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1 2 Testing Center, Yangzhou University, Yangzhou, Jiangsu, 225009, China 3 Dental Treatment Center, Shanghai Ninth People’s Hospital, Shanghai, Shanghai, 200000, China 4 The activation of the monocyte-macrophage system and the damage to the renal and pancreatic tissue are common complications in patients with diabetes induced by hyperglycemia. This study aimed to evaluate the effect and mechanism of butyrate (NaB), a metabolite of intestinal flora, on inhibiting the inflammatory response of human monocyte-macrophages (THP-1 cells) induced by high glucose and the damage of pancreatic and renal tissue in diabetic mice. The results showed that high concentration glucose significantly up-regulated the expressions of IL-1β, TNF-α, and NLRP3 in THP-1 cells and mouse spleen, and that NaB could inhibit the overexpression of those genes. The abundance of Beclin-1, LC3B and reactive oxygen species (ROS) in THP-1 cells is increased due to the high glucose concentration, and NaB can inhibit the genes responsible for upregulating the expression. In diabetic mice, vacuolar degeneration of renal tubules was observed. Then we observed that some of the epithelial cells of the renal tubules were exfoliated and some formed tubules. NaB could alleviate these pathological lesions, but NaB cannot alleviate pancreatic injury. Our results indicated that NaB could be used for the prevention and adjuvant treatment of diabetic kidney injury.

An efficient Agrobacterium-mediated transient expression method was developed, which contributed to the functional characterization of the transcription factor CqPHR1, and demonstrates the potential application of gene editing in quinoa. Chenopodium quinoa is a crop expected to ensure global food security in future due to its high resistance to multiple abiotic stresses and nutritional value. We cloned one of the paralogous genes of the Arabidopsis homolog PHR1 (PHOSPHATE STARVATION RESPONSE 1) in quinoa-inbred lines by reverse genetic approach. Overexpression of CqPHR1 driven by the constitutive CaMV 35S promoter in Arabidopsis phr1 mutant can complement its phenotypes, including the induction of phosphate starvation-induced (PSI) genes and anthocyanin accumulation in leaves. By Agrobacterium-mediated gene transient expression, we found that CqPHR1 localized in the nucleus of quinoa cells, and overexpression of CqPHR1 in quinoa cells promoted PSI genes expression, which further revealed the function of CqPHR1 as a transcription factor. We have also shown that the transient expression system can be used to express Cas9 protein in various quinoa-inbred lines and perform effective gene editing in quinoa tissue. The method developed in this study will be useful for verifying the effectiveness of gene-editing systems in quinoa cells and has potential application in the generation of gene-edited quinoa with heritable traits.

Hybrid ablation combines the advantages of surgical and catheter ablation. Many studies have explored the efficiency and safety of hybrid ablation in patients with nonparoxysmal AF.We systematically searched for prospective controlled trials that compared hybrid ablation with catheter/surgical ablation in PubMed, Web of Science, Wiley Library, and CNKI. Our main assessment indicators included maintenance of sinus rhythm (SR) without antiarrhythmic drugs for more than 12 months, major adverse events (MAEs), procedure time and fluoroscopy time.Of 1214 identified studies, five were eligible and were included in our analysis (N = 451 participants). The pooled results showed that hybrid ablation was more effective in maintaining SR than a single procedure (surgical ablation or catheter ablation) (OR = 2.52, 95% confidence interval [CI]: 1.63-3.89, p .001). Little significant heterogeneity was revealed (p = .32 for heterogeneity, IHybrid ablation was more effective than catheter ablation and was as effective as surgical ablation in patients with nonparoxysmal AF. Meanwhile, hybrid ablation, especially concomitant hybrid ablation, increases the incidence of MAEs and prolongs the procedure time.

Myocardial infarction (MI) causes peripheral organ injury, in addition to cardiac dysfunction, including in the liver, which is known as cardiac hepatopathy. Aerobic exercise (AE) can effectively improve liver injury, although the mechanism and targets are currently not well established. Irisin, mainly produced by cleavage of the fibronectin type III domain-containing protein 5 (FNDC5), is a responsible for the beneficial effects of exercise training. In this study, we detected the effect of AE on MI-induced liver injury and explored the role of irisin alongside the benefits of AE. Wildtype and Fndc5 knockout mice were used to establish an MI model and subjected to AE intervention. Primary mouse hepatocytes were treated with lipopolysaccharide (LPS), rhirisin, and a phosphoinositide 3-kinase (PI3K) inhibitor. The results showed that AE significantly promoted M2 polarization of macrophages and improved MI-induced inflammation, upregulated endogenous irisin protein expression and activated the PI3K/ protein kinase B (Akt) signaling pathway in the liver of MI mice, while knockout of Fndc5 attenuated the beneficial effects of AE. Exogenous rhirisin significantly inhibited the LPS-induced inflammatory response, which was attenuated by the PI3K inhibitor. These results suggest that AE could effectively activate the FNDC5/irisin-PI3K/Akt signaling pathway, promote the polarization of M2 macrophages, and inhibit the inflammatory response of the liver after MI.

Aerobic exercise mitigates oxidative stress and apoptosis caused by myocardial infarction (MI) even though the precise mechanisms remain completely elusive. In this study, we investigated the potential mechanisms of aerobic exercise in ameliorating the cardiac function of mice with MI. In vivo, MI was induced by left anterior descending (LAD) coronary artery ligation in wild-type mice, alcat1 knockout, and fgf21 knockout mice. The mice were exercised under a moderate-intensity protocol for 6 weeks at one week later post-MI. In vitro, H9C2 cells were treated with lentiviral vector carrying alcat1 gene, recombinant human FGF21 (rhFGF21), PI3K inhibitor, and H2O2 to explore the potential mechanisms. Our results showed that aerobic exercise significantly increased the FGF21 expression and decreased the ALCAT1 expression in the hearts of mice with MI. fgf21 knockout weakened the inhibitory effects of aerobic exercise on oxidative stress, endoplasmic reticulum (ER) stress, and apoptosis in mice with MI. Both/either alcat1 knockout and/or aerobic exercise improved cardiac function by inhibiting oxidative stress and apoptosis in the MI heart. rhFGF21 inhibited both H2O2 and overexpression of ALCAT1-induced oxidative stress and apoptosis by activating the PI3K/AKT pathway in H9C2 cells. In conclusion, our results showed that aerobic exercise alleviated oxidative stress and apoptosis by activating the FGF21/FGFR1/PI3K/AKT pathway or inhibiting the hyperexpression of ALCAT1, which ultimately improved the cardiac function in MI mice.

