels. Discontinuously welded stiffeners can improve the ultimate strength and ductility, but the amplitude is limited. Finally, a finite-element model was developed; the predicted results agree well with the test results.

Additional file 1: Table S1. Field codes for diseases of interest. Table S2. ICD codes for diseases of interest. Table S3. Matching analysis for diseases that were inversely associated with incident mortality. Table S4. Classification of diseases. Table S5. Death and the number of diseases. Table S6. Baseline characteristics of participants by mortality. Table S7. Disease contribution among individuals who were diagnosed with one disease only in life-course. Table S8. Risk for mortality associated with individual diseases of interest at baseline among individuals with complete data. Table S9. Prevalence of individual diseases by a number of diseases in life-course. Table S10. Number of events at baseline captured by self-reported and inpatient data.

Additional file 1: Table S1. Plasmids and E. coli stains used in this study. Table S2. Primers used in this study. Table S3. The schematic and sequences of the editing cassette used in this study. Table S4. The sequences of clone PCR products used to identity the E. coli variants. Figure S1. Stability of the chromosomal organization of E. coli0.10/4.54 and E. coli2.28/2.36. (A) Colony PCR analysis of the E. coli0.10/4.54 cells after culturing for more than 100 generations using the primer pairs f1/r1, f2/r2, f1/r2 and f2/r1. (B) Colony PCR analysis of E. coli2.28/2.36 after culturing for more than 100 generations using the primer pairs f3/r3, f4/r4, f3/r4 and f4/r3. Figure S2. Stability of the chromosomal organization of E. coli2.28/2.36 (mix with E. coliMut). A total of 11 rounds of inoculation were conducted, corresponding to approximately 100 generations. The culture of the first (0 generation), third (about 30 generations), fifth (about 50 generations), seventh (about 70 generations), ninth (about 90 generations) and last (about 100 generations) round of E. coli2.28/2.36 (mix with E. coliMut) was spread on LB agar plates, 24 single colonies of each strain were selected and four pairs of primers f5/r5, f6/r6, f5/f6 and r5/r6 were used to investigate the speed of transition of genomic instability with the passage of generations.

Additional file 2: Figure S1. Proportional hazards assumption test for cardiometabolic disorders and incident mortality. Figure S2. Proportional hazards assumption test for cardiometabolic disorders and incident mortality. Figure S3. Proportional hazards assumption test for cancers and incident mortality. Figure S4. Proportional hazards assumption test for musculoskeletal disorders, digestive disorders and incident mortality. Figure S5. Proportional hazards assumption test for other diseases and incident mortality.

Additional file 1: Table S1. Baseline characteristics of study participants stratified by discovery or replication dataset. Table S2. β coefficient of adjusted HR (95% CI) and P values of Incident Dementia for All 249 Metabolites in Cox Proportional Hazards Model. Table S3. Coefficients of selected 24 metabolites in elastic net regularized logistic regression model after 10-fold cross validation, their coefficients in e-net regression model in training dataset, and their VIFs in testing dataset.

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Additional file 3: Figure S6. Risk for mortality associated with individual diseases of interest in life-course. Figure S7. Disease trajectory in life-course among individuals who were diagnosed with two diseases before dying from any reasons. Figure S8. Disease trajectory in life-course among individuals who were diagnosed with three diseases before dying from any reasons. Figure S9. Disease trajectory in life-course among individuals who were diagnosed with four diseases before dying from any reasons. Figure S10. Disease trajectory in life-course among individuals who were diagnosed with five diseases before dying from any reasons. Figure S11. Disease trajectory in life-course among individuals who were diagnosed with six or more diseases before dying from any reasons.

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Additional file 4: Figure S12. Disease trajectory in the whole life-course among individuals who were diagnosed with two diseases before dying from cancer. Figure S13. Disease trajectory in the whole life-course among individuals who were diagnosed with three diseases before dying from cancer. Figure S14. Disease trajectory in the whole life-course among individuals who were diagnosed with four diseases before dying from cancer. Figure S15. Disease trajectory in the whole life-course among individuals who were diagnosed with five diseases before dying from cancer. Figure S16. Disease trajectory in the whole life-course among individuals who were diagnosed with six or more diseases before dying from cancer. Figure S17. Disease trajectory in the whole life-course among individuals who were diagnosed with two diseases before dying from cardiovascular disease. Figure S18. Disease trajectory in the whole life-course among individuals who were diagnosed with three diseases before dying from cardiovascular disease. Figure S19. Disease trajectory in the whole life-course among individuals who were diagnosed with four diseases before dying from cardiovascular disease. Figure S20. Disease trajectory in the whole life-course among individuals who were diagnosed with five diseases before dying from cardiovascular disease. Figure S21. Disease trajectory in the whole life-course among individuals who were diagnosed with six or more diseases before dying from cardiovascular disease.

