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Extracts of Stevia rebaudiana Bertoni plant leaves contain a mixture of diterpene glycosides which possess high sweetness and are used as non-caloric sweeteners in foods and beverages. One of the most abundant of these steviol glycosides is Rebaudioside C (Reb C), which bears one esterified β-D-glucose and one glycosidically linked α-L-rhamnosyl-(1→2)-[β-D-glucosyl-(1→4)]-D-glucose trisaccharide. In this work, we isolated Reb C from commercial Stevia extracts using an orthogonal normal-phase × reversed-phase purification strategy. We then demonstrated that Reb C could be used as a donor substrate for enzymatic trans glycosylation reactions using chemically synthesized 1-deoxy-1-fluoro-D-glucose and 1-deoxy-1-fluoro-D-galactose donors and two engineered glycosynthases derived from Agrobacterium and Streptomyces β-glycosidases. This chemoenzymatic glucosylation/galactosylation strategy may be of use to extend the current repertoire of steviol glycosides analogues for analysis or the sensory evaluation of these novel steviol glycosides.

Abstract Background Methamphetamine (METH) abuse causes serious health problems, including injury to the immune system, leading to increased incidence of infections and even making withdrawal more difficult. Of course, immune cells, an important part of the immune system, are also injured in methamphetamine abuse. However, due to different research models and the lack of bioinformatics, the mechanism of METH injury to immune cells has not been clarified. Methods We examined the response of three common immune cell lines, namely Jurkat, NK-92 and THP-1 cell lines, to methamphetamine by cell viability and apoptosis assay in vitro, and examined their response patterns at the mRNA level by RNA-sequencing. Differential expression analysis of two conditions (control and METH treatment) in three types of immune cells was performed using the DESeq2 R package (1.20.0). And some of the differentially expressed genes were verified by qPCR. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of differentially expressed genes by the clusterProfiler R package (3.14.3). And gene enrichment analysis was also performed using MetaScape ( www.metascape.org ). Results The viability of the three immune cells was differentially affected by methamphetamine, and the rate of NK-cell apoptosis was significantly increased. At the mRNA level, we found disorders of cholesterol metabolism in Jurkat cells, activation of ERK1 and ERK2 cascade in NK-92 cells, and disruption of calcium transport channels in THP-1 cells. In addition, all three cells showed changes in the phospholipid metabolic process. Conclusions The results suggest that both innate and adaptive immune cells are affected by METH abuse, and there may be commonalities between different immune cells at the transcriptome level. These results provide new insights into the potential effects by which METH injures the immune cells.

Cathepsin L (CTSL), a cysteine protease that can cleave and activate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, could be a promising therapeutic target for coronavirus disease 2019 (COVID-19). However, there is still no clinically available CTSL inhibitor that can be used. Here, we applied Chemprop, a newly trained directed-message passing deep neural network approach, to identify small molecules and FDA-approved drugs that can block CTSL activity to expand the discovery of CTSL inhibitors for drug development and repurposing for COVID-19. We found 5 molecules (Mg-132, Z-FA-FMK, leupeptin hemisulfate, Mg-101 and calpeptin) that were able to significantly inhibit the activity of CTSL in the nanomolar range and inhibit the infection of both pseudotype and live SARS-CoV-2. Notably, we discovered that daptomycin, an FDA-approved antibiotic, has a prominent CTSL inhibitory effect and can inhibit SARS-CoV-2 pseudovirus infection. Further, molecular docking calculation showed stable and robust binding of these compounds with CTSL. In conclusion, this study suggested for the first time that Chemprop is ideally suited to predict additional inhibitors of enzymes and revealed the noteworthy strategy for screening novel molecules and drugs for the treatment of COVID-19 and other diseases with unmet needs.

Iron–nitrogen doped carbon (Fe/N/C) electrocatalysts are among the most promising materials to replace Pt for the oxygen reduction reaction (ORR). Up to now, most work has been devoted to improving the performance of Fe/N/C catalysts by material design, while ignoring the design of the electrode/electrolyte interface environment. Considering the superior ORR performance of Fe/N/C catalysts in alkaline electrolyte, we attempt to construct a proton-deficient environment at the electrode surface to raise the local pH value. An anion-exchange ionomer with H+ blocking ability was chosen as the binder of the iron phthalocyanine (FePc) catalyst, a model molecule for Fe/N/C. The anion-exchange ionomer can increase the interface pH value as compared with commonly used Nafion binder, which was verified by the electrochemical shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) technique with CO32–/HCO3– as a probe. This strategy significantly improves the ORR activity and stability of the FePc catalyst in acidic medium.

