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Yan Yu,1,* Ti-wei Miao,1,* Wei Xiao,1 Bing Mao,1 Long-yi Du,1 Yan Wang,2 Juan-juan Fu1 1Division of Pulmonary Medicine, Department of Internal Medicine, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 2Research Core Facility, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China*These authors contributed equally to this workCorrespondence: Juan-juan Fu, Division of Pulmonary Medicine, Department of Internal Medicine, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, 37 Guoxue Street, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-18980606822, Email fu.juanjuan@scu.edu.cnPurpose: The aim of this study is to uncover the anti-inflammatory propertity of andrographolide (AGP) in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and the underlying mechanisms related to the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome pathway.Methods: An in vivo experiment was conducted on murine model of AECOPD through endotracheal atomization of elastase and lipopolysaccharide (LPS). Intraperitoneal AGP was administered four times. NLRP3 inflammasome pathway molecules were examined using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. By using enzyme-linked immunosorbent assay (ELISA), we tested interleukin (IL)-1β levels in bronchoalveolar lavage fluid. An in vitro study was conducted to determine how AGP impacts the NLRP3 inflammasome in THP-1 derived macrophages. The levels of molecules involved in the pathway were measured. Furthermore, molecular docking analyses were carried out to investigate the interactions between AGP and pathway targets.Results: In the in vivo study, NLRP3 inflammasome activation was observed in mice experiencing AECOPD. The administration of high-dose AGP demonstrated a mitigating effect on inflammatory cells infiltration in the lungs. Moreover, AGP administration effectively suppressed the expression of NLRP3, apoptosis associated speck-like protein that contains a CARD (PYCARD), cysteinyl aspartate-specific protease-1 (Caspase-1), IL-1β, and IL-18 at both the genetic and protein levels. In the in vitro experiment, IL-1β levels were significantly elevated in THP-1 derived macrophages with activated inflammasome compared to the control group. Furthermore, the downregulation of NLRP3, CASP1, and IL1B genes was observed upon the inhibition of NLRP3 expression through small interfering RNA (siRNA). AGP demonstrated inhibitory effects on the gene expression and protein levels of NLRP3, Caspase-1, and IL-1β. Additionally, molecular docking analysis confirmed that AGP exhibited a favorable binding affinity with all five targets of the pathway.Conclusion: AGP effectively inhibited NLRP3 inflammasome activation and mitigated the inflammatory reaction of AECOPD both in animal models and in vitro experiments, highlighting the potential of AGP as a treatment for AECOPD with anti-inflammatory properties.Keywords: andrographolide, NLRP3 inflammasome, IL-1β, chronic obstructive pulmonary disease

Peng Yu,1– 4 Ranran Kan,1,3 Xiaoyu Meng,1,3 Zhihan Wang,1,3 Yuxi Xiang,1,3 Beibei Mao,1,3 Xuefeng Yu1,3 1Department of Endocrinology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Endocrinology, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Branch of National Clinical Research Center for Metabolic Diseases, Hubei, People’s Republic of China; 4Key Laboratory for Molecular Diagnosis of Hubei Province, Wuhan, People’s Republic of ChinaCorrespondence: Xuefeng Yu, Department of Internal Medicine, Tongji Hospital, Huazhong University of Science and Technology, No. 1095, Jiefang Road, Wuhan, 430030, People’s Republic of China, Tel +8602783663331, Email xfyu188@163.comBackground: In China, the spectrum of causes for CKD has been changing in recent years, and the proportion of CKD caused by cardiometabolic diseases, such as diabetes and hypertension continues to increase. Thus, predicting CKD based on cardiometabolic risk factors can to a large extent help identify those at increased risk and facilitate the prevention of CKD. In this study, we aimed to develop a nomogram for predicting CKD risk based on cardiometabolic risk factors.Methods: We developed a nomogram for predicting CKD risk by using a subcohort population of the 4C study, which was located in central China. The prediction model was designed by using a logistic regression model, and a backwards procedure based on the Akaike information criterion was applied for variable selection. The performance of the model was evaluated by the concordance index (C-index), and Hosmer‒Lemeshow goodness-of-fit test. The bootstrapping method was applied for internal validation.Results: During the 3-years follow-up, 167 cases of CKD developed. By using univariate and multivariate logistic regression models, the following factors were identified as predictors in the nomogram: age, sex, HbA1c, baseline eGFR, low HDL-C levels, high TC levels and SBP. The bootstrap-corrected C-index for the model was 0.84, which indicated good discrimination ability. The Hosmer‒Lemeshow goodness-of-fit tests yielded chi-square of 13.61 (P=0.192), and the calibration curves demonstrated good consistency between the predicted and observed probabilities, which indicated satisfactory calibration ability.Conclusion: We developed a convenient and practicable nomogram for the 3‑year risk of incident CKD among a population in central China, which may help to identify high-risk individuals for CKD and contribute to the prevention of CKD.Keywords: CKD, cardiometabolic risk factors, nomogram