Anastomotic recurrence after bowel resection is problematic in patients with Crohn's disease. Antimesenteric functional end-to-end handsewn (Kono-S) anastomosis is associated with a low risk of anastomotic recurrence in patients with Crohn's disease.Kono-S anastomosis is effective but may be time-consuming. This study aimed to describe stapled antimesenteric functional end-to-end anastomosis for patients with Crohn's disease.The mesentery of the affected bowel segment was divided. A 5-cm-wide stapled functional end-to-end anastomosis was performed approximately 6 cm from the affected segment. The bowel was divided transversely exactly 90° to the intestinal lumen and the mesentery, and a supporting column was then constructed.From January 2018 to June 2021, 17 stapled antimesenteric functional end-to-end anastomoses were performed. The mean operative time was 106 (range, 80-135) minutes, and the time to construct the stapled antimesenteric functional end-to-end anastomosis was 21 (range, 18-28) minutes. The mean follow-up time was 8.9 (range, 1-15) months. In total, 10 patients underwent surveillance endoscopy. The average Rutgeerts score was 0.8 (range, 0-4), and the incidence of endoscopic recurrence was 11.8%. No postoperative mortality or anastomotic leakage was observed.Stapled antimesenteric functional end-to-end anastomosis may be a safe and time-saving procedure for patients with Crohn's disease.Further prospective studies with a large sample size are warranted.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide. We aimed to identify potential genetic markers that could predict the prognosis of HNSCC. A total of 44 samples of GSE83519 from Gene Expression Omnibus (GEO) datasets and 546 samples of HNSCC from The Cancer Genome Atlas (TCGA) were adopted. The differently expressed genes (DEGs) of the samples were screened by GEO2R. We integrated the expression information of DEGs with clinical data from GES42743 using the weighted gene co-expression network analysis (WGCNA). A total of 17 hub genes were selected by the module membership (|MM| > 0.8), and the gene significance (|GS| > 0.3) was selected from the turquoise module. GOLM1 and FAM49B genes were chosen based on single-gene analysis results. Survival analysis showed that the higher expression of GOLM1 and FAM49B genes was correlated with a worse prognosis of HNSCC patients. Immunohistochemistry and multiplex immunofluorescence techniques verified that GOLM1 and FAM49B genes were highly expressed in HNSCC cells, and high expressions of GOLM1 were associated with the pathological grades of HNSCC. In conclusion, our study illustrated a new insight that GOLM1 and FAM49B genes might be used as potential biomarkers to determine the development of HNSCC, while GOLM1 and FAM49B have the possibility to be prognostic indicators for HNSCC.

To construct models for predicting reintervention after thoracic endovascular aortic repair (TEVAR) of Stanford type B aortic dissection (TBAD). A total of 192 TBAD patients who underwent TEVAR were included; 68 (35.4%) had indications for reintervention. Clinical characteristics, aorta characteristics on pre- and postoperative computed tomography angiography, and aorta characteristics on immediate postoperative aortic digital subtraction angiography were collected. The least absolute shrinkage and selection operator (LASSO) regression was applied to identify the risk factors for reintervention. Eight classifiers were used for modeling. The models were trained on 100 train-validation random splits with a ratio of 2:1. The performance was evaluated by the receiver operating characteristic curve. Seven predictors of reintervention were identified, including maximum false lumen diameter, aortic diameter measured at the level of approximately 15 mm distal to the left subclavian artery, aortic diameter measured at the level of the diaphragm, false lumen diameter measured at the level of the celiac artery, number of bare-metal and covered stents, number of bare-metal stents, and residual perfusion of the false lumen. Logistic regression (LR) yielded the highest performance, with an area under the curve of 0.802. A nomogram built for clinical use showed good calibration. The cutoff value for dividing patients into low- and high-risk subgroups was 0.413. Kaplan-Meier curves showed that the overall survival of high-risk patients was significantly shorter than that of low-risk patients (both p < 0.05). Our nomogram could predict the reintervention after TEVAR in patients with TBAD, which may facilitate patient selection and surveillance strategies. • Seven risk factors of reintervention after TEVAR of TBAD were identified for modeling. • Logistic regression performed best in predicting reintervention with an AUC of 0.802. • Patients with a high risk of reintervention had shorter OS than those with a low risk.

Fasudil has the potential to prevent liver fibrosis by activating natural killer cells and inhibiting the proliferation of hepatic stellate cells. Fasudil may be a promising clinical therapeutic drug for the prevention and treatment of liver fibrosis.

Despite the substantial burden caused by childhood cancer globally, childhood cancer incidence obtained in a nationwide childhood cancer registry and the accessibility of relevant health services are still unknown in China. We comprehensively assessed the most up-to-date cancer incidence in Chinese children and adolescents, nationally, regionally, and in specific population subgroups, and also examined the association between cancer incidence and socioeconomic inequality in access to health services.In this national cross-sectional study, we used data from the National Center for Pediatric Cancer Surveillance, the nationwide Hospital Quality Monitoring System, and public databases to cover 31 provinces, autonomous regions, and municipalities in mainland China. We estimated the incidence of cancer among children (aged 0-14 years) and adolescents (aged 15-19 years) in China through stratified proportional estimation. We classified regions by socioeconomic status using the human development index (HDI). Incidence rates of 12 main groups, 47 subgroups, and 81 subtypes of cancer were reported and compared by sex, age, and socioeconomic status, according to the third edition of the International Classification of Childhood Cancer. We also quantified the geographical and population density of paediatric oncologists, pathology workforce, diagnoses and treatment institutions of paediatric cancer, and paediatric beds. We used the Gini coefficient to assess equality in access to these four health service indicators. We also calculated the proportions of cross-regional patients among new cases in our surveillance system.We estimated the incidence of cancer among children (aged 0-14 years) and adolescents (aged 15-19 years) in China from Jan 1, 2018, to Dec 31, 2020. An estimated 121 145 cancer cases were diagnosed among children and adolescents in China between 2018 and 2020, with world standard age-standardised incidence rates of 122·86 (95% CI 121·70-124·02) per million for children and 137·64 (136·08-139·20) per million for adolescents. Boys had a higher incidence rate of childhood cancer (133·18 for boys vs 111·21 for girls per million) but a lower incidence of adolescent cancer (133·92 for boys vs 141·79 for girls per million) than girls. Leukaemias (42·33 per million) were the most common cancer group in children, whereas malignant epithelial tumours and melanomas (30·39 per million) surpassed leukaemias (30·08 per million) in adolescents as the cancer with the highest incidence. The overall incidence rates ranged from 101·60 (100·67-102·51) per million in very low HDI regions to 138·21 (137·14-139·29) per million in high HDI regions, indicating a significant positive association between the incidence of childhood and adolescent cancer and regional socioeconomic status (p0·0001). The incidence in girls showed larger variation (48·45% from the lowest to the highest) than boys (36·71% from lowest to highest) in different socioeconomic regions. The population and geographical densities of most health services also showed a significant positive correlation with HDI levels. In particular, the geographical density distribution (Gini coefficients of 0·32-0·47) had higher inequalities than population density distribution (Gini coefficients of 0·05-0·19). The overall proportion of cross-regional patients of childhood and adolescent cancer was 22·16%, and the highest proportion occurred in retinoblastoma (56·54%) and in low HDI regions (35·14%).Our study showed that the burden of cancer in children and adolescents in China is much higher than previously nationally reported from 2000 to 2015. The distribution of the accessibility of health services, as a social determinant of health, might have a notable role in the socioeconomic inequalities in cancer incidence among Chinese children and adolescents. With regards to achieving the Sustainable Development Goals, policy approaches should prioritise increasing the accessibility of health services for early diagnosis to improve outcomes and subsequently reduce disease burdens, as well as narrowing the socioeconomic inequalities of childhood and adolescent cancer.National Major Science and Technology Projects of China, National Natural Science Foundation of China, Chinese Academy of Engineering Consulting Research Project, Wu Jieping Medical Foundation, Beijing Municipal Administration of Hospitals Incubating Program.

