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B-cell lymphoma is the most prevalent type of non-Hodgkin lymphoma, for which the standard treatment regimen includes rituximab combined with CHOP. However, some patients may develop interstitial pneumonitis (IP), which can be caused by various factors; one of the most important factors is Pneumocystis jirovecii. It is crucial to investigate the pathophysiology of IP and implement preventive measures since IP can be fatal for some people. The data were collected from the First Affiliated Hospital, Zhejiang University School of Medicine, where patients with B-cell lymphoma received the R-CHOP/R-CDOP regimen with or without prophylactic use of trimethoprim-sulfamethoxazole (TMP-SMX). Multivariable logistic regression and propensity score matching (PSM) were used to investigate any potential association. Eight hundred thirty-one patients with B-cell lymphoma were classified into two groups: the non-prophylaxis group without TMP-SMX (n=699) and the prophylaxis group with TMP-SMX (n = 132). IP occurred in 66 patients (9.4%, all in the non-prophylaxis group), with an onset median of three cycles of chemotherapy. Multiple logistic regression analysis demonstrated that IP incidence was associated with pegylated liposome doxorubicin (OR=3.29, 95% CI 1.84–5.90, P<0.001). After utilizing a 1:1 matching algorithm for PSM, 90 patients from each group were obtained. There was a statistical difference between the two cohorts in the IP incidence (non-prophylaxis 12.2% vs prophylaxis 0.0%, P <0.001). The prophylactic use of TMP-SMX could prevent the occurrence of IP whose risk factor was pegylated liposome doxorubicin after chemotherapy for B-cell lymphoma. [ABSTRACT FROM AUTHOR]

Single-pass transmembrane receptors (SPTMRs) represent a diverse group of integral membrane proteins that are involved in many essential cellular processes, including signal transduction, cell adhesion, and transmembrane transport of materials. Dysregulation of the SPTMRs is linked with many human diseases. Despite extensive efforts in past decades, the mechanisms of action of the SPTMRs remain incompletely understood. One major hurdle is the lack of structures of the full-length SPTMRs in different functional states. Such structural information is difficult to obtain by traditional structural biology methods such as X-ray crystallography and nuclear magnetic resonance (NMR). The recent rapid development of single-particle cryo-electron microscopy (cryo-EM) has led to an exponential surge in the number of high-resolution structures of integral membrane proteins, including SPTMRs. Cryo-EM structures of SPTMRs solved in the past few years have tremendously improved our understanding of how SPTMRs function. In this review, we will highlight these progresses in the structural studies of SPTMRs by single-particle cryo-EM, analyze important structural details of each protein involved, and discuss their implications on the underlying mechanisms. Finally, we also briefly discuss remaining challenges and exciting opportunities in the field. [ABSTRACT FROM AUTHOR]

Overhead contact systems are important power supply equipments for electrified railway locomotives. If there are faults in the equipment, it will threaten the safety of train operation. Dropper faults and foreign matter are two common types of Overhead contact systems faults, the fault regions of which occupy a relatively small area in the whole image, so it is difficult to detect the faults accurately by capturing detailed features using original Faster R-CNN. To solve the above problem, an improved Faster R-CNN based on convolutional neural networks, named multi-view Faster R-CNN, is proposed in order to extract more details of the fault regions by combining deep and shallow feature maps. Experiments on the images collected from the Lanzhou-Xinjiang Railway line show that the feature fusion can significantly enhance the mean average precision. The precision of our model on the test set was 89.53%, increasing by 3.5%, 9.65%, and 5.8% compared with YOLOv3, SSD, and Faster R-CNN, and the detection accuracies of our model for unforced droppers and foreign matter were 88.17% and 90.60%, respectively, under a recall rate of almost 1.0. Because the multi-view feature fusion model in our method can flexibly detect faults with various sizes, it has an important application value in the fault detection of an overhead contact system. [ABSTRACT FROM AUTHOR]

This article mainly focuses on the most common types of high-speed railways malfunctions in overhead contact systems, namely, unstressed droppers, foreign-body invasions, and pole number-plate malfunctions, to establish a deep-network detection model. By fusing the feature maps of the shallow and deep layers in the pretraining network, global and local features of the malfunction area are combined to enhance the network's ability of identifying small objects. Further, in order to share the fully connected layers of the pretraining network and reduce the complexity of the model, Tucker tensor decomposition is used to extract features from the fused-feature map. The operation greatly reduces training time. Through the detection of images collected on the Lanxin railway line, experiments result show that the proposed multiview Faster R-CNN based on tensor decomposition had lower miss probability and higher detection accuracy for the three types faults. Compared with object-detection methods YOLOv3, SSD, and the original Faster R-CNN, the average miss probability of the improved Faster R-CNN model in this paper is decreased by 37.83%, 51.27%, and 43.79%, respectively, and average detection accuracy is increased by 3.6%, 9.75%, and 5.9%, respectively. [ABSTRACT FROM AUTHOR]

Background: Androgenic alopecia (AGA) is the most common type of hair loss, in which dihyrotestosterone (DHT) plays a crucial role via modulating androgen receptors in hair follicles. Aims: The current objective is to search for new therapy of AGA. Methods: In the present study, we investigated the effects of sulforaphane, its precursor glucosinlates and glucosinlates‐enriched Brassica oleracea L.var.italic Planch extract (BOE) on the growth of hair follicle and the related matrix cell viability, as well as the possible underlying mechanisms in vitro and ex vivo. Results: We observed that BOE, glucosinlates, and sulforaphane can prevent the testosterone‐induced inhibition of dermal papilla (DP) cells viability. BOE and sulforaphane can even hinder the testosterone‐induced inhibition of HaCaT cells viability. Moreover, BOE, glucosinlates, and sulforaphane can up‐regulate the cytokeratin gene expression in HaCaT cells, prevent the increase in Bax gene levels induced by testosterone in DP, and promote the growth of hair follicle of mice. These effects can be linked to the enhancement of DP and HaCaT cells activities and the prevention of the testosterone‐induced cell apoptosis of DP cells. Conclusions: Taken together, BOE, glucosinlates, and sulforaphane can promote the growth of hair follicle of mice and can be used as potential treatment agents for androgenic alopecia. [ABSTRACT FROM AUTHOR]