Additional file : Text S1 Construction of plasmids for the chromosomal integration of heterologous genes. Text S2 The amino acid sequences of PCcrtZ. Text S3 The amino acid sequences of PacrtZ. Table S1. Primers used in this study. Table S2. Plasmids used in this study. Table S3. Caretenoids production by strains producing Zeaxanthin in shake flasks. Fig. S1. Flowchart illustrating the construction of the main strains used in this study Fig. S2. Carotenoids production of antxanthin producing strains. Fig. S3. Fed-batch fermentation results for canthaxanthin production by strains Can004 Fig. S4. Fed-batch fermentation results for astaxanthin production by strains Ast019.

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Circular RNAs (circRNAs) are a class of covalently closed non-coding RNAs and play crucial regulatory roles in human cancer biology. The purpose of the present study was to explore the expression pattern and biological role of circular RNA PVT1 (circPVT1) in non-small cell lung cancer (NSCLC). We firstly found that circPVT1 was overexpressed in clinical NSCLC tissues and cell lines. NSCLC patients with high expression of circPVT1 exhibited aggressive clinicopathological characteristics and poor prognosis. In vitro assays of the NSCLC cell lines (H1299 and A549 cells) demonstrated that knockdown of circPVT1 inhibited NSCLC cell proliferation and induced NSCLC cell apoptosis. We further found that circPVT1 served as a competing endogenous RNA of miR-497 and indirectly regulated Bcl-2 expression in NSCLC cells. Finally, inhibition of miR-497 abrogated the effects of circPVT1 knockdown in NSCLC cells. Taken together, the results from our study indicated circPVT1 acts as an oncogene in NSCLC, and may serve as a promising therapeutic target for NSCLC patients.

Additional file 8: Table S1. The sequences of primers and oligonucleotides used in this study.

Additional file 1: Primer and chimeric promoter sequences.

Colorectal cancer (CRC) is one of the major causes of cancer death worldwide. In general, early diagnosis for CRC and individual therapy have led to better survival for the cancer patients. Accumulating studies concerning biomarkers have provided positive evidence to improve cancer early diagnosis and better therapy. It is, however, still necessary to further investigate the precise biomarkers for cancer early diagnosis and precision therapy and predicting prognosis. In this study, AI-assisted systems with bioinformatics algorithm integrated with microarray and RNA sequencing (RNA-seq) gene expression (GE) data has been approached to predict microRNA (miRNA) biomarkers for early diagnosis of CRC based on the miRNA-messenger RNA (mRNA) interaction network. The relationships between the predicted miRNA biomarkers and other biological components were further analyzed on biological networks. Bayesian meta-analysis of diagnostic test was utilized to verify the diagnostic value of the miRNA candidate biomarkers and the combined multiple biomarkers. Biological function analysis was performed to detect the relationship of candidate miRNA biomarkers and identified biomarkers in pathways. Text mining was used to analyze the relationships of predicted miRNAs and their target genes with 5-fluorouracil (5-FU). Survival analyses were conducted to evaluate the prognostic values of these miRNAs in CRC. According to the number of miRNAs single regulated mRNAs (NSR) and the number of their regulated transcription factor gene percentage (TFP) on the miRNA-mRNA network, there were 12 promising miRNA biomarkers were selected. There were five potential candidate miRNAs (miRNA-186-5p, miRNA-10b-5, miRNA-30e-5p, miRNA-21 and miRNA-30e) were confirmed as CRC diagnostic biomarkers, and two of them (miRNA-21 and miRNA-30e) were previously reported. Furthermore, the combinations of the five candidate miRNAs biomarkers showed better prediction accuracy for CRC early diagnosis than the single miRNA biomarkers. miRNA-10b-5p and miRNA-30e-5p were associated with the 5-FU therapy resistance by targeting the related genes. These miRNAs biomarkers were not statistically associated with CRC prognosis. Funding Agencies|Swedish Cancer Foundation [CAN 2016/341]; Svenska Forskningsradet FormasSwedish Research Council Formas [2016-01098]