Background: Aggressive juvenile-onset recurrent respiratory papillomatosis (JORRP) threatens patient lives if not receives immediate surgical intervene. Even with surgical intervene, complete remission of this disease is not approachable. Therefore, understanding the factors relevant to disease severity and prognosis will do help to the treatment strategy and health management of this disease. Objective: This study aimed to explore the clinic, laboratory and socioeconomic characteristics of patients and evaluate the risk factors for aggressive JORRP. Methods: The information of clinical and socioeconomic status of the patients was reviewed and its association with disease severity was analyzed. Papilloma from JORRP patients undergone surgeries was used to determine HPV subtypes by real-time PCR. The profiles of mRNA expression in the papilloma were assessed using microarray. Results: Age at diagnosis and socioeconomic status were shown to associate with the severity of JORRP. There was no differential severity considering different HPV subtype. The mRNA expression of nucleotide binding oligomerization domain receptor protein 3 (NLRP3) and Gasdermin B (GSDMB) was reduced in papillomas. Conclusions: A younger age at diagnosis and low socioeconomic status were associated with the severity of JORRP. mRNA expression of NLRP3 and GSDMB in the papillomas of JORRP patients was significantly reduced.Abbreviation: JORRP: Juvenile-onset recurrent respiratory papillomatosis; RRP: Recurrent respiratory papillomatosis; OSAS: Obstructive sleep apnea syndrome; NLRP3: Nucleotide binding oligomerization domain receptor protein 3; GSDMB: Gasdermin B. Abbreviation: JORRP: Juvenile-onset recurrent respiratory papillomatosis; RRP: Recurrent respiratory papillomatosis; OSAS: Obstructive sleep apnea syndrome; NLRP3: Nucleotide binding oligomerization domain receptor protein 3; GSDMB: Gasdermin B.

This study aimed to investigate the association between the perivascular fat attenuation index (FAI) and the success of the antegrade percutaneous coronary intervention (PCI) for chronic total occlusion (CTO).This study evaluated patients with only one CTO lesion observed on conventional coronary angiography (CAG) who underwent coronary computed tomography angiography (CCTA)1 month before CAG, from 2018 to 2019. The clinical data, CCTA-based CTO lesion morphologic characteristics, and perivascular FAI of CTO lesions were recorded and analysed.In total, 156 patients with CTOs were enrolled in this study. Successful antegrade PCI (A-PCI) was achieved in 105 CTO lesions (67.3%). The perivascular FAI of the failed A-PCI group was significantly lower than the successful A-PCI group (-84.76 ± 10.44 Hounsfield unit (HU) vs. -67.54 ± 9.94 HU; p0.001), and the cut-off value determined by the receiver operating characteristic (ROC) curve was -77.50 HU. Multivariable analysis revealed no statistical significance in the clinical data, FAI ≤ -77.50 HU (odds ratio (OR): 33.96), negative remodeling (OR: 4.36), severe calcification degree (OR: 4.43) and occlusion length ≥ 20.25 mm (OR: 3.89) were independent predictors of A-PCI failure. The prediction performance of combining the three morphologic characteristics (severe calcification, occlusion length ≥ 20.25 mm, and negative remodeling) with FAI ≤ -77.50 HU was better than that of the three morphologic characteristics alone (0.93 versus 0.77, p0.001).As a non-invasive index for detecting coronary inflammation, FAI complements indicators based on coronary CTA well and may be helpful for choosing appropriate interventional strategies.• Perivascular FAI of CTO was significantly higher in the failed A-PCI group. • The combination of FAI with other morphological predictors showed higher predictive performance of failed A-PCI for CTOs. • FAI is a good complement to indicators based on coronary CTA.

Background Established prediction models of Diabetic kidney disease (DKD) are limited to the analysis of clinical research data or general population data and do not consider hospital visits. Construct a 3-year diabetic kidney disease risk prediction model in patients with type 2 diabetes mellitus (T2DM) using machine learning, based on electronic medical records (EMR). Methods Data from 816 patients (585 males) with T2DM and 3 years of follow-up at the PLA General Hospital. 46 medical characteristics that are readily available from EMR were used to develop prediction models based on seven machine learning algorithms (light gradient boosting machine [LightGBM], eXtreme gradient boosting, adaptive boosting, artificial neural network, decision tree, support vector machine, logistic regression). Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). Shapley additive explanation (SHAP) was used to interpret the results of the best performing model. Results The LightGBM model had the highest AUC (0.815, 95% CI 0.747–0.882). Recursive feature elimination with random forest and SHAP plot based on LightGBM showed that older patients with T2DM with high homocysteine (Hcy), poor glycemic control, low serum albumin (ALB), low estimated glomerular filtration rate (eGFR), and high bicarbonate had an increased risk of developing DKD over the next 3 years. Conclusions This study constructed a 3-year DKD risk prediction model in patients with T2DM and normo-albuminuria using machine learning and EMR. The LightGBM model is a tool with potential to facilitate population management strategies for T2DM care in the EMR era.

