Search

The outbreak of coronavirus disease 2019 (COVID-19) has been spreading rapidly in China and the Chinese government took a series of policies to control the epidemic. Therefore, it will be helpful to predict the tendency of the epidemic and analyze the influence of official policies. Existing models for prediction, such as cabin models and individual-based models, are either oversimplified or too meticulous, and the influence of the epidemic was studied much more than that of official policies. To predict the epidemic tendency, we consider four groups of people, and establish a propagation dynamics model. We also create a negative feedback to quantify the public vigilance to the epidemic. We evaluate the tendency of epidemic in Hubei and China except Hubei separately to predict the situation of the whole country. Experiments show that the epidemic will terminate around 17 March 2020 and the final number of cumulative infections will be about 78 191 (prediction interval, 74 872 to 82 474). By changing the parameters of the model accordingly, we demonstrate the control effect of the policies of the government on the epidemic situation, which can reduce about 68% possible infections. At the same time, we use the capital asset pricing model with dummy variable to evaluate the effects of the epidemic and official policies on the revenue of multiple industries.

Though the two-part tariff is a widely adopted pricing strategy, research on it is lacking. In this paper, we establish a model of a two-part tariff product with persuasive advertising, informative advertising, and process innovation using optimal control theory. We apply Taylor’s theorem to analyze the properties of the nonlinear dynamic system and the shooting method to solve the numerical problem. We find that the pricing strategy is consistent with a two-part tariff in the static state, with price affected only by process innovation. The relationship between the two types of advertisements is affected by the advertising spillover effect, which represents the similarity of the roles of the two types of advertisements. The more similar the roles of the advertisements are, the more likely they are to be supplemented. Meanwhile, the advertising spillover effect also indicates the quality of an advertisement. The firm with the higher advertising spillover effect is more likely to attract consumers, reducing marginal costs. Therefore, a firm should either diversify its advertisements or invest only in the one with the highest advertising spillover effect. The shooting method converges well and the numerical solution indicates that our model has a unique saddle point equilibrium.

Interleukin 37b (IL-37b) plays a key role in suppressing immune responses, partially by modulating the function of dendritic cells (DCs). However, the precise mechanisms are still largely unknown. Here, we investigated the effects of IL-37b on DC maturation and T cell responses induced by DCs, and explored the involved signaling pathways. It was found that IL-37b down-regulated the expressions of co-stimulatory molecules CD80 and CD86 on DCs in vitro. At the same time, the expressions of pro-inflammatory cytokines, such as TNF-α and IL-6, were suppressed, while the expression of the T cell inhibitory cytokine TGF-β was increased in IL-37b-treated DCs. In addition, the activation effect of DCs on T cells was impaired by IL-37b. We further revealed that extracellular single-regulated kinase (ERK), nuclear factor-κB (NF-κB), and mTOR-S6K signaling pathways were involved in the inhibition of DCs induced by IL-37b. This was confirmed by the similarly suppressive effect of chemical inhibitors against NF-κB, ERK, and S6K on the expressions of IL-6 and TNF-α in DCs. In conclusion, these results demonstrated that IL-37b suppressed DC maturation and immunostimulatory capacity in T cell priming by involving in ERK, NF-κB, and S6K-based inhibitory signaling pathways.

To comprehensively reflect the roles of Rpl11 on the transcriptome of zebrafish model of Diamond-Blackfan Anemia (DBA), we performed whole-genome transcriptome sequencing on the Illumina Hi-Seq 2000 sequencing platform. Two different transcriptomes of zebrafish Rpl11-deficient and control Morpholino (Mo) embryos were collected and analyzed. The experimental design and methods, including sample preparation, RNA-Seq data evaluation and treatment, were described in details so that representative high-throughput sequencing data were acquired for assessing the actual impacts of Rpl11 on zebrafish embryos. We provided the accession number GSE51326 for easy access to the database.

3-Mercaptopropyl acid-stabilized CdTe nanoparticles synthesized in aqueous solution are found to be able to conjugate with peptides or proteins mediated by N-hydroxysulfo-succinimide (NHS) but 1-ethyl-3(3-dimethylaminopropyl) carbodiimides hydrochloride (EDC). The reaction time and pH have been optimized. Gel-permeation HPLC was applied following the conjugation, which could quickly and simultaneously detect and purify the quantum dots (QDs) conjugates. The biological activities of QDs conjugates are maintained and give superior results in cell labeling. These results are encouraging regarding the application of QDs molecules for use in living cells, diagnostics and drug delivery.