Purpose This network meta-analysis (NMA) is designed to compare the efficacy and tolerability of various therapies and combinations for pulmonary arterial hypertension (PAH). Method We conducted a systematic search in databases PubMed, Embase, and Cochrane Library. Treatment efficacy and tolerability were compared by synthesizing direct and indirect evidence. The surface under the curve ranking area was utilized to rank multiple interventions. Result A total of 43 randomized clinical trials were included in our NMA. With regard to efficacy outcomes, including 6 min walking distance (6MWD), functional class amelioration (FCA), death, clinical worsening (CW), pulmonary vascular resistance (PVR), mean pulmonary artery pressure (mPAP), cardiac index (CI), and mean right atrial pressure (mRAP), endothelin receptor antagonists (ERA), phosphodiesterase 5 inhibitor (PDE-5Is), ERA combined with PDE-5Is (EAP), and prostacyclin analogs (PGI) combined with ERA (PAE) performed better than others. Meanwhile PAP and PGE demonstrated better than others in tolerability. Overall, EAP and PAE showed good efficacy and were well-tolerated among all therapies. Conclusion Overall, we recommend EAP as the optimal choice for patients with PAH in clinical practice and PAE as suboptimal in view of their desirable performance in efficacy. Most of the combination therapies performed better than monotherapies.

Aiming at the high embankment section of heavy-load Railway, a finite element model of dynamic response of subgrade structure under train load is established, and ZL-TNTLM program is used to apply load excitation. The results show that the dynamic stress on the top of the roadbed is a single peak curve under heavy train load, and the peak value of the vertical acceleration vibration changes obviously under heavy train load, and presents a periodic change With the increase of the train speed, the dynamic pressure stress of the track bed and the foundation bed does not increase obviously with the increase of the train speed, but fluctuates and changes slowly; the dynamic stress and the vertical acceleration in the roadbed attenuate non-linearly along the depth direction The attenuation of acceleration is greater than dynamic stress along the direction of subgrade depth. The results are of theoretical and engineering significance for revealing the dynamic stress and vertical acceleration mechanism of heavy-haul railway subgrade under the change of high-speed train speed.

The computer-aided detection (CADe) systems are developed to assist pathologists in slide assessment, increasing diagnosis efficiency and reducing missing inspections. Many studies have shown such a CADe system with deep learning approaches outperforms the one using conventional methods that rely on hand-crafted features based on field-knowledge. However, most developers who adopted deep learning models directly focused on the efficacy of outcomes, without providing comprehensive explanations on why their proposed frameworks can work effectively. In this study, we designed four experiments to verify the consecutive concepts, showing that the deep features learned from pathological patches are interpretable by domain knowledge of pathology and enlightening for clinical diagnosis in the task of lesion detection. The experimental results show the activation features work as morphological descriptors for specific cells or tissues, which agree with the clinical rules in classification. That is, the deep learning framework not only detects the distribution of tumor cells but also recognizes lymphocytes, collagen fibers, and some other non-cell structural tissues. Most of the characteristics learned by the deep learning models have summarized the detection rules that can be recognized by the experienced pathologists, whereas there are still some features may not be intuitive to domain experts but discriminative in classification for machines. Those features are worthy to be further studied in order to find out the reasonable correlations to pathological knowledge, from which pathological experts may draw inspirations for exploring new characteristics in diagnosis., Comment: v1

Currently, cell membrane is always utilized for the construction of biomimetic nanoparticles. By contrast, mimicking the intracellular activity seems more meaningful. Inspired by the specific killing mechanism of deoxy-hemoglobin (Hb) dependent drug (RRx-001) in hypoxic red blood cells (RBC), this work aims to develop an inner and outer RBC-biomimetic antitumor nanoplatform that replicates both membrane surface properties and intracellularly certain therapeutic mechanisms of RRx-001 in hypoxic RBC. Herein, RRx-001 and Hb are introduced into RBC membrane camouflaged TiO2 nanoparticles. Upon arrival at hypoxic tumor microenvironment (TME), the biomimetic nanoplatform (R@HTR) is activated and triggers a series of reactions to generate reactive nitrogen species (RNS). More importantly, the potent antitumor immunity and immunomodulatory function of RNS in TME are demonstrated. Such an idea would transfer the battlefield of RRx-001 from hypoxic RBC to hypoxic TME, enhancing its combat capability. As a proof of concept, this biomimetic nanoreactor of RNS exhibits efficient tumor regression and metastasis prevention. The battlefield transfer strategy would not only present meaningful insights for immunotherapy, but also realize substantial breakthroughs in biomimetic nanotechnology.