STING is a critical adaptor protein in the cGAS-mediated DNA-sensing innate immune pathway. Binding of the second messenger cGAMP generated by cGAS to STING induces the high-order oligomerization and activation of the STING dimer. STING is a promising target for diseases associated with the cGAS/STING pathway such as cancer and autoimmune diseases. Recent applications of cryo-EM to STING have led to exciting progress in the understanding of its regulatory mechanism. Cryo-EM structures of STING bound to either cGAMP mimetics or novel small molecule ligands not only revealed the action mechanisms of these ligands but also suggested new ways to modulate the activity of STING for therapeutic purposes. Some of these recent studies are highlighted here. [ABSTRACT FROM AUTHOR]

IKZF1 belongs to the IKAROS family of transcription factors, and its deletion/mutation frequently affects acute lymphoblastic leukemia. In acute myeloid leukemia, IKZF1 deletion has been demonstrated recurrent, but whether IKZF1 mutation also exists in AML remained largely unknown. Herein, we analyzed the IKZF1 mutation in AML. In our cohort, the frequency of IKZF1 mutation was 2.6% (5/193), and 5 frameshift/nonsense mutations as well as 2 missense mutations were identified in total. Molecularly, IKZF1 mutation was absent in fusion gene-positive AML, but it was demonstrated as the significant concomitant genetic alteration with SF3B1 or bi-alleleCEBPA mutation in AML. Clinically, two IKZF1, PTPN11 and SF3B1-mutated AML patients exhibited one aggressive clinical course and showed primary resistant to chemotherapy. Furthermore, we confirmed the recurrent IKZF1 mutation in AML with cBioPortal tool from OHSU, TCGA and TARGET studies. Interestingly, OHSU study also showed that SF3B1 mutation was the significant concomitant genetic alteration with IKZF1 mutation, indicating their strong synergy in leukemogenesis. In conclusion, IKZF1 mutation recurrently affected AML. [ABSTRACT FROM AUTHOR]

Cyclophosphamide (CP) is widely used in clinical fields. Beside its therapeutic effects, CP shows toxicity depending on dose and administration schedule. In this study, the urinary metabolic profiles were investigated in mice intraperitoneally injected with high-dose CP (150 mg/kg body weight) once a week over four weeks using nuclear magnetic resonance (NMR)-based metabolomics. Twenty-six metabolites were identified as potential biomarkers by multivariate statistical analysis. A decrease in isoleucine, alanine, N-acetylglutamic acid, proline, methionine, valine, phenylacetylglulamine, dimethylamine, hippurate, acetic acid, lactate, α-oxoglutarate, citrate, malonic acid, creatinine, niacin, β-hydroxybutyrate, and betaine, whereas an increase in leucine, glutamate, glycine, taurine, phenylacetylglycine, glucose, creatine, and choline were observed in the urine of high-dose CP-treated mice. Metabolites related to amino acid metabolism, energy metabolism, and gut microbial metabolism were changed markedly in the urine. Further metabolic pathway analysis suggested that seven metabolic pathways, including alanine, aspartate, and glutamate metabolism, arginine biosynthesis, glyoxylate, and dicarboxylate metabolism, glycine, serine and threonine metabolism, d -glutamine and d -glutamate metabolism, arginine, and proline metabolism, citrate cycle, as well as the gut microbiota metabolism, were significantly involved in response to high-dose CP treatment. These findings help to predict the toxicity of CP and understand the biological mechanism of the toxicity of CP. [Display omitted] • Cyclophosphamide-related toxic urinary biomarkers were analyzed by NMR-based metabolomics. • Twenty-six altered urinary metabolites were identified. • Seven metabolic pathways and gut microbiota metabolism were involved in response to cyclophosphamide. [ABSTRACT FROM AUTHOR]

This paper proposes a new virus spreading model, susceptible-infected-susceptible-recovered-susceptible, which is based on partial immunization and immune invalidity in a complex network. On the basis of mean-field theory, the epidemic dynamics behavior of this model in a uniform network and a scale-free network is studied. After modifying the formula for the effective spread rate, we obtain the theoretical result that the coexistence of partial immunization and immune failure does not affect the network spread threshold. At the same time, the experimental results show that the existence of the above two conditions greatly increases the spread of the virus and extends the diffusion range. The study also found that in the scale-free network, peak viral infection occurs at the beginning of the spreading process, and after the immunization strategy is applied, the early infection peak is effectively curbed. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection is a leading cause of chronic liver diseases and hepatocellular carcinoma (HCC) and Golgi protein 73 (GP73) is a serum biomarker for liver diseases and HCC. However, the mechanism underlying GP73 regulates HCV infection is largely unknown. Here, we revealed that GP73 acts as a novel negative regulator of host innate immunity to facilitate HCV infection. GP73 expression is activated and correlated with interferon-beta (IFN-β) production during HCV infection in patients’ serum, primary human hepatocytes (PHHs) and human hepatoma cells through mitochondrial antiviral signaling protein (MAVS), TNF receptor-associated factor 6 (TRAF6) and mitogen-activated protein kinase kinase/extracellular regulated protein kinase (MEK/ERK) pathway. Detailed studies revealed that HCV infection activates MAVS that in turn recruits TRAF6 via TRAF-interacting-motifs (TIMs), and TRAF6 subsequently directly recruits GP73 to MAVS via coiled-coil domain. After binding with MAVS and TRAF6, GP73 promotes MAVS and TRAF6 degradation through proteasome-dependent pathway. Moreover, GP73 attenuates IFN-β promoter, IFN-stimulated response element (ISRE) and nuclear factor κB (NF-κB) promoter and down-regulates IFN-β, IFN-λ1, interleukin-6 (IL-6) and IFN-stimulated gene 56 (ISG56), leading to the repression of host innate immunity. Finally, knock-down of GP73 down-regulates HCV infection and replication in Huh7-MAVSR cells and primary human hepatocytes (PHHs), but such repression is rescued by GP73m4 (a mutant GP73 resists to GP73-shRNA#4) in Huh7-MAVSR cells, suggesting that GP73 facilitates HCV infection. Taken together, we demonstrated that GP73 acts as a negative regulator of innate immunity to facilitate HCV infection by interacting with MAVS/TRAF6 and promoting MAVS/TRAF6 degradation. This study provides new insights into the mechanism of HCV infection and pathogenesis, and suggests that GP73 is a new potential antiviral target in the prevention and treatment of HCV associated diseases. [ABSTRACT FROM AUTHOR]

