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PDF file - 52K, Supplementary materials includes statistical analysis, antibodies and reagent information, supplementary references, and supplementary figure legend

PDF file - 36K, Specificity of qPCR primers for monitoring miR-103 and miR-107 expression, and effect of miR-103/107 on the expression of DAPK and KLF4 mRNAs

PDF file - 28K, Reporter analysis for examining the efficacies of miR-103 and miR-107 and their antagomirs

PDF file - 190K, miR-103/107 suppress the expression of epithelial markers but cannot induce EMT in CRC cells

PDF file - 51K, Re-expression of DAPK and KLF4 suppresses miR-103/107-induced migration and invasion in normoxia

PDF file - 91K, Supplementary Tables include miR-103/107 Expression Status with relation to tumor stage, as well as Multivariate Analysis

Adenosine-to-inosine (A-to-I) RNA editing is the most common posttranscriptional editing to create somatic mutations and increase proteomic diversity. However, the functions of the edited mutations are largely underexplored. To identify novel targets in lung adenocarcinoma (LUAD), we conducted a genome-wide somatic A-to-I RNA editing analysis of 23 paired adjacent normal and LUAD transcriptomes and identified 26,280 events, including known nonsynonymous AZIN1-S367G and novel RHOAiso2 (RHOA isoform 2)-R176G, tubulin gamma complex associated protein 2 (TUBGCP2)-N211S, and RBMXL1-I40 M mutations. We validated the edited mutations in silico in multiple databases and in newly collected LUAD tissue pairs with the SEQUENOM MassARRAY® and TaqMan PCR Systems. We selected RHOAiso2-R176G due to its significant level, isoform-specificity, and being the most common somatic edited nonsynonymous mutation of RHOAiso2 to investigate its roles in LUAD tumorigenesis. RHOAiso2 is a ubiquitous but low-expression alternative spliced isoform received a unique Alu-rich exon at the 3' RHOA mRNA to become an editing RNA target, leading to somatic hypermutation and protein diversity. Interestingly, LUAD patients harboring the RHOAiso2-R176G mutation were associated with aberrant RHOA functions, cancer cell proliferation and migration, and poor clinical outcomes in transcriptome analysis. Mechanistically, RHOAiso2-R176G mutation-expressing LUAD cells potentiate RHOA-guanosine triphosphate (GTP) activity to phosphorylate ROCK1/2 effectors and enhance cell proliferation and migration in vitro and increase tumor growth in xenograft and systemic metastasis models in vivo. Taken together, the RHOAiso2-R176G mutation is a common somatic A-to-I edited mutation of the hypermutated RHOA isoform 2. It is an oncogenic and isoform-specific theranostic target that activates RHOA-GTP/p-ROCK1/2 signaling to promote tumor progression.

Autism is a kind of biologically based neurodevelopmental condition, and the coexistence of atopic dermatitis (AD) is not uncommon. Given that the gut microbiota plays an important role in the development of both diseases, we aimed to explore the differences of gut microbiota and their correlations with urinary organic acids between autistic children with and without AD. We enrolled 61 autistic children including 36 with AD and 25 without AD. The gut microbiota was sequenced by metagenomic shotgun sequencing, and the diversity, compositions, and functional pathways were analyzed further. Urinary organic acids were assayed by gas chromatography–mass spectrometry, and univariate/multivariate analyses were applied. Spearman correlation analysis was conducted to explore their relationships. In our study, AD individuals had more prominent gastrointestinal disorders. The alpha diversity of the gut microbiota was lower in the AD group. LEfSe analysis showed a higher abundance of Anaerostipes caccae, Eubacterium hallii, and Bifidobacterium bifidum in AD individuals, with Akkermansia muciniphila, Roseburia intestinalis, Haemophilus parainfluenzae, and Rothia mucilaginosa in controls. Meanwhile, functional profiles showed that the pathway of lipid metabolism had a higher proportion in the AD group, and the pathway of xenobiotics biodegradation was abundant in controls. Among urinary organic acids, adipic acid, 3-hydroxyglutaric acid, tartaric acid, homovanillic acid, 2-hydroxyphenylacetic acid, aconitic acid, and 2-hydroxyhippuric acid were richer in the AD group. However, only adipic acid remained significant in the multivariate analysis (OR = 1.513, 95% CI [1.042, 2.198], P = 0.030). In the correlation analysis, Roseburia intestinalis had a negative correlation with aconitic acid (r = -0.14, P = 0.02), and the latter was positively correlated with adipic acid (r = 0.41, P = 0.006). Besides, the pathway of xenobiotics biodegradation seems to inversely correlate with adipic acid (r = -0.42, P = 0.18). The gut microbiota plays an important role in the development of AD in autistic children, and more well-designed studies are warranted to explore the underlying mechanism.