Luminescent quantum dots (QDs) are a promising alternative to organic dyes for biomedical assays and imaging. A new conjugation method, NHS mediated conjugating, for QDs and BSA was introduced. The QDs-BSA conjugates were confirmed, and their stability has been proved. Caenorhabdilis etegans (C. etegans) were used as animal models, and the imaging of QDs in the organism was studied.

Extensive studies of the genetic aberrations related to human diseases conducted over the last two decades have identified recurrent genomic abnormalities as potential driving factors underlying a variety of cancers. Over the time, a series of cutting-edge high-throughput genetic tests, such as microarrays and next-generation sequencing, have been developed and incorporated into routine clinical practice. Although it is a classical low-throughput cytogenetic test, fluorescence in situ hybridization (FISH) does not show signs of fading; on the contrary, it plays an increasingly important role in detecting specific biomarkers in solid and hematologic neoplasms and has therefore become an indispensable part of the rapidly developing field of personalized medicine. In this article, we have summarized the recent advances in FISH application for both de novo discovery and routine detection of chromosomal rearrangements, amplifications, and deletions that are associated with the pathogenesis of various hematopoietic and non-hematopoietic malignancies. In addition, we have reviewed the recent developments in FISH methodology as well.

The abnormal expression of macrophage colony stimulating factor (M-CSF) isoforms, i.e. membrane bound M-CSF (m-M-CSF) and intracellular M-CSF (c-M-CSF), and their receptor were reported in some leukemia and tumor cells. Furthermore, the nuclear localization of them may be related to poor prognosis and metastasis, while the mechanism is uncertain. We previously reported that m-M-CSF and its receptor played auto-juxtacrine and adhesion molecule role in human leukemia cell line J6-1. In this paper, we show that HL-60 cells highly express M-CSF and its receptor. The localization of positive reactions was mainly in cytoplasma and nuclear in HL-60 cells. In cytoplasma and nuclear, three isoforms of M-CSF were found with molecular weight (MW) of 20, 16 and 14 kDa, while one type of m-CSF receptor (M-CSFR) was discovered with MW of 120 kDa. Immunoprecipitation assay showed that these ligands could exist separately or binding with their receptor. Monoclonal antibody (McAb) against M-CSF and anti-sense oligodeoxynucleotides (ASON) blocking M-CSF expression inhibited the proliferation of HL-60 cells. McAb and ASON regulated the expression of cyclin D1/E, CDK2/4 and p16. Simultaneous administration of both McAb and ASON inhibited the proliferation of HL-60 cells and modulate the expression of cyclins at greater degrees. Our results suggested an autocrine and possible an intracrine loop of M-CSF/M-CSFR in HL-60 cells.

The variable domain of heavy chain (VH) and light chain (VL) genes of anti-CD20 monoclonal antibody HI47 were cloned from anti-CD20 ScFv expression vector pCANBTEcd20 by PCR and ligated into vector pYZF to construct chimeric anti-CD20 Fab’ fragment expression vector pYZFcd20. Chimeric anti-CD20 Fab’ fragment was expressed inE. coli 16C9 and purified by protein G affinity chromatography. Competitive inhibition assay showed that anti-CD20 Fab’ fragment inhibited binding of HI47 to CD20 on the surface of Daudi cells. Results from MTT assay indicated that chimeric anti-CD20 Fab’ fragment inhibited the proliferation of Daudi cells, IC50 = 69 μg/mL. Affinity of chimeric anti-CD20 Fab’ fragment was determined, Ka was about 8.9×108 (mol/L)−1.

The binding of recombinant human macrophage colony-stimulating factor (M-CSF) soluble receptor (rh-M-CSF-sR) to membrane-bound macrophage colony stimulating factor (m-M-CSF) and the internalization and recycling of rh-M-CSF-sR/m-M-CSF complexes mediated by m-M-CSF were studied with a model of J6-1 cell line. The results indicated that m-M-CSF bound rh-M-CSF-sR with high affinity (kd = 1.78×1012 mol/L) and mediated a temperature- and energydependent internalization of rh-M-CSF-sR, and that internalized rh-M-CSF-sR could return to the cell surface in an m-M-CSF-bound state, suggesting that m-M-CSF may have a capability to mediate the internalization and recycling of rh-M-CSF-sR/m-M-CSF complexes. In addition, the half-lives of cell-associated M-CSF and its receptor of stimulated normal human cord blood mononuclear cells (CBMCs) and 4 leukemic cell lines were measured by indirect immunofluorescence and flow cytometry. The results showed that the half-lives of the various kinds of M-CSF isoforms and M-CSF-R in 4 leukemic cells, except those of membrane-bound M-CSF receptor (M-CSF-mR) of K562 and HL-60 cells, were longer than those of corresponding M-CSF isoform and its receptor in stimulated normal human CBMCs, suggesting that there is a slow degradation rate of cell-associated M-CSF and its receptor in leukemic cells.