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas9 mediated gene editing systems have been used in a variety of organisms, including plants. This system can efficiently edit target genes to generate mutants, especially multiplex mutants, which are invaluable genetic materials for gene functional studies. Although the use of traditional hybridization technology to construct multiplex mutants has been widely used in plant research, the complex screening and identification, long construction cycle and other problems have always troubled researchers. Therefore, in the current plant science research, the use of CRISPR-Cas9 mediated multiplex genome editing to construct multiplex mutants has become a mainstream technology. Here, we designed an improved plant CRISPR-Cas9 mediated multiplex genome vector system. The In-fusion cloning technology was selected to conveniently assemble multiple tandem sgRNA (Single-guide RNA) expression frames. In this system, Cas9-free plants can be easily selected by examining mCherry fluorescence in T2 transgenic plants. By using this system, Cas9-free homozygous triple mutant was obtained, demonstrating the availability of our system.

Object detection models based on convolutional neural networks (CNN) have achieved state-of-the-art performance by heavily rely on large-scale training samples. They are insufficient when used in specific applications, such as the detection of military objects, as in these instances, a large number of samples is hard to obtain. In order to solve this problem, this paper proposes the use of Gabor-CNN for object detection based on a small number of samples. First of all, a feature extraction convolution kernel library composed of multi-shape Gabor and color Gabor is constructed, and the optimal Gabor convolution kernel group is obtained by means of training and screening, which is convolved with the input image to obtain feature information of objects with strong auxiliary function. Then, the k-means clustering algorithm is adopted to construct several different sizes of anchor boxes, which improves the quality of the regional proposals. We call this regional proposal process the Gabor-assisted Region Proposal Network (Gabor-assisted RPN). Finally, the Deeply-Utilized Feature Pyramid Network (DU-FPN) method is proposed to strengthen the feature expression of objects in the image. A bottom-up and a top-down feature pyramid is constructed in ResNet-50 and feature information of objects is deeply utilized through the transverse connection and integration of features at various scales. Experimental results show that the method proposed in this paper achieves better results than the state-of-art contrast models on data sets with small samples in terms of accuracy and recall rate, and thus has a strong application prospect.

Carbon atomic layers with encapsulated transition metal nanoparticles exhibit high catalytic activity for the oxygen reduction reaction (ORR), and good tolerance for poisoning species and acid leaching. However, the active sites and catalytic mechanism are not yet clear, mainly due to the highly heterogeneous structure of encapsulated types of catalysts. In this study, we developed a new model catalyst to mimic encapsulated types of catalysts by covering the well-defined active sites of iron phthalocyanine (FePc) with a monolayer of graphene. It was found that the FePc can activate the surface carbon layer to catalyze the ORR. Unlike exposed FePc on graphene, the embedded catalyst is insensitive to poisoning by SCN− ions. The designed model catalyst demonstrates that molecular type active sites, as well as metal nanoparticles, can form encapsulated catalysts for ORR. The simple and well-defined structure of this model catalyst is helpful for investigating the active sites and the catalytic mechanism at the atomic scale. Keywords: Oxygen reduction reaction, Model catalysts, Fe/N/C, Encapsulated catalysts, FePc, Graphene

Objective: The aim of this study was to reveal the exact changes during the occurrence of breast cancer to explore significant new and promising genes or factors related to this disease. Methods: We compared the gene expression profiles of breast cancer tissues with its uninvolved normal breast tissues as controls using the cDNA microarray analysis in seven breast cancer patients. Further, one representative gene, named IFI30, was quantitatively analyzed by real-time PCR to confirm the result of the cDNA microarray analysis. Results: A total of 427 genes were identified with significantly differential expression, 221 genes were up-regulated and 206 genes were down-regulated. And the result of cDNA microarray analysis was validated by detection of IFI30 mRNA level changes by real-time PCR. Genes for cell proliferation, cell cycle, cell division, mitosis, apoptosis, and immune response were enriched in the up-regulated genes, while genes for cell adhesion, proteolysis, and transport were significantly enriched in the down-regulated genes in breast cancer tissues compared with normal breast tissues by a gene ontology analysis. Conclusion: Our present study revealed a range of differentially expressed genes between breast cancer tissues and normal breast tissues, and provide candidate genes for further study focusing on the pathogenesis and new biomarkers for breast cancer. Keywords: Breast neoplasms, Candidate genes, Microarray

In order to cope with the energy crisis, the concept of an energy internet (EI) has been proposed as a novel energy structure with high efficiency which allows full play to the advantages of multi-energy coupling. In order to adapt to the multi-energy coupled energy structure and achieve flexible conversion and interaction of multi-energy, the concept of energy routing centers (ERCs) is proposed. A two-layered structure of an ERC is established. Multi-energy conversion devices and connection ports with monitoring functions are integrated in the physical layer which allows multi-energy flow with high flexibility. As for the EI with several ERCs connected to each other, energy flows among them are managed by an energy routing controller located in the information layer. In order to improve the efficiency and reduce the operating cost and environmental cost of the proposed EI, an optimal multi-energy management-based energy routing design problem is researched. Specifically, the voltages of the ERC ports are managed to regulate the power flow on the connection lines and are restricted on account of security operations. An artificial neural network (ANN)-based reinforcement learning algorithm was proposed to manage the optimal energy routing path. Simulations were done to verify the effectiveness of the proposed method.