Background Metastasis and chemoresistance are major culprits of cancer mortality, but factors contributing to these processes are incompletely understood. Methods Bioinformatics methods were used to identify the relations of Smyca expression to clinicopathological features of human cancers. RNA-sequencing analysis was used to reveal Smyca-regulated transcriptome. RNA pull-down and RNA immunoprecipitation were used to examine the binding of Smyca to Smad3/4 and c-Myc/Max. Chromatin immunoprecipitation and chromatin isolation by RNA purification were used to determine the binding of transcription factors and Smyca to various gene loci, respectively. Real-time RT-PCR and luciferase assay were used to examine gene expression levels and promoter activities, respectively. Xenograft mouse models were performed to evaluate the effects of Smyca on metastasis and chemoresistance. Nanoparticle-assisted gapmer antisense oligonucleotides delivery was used to target Smyca in vivo. Results We identify lncRNA Smyca for its association with poor prognosis of many cancer types. Smyca potentiates metabolic reprogramming, migration, invasion, cancer stemness, metastasis and chemoresistance. Mechanistically, Smyca enhances TGF-β/Smad signaling by acting as a scaffold for promoting Smad3/Smad4 association and further serves as a Smad target to amplify/prolong TGF-β signaling. Additionally, Smyca potentiates c-Myc-mediated transcription by enhancing the recruitment of c-Myc/Max complex to a set of target promoters and c-Myc binding to TRRAP. Through potentiating TGF-β and c-Myc pathways, Smyca synergizes the Warburg effect elicited by both pathways but evades the anti-proliferative effect of TGF-β. Targeting Smyca prevents metastasis and overcomes chemoresistance. Conclusions This study uncovers a lncRNA that coordinates tumor-relevant pathways to orchestra a pro-tumor program and establishes the clinical values of Smyca in cancer prognosis and therapy.

Background: The new media provides a convenient platform to access, use and exchange health information. And as a special group of health care, maternal health care is still of international concern due to their high mortality rate. Scientific research is a good way to provide advice on how to improve maternal health through stringent reasoning and accurate data. However, the dramatic increase of publications, the diversity of themes, and the dispersion of researchers may reduce the quality of information and increase the difficulty of selection. Thus, this study aims to analyze the research progress on maternal health under the global new media environment, exploring the current research hotspots and frontiers. Methods: A scientometric analysis was carried out by CiteSpace5.7.R1. In total, 2270 articles have been further analyzed to explore top countries and institutions, potential articles, research frontiers, and hotspots. Results: The publications ascended markedly, from 29 in 2008 to 472 publications by 2020. But there is still a lot of room to grow, and the growth rate does not conform to the Price’s Law. Research centers concentrated in Latin America, such as the University of Toronto and the University of California. The work of Larsson M, Lagan BM and Tiedje L had high potential influence. Most of the research subjects were maternal and newborn babies, and the research frontiers were distributed in health education and psychological problems. Maternal mental health, nutrition, weight, production technology, and equipment were seemingly hotspots. Conclusion: The new media has almost brought a new era for maternal health, mainly characterized by psychological qualities, healthy and reasonable physical conditions and advanced technology.

