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Introduction: The chemoresistance mechanism of diffuse large B-cell lymphoma (DLBCL) is still poorly understood, and patient prognosis remains unsatisfactory. This study aimed to investigate drug resistance mechanisms in non-germinal center B-cell-like (non-GCB) DLBCL. Methods: Doxorubicin (DOX)-resistant OCI-Ly3 cells were generated through long-term incubation of cells in a medium with gradually increasing DOX concentrations. The expression levels of genes related to drug metabolism were determined using a functional gene grouping polymerase chain reaction (PCR) array. Drug-resistant proteins were identified using bioinformatics, and molecular association networks were subsequently generated. The association and mechanism of key genes were determined using a dual-luciferase reporter assay System and chromatin immunoprecipitation (ChIP). The expression of drug-resistant genes and target genes was then measured using Western blotting and immunohistochemistry. The correlation between gene expressions was analyzed using Spearman's rank correlation coefficient. Results: Using the PCR array, MDR1 was identified as the key gene that regulates DOX resistance in OCI-Ly3/DOX-A100, a non-GCB DLBCL cell line. The dual-luciferase reporter assay system demonstrated that MDR1 transcription could be inhibited by PRDM1. ChIP results showed that PRDM1 had the ability to bind to the promoter region (−1,132 to −996) of MDR1. In OCI-Ly3/DOX cells, NF-κB activity and PRDM1 expression decreased with an increase in drug-resistant index, whereas MDR1 expression increased with enhanced drug resistance. Immunohistochemical analysis revealed that relative MDR1 expression was higher than that of PRDM1 in human DLBCL tissue samples. A negative correlation was observed between MDR1 and PRDM1. Conclusion: In non-GCB DLBCL cells, NF-κB downregulates PRDM1 and thereby promotes MDR1 transcription by terminating PRDM1-induced transcriptional inhibition of MDR1. Such a mechanism may explain the reason for disease recurrence in non-GCB DLBCL after R-CHOP or combined CHOP with bortezomib treatment. Our findings may provide a potential therapeutic strategy for reducing drug resistance in patients with DLBCL. [ABSTRACT FROM AUTHOR]

Keywords: asthma; eczema; environmental composite quality index score; rhinitis EN asthma eczema environmental composite quality index score rhinitis 1875 1879 5 06/18/21 20210601 NES 210601 Abbreviations COF cooking oil fume ECQI environmental composite quality index Asthma and allergy in childhood are common chronic diseases worldwide.1 Over the last few decades, the incidence of asthma and allergy among children increases year by year around the world,2 especially in developing countries. In the analyses for thirteen pollutants (outdoor components and indoor components) of the ECQI, distance from the factory (<=500 m) and distance from the chimney (<=500 m) were positively associated with the risk of asthma, eczema, and rhinitis. The risk of housing along the street and rhinitis was 1.47 (95% CI; 1.02-2.12), and the risk between polluting heating fuel and asthma was 2.34 (95% CI; 1.12-4.88). Our results showed that compared with a low ECQI score, a positive relationship among the risk of asthma and allergy, increasing with the accumulation of indoor and outdoor risk factors. [Extracted from the article]

Purpose: This study aimed to predict the presence and mechanism of busulfan drug-drug interactions (DDIs) in hematopoietic stem cell transplantation (HSCT) using pharmacokinetic interaction (PKI) network–based molecular structure similarity and network pharmacology. Methods: Logistic function models were established to predict busulfan DDIs based on the assumption that an approved drug tends to interact with the drug used in HSCT (DH) if structurally similar to the drugs in the PKI network of the DH. The PKI network of the DH represented the association between drugs and the proteins related to the PK of the DH. The most appropriate model was applied to predict busulfan DDIs in HSCT. Candidate targets for busulfan DDIs and their interacting were identified by network pharmacology. Results: Six of the top ten predicted busulfan DDIs were clinically relevant and involved voriconazole, fludarabine, itraconazole, cyclophosphamide, metronidazole, and melphalan. Candidate targets for these DDIs were CYP450s (3A4, 2B6, 2C9, and 2C19), GSTs (GSTA1, GSTP1, GSTT1, and GSTM1), and ABC transporters (ABCB1, ABCC1, ABCC2, and ABCC3), in the targets of drug-induced liver injury (DILI). The networks of interacting proteins and candidate targets indicated the regulatory potential of pregnane X receptor (PXR), as a nuclear receptor. Enrichment analysis showed the metabolism of drugs and xenobiotics, glutathione metabolism, and bile secretion associated with busulfan DDIs and DILI. Conclusions: This study has successfully predicted busulfan DDIs in HSCT through PKI-based molecular structure similarity. The mechanism of busulfan DDI and DILI was attributed mostly to CYP450s, GSTs, and ABC transporters, and PXR was identified as a potential target. [ABSTRACT FROM AUTHOR]