BACKGROUND Spirulina platensis is an excellent source of proteins (>60%) that can be hydrolyzed into bioactive peptides. RESULTS In this study, whole proteins of Spirulina platensis were extracted and hydrolyzed using three gastrointestinal endopeptidases (pepsin, trypsin and chymotrypsin). Subsequently, gel filtration chromatography was employed to separate hydrolysates, and four fractions (Tr1-Tr4) were obtained. Among them, Tr2 showed the strongest anti-proliferation activities on three cancer cells ( MCF-7, HepG-2 and SGC-7901), with IC50 values of <31.25, 36.42 and 48.25 µg mL−1, respectively. Furthermore, a new peptide, HVLSRAPR, was identified from fraction Tr1. This peptide exhibited strong inhibition on HT-29 cancer cells with an IC50 value of 99.88 µg mL−1. CONCLUSION Taken together, these peptides possessed anti-proliferation activities on cancer cells and low cytotoxicity on normal cells, suggesting that they might serve as a natural anticancer agent for nutraceutical and pharmaceutical industries. © 2016 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

In this study, Arthrospira platensis proteins were hydrolyzed using sequential digestion with alcalase/papain. Gel filtration chromatography was used to separate hydrolysates and five fractions D1-D5 were obtained. D1 showed the strongest antitumor effects on MCF-7 and HepG-2 cells, with the IC values of <31.25 and 49.36 μg mL, respectively. Subsequently, three small peptides with antitumor activities, including AGGASLLLLR, LAGHVGVR, and KFLVLCLR, were identified. The truncated peptide LCLR exhibited better activity than its parent peptide KFLVLCLR, with the inhibition rate of >60 % on MCF-7 and HepG-2 cells, but little cytotoxicity on L-O2 cells (∼6 %), at 500 μg mL. Moreover, D1 was confirmed to inhibit solid tumor growth in HepG-2-bearing nude mice, with the best inhibition achieved at day 11, up to 39.75 % at the dosage of 200 mg kg day. Taken together, the identified peptides possessed potent antitumor activities but low cytotoxicity on normal cells and could be used as nutraceuticals and pharmaceuticals. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection is one of the leading causes of chronic liver diseases and hepatocellular carcinoma (HCC). Golgi protein 73 (GP73), a resident Golgi membrane protein, is a novel serum biomarker for the diagnosis of liver diseases and HCC. Although previous studies have demonstrated that HCV upregulates GP73 expression and GP73 promotes HCV secretion through its interaction with apolipoprotein E (ApoE), the exact mechanism underlying GP73 regulates HCV secretion remains unclear. In this study, we demonstrated that GP73 mediates the interaction of ApoE with HCV NS5A protein to promote HCV secretion. We revealed that GP73 is colocalized with HCV replication complex in infected-Huh7.5.1 cells. Further studies demonstrated that GP73 interacted with both NS5A and ApoE proteins. Furthermore, knockdown of GP73 significantly reduced the binding of NS5A with ApoE, and the production of virus particles in culture supernatant. Taken together, our studies revealed that GP73 promotes HCV secretion by directly mediating the interaction of ApoE with HCV replication complex through binding with HCV NS5A. [ABSTRACT FROM AUTHOR]

Feature selection of text is one of the basic matters for intelligent classification of text. Textual feature generating algorithm adopts weighted textual vector space model generally at present. This model uses BP network evaluation function to calculate weight value of single feature and textual feature redundancy generated in this algorithm is high generally. For this problem, a textual feature generating algorithm based on clustering weighting is adopted. This new method conducts initial weighted treatment for feature candidate set first of all and then conducts further weighted treatment of features through semantic and information entropy and it removes redundancy features with features clustering at last. Experiment shows that the average classification accuracy rate of this algorithm is about 5% higher than that of traditional BP network algorithm. [ABSTRACT FROM AUTHOR]

MicroRNA 155 (miR-155) is a key proinflammatory regulator in clinical and experimental rheumatoid arthritis (RA). Here we generated a miR-155 genome knockout (GKO) RAW264.7 macrophage cell line using the clustered regulatory interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (CAS9) technology. While upregulating the Src homology-2 domain-containing inositol 5-phosphatase 1 (SHIP1), the miR-155 GKO line is severely impaired in producing proinflammatory cytokines but slightly increased in osteoclastogenesis upon treatment with receptor activator of nuclear factor-κB ligand (RANKL). Taken together, our results suggest that genome editing of miR-155 holds the potential as a therapeutic strategy in RA. [ABSTRACT FROM AUTHOR]

Online social networks have become embedded in our everyday lives so much that we cannot ignore it. One specific area of increased interest in social networks is that of detecting overlapping communities: instead of considering online communities as autonomous islands acting independently, communities are more like sprawling cities bleeding into each other. The assumption that online communities behave more like complex networks creates new challenges, specifically in the area of size and complexity. Algorithms for detecting these overlapping communities need to be fast and accurate. This research proposes method for detecting non-overlapping communities by using a CNM algorithm, which in turn allows us to extrapolate the overlapping networks. In addition, an improved index for closeness centrality is given to classify overlapping nodes. The methods used in this research demonstrate a high classification accuracy in detecting overlapping communities, with a time complexity of O( n 2 ). [ABSTRACT FROM AUTHOR]

Cyclophosphamide (CP) is the most commonly used drug in autoimmune disease, cancer, blood and marrow transplantation. Recent data revealed that therapy efficacy of CP is gut microbiota-dependent. So, it is very important to understand how CP affects intestinal microbiota and immune function. In this study, the effects of CP on mice immuno-activity were firstly evaluated, then, the fecal microbiota from normal and CP-treated mice was compared, and the characteristic bacterial diversity and compositions were identified, using 454 pyrosequencing technology. The results showed that CP reduced the diversity and shifted the fecal microbiota composition. Specifically, CP treatment decreased the proportion of Bacteroidetes while increased the proportion of Firmictutes in the microbial community. Most importantly, specific microbiota signatures belonging to Bacteroides acidifaciens , Streptococcaceae and Alistipes were also identified, which would provide new insight into the efficacy and side effects in clinical usage of CP. This should be helpful for further demonstration of CP's action mechanism, development of personalized therapy strategies, and prediction of potential side effects related to various treatment regimens of CP. [ABSTRACT FROM AUTHOR]