To verify the inhibitory mechanism of β-catenin-designed peptides in colorectal cancer(CRC) tumors, the following experiments were performed. In vitro colony formation, Transwell assays, and flow cytometry were performed to assess the biological effects of designed peptides (F18KD, F20A4-7k, F20A4-10k, and F20A3-9k + F20A4-10k + F20A5-9k) in HT-29 cells. In vivo xenograft experiments were performed and treated with peptides. Next, tumors were subjected to Hematoxylin and eosin staining (HE), immunohistochemical, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining assays to evaluate the inhibitory effect of peptides on tumors. β-Catenin levels were quantified via western blotting (WB) and quantitative real-time polymerase chain reaction, and β-catenin was located using confocal laser scanning microscopy. T-cell factor-4 (TCF-4), C-myc, and CCND1 levels were quantified via WB. Results were obtained as following. First, the peptides reduced viability, migration, and invasion; promoted apoptosis; and stabilized the S phase of HT-29 cells. Second, peptides suppressed tumor growth and downregulated the expression of CD34, vascular endothelial growth factor, and β-catenin in tumors. Furthermore, we found that peptides downregulated β-catenin expression in both the cytoplasm and nucleus; TCF-4, C-myc, and CCND1 expression was also downregulated. Notably, β-catenin-targeting peptides had a better inhibitory effect on CRC than non-β-catenin-target peptides, and a combination of peptides exerted a more potent inhibitory effect on CRC than single peptides. It suggested that β-Catenin-targeting peptides promote apoptosis in CRC tumors by inhibiting activation of the Wnt/β-catenin pathway.

The long-time retention issue of resistive random access memory (RRAM) brings a great challenge in the performance maintenance of large-scale RRAM-based computation-in-memory (CIM) systems. The periodic update is a feasible method to compensate for the accuracy loss caused by retention degradation, especially in demanding high-accuracy applications. In this paper, we propose a selective refresh strategy to reduce the updating cost by predicting the devices’ retention behavior. A convolutional neural network-based retention prediction framework is developed. The framework can determine whether an RRAM device has poor retention that needs to be updated according to its short-time relaxation behavior. By reprogramming these few selected devices, the method can recover the accuracy of the RRAM-based CIM system effectively. This work provides a valuable retention coping strategy with low time and energy costs and new insights for analyzing the physical connection between the relaxation and retention behavior of the RRAM device.

Objective. This study is aimed at exploring the role of nuclear transporting factor 2 (NUTF2) in head and neck squamous cell carcinoma (HNSCC) based on The Cancer Genome Atlas (TCGA) database. Methods. We obtained 528 HNSCC patients’ clinical data from TCGA and performed expression level analysis of NUTF2. Gene Sets Enrichment Analysis (GSEA) was conducted to identify NUTF2-associated regulatory mechanisms in HNSCC. In addition, several other tools were used to enrich the regulatory network. Results. We found that NUTF2 was significantly upregulated (P<0.001) in HNSCC. We then observed that higher NUTF2 is associated with poorer overall survival and disease-free survival. Further, by using Cox analyses, we determined high NUTF2 as an independent risk factor of predicting poorer overall survival. Tumor immune infiltration analysis revealed a significantly negative correlation between NUTF2 expression and the level of tumor infiltrated CD8+ T cell and B cell, suggesting that NUTF2 may be involved in the immune regulation of HNSCC. Gene sets related to T/B cell receptor signaling pathways were differentially enriched based on the NUTF2 expression phenotype. KEGG pathways were used to show that NUTF2 may affect proliferation, differentiation, and immune response of T/B cell through regulating PI3K/AKT, NFκB, MAPK, and Calcium signaling pathways. Conclusion. NUTF2 might be a valuable biomarker for HNSCC and correlated with T/B cell receptor signaling pathway.

The incidence and prevalence of anosognosia are highly variable in amnestic mild cognitive impairment (aMCI) patients. The study aims to explore the neuropathological mechanism of anosognosia in aMCI patients using two different but complementary technologies, including

This study aimed to develop non-invasive machine learning classifiers for predicting post–Glenn shunt patients with low and high risks of a mean pulmonary arterial pressure (mPAP) > 15 mmHg based on preoperative cardiac computed tomography (CT). This retrospective study included 96 patients with functional single ventricle who underwent a bidirectional Glenn procedure between November 1, 2009, and July, 31, 2017. All patients underwent post-procedure CT, followed by cardiac catheterization. Overall, 23 morphologic parameters were manually extracted from cardiac CT images for each patient. The Mann-Whitney U or chi-square test was applied to select the most significant predictors. Six machine learning algorithms including logistic regression, Naive Bayes, random forest (RF), linear discriminant analysis, support vector machine, and K-nearest neighbor were used for modeling. These algorithms were independently trained on 100 train-validation random splits with a 3:1 ratio. Their average performance was evaluated by area under the curve (AUC), accuracy, sensitivity, and specificity. Seven CT morphologic parameters were selected for modeling. RF obtained the best performance, with mean AUC of 0.840 (confidence interval [CI] 0.832–0.850) and 0.787 (95% CI 0.780–0.794); sensitivity of 0.815 (95% CI 0.797–0.833) and 0.778 (95% CI 0.767–0.788), specificity of 0.766 (95% CI 0.748–0.785) and 0.746 (95% CI 0.735–0.757); and accuracy of 0.782 (95% CI 0.771–0.793) and 0.756 (95% CI 0.748–0.764) in the training and validation cohorts, respectively. The CT-based RF model demonstrates a good performance in the prediction of mPAP, which may reduce the need for right heart catheterization in post–Glenn shunt patients with suspected mPAP > 15 mmHg. • Twenty-three candidate descriptors were manually extracted from cardiac computed tomography images, and seven of them were selected for subsequent modeling. • The random forest model presents the best predictive performance for pulmonary pressure among all methods. • The computed tomography–based machine learning model could predict post–Glenn shunt pulmonary pressure non-invasively.

Triptolide (TP) isolated from Tripterygium wilfordii Hook F. (TWHF) shows extensive anti-inflammation, immunosuppression and anti-tumor properties. However, its therapeutic potential is limited by its severe side effects, especially the nephrotoxicity. This study intended to explore the role of the GSK-3β/Fyn pathway in TP-induced oxidative damage and the potential mechanism of Nrf2 protein downregulation. Our data showed that TP induced oxidative stress and cell damage in the rat renal tubular epithelial cell line NRK-52E cells by activation of GSK-3β and nuclear translocation of Fyn, which resulted in decreased Nrf2 nuclear translocation. Moreover, TP significantly induced Nrf2 degradation by ubiquitination, which was blocked by the proteasome inhibitor MG132. In addition, cotreatment with a typical GSK-3β inhibitor, lithium chloride, promoted the nuclear translocation of Nrf2 and decreased the nuclear translocation of Fyn, which led to reduced cell damage, LDH leakage, glutathione depletion and cell apoptosis. Collectively, our results indicated that TP induced oxidative damage in NRK-52E cells by facilitating Nrf2 degradation by ubiquitination via the GSK-3β/Fyn pathway.

