Class-specific cost regulation extreme learning machine (CCR-ELM) can effectively deal with the class imbalance problems. However, its key parameters, including the number of hidden nodes, the input ...weights, the biases and the tradeoff factors are normally generated randomly or preset by human. Moreover, the number of input weights and biases depend on the size of hidden layer. Inappropriate quantity of hidden nodes may lead to the useless or redundant neuron nodes, and make the whole structure complex, even cause the worse generalization and unstable classification performances. Based on this, an adaptive CCR-ELM with variable-length brain storm optimization algorithm is proposed for the class imbalance learning. Each individual consists of all above parameters of CCR-ELM and its length varies with the number of hidden nodes. A novel mergence operator is presented to incorporate two parent individuals with different length and generate a new individual. The experimental results for nine imbalance datasets show that variable-length brain storm optimization algorithm can find better parameters of CCR-ELM, resulting in the better classification accuracy than other evolutionary optimization algorithms, such as GA, PSO, and VPSO. In addition, the classification performance of the proposed adaptive algorithm is relatively stable under varied imbalance ratios. Applying the proposed algorithm in the fault diagnosis of conveyor belt also proves that ACCR-ELM with VLen-BSO has the better classification performances.
The aim of this study was to investigate the potential therapeutic effects of a newly discovered osteopontin-derived synthetic peptide "RSKKFRR" in a rat model of ischemic stroke.
A total of 24 male ...SD rats were randomly divided into three groups. The model of ischemic stroke was made up of the middle cerebral artery occlusion (MACO). The rats were divided into sham operation group (Sham), control group (MACO + PBS) and treatment group (MACO + OPNpt9), eight rats in each group. In the control group and the treatment group, PBS or OPNpt9 was injected into the nasal cavity after MACO once a day, and the area of new blood vessels and the recovery of nerve function were observed 14 days later. Whether the proliferation, migration and tube formation of HUVECs were promoted by OPNpt9 was tested. The expression levels of related proangiogenic factors were also detected.
OPNpt9 was found to contribute to cerebral microvascular remodeling and neurological improvement in ischemic rats while promoting endothelial cell migration, proliferation and tube formation in vitro. These effects were mediated by activation of the p-ERK/MMP-9/VEGF pathway.
In conclusion, OPNpt9 promotes angiogenesis and neurological recovery after ischemic stroke.
In contrast to a plethora of macrocyclic and cage compounds, spirophanes have remained largely unexplored. We report herein the construction, structure and properties of unprecedented tetrahomo ...corona4arene-based ditopic and tritopic macrocycles of spiro structures. Synthesis was conveniently achieved by means of an efficient S
N
Ar reaction from simple and commercially available starting materials. Racemic samples were resolved into enantiopure chiral tetrahomo
i
-corona4arenes, spirophanes and bispirophanes which show interesting chiroptical properties. The acquired electron-deficient macrocyclic compounds were found to adopt unique conformational structures and to form distinct complexes with TTF in the solid state. Our study provides a new opportunity to develop multitopic macrocycles of different topologies which have potential applications in supramolecular chemistry.
Racemic and enantiopure spirophanes and bispirophanes consisting of orthogonally configured tetrahomo corona4arene and
i
-corona4arene macrocycles were obtained and they displayed interesting tetrathiafulvalene binding and chiroptical properties.
Background & Aims Esophageal squamous cell carcinoma (ESCC) is the most common subtype of esophageal cancer. Little is known about the genetic changes that occur in esophageal cells during the ...development of ESCC. We performed next-generation sequence analyses of esophageal nontumor, intraepithelial neoplasia (IEN), and ESCC tissues from the same patients to track genetic changes during tumor development. Methods We performed whole-genome, exome, or targeted sequence analyses of 227 esophageal tissue samples from 70 patients with ESCC undergoing resection at Shantou University Medical College in China from 2012 through 2015 (no patients had received chemotherapy or radiation therapy); we analyzed normal tissue, tissue with simple hyperplasia, dysplastic tissue (IEN), and ESCC tissues collected from different regions of the esophagus at the same time. We also obtained 1191 nontumor esophageal biopsy specimens from the Chaoshan region of China (a high-risk region for ESCC) and performed immunohistochemical and histologic analyses to detect inflammation. Results IEN and ESCC tissues had similar mutations and copy number alterations, at similar frequencies; these differed from mutations detected in tissues with simple hyperplasia. IEN tissues had mutations associated with apolipoprotein B messenger RNA editing enzyme, catalytic polypeptide-like–mediated mutagenesis (a DNA damage mutational signature). Genetic analyses indicated that most ESCCs formed from early stage IEN clones. Trunk mutations (mutations shared by >10% of paired IEN and ESCC tissues) were in genes that regulate DNA repair and cell apoptosis, proliferation, and adhesion. Mutations in TP53 and CDKN2A and copy number alterations in 11q (contains CCND1 ), 3q (contains SOX2 ), 2q (contains NFE2L2 ), and 9p (contains CDKN2A ) were considered to be trunk variants; these were dominant mutations detected at high frequencies in clones of paired IEN and ESCC samples. In the esophageal biopsy samples from high-risk individuals (residing in the Chaoshan region), 68.9% had evidence of chronic inflammation; the level of inflammation correlated with atypical cell structures and markers of DNA damage. Conclusions We analyzed mutations and gene copy number changes in nontumor, IEN, and ESCC samples, collected from 70 patients. IEN and ESCCs each had similar mutations and markers of genomic instability, including apolipoprotein B messenger RNA editing enzyme, catalytic polypeptide-like. Genomic changes observed in precancerous lesions might be used to identify patients at risk for ESCC. Binary sequence alignment/map (BAM) files are uploading to BioProject (accession number: PRJNA317404).