Lentinula edodes-derived polysaccharides possess many therapeutic characteristics, including anti-tumor and immuno-modulation. The gut microbes play a critical role in modulation of immune function. However, the impact of Lentinula edodes-derived polysaccharides on the gut microbes have not yet been explored. In this study, high-throughput pyrosequencing technique was employed to investigate the effects of a new heteropolysaccharide L2 from Lentinula edodes on microbiota diversity and composition of small intestine, cecum, colon and distal end of colon (feces) in mice. The results demonstrated that along mouse intestine the microbiota exhibit distinctly different space distribution. L2 treatment reduced the diversity and evenness of gut microbiota along the intestine, especially in the cecum and colon. In the fecal microbial communities, the decrease of Bacteroidetes by significantly increasing Proteobacteria were observed, which were characterized by the increased Helicobacteraceae and reduced S24-7 at family level. Some OTUs, corresponding to Bacteroides acidifaciens, Alistipes and Helicobacter suncus, were found to be significantly increased in L2 treated-mice. In particular, 4 phyla Chloroflexi, Gemmatimonadetes, Nitrospirae and Planctomycetes are exclusively present in L2-treated mice. This is helpful for further demonstrating healthy action mechanism of Lentinula edodes-derived polysaccharide L2. [ABSTRACT FROM AUTHOR]

The regulation of the guidance receptor plexin is incompletely understood. In this issue, Kong et al. (2016) present crystal structures of the full-length extracellular region of class A plexins, revealing its dual role in both autoinhibition and activation. [ABSTRACT FROM AUTHOR]

Objective To evaluate the safety of tumor necrosis factor-α ( TNF-α) monoclonal antibody (infliximab) therapy in patients with rheumatoid arthritis ( RA) and previous exposure to hepatitis B virus ( HBV) who had normal liver function. Methods This is a retrospective study from a 26-week, prospective, multicenter trial in 234 patients with RA who received infusions of infliximab (3 mg/kg at week 0, 2, 6, 14 and 22). The medical records of these patients were reviewed, including the information on disease duration, laboratory tests and HBV markers. The data on liver function during the study was analyzed, as well as comparison between patients with previous exposure to HBV and patients without such exposure. Results Forty-one patients with previous exposure to HBV were HBsAg(-). Forty patients had normal alanine aminotransferase ( ALT) and aspartate aminotransferase ( AST) and only one patient with positive anti- HBc showed an elevated ALT level before administration of infliximab, and had a further increase of ALT level at week 14, but decreased thereafter. The average ALT and AST levels rose slightly during the treatment but remained in normal range and the differences were insignificant compared with baseline. There was no statistically significant difference in the incidence of liver function abnormalities during the treatment of infliximab between the patients with previous exposure to HBV and those without such exposure. Conclusion In patients with RA and previous exposure to HBV but with a negative HBsAg and normal liver function at baseline, liver function abnormalities were not observed during infliximab treatment. [ABSTRACT FROM AUTHOR]

In this study, for the first time, the applications of two new methods, ionic liquid and low-temperature high-pressure cell breakage methods, to the extraction of whole proteins in Chlorella pyrenoidosa cells were explored. Meanwhile, the comparison with three traditional methods was also made. The results indicated that the extraction rate for ionic liquid is only at moderate level, but the new low-temperature high-pressure cell breakage method can obviously increase the protein extraction rate up to 2- to 15-fold. Subsequently, the hydrolysis of the extracted proteins was conducted with three enzymes (papain, trypsin and alcalase). The data presented that the degree of hydrolysis for each enzyme under the optimal conditions is in the order of: alcalase (18.31%) > papain (14.33%) > trypsin (8.47%), demonstrating the potential of C. pyrenoidosa protein hydrolysates obtained here in nutritional supplement and medical foods. [ABSTRACT FROM AUTHOR]

Sacha inchi meal (SIM) is a by-product of sacha inchi (considered as a "super-food") processing. In previous studies, we found that SIM protein hydrolysates exhibited pancreatic lipase inhibition activity. In this study, 10 bioactive peptides from those hydrolysates were identified. The top five peptides (NLYYKVV (NV-7), WWYVK (WK-5), WLLMWPYK (WK-8), EGLLMWPY (EY-8), and FPFFGYVWK (FK-9)) with strong pancreatic lipase inhibition activity had IC50 values of 34.01–246.50 µM, and displayed various inhibition types (mixed, non-competitive, and competitive type) by enzyme inhibition kinetics analysis. Fluorescence quenching analysis demonstrated that the interaction between the peptides and pancreatic lipase was mainly hydrogen bond and van der Waals force. The key residues involved in the peptide–enzyme interaction were determined by molecular docking. Moreover, the top two peptides were found to significantly inhibit fat accumulation and regulate lipid metabolism by alleviating the level of reactive oxygen species in HepG2 cells. Collectively, sacha inchi meal-derived peptides displayed potent lipid-lowering activity and could be used as materials of functional food. [ABSTRACT FROM AUTHOR]

In contrast to the active conformations of protein kinases, which are essentially the same for all kinases, inactive kinase conformations are structurally diverse. Some inactive conformations are, however, observed repeatedly in different kinases, perhaps reflecting an important role in catalysis. In this review, we analyze one of these recurring conformations, first identified in CDK and Src kinases, which turned out to be central to understanding of how kinase domain of the EGF receptor is activated. This mechanism, which involves the stabilization of the active conformation of an α helix, has features in common with mechanisms operative in several other kinases. [Copyright &y& Elsevier]

Abstract: Epidermal growth factor receptor (EGFR) and its family members, ErbB2, ErbB3 and ErbB4, are receptor tyrosine kinases which send signals into the cell to regulate many critical processes including development, tissue homeostasis, and tumorigenesis. Central to the signaling of these receptors is their intracellular kinase domain, which is activated by ligand-induced dimerization of the receptor and phosphorylates several tyrosine residues in the C-terminal tail. The phosphorylated tail then recruits other signaling molecules and relays the signal to downstream pathways. A model of the autoinhibition, activation and feedback inhibition mechanisms for the ErbB kinase domain has emerged from a number of recent structural studies. Meanwhile, recent clinical studies have revealed the relationship between specific ErbB kinase mutations and the responsiveness to kinase inhibitor drugs. We will review these regulation mechanisms of the ErbB kinase domain, and discuss the binding specificity of kinase inhibitors and the effects of kinase domain mutations found in cancer patients from a structural perspective. [Copyright &y& Elsevier]