Bin Dai, Zhiyong Xiao, Guangtong Zhu, Beibei Mao, Hui Huang, Feng Guan, Zhenyang Lin, Weicheng Peng, Xin Liang, Bolun Zhang, Zhiqiang Hu Department of Neurosurgery, Beijing Shijitan Hospital, Capital Medical University, Peking University Ninth School of Clinical Medicine, Beijing, People’s Republic of ChinaCorrespondence: Zhiqiang HuDepartment of Neurosurgery, Beijing Shijitan Hospital, Capital Medical University, Peking University Ninth School of Clinical Medicine, No. 10 Tieyi Road, Yangfangdian, Haidian District, Beijing 10038, People’s Republic of ChinaTel +86 10 63926627 Email huzhiqbj@sina.comBackground: Glioma is one of the important diseases that threaten human survival in today’s society. WD repeat domain 5 (WDR5) belongs to the components of the lysine methyltransferase complex. WDR5 is involved in gene transcription regulation, cell senescence, cancer and other biological events through methylation modification. However, its expression and function in glioma are still unclear.Materials and Methods: The expression of WDR5 was observed in glioma cells, and then a glioma cell line SW1783 knocked down WDR5 was established. The effects of the decrease of WDR5 expression on proliferation, migration, invasion and EMT of glioma cells were detected, respectively. The downstream regulators of WDR5 were identified by gene expression profiling technology, and the possible molecular mechanisms were identified.Results: In this study, we found that WDR5 could promote glioma cell’s proliferation, migration, invasion and tumor metastasis. In glioma, especially in metastatic glioma tissues, WDR5 levels were significantly increased, the higher expression level could also cause a significant reduction in overall survival of glioma patients. Second, the ability of cells’ proliferation, migration, invasion and tumor metastasis was significantly reduced in WDR5 knockdown cell lines. We also found a significant change in the expression level of epithelial and mesenchymal markers in WDR5 knockdown cell lines. Furthermore, we found that knockdown of WDR5 could inhibit the expression of zinc finger E-box binding homeobox 1 (ZEB1), and knockdown of ZEB1 could inhibit invasion, migration and epithelial–mesenchymal transformation (EMT) in WDR5 over-expression cell line. We also found that WDR5 may regulate ZEB1’s expression through H3K4me3.Conclusion: In summary, in this study, we have studied the relationship between WDR5 and glioma, and found that WDR5’s expression is positively correlated with the proliferation, migration, and invasion of glioma cells, which will help find the potential therapeutic target for glioma patients.Keywords: WDR5, ZEB1, glioma, migration, metastasis