Background: The new media provides a convenient digital platform to access, use and exchange health information. As a special group of health care, maternal is still of international concern due to their high mortality rate. Improving maternal health as a Millennium Development Goal of the United Nations is an important quest for the health care system. Scientific research provides advice on how to improve maternal health through stringent reasoning and accurate data. However, the dramatic increase of publications, the diversity of themes, and the dispersion of researchers may reduce efficiency. Objective: This study aims to analyze the research progress on maternal health under the global new media environment, exploring the current research hotspots and research frontiers. Methods: A scientometric analysis was carried out by CiteSpace5.7.R1, searching in the core database of Web of Science for articles published in English from 1998 to 2021, and combined topic words such as new media, maternal, and health. In total, 3312 articles have been retrieved, of which 2270 studies have been included for further analysis. Top countries and institutions, potentially high-impact literature, research frontiers, and hotspots were analyzed in this study. Results: The number of publications grew rapidly after 2008, from 29 publications sharply increasing to 472 publications by 2020. Research centers concentrated in Latin America, such as the University of Toronto, the University of California. The work of Larsson M, Lagan BM, Tiedje L, and Helle C had a high potential impact. Most of the research subjects were maternal and newborn babies, and the research frontiers focused on health education and maternal psychological problems. Maternal mental health, maternal and infant nutrition, weight, production technology, and equipment were hotspots. Conclusion: The development of new media has brought a new era for maternal health, characterized by psychological qualities, healthy and reasonable physical conditions, and advanced technology.

Precise noncoding RNA (ncRNA)-based network prediction is necessary to reveal ncRNA functions and pathological mechanisms. Here, we established a systemic pipeline to identify prognostic ncRNAs, predict their functions and explore their pathological mechanisms in lung adenocarcinoma (LUAD). After in silico and experimental validation based on evaluations of prognostic value in multiple LUAD cohorts, we selected the PTTG3P pseudogene from among other prognostic ncRNAs (MIR497HG, HSP078, TBX5-AS1, LOC100506990 and C14orf64) for mechanistic studies. PTTG3P upregulation in LUAD cells shortens the metaphase to anaphase transition in mitosis, increases cell viability after cisplatin or paclitaxel treatment, facilitates tumor growth that leads to poor survival in orthotopic lung models, and is associated with a poor survival rate in LUAD patients in the TCGA cohort who received chemotherapy. Mechanistically, PTTG3P acts as an ncRNA that interacts with the transcription factor FOXM1 to regulate the transcriptional activation of the mitotic checkpoint kinase BUB1B, which augments tumor growth and chemoresistance and leads to poor outcomes for LUAD patients. Overall, we established a systematic strategy to uncover prognostic ncRNAs with functional prediction methods suitable for pan-cancer studies. Moreover, we revealed that PTTG3P, due to its upregulation of the PTTG3P/FOXM1/BUB1B axis, could be a therapeutic target for LUAD patients.

Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide due to metastasis. Paraspeckle component 1 (PSPC1) upregulation has been identified as an HCC pro-metastatic activator associated with poor patient prognosis, but with a lack of targeting strategy. Here, we report that PSPC1, a nuclear substrate of PTK6, sequesters PTK6 in the nucleus and loses its metastasis driving capability. Conversely, PSPC1 upregulation or PSPC1-Y523F mutation promotes epithelial-mesenchymal transition, stemness, and metastasis via cytoplasmic translocation of active PTK6 and nuclear translocation of β-catenin, which interacts with PSPC1 to augment Wnt3a autocrine signaling. The aberrant nucleocytoplasmic shuttling of active PTK6/β-catenin is reversed by expressing the PSPC1 C-terminal interacting domain (PSPC1-CT131), thereby suppressing PSPC1/PTK6/β-catenin-activated metastasis to prolong the survival of HCC orthotopic mice. Thus, PSPC1 is the contextual determinant of the oncogenic switch of PTK6/β-catenin subcellular localizations, and PSPC1-CT131 functions as a dual inhibitor of PSPC1 and PTK6 with potential for improving cancer therapy., PSPC1 has a critical role in promoting EMT and metastasis. Here, the authors demonstrate that PSPC1 is the contextual determinant of the oncogenic switch of PTK6/β-catenin subcellular localizations to drive metastasis of hepatocellular carcinoma cells via a PSPC1/PTK6/β-catenin signaling.