Abstract: A key scientific objective of nutrition research is to determine the role of diet in metabolic regulation and to improve health. There are many new opportunities and challenges for the nutrition research in post-genome era. Novel omics technologies and bioinformatics tools offer enormous potential to investigate the complex relationship between nutrition and metabolism. An overview of omics technologies in nutrition research is presented in this paper, which focuses on recent applications of nutritranscriptomics, nutriproteomics and nutrimetabolomics in nutrition research. The potential limitations and future prospects are also discussed. The combination of various omics technologies, systems biology, will greatly facilitate the discovery of new biomarkers associated with specific nutrients or other dietary factors. It can be expected that the future omics-based human nutrition research can provide personalized dietary recommendations for disease prevention. [Copyright &y& Elsevier]

To improve treatment and reduce the mortality from cancer, a key task is to detect the disease as early as possible. To achieve this, many new technologies have been developed for biomarker discovery and validation. This review provides an overview of omics technologies in biomarker discovery and cancer detection, and highlights recent applications and future trends in cancer diagnostics. Although the present omic methods are not ready for immediate clinical use as diagnostic tools, it can be envisaged that simple, fast, robust, portable and cost-effective clinical diagnosis systems could be available in near future, for home and bedside use. [Copyright &y& Elsevier]

Summary: The mechanism by which the epidermal growth factor receptor (EGFR) is activated upon dimerization has eluded definition. We find that the EGFR kinase domain can be activated by increasing its local concentration or by mutating a leucine (L834R) in the activation loop, the phosphorylation of which is not required for activation. This suggests that the kinase domain is intrinsically autoinhibited, and an intermolecular interaction promotes its activation. Using further mutational analysis and crystallography we demonstrate that the autoinhibited conformation of the EGFR kinase domain resembles that of Src and cyclin-dependent kinases (CDKs). EGFR activation results from the formation of an asymmetric dimer in which the C-terminal lobe of one kinase domain plays a role analogous to that of cyclin in activated CDK/cyclin complexes. The CDK/cyclin-like complex formed by two kinase domains thus explains the activation of EGFR-family receptors by homo- or heterodimerization. [Copyright &y& Elsevier]

Abstract: We recently published experimental results that indicated Aurintricarboxylic Acid (ATA) could selectively inhibit SARS-CoV replication inside host cells by greater than 1000 times. This inhibition suggested that ATA could be developed as potent anti-viral drug. Here, to extend our experimental observation, we have incorporated protein structural studies (with positive/negative controls) to investigate the potential binding modes/sites of ATA onto RNA-dependent RNA polymerase (RdRp) from SARS-CoV and other pathogenic positive-strand RNA-viruses, as well as other proteins in SARS-CoV based on the fact that ATA binds to Ca2+-activated neutral protease (m-calpain), the protein tyrosine phosphatase (PTP) and HIV integrase which have existing crystal structures. Eight regions with homologous 3D-conformation were derived for 10 proteins of interest. One of the region, R binding (754–766 in SARS-CoV''s RdRp), located in the palm sub-domain mainly constituted of anti-parallel β-strand-turn-β-strand hairpin structures that covers two of the three RdRp catalytic sites (Asp 760, Asp761), was also predicted by molecular docking method (based on free energy of binding ΔG) to be important binding motif recognized by ATA. The existence of this strictly conserved region that incorporated catalytic residues, coupled with the homologous ATA binding pockets and their consistent ΔG values, suggested strongly ATA may be involved in an analogous inhibition mechanism of SARS-COV''s RdRp in concomitant to the case in m-calpain, PTP and HIV integrase. [Copyright &y& Elsevier]

PD-1, a member of the CD28/CTLA-4/ICOS costimulatory receptor family, delivers negative signals that have profound effects on T and B cell immunity. The 2.0 A˚ crystal structure of the extracellular domain of murine PD-1 reveals an Ig V-type topology with overall similarity to the CTLA-4 monomer; however, there are notable differences in regions relevant to function. Our structural and biophysical data show that PD-1 is monomeric both in solution as well as on cell surface, in contrast to CTLA-4 and other family members that are all disulfide-linked homodimers. Furthermore, our structure-based mutagenesis studies identify the ligand binding surface of PD-1, which displays significant differences compared to those present in the other members of the family. [Copyright &y& Elsevier]

The cell-mediated immune response involves a series of specific molecular interactions between cell surface molecules on T cells and antigen-presenting cells. Of particular importance for the regulation of T cell activity is the interaction of the B7 isoforms, B7-1 and B7-2, with the T cell surface costimulatory receptors, CD28 and CTLA-4. The binding of CD28 by B7-1/B7-2 results in an enhancement of T cell responses initiated by the interaction between a clonotypic T cell receptor and its specific, antigenic MHC-peptide complex, whereas the subsequent engagement of CTLA-4 by B7-1/B7-2 leads to a down-regulation of the response. Here we report the expression, refolding, purification, characterization, and crystallization of the receptor-binding domain of human B7-2. The receptor-binding domain of human B7-2 was overexpressed in Escherichia coli as inclusion bodies, solubilized in 6 M guanidine-hydrochloride, and then refolded in vitro by rapid dilution into a renaturing buffer. Refolded B7-2 was subsequently purified to homogeneity by anion-exchange chromatography. Gel-filtration chromatography and native PAGE analysis showed that the receptor-binding domain of B7-2 is exclusively monomeric in solution. Purified B7-2 binds tightly to bacterially expressed monomeric and disulfide-linked homodimeric human CTLA-4 as shown by gel-filtration chromatography and native PAGE. This suggests that glycosylation is not important for the proper folding of the receptor-binding domain of B7-2 nor for its binding to CTLA-4. In addition, these results suggest that refolded B7-2 is biologically active and may be a useful therapeutic and experimental reagent for regulating T cell activity. Refolded and purified B7-2 was crystallized by the hanging-drop vapor diffusion method, allowing for the initiation of an X-ray crystallographic study. [Copyright &y& Elsevier]