In recent years, deep convolutional neural networks have played an increasingly important role in single-image super-resolution (SR). However, with the increase of the depth and width of networks, the super-resolution methods based on convolution neural networks are facing training difficulties, memory consumption, running slowness and other problems. Furthermore, most of the methods do not make full use of the image gradient information which leads to the loss of geometric structure information of the image. To solve these problems, we propose a gradient information distillation network in this paper. On the one hand, the advantages of fast and lightweight are maintained through information distillation. On the other hand, the SR performance is improved by gradient information. Our network has two branches named gradient information distillation branch (GIDB) and image information distillation branch. To combine features in both branches, we also introduce a residual feature transfer mechanism (RFT). Under the function of GIDB and RFT, our network can retain the rich geometric structure information which can make the edge details of the reconstructed image sharper. The experimental results show that our method is superior to the existing methods while well limits the parameters, computation and running time of the model. It provides the possibility for real-time image processing and mobile applications. [ABSTRACT FROM AUTHOR]

Carbon fibre (CF) is one of the most effective materials in improving the conductivity of the composites by developing a conductive network within the matrix, which also enhanced the piezoresistivity behaviour of the cementitious composites and has a potential application for structural health monitoring. A systematic study of the effect of sizing condition and fibre length on the piezoresistivity behaviour of cementitious composites by adopting unsized CF with the length of 3, 6 and 12 mm, and desized CF of 6 and 12 mm as functional fillers. Each type of CF was added at four different weight fractions of 0.1, 0.3, 0.5 and 0.7% to determine the optimal fibre content. Electrical resistivity and piezoresistivity tests were conducted for samples before and after drying treatment to evaluate the effect of water content on electrical properties. Besides, fresh properties of the fresh mixture, mechanical properties and microstructure of the composites were also investigated. Results showed that unsized CF is more effective in enhancing composites flexural strength and reducing the electrical resistivity, which also showed a stronger bonding with the cement matrix and also demonstrated a better dispersive ability. In terms of piezoresistivity behaviour, for a given fibre length, desized CF showed higher sensitivity and repeatability compared to unsized CF; however, the signals showed more noise. The best piezoresistivity behaviour was obtained for composites containing 3 mm CF at 0.7 wt%, which showed a fractional change in resistivity (FCR) value of approximately 70%. An equation was developed, which can successfully describe the relationship between the FCR of cementitious composites containing CF and the applied external stress. [ABSTRACT FROM AUTHOR]

Magnetism in double perovskite oxides of the formula A2BB'O6 has been a subject of great interest and intensive research in condensed matter physics. In this paper, Ln2CuRuO6 (A = La, Pr) samples were synthesized by solid-state reaction method, and we investigated their structural and magnetic properties. The new double perovskite compound Pr2CuRuO6 stabilizes in the monoclinic P21/n structure with an antisite defect fraction of ~ 3% between Cu and Ru sites. Our structural analysis indicates the severe deformation of Cu-O-Ru bond angle, as La3+ is replaced by the smaller rare earth ion Pr3+. For Pr2CuRuO6, the observed ferromagnetic transition temperature (Tc = 32 K) is higher than that of La2CuRuO6 (Tc = 15 K), which may be possibly associated with the enhanced magnetic interaction due to the distorted Cu-O-Ru bond angle. In addition, the anomalous phenomenon of ZFC susceptibility at low temperature suggests a degree of magnetic frustration and can be attributable to the intrinsic antisite defect in Pr2CuRuO6. The first principle calculations confirm a ferromagnetic Cu-Ru exchange interaction in Pr2CuRuO6, which is different from the antiferromagnetic case for La2CuRuO6. [ABSTRACT FROM AUTHOR]