Penicillium digitatum is the most common cause of postharvest decay in citrus fruits around the world. Previous studies revealed that the bZIP gene family plays crucial roles in development, stress adaptation, and pathogenicity in fungi. However, little is known about the bZIP genes in P. digitatum. In this study, we systematically identified the bZIP family in 23 Penicillium species and analyzed their evolutionary relationships. We found that gene loss and gene duplication shaped the evolution of the Penicillium bZIP family. P. digitatum experienced 3 bZIP gene loss events, but with no gene duplication. We subsequently characterized the biological functions of one important member, PdatfA in P. digitatum by constructing the deletion mutant. Results showed that ΔPdatfA exhibited a moderate growth defect, reduced pigmentation, and slightly increased resistance to fungicides iprodione and fludioxonil. However, ΔPdatfA displayed similar rot symptoms to that of the wild-type. The ΔPdatfA mycelia were not affected in response to oxidative stress while its conidia showed enhanced resistance due to the upregulation of catalases. Our results provide new insights into the evolution and functions of the bZIP gene family in Penicillium.

The application of plastic film mulching can greatly improve dryland productivity, while the release of toxic phthalate esters (PAEs) from the plastic film has generated concern. This study investigated the effects of mulched plastic film and residual plastic film on the PAE concentrations in the soil-crop system and assessed the risks to people eating crop products. The PAEs concentration in the 0–25 cm soil layer of plastic mulched farmland was 0.45–0.81 mg/kg, while the average PAEs concentration of 0.37–0.73 mg/kg in non-mulched farmland decreased by 19%. The PAEs concentration in mulched soil reached the highest in July, being 0.80–0.84 mg/kg, while in the non-mulched soil, the PAEs also appeared and gradually decreased from May at 0.62–0.74 mg/kg to October, and the PAEs concentrations were almost the same in the mulched and non–mulched soils at the harvest time in October at 0.37–0.44 mg/kg. With the amounts of residual film in farmland increasing from 0 kg/ha to 2700 kg/ha (equivalent to the total amount of residual film after 60 years of continuous plastic film mulching), the PAEs concentrations were no significant changes, being 0.54–0.93 mg/kg. Maize (Zea mays L.) roots could absorb and accumulate PAEs, and the bio-concentration factor (BCF) was 1.6–2.3, and the average PAEs concentrations in stems, leaves, and grains were 79%–80% of those in roots at 0.77–1.47 mg/kg. For the ingestion of maize grains or potato (Solanum tuberosum L.) tubers grown in plastic film mulched farmland or farmland containing residual film of 450–2700 kg/ha, the hazard index (HI) were less than 1, the carcinogenic risks (CRs) were 2.5 × 10−7–2.2 × 10−6, and the estrogenic equivalences were 6.17–17.73 ng E2/kg. This study provides important data for the risk management of PAEs in farmlands.

An amendment to this paper has been published and can be accessed via the original article.

Peroxisome proliferator-activated receptors (PPARs), members of the nuclear hormone receptor family, attract wide attention as promising therapeutic targets for the treatment of multiple diseases, and their target selective ligands were also intensively developed for pharmacological agents such as the approved drugs fibrates and thiazolidinediones (TZDs). Despite their potent pharmacological activities, PPARs are reported to be involved in agent- and pollutant-induced multiple organ toxicity or protective effects against toxicity. A better understanding of the protective and the detrimental role of PPARs will help to preserve efficacy of the PPAR modulators but diminish adverse effects. The present review summarizes and critiques current findings related to PPAR-mediated types of toxicity and protective effects against toxicity for a systematic understanding of PPARs in toxicology and applied pharmacology.

The number of circulating tumor cells (CTCs) and the presence of circulating tumor microemboli (CTM) were determined in the peripheral blood of patients with liver cancer (LC). The relationship between CTCs, CTM, clinicopathologic features, and prognosis of LC was analyzed. The objective of this study was to determine the diagnostic and prognostic value of CTCs/CTM in LC.Patients with LC were enrolled between May 2013 and August 2017, and 67 patients were included in the study. Overall survival curves were built using the Kaplan-Meier method and the log-rank test to identify risk factors. The results were analyzed using a Cox proportional hazards model and expressed as hazard ratio and 95% confidence interval (95% CI).CTCs and either CTCs or CTM were detected in 27 patients (40.3%) and 29 patients (43.3%). CTM were found in four patients. One-year, 3-year, and 5-year survival rates were 42%, 20%, and 15%, respectively. Univariate Cox regression analysis showed that alpha-fetoprotein (AFP), number of CTCs, presence of CTM, and positive CTC/CTM were associated with survival time. Multivariate Cox regression analysis showed that alpha fetoprotein (AFP), number of CTCs, and presence of CTM were independent risk factors for survival in patients with LC.There was no significant correlation between the number of CTCs, the presence of CTM, and clinicopathologic factors. AFP, number of CTCs, and presence of CTM were independent risk factors for survival in patients with LC.

With the aim to support the experimental tests in a circulating fluidized bed pilot plant, the pyrolysis processes of coal, corn, and coal-corn blend have been studied with an online pyrolysis photoionization time-of-flight mass spectrometry (Py–PI–TOFMS). The mass spectra at different temperatures (300–800 °C) as well as time-evolved profiles of selected species were measured. The pyrolysis products such as alkanes, alkenes, phenols, aromatics, as well as nitrogen- and sulfur-containing species were detected. As temperature rises, the relative ion intensities of high molecular weight products tend to decrease, while those of aromatics increase significantly. During the co-pyrolysis, coal can promote the reaction temperature of cellulose in corn. Time-evolved profiles demonstrate that coal can affect pyrolysis rate of cellulose, hemicellulose, and lignin of corn in blend. This work shows that Py–PI–TOFMS is a powerful approach to permit a better understanding of the mechanisms underlying the co-pyrolysis of coal and biomass.

Various stimuli have been applied to harvest complete cell sheets, including temperature, magnetic, pH, and electrical stimuli. Cell sheet technology is a convenient and efficient approach with beneficial effects for tissue regeneration and cell therapy. Lights of different wavelengths, such as ultraviolet (UV), visible light, and near infrared ray (NIR) light, were confirmed to aid in fabricating a cell sheet. Changes in the wettability, potential, or water content of the culturing surfaces that occur under light illumination induce conformational changes in the adhesive proteins or collagens, which then leads to cell sheet detachment. However, the current approaches face several limitations, as few standards for safe light illumination have been proposed to date, and require a careful control of the wavelength, power, and irradiation time. Future studies should aim at generating new materials for culturing and releasing cell sheets rapidly and effectively.