Recent studies have highlighted the structural requirements for T cell costimulation and have revealed unusual modes of dimerization for the cytolytic T lymphocyte-associated antigen 4 (CTLA-4) costimulatory receptor and its B7 ligands. These distinctive quaternary structures potentially endow both receptor and ligand with bivalent binding properties, which suggests a number of mechanistic features relevant to signaling. These include the potential to form a highly ordered, alternating network of CTLA-4 and B7 homodimers that may represent the organization of these molecules and their associated signaling partners within the immunological synapse. Primary sequence and structural considerations suggest that some aspects of the organizational and mechanistic features associated with the CTLA-4-B7 complexes may extend to other members of the costimulatory receptor-ligand family. An examination of the signaling mechanisms within the costimulatory receptor-ligand family provides an excellent framework to consider the general principles that are relevant to cell surface receptor-mediated signaling events. [ABSTRACT FROM AUTHOR]

Primary liver cancer (PLC) is the second leading cause of cancer mortality worldwide, and its morbidity unceasingly increases these years. Hepatitis B virus (HBV) infection accounted for approximately 50% of hepatocellular carcinoma (HCC) cases globally in 2015. Due to the lack of an effective model to study HBV-associated liver carcinogenesis, research has made slow progress. Organoid, an in vitro 3D model which maintains self-organization, has recently emerged as a powerful tool to investigate human diseases. In this review, we first summarize the categories and development of liver organoids. Then, we mainly focus on the functions of culture medium components and applications of organoids for HBV infection and HBV-associated liver cancer studies. Finally, we provide insights into a potential patient-derived organoid model from those infected with HBV based on our study, as well as the limitations and future applications of organoids in liver cancer research. [ABSTRACT FROM AUTHOR]

Due to the high transmission rate and high pathogenicity of the novel coronavirus (COVID-19), there is an urgent need for the diagnosis and treatment of outbreaks around the world. In order to diagnose quickly and accurately, an auxiliary diagnosis method is proposed for COVID-19 based on federated learning and blockchain, which can quickly and effectively enable collaborative model training among multiple medical institutions. It is beneficial to address data sharing difficulties and issues of privacy and security. This research mainly includes the following sectors: in order to address insufficient medical data and the data silos, this paper applies federated learning to COVID-19's medical diagnosis to achieve the transformation and refinement of big data values. With regard to third-party dependence, blockchain technology is introduced to protect sensitive information and safeguard the data rights of medical institutions. To ensure the model's validity and applicability, this paper simulates realistic situations based on a real COVID-19 dataset and analyses problems such as model iteration delays. Experimental results demonstrate that this method achieves a multiparty participation in training and a better data protection and would help medical personnel diagnose coronavirus disease more effectively. [ABSTRACT FROM AUTHOR]

In this study, 16 marine shellfish proteins were selected for in silico hydrolysis. The binding abilities of the obtained oligopeptides to the two targets (COVID-19 spike protein and type 2 diabetes mellitus-related alpha-glucosidase) were evaluated. The results showed that 3 oligopeptides (PICQF, VIDVW, SVGPW) were identified as dual binders to the two targets. The in vitro test confirmed their inhibitory activities on alpha-glucosidase (19.58%, 23.02%, and 21.09%, respectively), which are close to drug Acarbose (21.87%), at the concentration of 1.5 mM. In conclusion, some marine shellfish-derived oligopeptides could be used as lead compounds to design potential inhibitors against COVID-19 and T2DM. [ABSTRACT FROM AUTHOR]

This study was to investigate the inhibitory activity of small hairtail-related peptides (VFEVFW, LPNSLYQQ, LPNSLYQK, and FADAME) on intracellular monoamine oxidase-A (MAO-A) and their protective effects in a cell model. Specifically, the inhibition activity in SH-SY5Y cells indicated that VFEVFW and LPNSLYQK reduced ∼50% of MAO-A activity in cells, at 0.5 m  m. The survival experiment demonstrated that the toxic effect of dexamethasone (DEX) on cells can be significantly alleviated in the presence of peptides, and these peptides can restore (>20%) the mitochondrial membrane potential of SH-SY5Y cells reduced by DEX. Circular dichroism displayed that peptides affected the secondary structure of MAO-A in a concentration-dependent manner. Finally, the real-time quantitative polymerase chain reaction assay revealed that the MAO-A inhibitory activity of the peptides was associated with the upregulation of brain derived neurotrophic factor/cAMP (Cyclic adenosine monophosphate) response element binding protein)/B-cell lymphoma-2 mRNA levels. [ABSTRACT FROM AUTHOR]

Clostridium difficile infection (CDI) is increasing in incidence and severity. Clinically, diarrhea frequently occurs, but severe hematochezia is rarely seen with CDI. We describe here a hematopoietic stem cell transplantation (HSCT) recipient who experienced life-threatening gastrointestinal bleeding due to severe CDI. Subsequent stool surveillance and molecular typing observed the patient who had two episodes of recurrence with a new strain of C. difficile distinct from the initial infection. We analyze C. difficile strains obtained from the patient, and also discuss the diagnosis and treatment of this case. [ABSTRACT FROM AUTHOR]

Mahonia bealei (Fortune) Carrière (M. bealei) is a traditional medicine widely used by the Hmong community in Guizhou. It possesses diverse biological activities and shows promise in cancer treatment; however, contemporary pharmacological research in this area is lacking. This study aimed to investigate the effects and underlying mechanisms of M. bealei on alcoholic hepatocellular carcinoma (HCC). We initially employed the LC-MS/MS method to identify the compounds present in M. bealei serum. Subsequently, its potential targets were predicted using public databases. Bioinformatics and network pharmacology approaches, such as univariate Cox regression and random forest (RF) algorithms, were utilized to identify differentially expressed genes (DEGs) associated with the prognosis of alcoholic HCC. Survival curve and receiver operating characteristic (ROC) analyses were conducted using alcoholic HCC-related data from TCGA and GEO to determine the diagnostic value of the identified DEGs. Molecular docking using the CDOCKER approach based on CHARMm was performed to validate the affinity between the predictive compounds and targets. Additionally, we evaluated the impact of M. bealei on cell proliferation, migration, and conducted western blot assays. The LC-MS/MS approach identified 17 therapeutic components and predicted 483 component-related targets, of which 63 overlapped with alcoholic HCC targets and were considered potential therapeutic targets. GO and KEGG pathway analysis revealed significant associations between the 63 overlapping targets and alcoholic HCC progression. Through various approaches in the Cytoscape 3.9.0 software, we confirmed 9 hub genes (CDK1 , CXCR4 , DNMT1 , ESR1 , KIT , PDGFRB , SERPINE1 , TOP2A , and TYMS) as core targets. TOP2A and CDK1 genes were identified as advantageous for diagnosing alcoholic HCC using univariate Cox regression, RF, survival curve, and ROC analysis. Molecular docking analysis demonstrated strong binding affinity between key bioactive components cyclamic acid, perfluoroalkyl carboxylic acid, perfluorosulfonic acid, alpha-linolenic acid, adenosine receptor antagonist (CGS 15943), and Prodigiosin and TOP2A and CDK1. In vitro experiments confirmed that M. bealei significantly suppressed cell proliferation and migration of HepG2 cells, while downregulating TOP2A and CDK1 expression. This study highlights the potential of M. bealei as a natural medicine for the treatment of alcoholic HCC. Six compounds (cyclamic acid, perfluoroalkylic carboxylic acids, perfluorosulfonic acid, alpha-linolenic acid, adenosine receptor antagonist (CGS 15943), and Prodigiosin) present in M. bealei serum may exhibit therapeutic effects against alcoholic HCC by downregulating CDK1 and TOP2A expression levels in vitro. [Display omitted] [ABSTRACT FROM AUTHOR]