Dysregulation of nucleocytoplasmic shuttling is commonly observed in cancers and emerging as a cancer hallmark for the development of anticancer therapeutic strategies. Despite its severe adverse effects, selinexor, a selective first-in-class inhibitor of the common nuclear export receptor XPO1, was developed to target nucleocytoplasmic protein shuttling and received accelerated FDA approval in 2019 in combination with dexamethasone as a fifth-line therapeutic option for adults with relapsed refractory multiple myeloma (RRMM). To explore innovative targets in nucleocytoplasmic shuttling, we propose that the aberrant contextual determinants of nucleocytoplasmic shuttling, such as PSPC1 (Paraspeckle component 1), TGIF1 (TGF-β Induced Factor Homeobox 1), NPM1 (Nucleophosmin), Mortalin and EBP50, that modulate shuttling (or cargo) proteins with opposite tumorigenic functions in different subcellular locations could be theranostic targets for developing anticancer strategies. For instance, PSPC1 was recently shown to be the contextual determinant of the TGF-β prometastatic switch and PTK6/β-catenin reciprocal oncogenic nucleocytoplasmic shuttling during hepatocellular carcinoma (HCC) progression. The innovative nucleocytoplasmic shuttling inhibitor PSPC1 C-terminal 131 polypeptide (PSPC1-CT131), which was developed to target both the shuttling determinant PSPC1 and the shuttling protein PTK6, maintained their tumor-suppressive characteristics and exhibited synergistic effects on tumor suppression in HCC cells and mouse models. In summary, targeting the contextual determinants of nucleocytoplasmic shuttling with cargo proteins having opposite tumorigenic functions in different subcellular locations could be an innovative strategy for developing new therapeutic biomarkers and agents to improve cancer therapy.

The thermodynamic stability and kinetic inertness represent substantial obstacles for direct chemical transformation of CO2. Consequently, conversion of the CO2 equivalent in an efficient and energy-saving manner has gained much attention being viewed as an indirect pathway to chemical utilization of CO2. In this article, we would like to report the synthesis of oxazolidinones via the carboxylative cyclization of anilines with cyclic carbonate using protic ionic liquid 1,8-diazabicyclo[5.4.0]-7-undecenium imidazolide [HDBU][Im] as the bifunctional catalyst under mild conditions without addition of conventional organic solvents. The distinguished features of this protocol include low catalyst loading, wide functionality tolerance and convenient recycling of the catalyst. A series of functional groups such as Cl, Br, CH3, OCH3 and NO2 can be well tolerated under the reaction conditions, providing the corresponding products in moderate to good yields (61–92%). In addition, to shed light on the cooperative interactions of [HDBU][Im]/EC and [HDBU][Im]/aniline, NMR technique and DFT study were also performed, respectively.

Paraspeckle protein 1 (PSPC1) overexpression in cancers is known to be the pro-metastatic switch of tumor progression associated with poor prognosis of cancer patients. However, the detail molecular mechanisms to facilitate cancer cell migration remain elusive. Here, we conducted integrated analysis of human phospho-kinase antibody array, transcriptome analysis with RNA-seq, and proteomic analysis of protein pulldown to study the molecular detail of PSPC1-potentiated phenotypical transformation, adhesion, and motility in human hepatocellular carcinoma (HCC) cells. We found that PSPC1 overexpression re-assembles and augments stress fiber formations to promote recruitment of focal adhesion contacts at the protruding edge to facilitate cell migration. PSPC1 activated focal adhesion-associated kinases especially FAK/Src signaling to enhance cell adhesion and motility toward extracellular matrix (ECM). Integrated transcriptome and gene set enrichment analysis indicated that PSPC1 modulated receptor tyrosine kinase IGF1R involved in the focal adhesion pathway and induction of diverse integrins expression. Knockdown IGF1R expression and treatment of IGF1R inhibitor suppressed PSPC1-induced cell motility. Interestingly, knockdown PSPC1-interacted paraspeckle components including NONO, FUS, and the lncRNA Neat1 abolished PSPC1-activated IGF1R expression. Together, PSPC1 overexpression induced focal adhesion formation and facilitated cell motility via activation of IGF1R signaling. PSPC1 overexpression in tumors could be a potential biomarker of target therapy with IGF1R inhibitor for improvement of HCC therapy.

