Retraction Note: The role of apatinib combined with paclitaxel (aluminum binding type) in platinum-resistant ovarian cancer

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13048-021-00785-1.

Handling

This chapter asks how readers in this period physically handled books containing verse. Handling is explored through three qualities which significantly affect it: size, shape, and weight. The chapter explores some epistemological problems with the concept of size in the study of medieval manuscripts, and then offers the largest quantitative survey yet published of size and shape in manuscripts containing Middle English verse. Size evidence provides a broad overview of the ways in which particular texts might have been read. The shapes of books, meanwhile, appear to have been affected by literary form. The chapter then turns to weight, with the first ever survey of the weight of manuscripts from this period which retain period bindings. This survey reveals that the portability of poetry cannot be inferred simply from size or binding type, but must instead be worked out by considering size, shape, materials, and binding together. The chapter’s conclusions indicate how deeply embedded thought about form and the anticipation of future reading were in the production of manuscripts containing Middle English verse.

The role of Apatinib combined with Paclitaxel (aluminum binding type) in drug-resistant ovarian cancer

Objective To assess the antitumor effects and side reactions of different dosages of Paclitaxel (albumin binding) combined with Apatinib in drug-resistant ovarian cancer cell line and xenotransplantation tumor model. Methods Conventional cell experiments were used to evaluate the effects of Apatinib and Paclitaxel (albumin binding), SKOV-3/DDP were selected as research object and divided into 3 groups for study, a): control group, no drug intervention; b): nab-P group, Paclitaxel (albumin binding type) 40 µmol/l; c): Apatinib group, Apatinib 50 µmol/l. The IC-50 value of the drug was detected by MTT test, apoptosis related protein(Bax, bcl-2), vascular related protein(p-VEGFR-2), invasion related protein(MMP-2) expression were detected by Western blot and Cellular immunofluorescence, the invasion and migration ability of tumor cells were detected by Transwell and Cell scratch test. Based on these dates, establishing different dosages of Paclitaxel (albumin binding type) combined with Apatinib, a): Control group, no drug intervention; b): Group-1, Paclitaxel (albumin binding type) 5 µmol/l + Apatinib 10 µmol/l, c): Group-2, Paclitaxel (albumin binding type) 4.5 µmol/l + Apatinib 10 µmol/l, d): Group-3, Paclitaxel (albumin binding type)4 µmol/l + Apatinib 10 µmol/l, the index of combined use was analyzed by Compusyn software, Western blot, Immunofluescence, Transwell, Cell scratch test also were chose to change of inhibition effect. On the other hand, we used xenograft tumor model to verify the results in vivo. BALB/c female nude mice were randomly divided into 4 groups, a): Control group, no drug intervention; b): Paclitaxel (albumin binding type) 20 mg/kg + Apatinib 150 mg/kg, c): Paclitaxel (albumin binding type) 18 mg/kg + Apatinib 150 mg/kg, d): Paclitaxel (albumin binding type) 16 mg/kg + Apatinib 150 mg/kg. The tumor growth curve was analyzed during the test. The apoptosis related protein (Bax, bcl-2), angiogenesis related protein (CD31, p-VEGFR-2) and invasion related protein(MMP-2) were analyzed by Western blot, Immunofluescence and Immunohistochemistry to analysis the effect of antitumor and side reactions Result (1) The IC-50 value of SKOV-3/DDP to paclitaxel (albumin binding type) was 45.53 ± 4.06 µmol/l, while the role of Apatinb was 50.66 ± 4.96umol/L(48 h). (2) the expressions of bcl-2(nab-P group, AP group), p-VEGFR-2(AP group), MMP-2(nab-P group, AP group) were higher than Control group, while Bax(nab-P group, AP group) lower (P < 0.01). (3) The invasion and migration of the cells decreased after the nab-P and AP treatment(P < 0.01). (4) nab-P combined with AP can increased their antitumor effect, according to Compusyn software, CL < 1. (5) After combined with AP, when nab-P were reduced dose in proper quantity, there were no obvious different in drug effect. (6) Reduced nab-P can increased nude mice’s quality of life. Conclusion Paclitaxel (albumin binding type), a chemotherapeutic agent, can play an anti-tumor role in drug-resistant ovarian cancer, but it can also reduce the tumor load and increase the expression of tumor vascular endothelial growth factor. When combined with Apatinib, the target drug of anti vascular endothelial growth factor, the two drugs have synergistic effect, which can improve the effect of single drug. In addition, when combined with Apatinib, the dosage of Paclitaxel (albumin binding type) can be appropriately reduced under the standard of recommended dosage to reduce the toxicity of chemotherapy drugs, without affecting the anti-tumor effect.