Objectives
To explore and evaluate the feasibility of radiomics in stratifying nasopharyngeal carcinoma (NPC) into distinct survival subgroups through multi-modalities MRI.
Methods
A total of 658 ...patients (training cohort: 424; validation cohort: 234) with non-metastatic NPC were enrolled in the retrospective analysis. Each slice was considered as a sample and 4863 radiomics features on the tumor region were extracted from T1-weighted, T2-weighted, and contrast-enhanced T1-weighted MRI. Consensus clustering and manual aggregation were performed on the training cohort to generate a baseline model and classification reference used to train a support vector machine classifier. The risk of each patient was defined as the maximum risk among the slices. Each patient in the validation cohort was assigned to the risk model using the trained classifier. Harrell’s concordance index (C-index) was used to measure the prognosis performance, and differences between subgroups were compared using the log-rank test.
Results
The training cohort was clustered into four groups with distinct survival patterns. Each patient was assigned to one of the four groups according to the estimated risk. Our method gave a performance (C-index = 0.827,
p
< .004 and C-index = 0.814,
p
< .002) better than the T-stage (C-index = 0.815,
p
= .002 and C-index = 0.803,
p
= .024), competitive to and more stable than the TNM staging system (C-index = 0.842,
p
= .003 and C-index = 0.765,
p
= .050) in the training cohort and the validation cohort.
Conclusions
Through investigating a large one-institutional cohort, the quantitative multi-modalities MRI image phenotypes reveal distinct survival subtypes.
Key Points
• Radiomics phenotype of MRI revealed the subtype of nasopharyngeal carcinoma (NPC) patients with distinct survival patterns.
• The slice-wise analysis method on MRI helps to stratify patients and provides superior prognostic performance over the TNM staging method.
• Risk estimation using the highest risk among slices performed better than using the majority risk in prognosis.
In this paper, we realize tunable Fano and electromagnetically induced transparency (EIT)-like resonances in the outputs of a nested feedback ring resonator. Compared with the traditional add-drop ...ring resonator, the feedback arm introduces interference between different resonance modes. Using coupled mode theory, we reveal that the output Fano resonances are the interference of discrete modes and continuum modes, whereas the EIT-like resonance only appears in the over-coupled state. We experimentally confirm the two effects using optical fiber ring resonators, finding that the Fano effect can be easily controlled with phase shifts in the feedback arm. Moreover, we achieve the double Fano resonance, which displays an 'X' type lineshape utilizing one ring resonator, predicting it to be a good candidate in wavelength monitor. The proposed simple configuration provides a platform to study Fano and EIT-like effect, which is useful in the optical filter, fast and slow light, optical switching, and optical sensing.
Rice (Oryza sativa), a major staple throughout the world and a model system for plant genomics and breeding, was the first crop genome sequenced almost two decades ago. However, reference genomes for ...all higher organisms to date contain gaps and missing sequences. Here, we report the assembly and analysis of gap-free reference genome sequences for two elite O. sativa xian/indica rice varieties, Zhenshan 97 and Minghui 63, which are being used as a model system for studying heterosis and yield. Gap-free reference genomes provide the opportunity for a global view of the structure and function of centromeres. We show that all rice centromeric regions share conserved centromere-specific satellite motifs with different copy numbers and structures. In addition, the similarity of CentO repeats in the same chromosome is higher than across chromosomes, supporting a model of local expansion and homogenization. Both genomes have over 395 non-TE genes located in centromere regions, of which ∼41% are actively transcribed. Two large structural variants at the end of chromosome 11 affect the copy number of resistance genes between the two genomes. The availability of the two gap-free genomes lays a solid foundation for further understanding genome structure and function in plants and breeding climate-resilient varieties.
This study reports two gap-free reference genomes for Oryza sativa xian/indica varieties ZS97 and MH63, which are used as a model system for studying rice heterosis and yield. Further genomic analyses show that the architectures of functional centromeres are extensively variable at the sequence level. These two gap-free rice genomes provide a new standard for assembling reference genomes of other plant species.
The tumor immune microenvironment (TIME) has an important impact on response to cancer immunotherapy using immune checkpoint inhibitors. Specifically, an "infiltrated-excluded"/"cold" TIME is ...predictive of poor response. The antidiabetic agent metformin may influence anticancer immunity in esophageal squamous cell carcinoma (ESCC).