In the present study, actions of phenothiazines (PTZ) in reversing multidrug resistance (MDR) and inhibiting PKC activity were investigated. It was found that the three PTZs caused 2.49, 36.58 and 75.78 fold reversal of K562/AO2 MDR cells resistant to adriamycin, respectively, while the chemosensitizer verapamil caused 40 fold reversal in the same condition, indicating that PTZ11 is a novel reversal agent of MDR and a potential chemotherapeutic reagent for tumor therapy. PKC activity analysis in the presence of PTZs showd that PTZ6 and PTZ11 inhibited rat brain protein kinase C activity in a manner of dose-dependent. The IC50 values were (489.77 ± 31.4) and (113 ± 9.64) μtmol/L, respectively. PTZ7 had no inhibition on PKC activity. Further study showed that PTZ11 could reduce PMA-mediated activation of PKC in a manner of dose-dependent, suggesting that PTZ11 might compete for the high-affinity phorbol ester binding site within PKC molecule. Recently, an X-ray structure of PMA in complex with PKC Cys2 activator-binding domain was solved. We therefore decided to explore the possible binding model of PTZ11 with PKC molecule using SYBYL 6.02 program. It was shown that the binding site of PTZ11 with PKC molecule partially overlapped with that of PMA, providing for the first time new data for designing PKC inhibitors and MDR reversal drugs.

Overexpressing of P-glycoprotein (Pgp) has been shown to be responsible for cancer resistance to multiple chemotherapeutic agents. Immunotherapy with biological agents, such as bispecific antibodies (BsAbs), may represent a promising approach to overcome the emergence of drug resistance. Here we constructed a recombinant BsAb, a diabody, with specificities to both CD3 on human T-lymphocyte and Pgp on cancer cells. The diabody was produced in Escherichia coli in a soluble functional form and purified by an affinity chromatography with a yield of >4 mg/l culture medium in shaker flask. The diabody binds to both CD3 on T-lymphocytes and Pgp on multidrug-resistant (MDR) tumor cells with affinities that are comparable to its respective parental single chain Fv molecules. In the presence of activated human peripheral blood lymphocytes (PBLs), the diabody mediates effectively the lysis of the Pgp-overexpressing human leukemia K562/A02 and epidermoid carcinoma KBv(200) cells, but is much less potent in mediating the lysis of the parent K562 and KB cells. Further, the diabody localized selectively within the K562/A02 xenografts in mice. When combined with activated PBL, the diabody significantly inhibited the growth of K562/A02 and KBv(200), but had no effect on K562 and KB xenografts. In contrast, treatment with doxorubicin, a standard chemotherapeutic agent, only inhibited the growth of K562 and KB, but had no effect on K562/A02 and KBv(200) xenografts. Taken together, our results suggest that the anti-Pgp x anti-CD3 diabody may have a great potential in the treatment of various MDR cancers.

Antihuman platelet tetraspanin (CD9 antigen) monoclonal antibodies, HI117 and SJ9A4, can induce human platelet aggregation and secretion. As platelet aggregation is mediated by fibrinogen binding to its receptors exposed on platelet glycoprotein IIb/IIIa complex, we, therefore, investigated the induction of platelet fibrinogen receptors by HI117 and SJ9A4. It was found that HI117 and SJ9A4 induced specific fibrinogen binding to human platelets, suggesting that the two monoclonal antibodies evoked obvious exposure of fibrinogen receptors on human platelets. But in the absence of fibrinogen, the monoclonal antibody-exposed fibrinogen receptors gradually lost their capacity to bind fibrinogen and closed. Our results also showed that HI117 and SJ9A4, when activating platelets, caused a conformational change in glycoprotein IIb/IIIa complex, which must contribute to the exposure of functional fibrinogen receptors on this integrin. The effect of HI117 and SJ9A4 on glycoprotein IIb/IIIa complex seems, however, to be indirect, because the HI1117 and SJ9A4-induced fibrinogen binding was reduced by pretreatment of platelets with sphingosine, aspirin, apyrase, and/or PGI2. Taken together, we conclude that the antihuman platelet tetraspanin monoclonal antibodies, HI117 and SJ9A4, reversibly expose platelet fibrinogen receptors via inducing a conformational change in glycoprotein IIb/IlIa complex. Three signaling pathways, that is, thromboxane, secreted ADP, and cAMP pathways may be involved in this process, while protein kinase C activation seems to be the final common step of the three pathways.