Triptolide (TP), a principal bioactive component extracted from traditional Chinese medicine Tripterygium wilfordii Hook. F. (TWHF), has attracted wide attention of its therapeutic effects on inflammation and autoimmune diseases. However, the therapeutic application of TP is hindered by severe cardiomyocyte toxicity and narrow therapeutic window. We previously identified that the p53 was an indispensable contributor in TP-induced myocardial injury. p53 has an inhibitory effect on IKKβ-NF-κB pathway that regulates glucose transporters (GLUT) expression. Based on these evidences, we speculate that p53 mediates TP-disturbed glucose uptake by blocking IKKβ-NF-κB signaling. This study focused on the effect of TP on cardiac glucose uptake and the role of p53 in glucose metabolism in cardiomyocytes, and p53 −/− mice. TP treatment depressed glucose consumption and ATP production resulting in myocardial damage. Incubation with ATP (5 mM) remarkably decreased the cellular damage. Immunoblotting and immunofluorescence identified that TP suppressed glucose uptake by restricting IKKβ-NF-κB signaling activation, GLUT1 and GLUT4 expression. p53 inhibition alleviated the cell damage and the compromise of glucose uptake. Mechanistically, p53 antagonist PFTα abolished TP-induced the inhibition of IKKβ, IκBα phosphorylation, p65 nuclear translocation, and GLUT1, GLUT4 expression. Consistently, in acute heart injury models, p53 deficiency upregulated IKKβ-NF-κB activation and GLUT1, GLUT4 protein levels which was also indicated as amelioration of heart histological injury after 1.2 mg kg−1 TP administration. The present findings indicate that TP-induced p53 overactivation suppresses glucose uptake by inhibiting IKKβ–NF-κB pathway and downregulating NF-κB-dependent GLUT1 and GLUT4 expression.

A paucity of advances in the development of novel therapeutic agents for squamous cell carcinomas of the head and neck, oral cavity (OSCC) and oropharynx, has stagnated disease free survival rates over the past two decades. Although immunotherapies targeted against checkpoint inhibitors such as PD-1 or CTLA-4 are just now entering the clinic for late stage disease with regularity the median improvement in overall survival is only about three months. There is an urgent unmet clinical need to identify new therapies that can be used alone or in combination with current approaches to increase survival by more than a few months. Activation of the apoptotic arm of the unfolded response (UPR) with small molecules and natural products has recently been demonstrated to be a productive approach in pre-clinical models of OSCC and several other cancers. The aim of current study was to perform a high throughput screen (HTS) with a diverse chemical library to identify compounds that could induce CHOP, a component of the apoptotic arm of the UPR. Disulfiram (DSF, also known as Antabuse) the well-known aversion therapy used to treat chronic alcoholism emerged as a hit that could generate reactive oxygen species, activate the UPR and apoptosis and reduce proliferation in OSCC cell cultures and xenografts. A panel of murine embryonic fibroblasts null for key UPR intermediates (e.g., Chop and Atf4) was resistant to DSF suggesting that an intact UPR is a key element of the mechanism regulating the antiproliferative effects of DSF.

Membranous nephropathy (MN) is an autoimmune inflammatory disease in which proteins related with plenty of biological processes play an important role. However, the role of these proteins in the pathogenesis of MN is still unclear. This study aimed to screen differential proteins in kidney tissue samples from MN patients by using protein arrays and determine the pathways involved in the pathogenesis of MN. This study first tested a quantitative protein array (QAH-INF-3) and two semiquantitative protein arrays (L-493 and L-507) with normal renal tissue and identified L-493 as the most appropriate assay to compare protein levels between MN tissues and normal control tissues. The L-493 array identified 66 differentially expressed proteins (DEPs) that may be associated with MN. The gene oncology (GO) and protein-protein interaction (PPI) analyses revealed several processes potentially involved in MN, including extracellular matrix disassembly and organization, cell adhesion, cell-cell signaling, cellular protein metabolic process, and immune response (P<0.05). We suggest that these different pathways work together via protein signaling and result in the pathogenesis and progression of MN.

The anionic form-dependent binding interaction of halo-phenolic substances with human transthyretin (hTTR) has been observed previously. This indicates that ionizable compounds should be the primary focus in screening potential hTTR disruptors. Here, the potential binding potency of halo-benzoic acids, halo-benzenesulfonic acids/sulfates and halo-phenylboronic acids with hTTR was determined and analyzed by competitive fluorescence displacement assay integrated with computational methods. The laboratorial results indicated that the three test groups of model compounds exhibited a distinct binding affinity to hTTR. All the tested halo-phenylboronic acids, some of the tested halo-benzoic acids and halo-benzenesulfonic acids/sulfates were shown to be inactive with hTTR. Other halo-benzoic acids and halo-benzenesulfonic acids/sulfates were moderate and/or weak hTTR binders. The binding affinity of halo-benzoic acids and halo-benzenesulfonic acids/sulfates with hTTR was similar. The low distribution ability of the model compounds from water to hTTR may be the reason why they exhibited the binding potency observed with hTTR. By introducing other highly hydrophobic compounds, we observed that the binding affinity between compounds and hTTR increased with increasing molecular hydrophobicity. Those results indicated that the highly hydrophobic halo-benzoic acids and halo-benzenesulfonic acids/sulfates may be high-priority hTTR disruptors. Finally, a binary classification model was constructed employing three predictive variables. The sensitivity (Sn), specificity (Sp), predictive accuracy (Q) values of the training set and validation set were >0.83, indicating that the model had good classification performance. Thus, the binary classification model developed here could be used to distinguish whether a given ionizable compound is a potential hTTR binder or not.

Photorespiration is an essential process for plant photosynthesis, development and growth in aerobic conditions. Recent studies have shown that photorespiration is an open system integrated with the plant primary metabolism network and intracellular redox systems, though the mechanisms of regulating photorespiration are far from clear. Through a forward genetic method, we identified a photorespiratory mutant pr1 (photorespiratory related 1), which produced a chlorotic and smaller photorespiratory growth phenotype with decreased chlorophyll content and accumulation of glycine and serine in ambient air. Morphological and physiological defects in pr1 plants can be largely abolished under elevated CO2 conditions. Genetic mapping and complementation confirmed that PR1 encodes an FtsH (Filamentation temperature-sensitive H)-like protein, FtsHi5. Reduced FtsHi5 expression in DEX-induced RNAi transgenic plants produced a similar growth phenotype with pr1 (ftsHi5-1). Transcriptome analysis suggested a changed expression pattern of redox-related genes and an increased expression of senescence-related genes in DEX: RNAi-FtsHi5 seedlings. Together with the observation that decreased accumulation of D1 and D2 proteins of photosystem II (PSII) and over-accumulation of reactive oxygen species (ROS) in ftsHi5 mutants, we hypothesize that FtsHi5 functions in maintaining the cellular redox balance and thus regulates photorespiratory metabolism.