Yuqiao Chen,1 Huan Chen,2 Beibei Mao,2 Yuan Zhou,1 Xinying Shi,2 Lu Tang,1 Hong Jiang,3 Guo Wang,4 Wei Zhuang1 1Department of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People’s Republic of China; 2Beijing Genecast Biotechnology Co., Beijing 100000, People’s Republic of China; 3Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People’s Republic of China; 4Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People’s Republic of ChinaCorrespondence: Wei ZhuangXiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, People’s Republic of ChinaTel +86-152-0089-9869Fax +86-731-8432-7623Email zhuangwei@csu.edu.cnObjective: We investigated the relationship of the transcriptional tumor immune microenvironment with prognosis of patients with locally advanced lung adenocarcinoma (LUAD).Materials and methods: A targeted RNA-Seq approach was used to measure the abundance of 395 immune-related transcripts of 24 formalin-fixed paraffin embedded (FFPE) tumor specimens from our institution and transcription data of 85 matched LUAD samples from The Cancer Genome Atlas (TCGA). Gene set variation analysis (GSVA) was used to identify gene sets related to prognosis, and the microenvironment cell-population (MCP)-counter method was used to quantify infiltrated immune cells. Survival analysis with the log rank test was used to determine the relationships of different immune-related transcripts with prognosis. Cox proportional hazards models were also used to identify risk factors associated with poor prognosis.Results: Among our patients, GSVA and the log rank test demonstrated that enrichment of the antigen processing pathway (P = 0.01) correlated with a favorable prognosis. MCP-counter and survival analysis demonstrated that greater CD8 T cell infiltration correlated with a favorable prognosis (P = 0.05), but greater infiltration of neutrophils (P = 0.014) and NK cells (P = 0.015) correlated with poor prognoses. Cox hazard analysis showed that greater infiltration of neutrophils was an independent risk factor for poor prognosis. These results were consistent with LUAD data from TCGA.Conclusion: When integrated with computational bioinformatics methods, targeted RNA-Seq from FFPE specimens provides profiles of the tumor immune microenvironment that have prognostic value for patients with locally advanced LUAD.Keywords: NSCLC, lung adenocarcinoma, RNA-Seq, tumor immune microenvironment, transcriptomic markers

The strict requirements on splitting ratios of optical power and radio-frequency (RF) voltage affect the performance of the Dual Parallel Mach-Zehnder modulator (DPMZM). In this paper, a modified DPMZM with three Multimode Interference (MMI) couplers (MMI-DPMZM) is proposed. The three MMI couplers, comprised of a reconfigurable one and two 3 dB ones, function as optical splitters. The theoretical analysis shows that the structure can prohibit the third-order intermodulation distortion (IMD3) from the third order term and fifth order term of the transfer function’s Taylor series, leading to the peak Spurious-Free Dynamic Range (SFDR) as high as 104.12 dB. The adjustment of the tunable MMI coupler ensures the SFDR is kept above 104.00 dB even the radio frequency (RF) signal’s voltage splitting ratio deviates from its optimum value. It is also demonstrated that the SFDR can reach 104.10 dB with the precision and uniformity of MMI couplers considered.

Utilizing ambient pressure X-ray photoelectron spectroscopy (AP-XPS), the surface segregation and oxidation of Pt3Ni(1 1 1) alloys are investigated as a function of temperature and oxygen pressure. The in situ AP-XPS measurements of oxygen oxidation process show that the Pt "skin" surface is not stable under the exposure of oxygen pressure of 100 mTorr at room temperature. As the temperature and pressure are elevated, the formations of Ni2O3, NiOx, and NiO are observed on surface while Pt atom starts to reduce its adsorbed oxygen, which is a clear sign of surface segregation of Ni to surface. Upon the evacuation of oxygen gas, i.e. ultrahigh vacuum condition, both of NiOx and NiO oxide get reduced and Ni2O3 remains on the surface. The DFT calculation is employed to explain the formation of surface oxides under oxidation condition.

Utilizing ambient pressure X-ray photoelectron spectroscopy (AP-XPS), the surface segregation and oxidation of Pt3Ni(1 1 1) alloys are investigated as a function of temperature and oxygen pressure. The in situ AP-XPS measurements of oxygen oxidation process show that the Pt "skin" surface is not stable under the exposure of oxygen pressure of 100 mTorr at room temperature. As the temperature and pressure are elevated, the formations of Ni2O3, NiOx, and NiO are observed on surface while Pt atom starts to reduce its adsorbed oxygen, which is a clear sign of surface segregation of Ni to surface. Upon the evacuation of oxygen gas, i.e. ultrahigh vacuum condition, both of NiOx and NiO oxide get reduced and Ni2O3 remains on the surface. The DFT calculation is employed to explain the formation of surface oxides under oxidation condition.

