The mechanisms of Yu Ping Feng San in tracking the cisplatin-resistance by regulating ATP-binding cassette transporter and glutathione S-transferase in lung cancer cells

Cisplatin is one of the first line anti-cancer drugs prescribed for treatment of solid tumors; however, the chemotherapeutic drug resistance is still a major obstacle of cisplatin in treating cancers. Yu Ping Feng San (YPFS), a well-known ancient Chinese herbal combination formula consisting of Astragali Radix, Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix, is prescribed as a herbal decoction to treat immune disorders in clinic. To understand the fast-onset action of YPFS as an anti-cancer drug to fight against the drug resistance of cisplatin, we provided detailed analyses of intracellular cisplatin accumulation, cell viability, and expressions and activities of ATP-binding cassette transporters and glutathione S-transferases (GSTs) in YPFS-treated lung cancer cell lines. In cultured A549 or its cisplatin-resistance A549/DDP cells, application of YPFS increased accumulation of intracellular cisplatin, resulting in lower cell viability. In parallel, the activities and expressions of ATP-binding cassette transporters and GSTs were down-regulated in the presence of YPFS. The expression of p65 subunit of NF-κB complex was reduced by treating the cultures with YPFS, leading to a high ratio of Bax/Bcl-2, i.e. increasing the rate of cell death. Prim-O-glucosylcimifugin, one of the abundant ingredients in YPFS, modulated the activity of GSTs, and then elevated cisplatin accumulation, resulting in increased cell apoptosis. The present result supports the notion of YPFS in reversing drug resistance of cisplatin in lung cancer cells by elevating of intracellular cisplatin, and the underlying mechanism may be down regulating the activities and expressions of ATP-binding cassette transporters and GSTs

Identification of Multiple Cracks in Composite Laminated Beams Using Perturbation to Dynamic Equilibrium

Identification of cracks in beam-type components is significant to ensure the safety of structures. Among the approaches relying on mode shapes, the concept of transverse pseudo-force (TPF) has been well proved for single and multiple crack identification in beams made of isotropic materials; however, there is a noticeable gap between the concept of TPF and its applications in composite laminated beams. To fill this gap, an enhanced TPF approach that relies on perturbation to dynamic equilibrium is proposed for the identification of multiple cracks in composite laminated beams. Starting from the transverse equation of motion, this study formulates the TPF in a composite laminated beam for the identification of multiple cracks. The capability of the approach is numerically verified using the FE method. The applicability of the approach is experimentally validated on a carbon fiber-reinforced polymer laminated beam with three cracks, the mode shapes of which are acquired through non-contact vibration measurement using a scanning laser vibrometer. In particular, a statistic manner is utilized to enable the approach to be feasible to real scenarios in the absence of material and structural information; besides, an integrating scheme is utilized to enable the approach to be capable of identifying cracks even in the vicinity of nodes of mode shapes

Transient extra copy of Y chromosome without driver mutation after autologous hematopoietic stem cell transplantation for acute myeloid leukemia: a case report and literature review

Therapy-related myeloid neoplasms (t-MNs) are associated with chemotherapy, radiotherapy, or autologous hematopoietic stem cell transplantation (auto-HSCT). Clonal abnormalities after auto-HSCT are not rare and do not always indicate t-MNs. We describe a rare case of transient clonal chromosomal abnormality after auto-HSCT for acute myeloid leukemia (AML). In this case, an extra copy of the Y chromosome accompanied by slight bone marrow dysplasia lasted for approximately 11 months and disappeared without therapy. Genetic testing of 236 hematologic malignancies showed no somatic mutations. From previously reported literature, 10 cases with the appearance of clonal chromosomal abnormalities after auto-HSCT for AML were analyzed. Six of these cases presented with persistent chromosomal abnormalities that did not develop t-MNs, one presented with inv(16) associated with therapy-related AML, and the remaining three presented with transient abnormalities. Most persistent or transient clonal chromosomal abnormalities occurring after auto-HSCT for AML could indicate a good prognosis

Investigations of brain-wide functional and structural networks of dopaminergic and CamKIIα-positive neurons in VTA with DREADD-fMRI and neurotropic virus tracing technologies

Abstract Background The ventral tegmental area (VTA) contains heterogeneous cell populations. The dopaminergic neurons in VTA play a central role in reward and cognition, while CamKIIα-positive neurons, composed mainly of glutamatergic and some dopaminergic neurons, participate in the reward learning and locomotor activity behaviors. The differences in brain-wide functional and structural networks between these two neuronal subtypes were comparatively elucidated. Methods In this study, we applied a method combining Designer Receptors Exclusively Activated by Designer Drugs (DREADD) and fMRI to assess the cell type-specific modulation of whole-brain neural networks. rAAV encoding the cre-dependent hM3D was injected into the right VTA of DAT-cre or CamKIIα-cre transgenic rats. The global brain activities elicited by DREADD stimulation were then detected using BOLD-fMRI. Furthermore, the cre-dependent antegrade transsynaptic viral tracer H129ΔTK-TT was applied to label the outputs of VTA neurons. Results We found that DREADD stimulation of dopaminergic neurons induced significant BOLD signal changes in the VTA and several VTA-related regions including mPFC, Cg and Septum. More regions responded to selective activation of VTA CamKIIα-positive neurons, resulting in increased BOLD signals in VTA, Insula, mPFC, MC_R (Right), Cg, Septum, Hipp, TH_R, PtA_R, and ViC_R. Along with DREADD-BOLD analysis, further neuronal tracing identified multiple cortical (MC, mPFC) and subcortical (Hipp, TH) brain regions that are structurally and functionally connected by VTA dopaminergic and CamKIIα-positive neurons. Conclusions Our study dissects brain-wide structural and functional networks of two neuronal subtypes in VTA and advances our understanding of VTA functions

Sequential Recommender via Time-aware Attentive Memory Network

Recommendation systems aim to assist users to discover desirable contents from an ever-growing corpus of items. Although recommenders have been greatly improved by deep learning, they still face several challenges: (1) behaviours are much more complex than words in sentences, so traditional attention and recurrent models have limitations capturing the temporal dynamics of user preferences. (2) The preferences of users are multiple and evolving, so it is difficult to integrate long-term memory and short-term intent. In this paper, we propose a temporal gating methodology to improve the attention mechanism and recurrent units, so that temporal information can be considered for both information filtering and state transition. Additionally, we propose a hybrid sequential recommender, named Multi-hop Time-aware Attentive Memory network (MTAM), to integrate long-term and short-term preferences. We use the proposed time-aware GRU network to learn the short-term intent and maintain prior records in user memory. We treat the short-term intent as a query and design a multi-hop memory reading operation via the proposed time-aware attention to generate user representation based on the current intent and longterm memory. Our approach is scalable for candidate retrieval tasks and can be viewed as a non-linear generalisation of latent factorisation for dot-product based Top-K recommendation. Finally, we conduct extensive experiments on six benchmark datasets and the experimental results demonstrate the effectiveness of our MTAM and temporal gating methodology