Cornstarch/polycaprolactone (SPCL) blends were prepared and used as external carbon source for biological denitrification in a constructed wetland. The denitrification performances, components of dissolved organic matter (DOM) and microbial diversity were investigated. The results showed that nitrate was removed mainly in the layer filled with SPCL, and the average denitrification rate was 0.069 kg/m 3 d (nitrate removal efficiency was 98.23%). The major component of DOM was polysaccharides which mainly consisted of reducing sugar. Besides, the concentrations of polysaccharides and reducing sugar decreased along the height of the constructed wetland. Therefore, the dissolved organic carbon (DOC) of effluent decreased to 6.54 mg/L. Denitrifying bacteria Bacillus (24.25%) and Thauera (9.36%) were the most abundant genera in the biofilm attached on the surface of SPCL.

The influence of organic loading rate (OLR) on the performance of hydrolytic acidification process for treating 2-butenal manufacture wastewater was comprehensively studied, while its impact on microbial community was thoroughly investigated. The results demonstrated that over 21.0% of the average COD removal rate was observed in the range of OLR from 0.52 to 3.98 g COD/L·d, whereas it reduced to 15.3% with increasing OLR to 6.09 g COD/L·d. The acidification degree dramatically decreased from 17.1% to 4.7% when OLR increased from 3.98 to 6.09 g COD/L·d. In addition, the removal rates of three kinds of typical matters were less than 65% at the OLR 6.09 g COD/L·d. Illumina MiSeq sequencing revealed that Proteobacteria, Chloroflexi, Firmicutes, and Bacteroidetes were dominant phyla at different OLRs. Finally, multivariate analysis suggested that the genera Longilinea and T78 had a positive correlation with the degradation of three kinds of typical matters and COD removal rates.

Aims Myocardial infarction (MI) is commonly associated with body weight loss and skeletal muscle atrophy. Studies have shown that exercise training could give beneficial effects on skeletal muscle growth. Leukemia inhibitory factor (LIF) is a key regulator of muscle growth and regeneration. The aim of this study was to investigate the effects of interval exercise training (IET) on the expression of LIF and the MI-induced skeletal muscle atrophy. Main methods Male Sprague-Dawley rats were used to establish the MI model by ligation of the left anterior descending coronary artery. Infarcted Rats were divided into two groups: sedentary MI group (MI) and MI with interval exercise group (ME), and compared to sham-operated group (Sham). Exercise-trained animals were subjected to eight weeks of IET. Cardiac function, collagen volume fraction, expression of LIF and its receptor LIFR, myofiber size, apoptosis and proliferation in gastrocnemius muscle were analyzed. Key findings IET increased heart functional performance and was accompanied with reversing cardiac pathological remodeling. Moreover, IET increased the expression of LIF and LIFR, activated signal transducer and activator of transcription (STAT3), reduced apoptosis and promoted proliferation in gastrocnemius muscle compared with the MI group. In addition, there was a significant negative correlation between skeletal muscle atrophy and LIF expression which was stimulated by IET in infarcted rats. Significance IET reverses MI-induced cardiac dysfunction and skeletal muscle atrophy. In addition, IET up-regulates the expression of muscle LIF/LIFR and activates the STAT3.

In this paper, by using the Euler-Maclaurin expansion, we establish an inequality of a weight coefficient. Using this inequality, we derive a reverse Hilbert's type inequality. As applications, an equivalent form is obtained.

Based on the problem of industrial wastewater of 4-Toluene Sulfonic Acid (4-TSA) with characteristics of high concentration and high toxicity, also low treatment efficiency by common biological treatment , this study was used aerobic biological fluidized bed (ABFB) to analyze the impact of 4-TSA treatment by changing water load chemical oxygen demand (COD), aeration amount, and pH value of input water, and so on technological parameters. The result showed that the average degradation rate of 4-TSA in wastewater can researched to 96.9% under condition of reactor steadily running, HRT=9 h, temperature 25°C, pH=8.0, ORP-141~-93 mV,DO 3.5~8.72 mg/L, the inflow water 4-TSA concentration 600 mg/L, aerobic amount 210 L/h. Therefore, the best aerobic amount to treat wastewater contained 4-TSA is 210 L/h in aerobic biological fluidized bed. The degradation rate of 4-TSA is decreased as the increasing of water load. The scanning electronic microscope (SEM) indicated that the bacillus is the mainly part on the biological carrier, suspended sludge is composed by aurous and bacillus.

Thermal performance calculation is the core task of designing power station boiler. By abstracting generalized components and generalized fluid nodes, and defining the process unit and process section at the logic level, the universal physical model of boiler was built in a particular form of flowsheet. Meanwhile, a sequential modular approach was proposed as the main algorithm for boiler thermal calculation based on process system steady-state simulation theory. Two key problems in the algorithm, i.e., module calculations and the logics of calling the modules calculations were explained. Finally, a practically developed system BESS, which has excellent flexibility and extensibility was presented. It turns out that the model and algorithm can be successfully employed in developing the general-purpose software for boiler thermal calculation.

As the outerwear of a building, its color is one of the most significant features of a city. During thousands years of development the colors not only served for protection and decoration, but have been endowed with many intensions in the field of philosophy, politics, religion, culture and so on. Hence there has been formed a unique and integrated culture of colors. As many other cities, Xian is faced with the problem of maintaining its feature in the course of its development. On the basis of protecting the original style and features of the old town, delivering the profound cultural deposits, exploring the connection between traditional culture and modern architectural creation has become a common starting point for the architects in Xian. Based on the culture of Tang dynasty, the new Tang dynasty architecture is a bold attempt to shape a modern city and is also a direct reflection of the architects feeling about Chinese traditional architecture. In this paper, the writer studied the relationship between the colors of the new Tang dynasty architectural style and the creation of the modern Xian architecture from the point of architectural history and architectural design. Also, the paper explored its impact and inspiration on the modern architectural creation of Xian from the perspective of time feature. Moreover, it disclosed the value of the new Tang dynasty architectural style in a modern way and provided references, enlightenments and new ideas for the modern architectural creation in a historic city.

Taking the student dormitory building in Changan campus of Northwestern Polytechnical University as an example, this thesis investigates the behavior and psychology of the habitants in the use process. It analyzes the current using situation and characteristics of existing dormitory mode, discusses the dormitory space mode suitable for contemporary college students to live, in order to improve the college dormitory environment.