Objectives: The goal of the present study is to investigate the status of alexithymia and social support among ICU nurses，and to investigate the correlation between the alexithymia and social support of ICU nurses. Methods: From June to November 2016，400 ICU nurses were sampled from 7 general hospitals in Changchun with convenient sampling method， there were 375 valid questionnaires. The efficiency was 93.75%. The questionnaire includes the self-designed general situation questionnaire，Toronto Alexithymia Scale (TAS-20) and Social Support Rating Scale (SSRS). Results: 1. The total score of the alexithymia of ICU nurses was 55.07± 7.85，and the mean score of alexithymia was 2.75±0.39. 2. The total score of social support of ICU nurses was 37.14± 6.75，and the mean score of social support was 2.86±0.52. 3. The total score of the alexithymia was negatively correlated with the subjective support，objective support，supportive utilization and the total score of social support(P Conclusions: 1. ICU nurses generally have a certain degree of empathy， and at a moderate level. The job title，working years，with or without children， marital status were the factors that affect the ICU nurses9 alexithymia. 2. The social support of ICU nurses was at the middle level. Gender，age， job title，working years，with or without children and marital status were the factors affecting the social support of ICU nurses. 3. The alexithymia of ICU nurses was negatively correlated with the subjective support.

This paper analyzes an indoor positioning system using white lighting LEDs. The performance of the positioning system is determined by the layout of LEDs, the receiver circuit, incidence angle of light, LED light source, and the photodiode. The Cramer–Rao bound as the theoretical accuracy limitation of received signal strength indicator algorithm is derived. The influences to positioning accuracy of multipath reflections and unparallel optical axis of LEDs and receivers are analyzed in certain scenarios. It is concluded that if the diffuse channel gain is measured previously in a certain environment and the modulation speed is far less than the channel cutoff frequency, the theoretical accuracy limit is not affected by multipath link. Multiple noises of system are analyzed in detail. The influence to positioning accuracy of indoor uniform illumination is also discussed. The result proves that the theoretical estimated accuracy of triangular LEDs array is higher than square LEDs array. With typical parameter values, the simulated theoretical accuracy of system is up to the level of centimeter.

Objective: clinical use atomization inhalation as adjuvant therapy, monitoring of exhaled NO content in patients with bronchial asthma airway, study of atomization inhalation effect about the existence of the NO content in the airway. Methods: select a 3 armour hospital respiratory asthma history for more than five years, no smoking, no patients with other diseases, 100 randomly selected as the research object. Experimental group in addition to the given routine therapy, randomly selected from 50 people, given budesonide suspension 2 mg and 0.48 mg salbutamol sulfate aerosol inhalation,; Physiological saline control group given conventional treatment, the use of placebo atomization inhalation, atomization inhalation once every seven hours, 2 times a day, at 0, 4, 8, respectively the NO concentration monitoring in the airway. Results: the experimental group was NO content in the airway in patients with bronchial asthma fall faster. Conclusion: use of budesonide suspension and salbutamol sulfate atomization can decrease the NO content in patients with bronchial asthma airway faster, make earlier control of the inflammation, which can be taken as reference to clinical treatment.

Objective: To investigate the effectiveness of airway clearance by utilizing different inhalation methods in moderate and severe AECOPD patients. Methods: According to the GOLD(2013) totle 92 moderate and severe AECOPD patients (range 65-73 years old, mean age 67.3+2.1,65.3% male) who were treated in our department from January 2014 to January 2015 were enrolled with a first episode of thick and tenacious sputum discharge. Patients were randomized into two groups(control group and experimental group) and each group included 46 cases. Mucosolvin as the nebulizing drug was given to both groups. Patients in control group using the ultrasonic atomizing inhalation while the experimental group using the high flow oxygen(6-8L/Min) driven atomization inhalation therapy. After 1 week of treatment, SPO2, PaCO2, clinical symptoms and pulmonary function examinations were compared before and after treatments. Results: After the treatment comparing the control group, SPO2 in the experimental group were (97.03+3.31)% higher than that of the control group (92.10+2.67)% ( p Conclusion: In the process of aiding sputum discharge for the moderate and severe AECOPD patients high flow oxygen(6-8L/Min) driven atomization inhalation was more effective than ultrasonic atomization inhalation therapy in improving the aspects of Spo2, PCO2, lung functions and clinical symptoms.