Tumor immunosurveillance is known to be of critical importance in controlling tumorigenesis and progression in various cancers. The role of gamma-interferon-inducible lysosomal thiol reductase (GILT) in tumor immunosurveillance has recently been studied in several malignant diseases, but its role in breast cancer remains to be elucidated. In the present study, we found GILT as a significant different expressed gene by cDNA microarray analysis. To further determine the role of GILT in breast cancer, we examined GILT expression in breast cancers as well as noncancerous breast tissues by immunohistochemistry and real-time PCR, and assessed its association with clinicopathologic characteristics and patient outcome. The absence of GILT expression increased significantly from 2.02% (2/99) in noncancerous breast tissues to 15.6% (34/218) in breast cancer tissues (P

The purpose was to investigate the prevalence rate, characteristics and related factors of breast cancer among women in Eastern China. A total of 122,058 female subjects completed the study, with 320 confirmed cases of breast cancer (crude prevalence: 262.5/100,000; standardized prevalence: 207.7/100,000). Among all of the identified breast cancer cases, 91.6% were diagnosed after the age of 35 and 60.0% were diagnosed before menopause. The odds ratios (95% confidence interval) of those breast cancer risk factors as selected through multivariate logistic regression were as follows: 5.438 (1.553-19.004) for family history of breast cancer, 3.556 (1.880-6.728) for high behavior intervention score, 3.556 (0.904-13.994) for history of diabetes, 3.357 (1.131-9.969) for history of benign breast tumors, 2.196 (1.355-3.556) for poor overall life satisfaction, 1.826 (0.995-3.350) for premenopause of breast cancer, 1.528 (1.083-2.155) for high BMI index, 1.500 (0.920-2.446) for poor financial status, 1.497 (1.014-2.211) for multiple miscarriages/abortions, and 1.231 (0.972-1.559) for infrequent consumption of garlic (frequent garlic consumption is a protective factor). There were significantly more cases of breast cancer diagnosed prior to menopause than after menopause, and most of the patients were diagnosed after the age of 35. These findings suggest that attention should be focused on the incidence of breast cancer among premenopausal women older than 35.

The title compound, [AgCd(NCS)3(C22H17N3)]n, is a heteroatom ribbon coordination polymer. The central Cd atom is chelated by the 4′-p-tolyl-2,2′:6′,2′′-terpyridine ligand and is coordinated by the N atoms of three thiocyanate ions in an octahedral geometry whereas the Ag atom is coordinated by the four S atoms of four thiocyanate ions in a distorted tetrahedral geometry. Of the three thiocyanate ions, one functions in a μ2-bridging mode and two in a μ3-bridging mode. The ribbon coordination polymer propagates along the a-axis.

The whole-genome duplication (WGD) may provide a basis for the emergence of the very characteristic life style of Saccharomyces cerevisiae-its fermentation-oriented physiology and its capacity of growing in anaerobiosis. Indeed, we found an over-representation of oxygen-responding genes in the ohnologs of S. cerevisiae. Many of these duplicated genes are present as aerobic/hypoxic(anaerobic) pairs and form a specialized system responding to changing oxygen availability. HYP2/ANB1 and COX5A/COX5B are such gene pairs, and their unique orthologs in the 'non-WGD' Kluyveromyces lactis genome behaved like the aerobic versions of S. cerevisiae. ROX1 encodes a major oxygen-responding regulator in S. cerevisiae. The synteny, structural features and molecular function of putative KlROX1 were shown to be different from that of ROX1. The transition from the K. lactis-type ROX1 to the S. cerevisiae-type ROX1 could link up with the development of anaerobes in the yeast evolution. Bioinformatics and stochastic analyses of the Rox1p-binding site (YYYATTGTTCTC) in the upstream sequences of the S. cerevisiae Rox1p-mediated genes and of the K. lactis orthologs also indicated that K. lactis lacks the specific gene system responding to oxygen limiting environment, which is present in the 'post-WGD' genome of S. cerevisiae. These data suggested that the oxygen-responding system was born for the specialized physiology of S. cerevisiae.