The solvation effect of compressed CO2 on the curing reaction process of epoxy resin was investigated by using the in-situ FTIR. The isothermal curing kinetic constant and activation energy of diglycidyl ether of bisphenol A (DGEBA) with m-xylylenediamine (MXDA) was calculated via Kamal autocatalytic model. The autocatalyzed rate constants and activation energy under 0.1 MPa CO2 are 0.7139 min−1 and 50.83 kJ/mol at 393 K, while those under 18 MPa CO2 are 1.0928 min−1 and 36.36 kJ/mol, respectively. The increased kinetic constant and reduced activation energy suggests that the plasticization effect of CO2 eases the chain movement, promotes the curing of epoxy resin, and increases the final conversion at relatively low temperature. Then, an amended Kamal model involving the diffusion factor was applied to better describe the curing process, which suggests that the high pressure CO2 plays an important role to reduce the mass transfer resistance and intensify the curing process. Meanwhile, the activation energy determined by the isoconversional method, also decreases with CO2 pressure at the same conversion. Especially, the activation energy at 90% conversion under 0.1 and 18 MPa CO2 are 46.52 and 36.19 kJ/mol, respectively, which further confirms the solvation effect of CO2 accelerates the curing of epoxy resin.

Chemical valorization of CO2 to access various value-added compounds has been a long-term and challenging objective from the viewpoint of sustainable chemistry. Herein, a one-pot three-component reaction of terminal propargyl alcohols, CO2 , and 2-aminoethanols was developed for the synthesis of 2-oxazolidinones and an equal amount of α-hydroxyl ketones promoted by Ag2 O/TMG (1,1,3,3-tetramethylguanidine) with a TON (turnover number) of up to 1260. By addition of terminal propargyl alcohol, the thermodynamic disadvantage of the conventional 2-aminoethanol/CO2 coupling was ameliorated. Mechanistic investigations including control experiments, DFT calculation, kinetic and NMR studies suggest that the reaction proceeds through a cascade pathway and TMG could activate propargyl alcohol and 2-aminoethanol through the formation of hydrogen bonds and also activate CO2 .

Copy number variations (CNVs) play an important role in many types of cancer. With the rapid development of next generation sequencing (NGS) techniques, many methods for detecting CNVs of a single sample have emerged: (i) require genome-wide data of both case and control samples, (ii) depend on sequencing depth and GC content correction algorithm, (iii) rely on statistical models built on CNV positive and negative sample datasets. These make them costly in the data analysis and ineffective in the targeted sequencing data. In this study, we developed a novel alignment-free method called DL-CNV to call CNV from the target sequencing data of a single sample. Specifically, we collected two sets of samples. The first set consists of 1301 samples, in which 272 have CNVs in ERBB2 and the second set is composed of 1148 samples with 63 samples containing CNVs in MET. Finally, we found that a testing AUC of 0.9454 for ERBB2 and 0.9220 for MET. Furthermore, we hope to make the CNV detection could be more accurate with clinical "gold standard" (e.g. FISH) information and provide a new research direction, which can be used as the supplement to the existing NGS methods.

Cancer stemness drives tumor initiation, progression, metastasis, recurrence, and therapy resistance. However, mechanisms that potentiate the acquisition and maintenance of stemness fate of cancer cells remain incompletely understood. Here, we show that miR-103/107 stimulate multiple stem-like features in colorectal cancer, including expression of stem-like markers, appearance of side-population cells, and capabilities in self-renewal, tumor initiation, recurrence, and chemoresistance. Mechanistically, these stemness-promoting functions are mediated by miR-103/107-dependent repression of Axin2, a negative feedback regulator of Wnt/β-catenin signaling. Through inhibiting Axin2, miR-103/107 trigger a prolonged duration of Wnt/β-catenin signaling and a sustained induction of Wnt responsive genes. In colorectal cancer patients, miR-103/107 expression correlates inversely with Axin2 expression and a signature of miR-103/107 high and Axin2 low expression profile correlates with poor prognosis. Together, our study identifies a novel function of miR-103/107 in promoting colorectal cancer stemness by targeting Axin2 and elucidates the clinical relevance and prognostic value of this axis in colorectal cancer.