In order to rule overload and oversize transportation, regulate the produce of vehicles, mandatory standard GB 1589-2004 “Limits of dimensions, axle load and masses for road vehicles” was promulgated and implemented in China. With the implement of standard GB 1589-2004, it achieved the expected result. However, with the improvement of vehicle technology, road and the facilities, related technical regulations should more closely conform to international regulations. Besides, some factors which didn’t meet actual situations were found after the implement of this standard. A comparative analysis was discussed in this paper about the dimensions, axle load and masses of vehicle in order to make the standard more suitable for road transport’s actual needs, road facilities’ requirements at home and abroad. Finally, this paper puts forward opinions and suggestions which will be useful for the revision of the standard.

The development of an IoT deployment benchmarking framework is proposed. The framework, aimed at supporting policy decision process, expresses visions from 4 different stakeholders and proposes a comprehensive approach including 7 dimensions within a taxonomy to be used as a basis for the selection of benchmarking indicators. A consultative approach based on web survey and stakeholders interviews is proposed to evaluate robustness of the proposed benchmark.

Drop and pull transport has been widely used in developed countries. The advantage in energy saving and efficiency in transportation for this transport method are widely recognizable. However, there are some obstacles which hinder the popularization of drop and pull transport in China. This paper mainly discusses the difference between China and abroad, such as the diversity of tractors and trailers, vehicle management system, station yard building and theoretical research, operation organization and scheduling. In the end, this paper puts forward to the solution to eliminate these gaps which hinder adoption of this method in China.

The mode of road freight transportation changes from single vehicle transport to drop and pull transport. The efficiency, safety, and reliability of coupling between semi-trailer towing vehicle and semi-trailers is the key to developing drop and pull transport. Some technical clauses of standards on connection between semi-trailer towing vehicle and semi-trailers are not suitable requirements for drop and pull transport, and application status is not optimistic. This paper puts forward some suggestions based on analysis of articulated vehicle dimensions, interchangeability between semi-trailer towing vehicle and semi-trailers, electrical and pneumatic connector, fifth wheel kingpin, trailer landing gears, and so on, that would provide a reference to revise the relevant standards. INTORDUCTION To thoroughly implement the spirit of “The Announcement on Promoting the Development of Drop and Pull Transport” issued by Ministries and Commissions, The Ministry of Transport (MOT) of the People’s Republic of China, and National Development and Reform Commission (NDRC) People's Republic of China jointly issued “The Announcement on Printing and Distributing Implementation Scheme about Drop and Pull Transport Experimental Work.” Annex 4, “The General Requirement for Recommended vehicle types,” in this announcement is the primary basis for auditing recommended vehicle types. During the establishment of basic requirements, subsequent on-site audits, and matching tests for recommended vehicle types, some problems have been found. There are some conflicts among standards for drop and pull transport vehicles, therefore the actual effect of some present standards is not perfect. Therefore, the research on conflicted clauses should be developed. The establishment or revision of standards needs to launch further in order to accommodate the requirements of transportation’s development.

Interleukin-6 (IL-6) induced STAT3 activation is viewed as crucial for multiple tumor growth and metastasis, including colon cancer. However, the molecular mechanisms remain largely unexplored. Here, we show that expression of ubiquitin-specific protease 7 (USP7), a deubiquitylating enzyme, is decreased in STAT3-positive tumors. IL-6 administration or transfection of a constitutively activated STAT3 in SW480 cells also repressed USP mRNA expression. Using luciferase reporter and ChIP assay, we found that STAT3 bound to the promoter region of USP7 and inhibited its activity through recruiting HDAC1. As a result of the decline of USP7 expression, endogenous P53 protein level was decreased. Thus, our results suggest a previously unknown STAT3-USP7-P53 molecular network controlling colon cancer development.Structured summary of protein interactions:STAT3 physically interacts with HDAC1 by anti bait coimmunoprecipitation (View interaction)