Auxin regulates plant growth and development through downstream signaling pathways, including the best-known SCFTIR1/AFB-Aux/IAA-ARF pathway and several other less characterized "noncanonical" pathways. Recently, one SCFTIR1/AFB-independent noncanonical pathway, mediated by Transmembrane Kinase 1 (TMK1), was discovered through the analyses of its functions in Arabidopsis apical hook development. Asymmetric accumulation of auxin on the concave side of the apical hook triggers DAR1-catalyzed release of the C-terminal of TMK1, which migrates into the nucleus, where it phosphorylates and stabilizes IAA32/34 to inhibit cell elongation, which is essential for full apical hook formation. However, the molecular factors mediating IAA32/34 degradation have not been identified. Here, we show that proteins in the CYTOKININ INDUCED ROOT WAVING 1 (CKRW1)/WAVY GROWTH 3 (WAV3) subfamily act as E3 ubiquitin ligases to target IAA32/34 for ubiquitination and degradation, which is inhibited by TMK1c-mediated phosphorylation. This antagonistic interaction between TMK1c and CKRW1/WAV3 subfamily E3 ubiquitin ligases regulates IAA32/34 levels to control differential cell elongation along opposite sides of the apical hook. [ABSTRACT FROM AUTHOR]

Background: BRCA2 plays a key role in homologous recombination. However, information regarding its mutations in Chinese patients with breast cancer remains limited. Objectives: This study aimed to assess the clinicopathological characteristics of BRCA2 mutation breast cancer and explore the mutation’s effect on hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer survival in China. Design: This hospital-based cohort study prospectively included 629 women with breast cancer diagnosed from 2008 to 2023 at Zhejiang Cancer Hospital in China. Methods: We compared the clinicopathological characteristics and metastatic patterns and analysed the invasive disease-free survival (iDFS), distant relapse-free survival (DRFS) and first-line progression-free survival (PFS1) of patients with HR-positive/HER2-negative breast cancer according to BRCA2 mutations. Results: Among the 629 patients, 78 had BRCA2 mutations (12.4%) and 551 did not (87.6%). The mean age at diagnosis was lower in the BRCA2 mutation breast cancer group than in the non-mutation breast cancer group (38.91 versus 41.94 years, p = 0.016). BRCA2 mutation breast cancers were more likely to be lymph node-positive than non-mutation breast cancers (73.0% versus 56.6%, p = 0.037). The pathological grade was higher in 47.1% of BRCA2 mutation breast cancers than in 29.6% of non-mutation breast cancers ( p = 0.014). The proportions of patients with BRCA2 mutations who developed contralateral breast cancer (19.2% versus 8.8%, p = 0.004), breast cancer in the family (53.8% versus 38.3%, p = 0.009) and ovarian cancer in the family (7.6% versus 2.4%, p = 0.022) were higher than those of patients without the mutation. The median follow-up time was 92.78 months. Multivariate analysis showed that BRCA2 mutation was not associated with poorer iDFS [hazard ratio = 0.9, 95% confidence interval (CI) = 0.64–1.27, p = 0.56] and poorer distant relapse-free survival (DRFS) (hazard ratio = 1.09, 95% CI = 0.61–1.93, p = 0.76). There was no significant difference between the two groups with regard to metastatic patterns in the advanced disease setting. In the first-line metastatic breast cancer setting, PFS1 expression was broadly similar between the two groups irrespective of chemotherapy or endocrine therapy. Conclusion: HR-positive/HER2-negative breast cancer with BRCA2 mutations differs from those without mutations in clinical behaviour and reflects more aggressive tumour behaviour. Our results indicate that BRCA2 mutations have no significant effect on the survival of Chinese women with HR-positive/HER2-negative breast cancer.

Underwater images often encounter challenges such as attenuation, color distortion, and noise caused by artificial lighting sources. These imperfections not only degrade image quality but also impose constraints on related application tasks. Improving underwater image quality is crucial for underwater activities. However, obtaining clear underwater images has been a challenge, because scattering and blur hinder the rendering of true underwater colors, affecting the accuracy of underwater exploration. Therefore, this paper proposes a new deep network model for single underwater image enhancement. More specifically, our framework includes a light field module (LFM) and sketch module, aiming at the generation of a light field map of the target image for improving the color representation and preserving the details of the original image by providing contour information. The restored underwater image is gradually enhanced, guided by the light field map. The experimental results show the better image restoration effectiveness, both quantitatively and qualitatively, of the proposed method with a lower (or comparable) computing cost, compared with the state-of-the-art approaches.