Bifunctional Zn-salen complexes with multiple hydrogen bonding donors and protic ammonium bromides were developed as efficient catalysts for the formation of 4-phenyl-1,3-dioxolan-2-one from styrene oxide and CO2. Owing to synergistic effects of multiple sites on epoxide activation (Lewis acidic zinc, phenolic hydroxyl group and protonated tertiary ammonium able to activate epoxide and bromide anion acting as a nucleophile), the easily-synthesized Zn-salen complexes showed outstanding performance at mild reaction conditions (CO2 0.1 MPa, 100 °C) using only 0.3 mol% catalyst amount. Besides, this protocol is applicable to a variety of epoxides including internal epoxide, giving the corresponding cyclic carbonates in good to excellent yields. Notably, 200 mmol-scale experiment was successfully conducted and TON of 49288 ± 13 and TOF of 39473 ± 8 h−1 were achieved.

Cullin 3 (Cul3)-family ubiquitin ligases use the BTB-domain-containing proteins for the recruitment of substrates, but the regulation of this family of ubiquitin ligases has not been completely understood. KLHL20 is a BTB-family protein and targets tumor suppressor promyelocytic leukemia protein (PML) and death-associated protein kinase (DAPK) to its kelch-repeat domain for ubiquitination and degradation. Here, we show that another BTB-kelch protein KLHL39 is recruited to the substrate-binding domain of KLHL20 but is not a substrate of Cul3-KLHL20 complex. Interestingly, KLHL39 does not bind Cul3 because of the absence of certain conserved residues in the BTB domain. Instead, KLHL39 blocks KLHL20-mediated ubiquitination of PML and DAPK by disrupting the binding of these substrates to KLHL20 as well as the binding of KLHL20 to Cul3. Through the two mechanisms, KLHL39 increases the stability of PML and DAPK. In human colon cancers, downregulations of KLHL39, PML and DAPK are associated with metastatic progression. Furthermore, preclinical data indicate that KLHL39 promotes colon cancer migration, invasion and survival in vitro and metastasis in vivo through a PML- and DAPK-dependent mechanism. Our study identifies KLHL39 as a negative regulator of Cul3-KLHL20 ubiquitin ligase and reveals a role of KLHL39-mediated PML and DAPK stabilization in colon cancer metastasis.

An easily prepared amino acid ionic liquid (AAIL) i.e. [TBP][Arg] comprising a tetra-butylphosphonium cation and an arginine anion was found to be an efficient and recyclable catalyst for the synthesis of quinazoline-2,4(1H,3H)-diones from 2-aminobenzonitriles and CO2 under solvent-free conditions. As a result, various 2-aminobenzonitriles bearing electron-withdrawing or electron-donating substituents worked well to afford quinazoline-2,4(1H,3H)-diones in excellent yields. Notably, this type of AAIL showed good stability, and could be easily recovered and reused five times without significant loss of its catalytic activity. This process represents an alternative approach for greener chemical fixation of CO2 to afford valuable compounds.

Protein-tyrosine kinase 6 (PTK6) sequestrated by its substrate paraspeckle component 1 (PSPC1) in nucleus is a tumor suppressor. PSPC1 functions as a contextual determinant of oncogenic subcellular translocations to synergize PSPC1/β-catenin and PTK6 tumorigenesis. Besides, PSPC1 C-terminal interacting domain (PSPC1-CT131), a dual inhibitor of PSPC1 and PTK6, suppresses cancer progression.

An integrated process of CO2 capture and in situ hydrogenation into formate was achieved in 95–99% yield using a tunable ethoxyl-functionalized amidine and Rh/bisphosphine system, being regarded as an alternative carbon capture and utilization approach to supply fuel-related products, to circumvent the energy penalty in carbon capture and storage. CO2 was captured by non-volatile amidine derivatives with simultaneous activation to form zwitterionic amidinium carbonate, and subsequent hydrogenation was facilitated by Rh/bisphosphine. The adsorption capacity and hydrogenation efficiency can be optimized by tuning the ethoxyl side chain. Particularly, the alkanolamidine bearing an intramolecular hydrogen donor derived from 1,8-diazabicyclo[5.4.0]-undec-7-ene (DBU) gave both a high CO2 uptake (molar ratio of 0.95:1) and excellent hydrogenation yield (99%). Furthermore, the silica-supported alkanolamidine was readily recovered and reused with the retention of good performance. This kind of carbon capture and utilization pathway could be a potential energy-saving option for industrial upgrading of CO2 from waste to fuel-related products in a carbon neutral manner.