Multilateralism 2.0: It Is Here—Are We Ready for It?

This article argues that one of the key questions—or even the key question—of our times is how to foster enhanced compatibility between national policy-making sovereignty and effective multilateral cooperation. There are multiple reasons for this. First, given the growing importance of global public good-type policy challenges and the rising trend toward multipolarity, the relationships among countries are now de facto marked by universal multilateralism. International cooperation is no longer only an option, as it conventionally was (especially for the major powers), but a compulsion. This new, binding type of multilateralism is called here “multilateralism 2.0” to distinguish it from the conventional, more optional type of multilateralism. Second, necessary systematic reforms to make global governance fit for the new reality of multilateralism 2.0 are still lacking, because states value their sovereignty. However, a persuasive reform vision and reform leadership have not yet emerged; currently, uncertainty exists about how to have both sovereignty and effective cooperation. The world is experiencing a “Kindleberger moment”: crisis and no leadership. Accordingly, this article offers concrete suggestions on possible ways forward. It suggests that the most important and urgent reform is to forge consensus on a new principle: the “dual-compatibility principle” calling for a commitment of states to (i) more sovereignty-compatible multilateral cooperation and (ii) an exercise of national policy-making sovereignty that is more compatible with multilateral cooperation. To clearly see the critical importance of this principle, a prior, eminently doable reform step is needed: widening the analytical lens of multilateralism to capture both the “real” and the “political” sides of this phenomenon and to recognize that the former is, in effect, the independent variable and the latter the dependent one.

Design, Synthesis and Cytotoxicity Study of Primary Amides as Histone Deacetylase Inhibitors

Primary amide derivatives as histone deacetylase inhibitors (HDACIs) are very rare. This paper describes the synthesis of primary amide derivatives (compounds 6 and 7) that have the requirements to be histone deacetylase inhibitors of the zinc-binding type. Both of them exhibited good cytotoxicity against the tested cancer cell lines with much lower cytotoxicity against normal cell line.

Genome-wide identification and analyses of bHLH family genes in Brassica napus

The bHLH (basic/helix-loop-helix) protein is one of the largest transcription factors (TFs) that is essential in regulating plant growth and development. Although the bHLH family has been identified in some organisms, a systemic study has not been performed in Brassica napus, which is the third most important oilseed crop worldwide. In the present study, a total of 460 bHLH TFs were identified from the genome of B. napus and clustered into 25 subfamilies. Structural analysis was used to identify the DNA binding type and conserved amino residues of the identified sequence in the bHLH domain. In addition, a comparative genomic analysis of B. napus and its progenitors (Brassica rapa and Brassica oleracea) and two basal angiosperms (Amborella trichopoda and Vitis vinifera) was performed to trace the change during expansion and evolution of the bHLH family. The bHLH TFs in leaves and roots showed various expression patterns. The homologs of the AA-subgenome and CC-subgenome exhibited similar expression patterns, but were more divergent between the homologs caused from other duplicate events.

Defining a new nomenclature for the structures of active and inactive kinases

Targeting protein kinases is an important strategy for intervention in cancer. Inhibitors are directed at the active conformation or a variety of inactive conformations. While attempts have been made to classify these conformations, a structurally rigorous catalog of states has not been achieved. The kinase activation loop is crucial for catalysis and begins with the conserved DFGmotif. This motif is observed in two major classes of conformations, DFGin—a set of active and inactive conformations where the Phe residue is in contact with the C-helix of the N-terminal lobe—and DFGout—an inactive form where Phe occupies the ATP site exposing the C-helix pocket. We have developed a clustering of kinase conformations based on the location of the Phe side chain (DFGin, DFGout, and DFGinter or intermediate) and the backbone dihedral angles of the sequence X-D-F, where X is the residue before the DFGmotif, and the DFG-Phe side-chain rotamer, utilizing a density-based clustering algorithm. We have identified eight distinct conformations and labeled them based on the Ramachandran regions (A, alpha; B, beta; L, left) of the XDF motif and the Phe rotamer (minus, plus, trans). Our clustering divides the DFGin group into six clusters including BLAminus, which contains active structures, and two common inactive forms, BLBplus and ABAminus. DFGout structures are predominantly in the BBAminus conformation, which is essentially required for binding type II inhibitors. The inactive conformations have specific features that make them unable to bind ATP, magnesium, and/or substrates. Our structurally intuitive nomenclature will aid in understanding the conformational dynamics of kinases and structure-based development of kinase drugs.