A correction is presented to the article "GP73 represses host innate immune response to promote virus replication by facilitating MAVS and TRAF6 degradation".

With the advent of software-defined networking, network configuration through programmable interfaces becomes practical, leading to various on-demand opportunities for network routing update in multi-tenant datacenters, where tenants have diverse requirements on network routings such as short latency, low path inflation, large bandwidth, high reliability, etc. Conventional solutions that rely on topology search coupled with an objective function to find desired routings have at least two shortcomings: ${\sf (i)}$(i) they run into scalability issues when handling consistent and frequent routing updates and ${\sf (ii)}$(ii) they restrict the flexibility and capability to satisfy various routing requirements. To address these issues, this paper proposes a novel search and optimization decoupled design, which not only saves considerable topology search costs via search result reuse, but also avoids possible sub-optimality in greedy routing search algorithms by making decisions based on the global view of all possible routings. We implement a prototype of our proposed system, OpReduce, and perform extensive evaluations to validate its design goals. [ABSTRACT FROM AUTHOR]

Bacillus coagulans has a potential role in improving intestinal injury. However, the specific mechanism is still unclear. In this study, the protective effect of B. coagulans MZY531 on intestinal mucosa injury in cyclophosphamide (CYP)-induced immunosuppressed mice were investigated. The results indicated that the immune organ (thymus and spleen) indices of B. coagulans MZY531 treatment groups were significantly increased compared to the CYP group. B. coagulans MZY531 administration promotes the expression of immune proteins (IgA, IgE, IgG, and IgM). B. coagulans MZY531 could upregulate the ileum levels of IFN-γ, IL-2, IL-4, and IL-10 in immunosuppressed mice. Moreover, B. coagulans MZY531 restores the villus height and crypt depth of the jejunum and alleviates injury of intestinal endothelial cells caused by CYP. Furthermore, the western blotting results showed that B. coagulans MZY531 ameliorated CYP-induced intestinal mucosal injury and inflammatory via up-regulates the ZO-1 pathway and down-regulates the expression of the TLR4/MyD88/NF-κB pathway. After treatment with B. coagulans MZY531, the relative abundance of Firmicutes phylum was dramatically increased, as well as the genera of Prevotella and Bifidobacterium, and reducing harmful bacteria. These findings suggested that B. coagulans MZY531 has a potential immunomodulatory activity on chemotherapy-induced immunosuppression. [ABSTRACT FROM AUTHOR]

Due to the rigid cell wall of Chlorella species, it is still challenging to effectively extract significant amounts of protein. Mass methods were used for the extraction of intracellular protein from microalgae with biological, mechanical and chemical approaches. In this study, based on comparison of different extraction methods, a new protocol was established to maximize extract amounts of protein, which was involved in ethanol soaking, enzyme digest, ultrasonication and homogenization techniques. Under the optimized conditions, 72.4% of protein was extracted from the microalgae Chlorella pyrenoidosa , which should contribute to the research and development of Chlorella protein in functional food and medicine. [ABSTRACT FROM AUTHOR]

BACKGROUND: Sacha inchi meal (SIM) is a by‐product of oil processing. Our previous studies showed that SIM hydrolysates exhibited dipeptidyl peptidase‐IV (DPP‐IV) inhibition activity. The objective of the present work was to identify and characterize the bioactive peptides from protein hydrolysates of SIM; enzyme kinetics and peptide–enzyme interaction were also investigated. RESULTS: From SIM hydrolysates, ten peptides responsible for the activity were identified: GPSRGF (GF‐6), FPILSPDPA (FA‐9), APYRRGGKI (AI‐9), WPYH (WH‐4), DPATWLALPT (DT‐10), NPEDEFRQQ (NQ‐9), APESKPVGV (AV‐9), LEWRDR (LR‐6), APVYWVQ (AQ‐7) and LLMWPY (LY‐6). The IC50 values of five peptides (GF‐6, WH‐4, AQ‐7, AV‐9 and LY‐6) with better inhibitory activity on DPP‐IV were within the range of 23.43–128.40 μmol L−1. AQ‐7 had the best activity, with an IC50 value of 23.43 μmol L−1. Enzyme kinetics indicated the presence of various inhibition types (mixed, non‐competitive and competitive). Isothermal titration microcalorimetry showed that the main forces of the binding sites between peptide (GF‐6 or AQ‐7) and DPP‐IV were hydrogen bond, hydrophobic interaction and van der Waals force. The key residues involved in peptide–enzyme interaction were determined by molecular docking. Furthermore, at a concentration of 800 μmol L−1, GF‐6 was found to significantly increase the glucose consumption in insulin‐resistant HepG2 cells (P < 0.05) compared with the model group. CONCLUSION: Sacha inchi meal‐derived peptides displayed potent DPP‐IV inhibition activity and could be used in the health food industry and as lead compounds for diabetes therapy. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