Efficient nonlinear programming (NLP) algorithms and modeling platforms have led to powerful process optimization strategies. Nevertheless, these algorithms are challenged by recent evolution and deployment of multi-scale models (such as molecular dynamics and complex fluid flow) that apply over broad time and length scales. Integrated optimization of these models requires accurate and efficient reduced models (RMs). This study develops a rigorous multi-scale optimization framework that substitutes RMs for complex original detailed models (ODMs) and guarantees convergence to the original optimization problem. Based on trust region concepts this framework leads to three related NLP algorithms for RM-based optimization. The first follows the classical gradient-based trust-region method, the second avoids gradient calculations from the ODM, and the third avoids frequent recourse to ODM evaluations, using the concept of ϵ-exact RMs. We illustrate these algorithms with small examples and discuss RM-based optimization case studies that demonstrate their performance and effectiveness.

Barrier nonlinear programming (NLP) solvers exploit sparse Newton-based algorithms and are characterized by fast performance and global convergence properties. This makes them especially suitable for very large process optimization problems. On the other hand, they are frequently challenged by degenerate and indefinite problems, which lead to ill-conditioned Karush–Kuhn–Tucker (KKT) systems. Such problems arise when process optimization models contain linearly dependent constraints, or the reduced Hessian is not positive definite at the solution. This can lead to poor solver performance and may preclude finding successful NLP solutions. Moreover, such optimization models occur in blending problems and NLP subproblems generated by MINLP or global optimization strategies. To deal with these difficulties we present a structured regularization strategy for barrier methods that identifies and excludes dependent constraints in the KKT system while leaving independent constraints unchanged. As a result, more accurate Newton directions can be obtained and much faster convergence can be expected for the KKT system over the conventional regularization approach. Numerical experiments with examples derived from the CUTE and COPS test sets as well as two nonlinear blending problems demonstrate the effectiveness of the proposed method and significantly better performance of the NLP solver.

A novel intumescent flame retardant was incorporated into polypropylene to prepare novel intumescent flame retardant composites (PP/IFR) with good flame retardant properties. The flame retardant mechanism was investigated by means of Laser Raman spectroscopy (LRS), X-ray photoelectron spectroscopy (XPS), Thermogravimetric analysis/infrared spectrometry (TGA-IR), Fourier Transform infrared spectroscopy (FTIR) and Energy Dispersive Spectrometer (EDS). It was found that the IFR could decrease the degradation rate of PP; the formed intumescent char was containing unorganized carbon structure and graphitic structure, and consisting of P, N, O and C elements. FTIR analysis showed that the network with P-O-P and P-O-C were formed. EDS analysis results revealed that some P elements were connected to the polyaromatic rings and could form huge connected network.

Reduced-space barrier NLP algorithms are particularly useful for optimization of large structured systems with few degrees of freedom. Such optimization algorithms are often applied on process models developed within equation oriented process simulators. By partitioning the search direction into tangential and normal steps, these methods can exploit the structure of the equality constraints and adjust the remaining degrees of freedom in a lower dimensional space. Moreover, as shown in previous work, the barrier approach extended with a novel filter linear search algorithm has global and fast local convergence properties. However, convergence properties of the reduced-space barrier algorithm require regularity assumptions. In particular, the method may fail in the presence of linearly dependent active constraints. To deal with these questions, we modify the reduced-space barrier method in two ways. First, as the filter line search requires a feasibility restoration step, we develop and analyze an improved algorithm for this step, which is tailored to the reduced-space method. In addition, a dimension change procedure is proposed to address decomposition of problems with linearly dependent constraints. Finally, both approaches are implemented within a reduced-space version of IPOPT and numerical tests demonstrate the performance of the proposed modifications.