We analyzed matched pre- and posttreatment ESCC specimens in a phase II clinical trial of low-dose metformin treatment (250 mg/day) to evaluate direct anti-ESCC activity and TIME reprogramming. Follow-up correlative studies using a carcinogen-induced ESCC mouse model were performed with short-term (1 week) or long-term (12 weeks) low-dose metformin (50 mg/kg/day) treatment.
In the clinical trial, low-dose metformin did not affect proliferation or apoptosis in ESCC tumors as assayed by Ki67 and cleaved caspase-3 immunostaining. However, metformin reprogrammed the TIME toward "infiltrated-inflamed" and increased the numbers of infiltrated CD8
cytotoxic T lymphocyte and CD20
B lymphocyte. Further, an increase in tumor-suppressive (CD11c
) and a decrease in tumor-promoting (CD163
) macrophages were observed. Metformin augmented macrophage-mediated phagocytosis of ESCC cells
. In the ESCC mouse model, short-term metformin treatment reprogrammed the TIME in a similar fashion to humans, whereas long-term treatment further shifted the TIME toward an active state (e.g., reduction in CD4
FoxP3
regulatory T cells) and inhibited ESCC growth. In both humans and mice, metformin triggered AMPK activation and STAT3 inactivation, and altered the production of effector cytokines (i.e., TNFα, IFNγ, and IL10) in the immune cells.
Low-dose metformin reprograms the TIME to an activated status and may be a suitable immune response modifier for further investigation in patients with ESCC.
•The addition of barium ion obviously improved the flame retardancy of alginate.•The addition of barium ion changed the thermal degradation behaviors of alginate.•Pyrolysis process of barium alginate ...produced much less gaseous compounds.•Possible thermal degradation mechanism of barium alginate was proposed according to the results of TG-FTIR and Py-GC–MS.
A bio-based barium alginate film was prepared via a facile ionic exchange and casting approach. Its flammability, thermal degradation and pyrolysis behaviors, thermal degradation mechanism were studied systemically by limiting oxygen index (LOI), vertical burning (UL-94), microscale combustion calorimetry (MCC), thermogravimetric analysis (TGA) coupled with Fourier transform infrared analysis (FTIR) and pyrolysis-gas chromatography–mass spectrometry (Py-GC–MS). It showed that barium alginate film had much higher LOI value (52.0%) than that of sodium alginate film (24.5%). Moreover, barium alginate film passed the UL-94 V-0 rating, while the sodium alginate film showed no classification. Importantly, peak of heat release rate (PHRR) of barium alginate film in MCC test was much lower than that of sodium alginate film, suggested that introduction of barium ion into alginate film significantly decreased release of combustible gases. TG-FTIR and Py-GC–MS results indicated that barium alginate produced much less flammable products than that of sodium alginate in whole thermal degradation procedure. Finally, a possible degradation mechanism of barium alginate had been proposed.
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•Puerariae Lobatae Radix Flavonoids (PLF) and puerarin alleviated alcohol-induced hepatic steatosis in zebrafish larvae.•The underlying mechanism of anti-AFLD effect was that PLF and ...puerarin regulated alcohol and lipid metabolism.•PLF and puerarin affect lipid accumulation via AMPKα-ACC pathways in zebrafish larvae with AFLD.
Exessive drinking is commonly associated with a wide spectrum of liver injuries. The term alcoholic liver disease (ALD) is generally used to refer to this spectrum of hepatic abnormalities, and the term hepatic steatosis denotes early lesions. Puerariae Lobatae Radix (PLR) is a common traditional Chinese medicine and has been widely used as an efficient treatment for alcohol-induced damage. Flavonoids are the principal components of PLR that could potentially be responsible for the activation of alcohol metabolism and lipid-lowering effects. However, little is known about the mechanisms underlying their activity against alcoholic injury. In this study, PLR flavonoids (PLF) were obtained by microwave extraction. A 2% ethanol solution was used to establish a model of alcoholic fatty liver disease by exposure of zebrafish larvae for 32 h, and then the zebrafish were administered PLF and puerarin. The results showed that PLF and puerarin significantly decreased lipid accumulation and the levels of total cholesterol and triglycerides in zebrafish larvae. Moreover, PLF and puerarin downregulated the expression of genes related to alcohol and lipid metabolism (CYP2y3, CYP3a65, ADH8a, ADH8b, HMGCRB, and FASN), endoplasmic reticulum stress, and DNA damage (CHOP, EDEM1, GADD45αa, and ATF6) and reduced levels of inflammatory factors (IL-1β, TNF-α) in zebrafish larvae. PLF and puerarin increased the phosphorylation of AMP-activated protein kinase-α (AMPKα) and decreased the total protein level of ACC1. The findings suggested that PLF and puerarin alleviated alcohol-induced hepatic steatosis in zebrafish larvae by regulating alcohol and lipid metabolism, which was closely related to the regulation of the AMPKα-ACC signaling pathway. In conclusion, the study provided a possible therapeutic drug for ALD treatment.