SMAD4 is a downstream mediator of transforming growth factor beta. While its tumor suppressor function has been investigated as a prognostic biomarker in several human malignancies, its role as a prognostic marker in breast carcinoma is still undefined. We investigated SMAD4 expression in breast carcinoma samples of different histologic grades to evaluate the association between SMAD4 and outcome in breast cancer. We also investigated the role of SMAD4 expression status in MDA-MB-468 breast cancer cells in responding to TGF-β stimulation. SMAD4 expression was assessed in 53 breast ductal carcinoma samples and in the surrounding normal tissue from 50 of the samples using immunohistochemistry, Western blot, and real-time PCR. TGF-β-SMAD and non-SMAD signaling was assessed by Western blot in MDA-MB-468 cells with and without SMAD4 restoration. SMAD4 expression was reduced in ductal breast carcinoma as compared to surrounding uninvolved ductal breast epithelia (p

This paper analyses the influence factors of the intercity railway station location selection. According to the actual situation of railway station, establish the grey correlation analysis model with the entropy method to evaluate the intercity railway station setting-up plan. Thus the deviation of evaluation results caused by the subjective factors can be avoided effectively. A numerical example and relative conclusions were given then to show that the intercity railway passenger station location problem can be solved by setting up the grey correlation analysis model which was combined with the entropy method and to provide a scientific basis for the decision-making of the intercity railway station location selection.

Rat bone marrow mesenchymal stem cell sheets (rBMSC sheets) are attractive for cell-based tissue engineering. However, methods of culturing rBMSC sheets are critically limited. In order to obtain intact rBMSC sheets, a light-induced cell sheet method was used in this study. TiO2 nanodot films were coated with (TL) or without (TN) laminin-521. We investigated the effects of laminin-521 on rBMSCs during cell sheet culturing. The fabricated rBMSC sheets were subsequently assessed to study cell sheet viability, reattachment ability, cell sheet thickness, collagen type I deposition, and multilineage potential. The results showed that laminin-521 could promote the formation of rBMSC sheets with good viability under hyperconfluent conditions. Cell sheet thickness increased from an initial 26.7 ± 1.5 μm (day 5) up to 47.7 ± 3.0 μm (day 10). Moreover, rBMSC sheets maintained their potential of osteogenic, adipogenic, and chondrogenic differentiation. This study provides a new strategy to obtain rBMSC sheets using light-induced cell sheet technology.

The effects of traumatic spinal cord injury (SCI) on the changes in the central nervous system (CNS) over time may depend on the dynamic interaction between the structural integrity of the spinal cord and the capacity of the brain plasticity. Functional magnetic resonance imaging (fMRI) was used in a longitudinal study on five rhesus monkeys to observe cerebral activation during upper limb somatosensory tasks in healthy animals and after unilateral thoracic SCI. The changes in the spinal cord diameters were measured, and the correlations among time after the lesion, structural changes in the spinal cord, and primary somatosensory cortex (S1) reorganization were also determined. After SCI, activation of the upper limb in S1 shifted to the region which generally dominates the lower limb, and the rostral spinal cord transverse diameter adjacent to the lesion exhibited obvious atrophy, which reflects the SCI-induced changes in the CNS. A significant correlation was found among the time after the lesion, the spinal cord atrophy, and the degree of contralateral S1 reorganization. The results indicate the structural changes in the spinal cord and the dynamic reorganization of the cerebral activation following early SCI stage, which may help to further understand the neural plasticity in the CNS.

Background Guizhi-Shaoyao-Zhimu decoction (GSZD) has been extensively used for rheumatoid arthritis (RA) therapy. Marked therapeutic efficacy of GSZD acting on RA has been demonstrated in several long-term clinical trials without any significant side effects. However, its pharmacological mechanisms remain unclear due to a lack of appropriate scientific methodology. Methods GSZD’s mechanisms of action were investigated using an integrative approach that combined drug target prediction, network analysis, and experimental validation. Results A total of 77 putative targets were identified for 165 assessed chemical components of GSZD. After calculating the topological features of the nodes and edges in the created drug-target network, we identified a candidate GSZD-targeted signal axis that contained interactions between two putative GSZD targets [histone deacetylase 1 (HDAC1) and heat shock protein 90 kDa alpha, class A member 1 (HSP90AA1)] and three known RA-related targets [NFKB2; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta (IKBKB); and tumor necrosis factor-alpha (TNF-α)]. This signal axis could connect different functional modules that are significantly associated with various RA-related signaling pathways, including T/B cell receptor, Toll-like receptor, NF-kappa B and TNF pathways, as well as osteoclast differentiation. Furthermore, the therapeutic effects and putative molecular mechanisms of GSZD’s actions on RA were experimentally validated in vitro and in vivo. Conclusions GSZD may partially attenuate RA by reversing inflammation-immune system imbalance and regulating the HDAC1–HSP90AA1–NFKB2–IKBKB–TNF-α signaling axis.

Chinese traditional five-color aesthetic is developed for thousands of years, but it is still not obsolete. It is regarded as an important classical of Chinese civilization, and is one cultural system lacking the modern scientific methods management as well. Based on the sustainable development concept, firstly, this paper analyzes the feasibility of the introduction of the management methods to manage traditional five-colors aesthetic. Secondly, we specifically discuss how to use the management principles to manage it. Finally, we carry on the cultural innovation of the traditional Chinese five-color aesthetic. For example, the theory of mathematical language conversion, digital color label and computer graphics showing, and so on are discussed. The research of the knowledge management and culture of innovation not only can be used for social creative design and universities design education, but also can be shared with the world.

The Chinese traditional color-culture (CTCC) is not only an important classical of Chinese civilization, but also one cultural system lacking the modern scientific methods of management. Based on the sustainable development concept, this paper firstly analyzes the feasibility of introduction management methods in CTCC. Secondly, we discuss how to use the management principles to manage CTCC. Thirdly, we try to reform design education based on CTCC. Finally, use it to carry on widely confirms in the modern design practice. This research work can not only be used to improve the levels of training for the creative design talents, but also solve the problems of the misunderstanding and the friction between different nationalities due to no color-culture knowledge in the world cultural exchange and economic activities.

Chinese traditional color culture (CTCC) is an essential foundation of building the human color cultural discipline, also is an important direction of educational reform for perfectly training design talents. Based on interdisciplinary methods, firstly, the paper uses Game theory to analyze the necessity of the knowledge management and cultural innovation for CTCC. Secondly, the paper utilizes the management principles to carry on knowledge management of CTCC, and explains culture innovative ways for it. Finally, we discuss methods of application CTCC and color education reform. Through cultural innovation research of CTCC and the introduction of it into universities design education, it can not only surmount the malpractice of that just has a single modern chromatics without any element of national color culture, but also greatly improve the situation of that the designer has not any principles to abide by.