High-assurance systems found in safety-critical infrastructures are facing steadily increasing cyber threats. These critical systems require rigorous guarantees in information flow security to prevent confidential information from leaking to an unclassified domain and the root of trust from being violated by an untrusted party. To enforce bit-tight information flow control, gate-level information flow tracking (GLIFT) has recently been proposed to precisely measure and manage all digital information flows in the underlying hardware, including implicit flows through hardware-specific timing channels. However, existing work in this realm either restricts to two-level security labels or essentially targets two-input primitive gates and several simple multilevel security lattices. This article provides a general way to expand the GLIFT method for multilevel security. Specifically, it formalizes tracking logic for an arbitrary Boolean gate under finite security lattices, presents a precise tracking logic generation method for eliminating false positives in GLIFT logic created in a constructive manner, and illustrates application scenarios of GLIFT for enforcing multilevel information flow security. Experimental results show various trade-offs in precision and performance of GLIFT logic created using different methods. It also reveals the area and performance overheads that should be expected when expanding GLIFT for multilevel security.

The spatial-temporal imbalance of demand will affect the formulation of urban rail transit public welfare fare schemes, and then affect the passenger benefits and the traffic structure. A bi-level programming model considering multi-period and different direction demands is established. The upper model takes the maximization of social welfare as the objective function, and considers public welfare constraints; the lower model is a stochastic user equilibrium model. A heuristic hybrid algorithm which combines multi-population genetic algorithm, continuous average method and parallel computation is designed. The results show that: compared with for-profit pricing scheme, when public welfare pricing scheme is adopted, ticket price is reduced by 43%; the generalized travel cost per passenger is decreased by 19% and 4% in peak and off-peak periods respectively in up direction, 16% and 6% in down direction; the consumer surplus is increased by 15.2% and 5.7% in peak and off-peak periods respectively in up direction, 12% and 7% in down direction; the urban rail transit sharing rate is increased by 40% and 71% in peak and off-peak periods respectively in up direction, 36% and 66% in down direction. This model provides some reference for government to formulate the fare and management strategy. [ABSTRACT FROM AUTHOR]

Modern food microbiology is a core compulsory course of Food Science and Engineering and an important course in the teaching system of Food majors. We have conducted a research on teaching reform in response to the current problems of outdated teaching content, single teaching methods, and unscientific teaching assessment methods in curriculum teaching. We have taken multiple strategies, including introducing hot cases related to food microbiology in class to update the teaching content, encouraging students to conduct microbiological thematic discussions and presentations in class, adding feedbacks after the “homework submission-review scoring” to achieve a closed-loop teaching. After three rounds of teaching reform practice, the students’ feedback was good, and the teaching effects of modern food microbiology has been significantly improved.

As the control center of the natural gas long-distance pipeline network, the SCADA system shoulders the important tasks of data collection and monitoring of the whole long-distance pipeline, gas transmission management, production scheduling, operation and maintenance coordination in production, and plays a very important role in the whole oil and gas pipeline. In this paper, firstly, the SCADA system for localized long-distance pipelines is explained in detail, including its basic structure and special solutions to problems. Secondly, the AdaBoost algorithm, which combines the MapReduce parallel computing framework, is introduced to collect and process data from the operation logs of the SCADA system and normalize the logs. Finally, to test the interaction between the improved AdaBoost algorithm and the SCADA system, a system test was conducted. The results show that the average latency of scheduling the logs of the SCADA system by AdaBoost algorithm with MapReduce parallel computing framework is only 39.82ms, the average processing speed of the log normalization file data under the multi-threaded mode of the system reaches 86.51GB/s, and the effective accuracy of the fault diagnosis is as high as 90.36%. This shows that the oil and gas pipeline SCADA system interacting with data visualization technology can process operation logs more quickly and can carry out real-time intelligent supervision of the working status and operation parameters of the whole auxiliary system, promoting the intelligent development of the oil and gas pipeline SCADA system.