In this paper, a fast pre-classified-based super-resolution model has been proposed to overcome the problems of degraded imaging in weak-target real-time detection system, specialized to copper defect detection. To accurately characterize the defected image, textural features based on the statistical function of gray-gradient are presented. Furthermore, to improve the effectiveness and practicality of the online detection, a concept of pre-classified learning is introduced and an edge smoothness rule is designed. Some experiments are carried out on defect images in different environments and the experimental results show the efficiency and effectiveness of the algorithm. [ABSTRACT FROM AUTHOR]

Compound K (CK) is the metabolite and final active ingredient of diol-type ginsenosides. In this study, we investigated the effect of CK on mitochondrial apoptosis in SMMC-7721 and BEL-7404 cells and the regulatory mechanism through in vitro and in vivo experiments. The results demonstrated that CK inhibited Hepatocellular carcinoma (HCC) cells proliferation and arrested the cells in G0/G1 phase. CK induces mitochondrial apoptosis in HCC cells and inhibited p-ERK expression. Bcl-2 associated transcription factor 1 (Bclaf1) was distributed in the nucleus and cytoplasm, and CK inhibited its expression. Treatment of a nude mouse xenograft model bearing SMMC-7721 cells with CK decreased the expression of Bclaf1, p-ERK, and Bcl-2 but increased that of Bax. In summary, ginsenoside CK downregulated Bclaf1 expression, inhibited the activation of the ERK pathway, and triggered mitochondrial apoptosis in HCC. These findings uncovered a potential therapeutic strategy leveraging the anti-tumor effects of CK against HCC. [ABSTRACT FROM AUTHOR]

Curcumin, a kind of natural compound extracted from the rhizome of Zingiberaceae such as turmeric, has many pharmacological effects such as anti-cancer effects. This study investigated the effect of curcumin on the invasion and metastasis of hepatocellular carcinoma (HCC) cell lines HepG2 and SK-Hep-1 through the Wnt/β-catenin signalling pathway and the regulatory mechanism of Bcl-2-associated transcription factor 1 (Bclaf1). Curcumin significantly inhibited the migration and invasion of HepG2 and SK-Hep-1 cells and inhibited the Wnt/β-catenin signalling pathway and reduced Bclaf1 expression in human hepatoma cells. In nude mice, intraperitoneal injection of curcumin significantly inhibited the growth of subcutaneously transplanted tumours and reduced lung metastasis of the tumour cells, downregulated the expression of Bclaf1, and inhibited the Wnt/β-catenin pathway. This study suggests that curcumin is a novel candidate drug to prevent cancer metastasis and that Bclaf1 is a new gene target related to the proliferation, invasion, and metastasis of hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

aim of this study is to evaluate patients' preferences for self-injection devices in RA, and to elicit their willingness to pay (WTP) for injector devices in China. Methods: RA patients were recruited from Beijing, Shanghai, Guangzhou, Chengdu, Wuhan and Xi'an in China. A discrete choice experiment (DCE) was employed to elicit patient preferences. Patients were presented with 15 choice sets that consisted of seven attributes, which were developed based on literature review and further validated by physicians. The seven attributes were as follows: operation steps, injection pain, feedback indication, needle visibility, needle protection, size and out-of-pocket costs. A mixed logit model was used to analyze the relative importance of seven attributes and to calculate the WTP for a changed attribute level. Results: Analyses included 114 adults with RA (mean age of 44.6 years old). When choosing the injection device, all attributes had significant influence. Among nonmonetary attributes, very slight injection pain was the most preferred for patients, followed by auto-injection method, thicker size, hidden needle, with needle protection and multiple feedback indication. Patients had a negative preference for increasing out-of-pocket costs. Patients were willing to pay CNY 45.26 for improving slight injection pain to very slight injection pain, CNY 13.26 for the auto-injection method, CNY 12.22 for the thicker size, CNY 10.06 for the hidden needle, CNY 9.82 for needle protection, and CNY 9.70 for multiple feedback indicators. Conclusion: The results suggested that injection pain was the most important attribute for RA patients. Meanwhile, all other enhanced attributes of self-injection devices also significantly influence patients' selection on injection devices. Findings suggested that there is significant potential value in developing self-injection devices that could further help improve treatment adherence and promote patient-centered care in autoimmune diseases. [ABSTRACT FROM AUTHOR]

Fecal microbial transplantation provides a high curative rate for recurrent Clostridium difficile infection (CDI). However, limitations associated with FMT drive the need to identify key taxa for selective probiotic therapy for prevention, treatment and cure of human CDI. CDI-associated changes in gut microbiota were investigated in adult patients in the Western countries and among infant population in China. However, there has been no such study involving adult patients in China. Therefore, using high throughput sequencing of the 16S ribosomal RNA V3 region and real-time quantitative polymerase chain reaction, we identified CDI-associated key taxa by comparing the fecal microbiota composition of 15 adult patients with CDI with those of 18 individuals with C. difficile -negative nosocomial diarrhea (CDN) and 25 healthy control subjects. Reduced fecal bacterial diversity and dramatic shifts of intestinal microbial composition in CDI and CDN groups were observed compared with healthy controls. Putative butyrate-producing anaerobic bacteria were significantly depleted whereas endotoxin-producing opportunistic pathogens and lactate-producing phylotypes increased dramatically in patients with CDI compared with healthy controls. Further screening of specific microbes causing diarrheal diseases and resistance against CDI is necessary. [ABSTRACT FROM AUTHOR]

Aim: The objective of this study was to identify proteomic biomarkers specific for rheumatoid arthritis (RA) by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) in combination with weak cationic exchange (WCX) magnetic beads. Methods: Serum samples from 50 patients with RA and 110 disease controls (50 SLE and 60 SS) and 51 healthy individuals were analyzed. The samples were randomly divided into a training set or test set to develop a diagnostic model for RA. Results: A total of 83 protein peaks were identified to be related with RA, in which four of the peaks with mass-charge ratio (m/z) at 8133.85, 5844.60, 13 541.3 and 14 029.0 were selected to establish a model for diagnosis of RA. This classification model could separate patients with RA from diseased and healthy controls with sensitivity of 84.0% and specificity of 92.5%, and its accuracy was confirmed in the blind testing set with high sensitivity and specificity of 80.0% and 93.3%, respectively. Conclusions: This study suggested that potential serum biomarkers for RA diagnosis could be discovered by MALDI-TOF-MS. The classification tree model set up in this study might be used as a novel diagnostic tool for RA. [ABSTRACT FROM AUTHOR]