Integrated gasification combined cycle (IGCC) plants have significant advantages for efficient power generation with carbon capture. Moreover, with the development of accurate CFD models for gasification and combined cycle combustion, key units of these processes can now be modeled more accurately. However, the integration of CFD models within steady-state process simulators, and subsequent optimization of the integrated system, still presents significant challenges. This study describes the development and demonstration of a reduced order modeling (ROM) framework for these tasks. The approach builds on the concepts of co-simulation and ROM development for process units described in earlier studies. Here we show how the ROMs derived from both gasification and combustion units can be integrated within an equation-oriented simulation environment for the overall optimization of an IGCC process. In addition to a systematic approach to ROM development, the approach includes validation tasks for the CFD model as well as closed-loop tests for the integrated flowsheet. This approach allows the application of equation-based nonlinear programming algorithms and leads to fast optimization of CFD-based process flowsheets. The approach is illustrated on two flowsheets based on IGCC technology.

Living Cephalotaxus (plum yews) occurs mainly in East Asia and North of Indo-China peninsula. The study of original taxonomic literatures found that, in early days, the plum yews had ever been described as palnts of Taxus (Taxaceae). Since after the genus name Cephalotaxus Sieb. & Zucc. was firstly cited (from inedited and unpublished Flora Japonica) by Endlicher in 1842, most taxonomist thought which is the earliest time of the genus Cephalotaxus Sieb. & Zucc. was set. However, the genus Cephalotaxus Sieb. & Zucc. was formally effective and valid published by Sieb. & Zucc. in Flora Japonica in 1870 so that there exists some confusions in chronological order. Originally as a genus, Cephalotaxus was included in family Taxaceae and Neger (1907) separated Cephalotaxus from Taxaceae and set family Cephalotaxaceae. Later, Fu (1984) divided Cephalotaxus up into two sections of Cephalotaxus Sieb. & Zucc. sect. Pectinatae L. K. Fu and Cephalotaxus Sieb. & Zucc. sect. Cephalotaxus L. K. Fu on the bases of C. oliveri Masters differ significantly from other taxa of Cephalotaxus in morphological characteristics. Although the plum yews was a little genus of conifers, up to now, about 77 taxa have still been published by taxonomist in different countries or regions. Among them, C. tardiva Sieb. ex Endl. (1847), C. umbraculifera Sieb. ex Endl. (1847), C. sumatrana Miq. (1856) and C. celebica Warb. (1900) have been combined to Taxus, and C. argotaenia (Hance) Pilger (1903) has been combined to Amentotaxus. And at the same time, those taxa existing in Cephalotaxus courently which were accepted by most taxonomist in different countries was also cited in acticle. Lastly, the paper thought presently there still exists many debates about binary classification of Cephalotaxus and the nomenclature of this genus still particularly confusing. Based on some controversial problems, we also point out some taxonomically researching directions at creating some order out of the chaos.

Background: Mechanical ventilation with a high tidal volume (VT) increases lung and systemic plasminogen activator inhibitor (PAI)-1 levels and alveolar fibrin deposition. Activated protein C (APC) may decrease PAI activity in endothelial cell-conditioned medium and thus enhance fibrinolysis. Objectives: The aims of this study were to test the hypothesis that APC can neutralize PAI-1 activity and improve lung function in an animal model of ventilator-induced lung injury. Methods: Rats were ventilated with a high-volume zero positive end-expiratory pressure (PEEP; HVZP) protocol by a volume-cycled ventilator for 2 h at a VT of 30 ml/kg, a respiratory rate of 25 breaths/min, and an FiO2 of 0.21. Fifteen minutes before ventilation, the rats received intravenous APC (250 µg/kg, HVZP+APC group) or normal saline (vehicle; HVZP group). Another group that received no ventilation served as the control group. Results: Levels of arterial blood gas tension were comparable between the two ventilation groups throughout the study period. Rats treated with the HVZP protocol exhibited significantly higher total protein and macrophage inflammatory protein-2 concentrations in bronchoalveolar lavage fluid (BALF) and higher lung PAI-1 mRNA expression and plasma active PAI-1 levels than did the control group. Administration of APC tended to reduce the BALF protein content and systemic PAI-1 activity but did not improve the lung histology in the HVZP+APC group. Plasma levels of D-dimers were comparable among the three study groups. Conclusions: These results suggest that APC administered at a higher dosage might improve lung function by reducing alveolar protein leakage and systemic coagulation.