Post-transplantation cyclophosphamide (PT-Cy) alone or in combination with other immunosuppressive drugs has emerged as a promising strategy in the setting of allogeneic hematopoietic stem cell transplantation. Improved survival rate was reported in lymphoid malignancies following PT-Cy strategy compared with myeloid disease in non-myeloablative bone marrow transplant setting. Thus, we aimed to evaluate the safety and efficacy of PT-Cy combined with cyclosporine as graft-versus-host disease (GVHD) prophylaxis after myeloablative conditioning and T cell-replete peripheral stem cell transplantation in lymphoid malignancies. This single-arm phase II clinical trial (NCT01435447) involving 31 adult patients was conducted from January 2013 to June 2018. The donor-type neutrophil engraftment rate was 100%, and the overall incidence of grade II to IV and grade III to IV acute GVHD was 39% and 24%, respectively. The cumulative incidence rates of chronic GVHD (35%), including moderate to severe forms (10%), were reduced compared with those of the historical group (P = 0.03 and P = 0.04, respectively). With a median follow-up of 18 months, the estimated 2-year overall and event-free survival was 64.8% (95% confidence interval: 47.8%–86.7%) and 58.4% (95% CI: 41.9%–81.7%), respectively. The 2-year cumulative incidence rate of relapse was 19.5% (95% CI: 9.0%–35.8%), whereas the non-relapse mortality rate was 21.8% (95% CI: 11.3%–38.1%). These results demonstrated the feasibility of PT-Cy as GVHD prophylaxis in this clinical setting. This strategy could significantly reduce the incidence of chronic GVHD and its moderate to severe forms but not of acute GVHD and results in similar survival outcomes compared with the historical group. A prospective study with additional patients is warranted to confirm the role of PT-Cy in lymphoid malignancy. [ABSTRACT FROM AUTHOR]

Neutrophils are the most abundant leukocytes in the blood. Moreover, neutrophils form the first line of host immune defense against bacterial and fungal invasion, and also play an important part in inflammatory and immune system responses. Intravesical bacillus Calmette–Guérin (BCG) has been shown to reduce and delay tumor progression to muscle-invasive disease after transurethral resection of bladder tumors (TRUBTs). Following intravesical BCG, neutrophils gather around tissues infected by BCG in the early stage of inflammatory and immune responses. In our previous study, we reported that BCG induced the formation of neutrophil extracellular traps (NETs), which play an important role in tumor treatment. Therefore, in the present study, we analyzed the gene expression profile of neutrophils stimulated by BCG through high-throughput arrays, which helped us determine the potential roles of neutrophils in BCG immunotherapy. The results showed that the expression of neutrophil genes led to changes in the early stage of BCG stimulation. The changed genes were involved in many functions of neutrophils such as mobility, proliferation, and secretion of cytokines, chemokines, and adhesion molecules. These changes in neutrophil biological functions may play an essential role in BCG induction of inflammatory and immune responses, and in anti-tumor processes. [ABSTRACT FROM AUTHOR]

With increases in the economy and standards of living, energy consumption has grown significantly in China, which has resulted in serious local air pollution and greenhouse gas emissions. Because both carbon dioxide (CO2) and air pollutant emissions mainly stem from fossil energy use, a co-control strategy is simulated and compared with single control in China, using an integrated assessment model (Global Change Assessment Model-Tsinghua University (GCAM-TU)) in this paper. We find that end-of-pipe (EOP) control measures play an important role in reducing air pollution in the near future, but in the long run, optimizing the energy system is an effective way to control both emissions. Reducing air pollutant might take a "free-ride" of decarbonizing the energy system. Compared with a single control of air pollutants, a co-control strategy is likely to reduce the requirement of EOP control measures. The result guides the Chinese government to consider a systemic and scientific plan for decarbonizing the energy system and co-controlling CO2 and air pollutant, in order to avoid duplicate investments in infrastructure and lockup effect. The solution could be extended to many other developing countries, such as India and Africa, which is helpful to realize the goals of United Nations (UN) Sustainable Development Agenda. [ABSTRACT FROM AUTHOR]

Hollow glass microsphere (HGM) is a kind of ultra‐lightweight inorganic non‐metallic material with hollow structure, and it is a versatile and high‐performance new lightweight material developed in recent years. HGMs comprising at least 45 wt% of recycled glass based on the total weight of a feed composition from which the hollow microspheres are derived. The purpose of this study is to develop high‐performance lightweight engineered cementitious composites (LWECCs) using efficiently waste recycled HGMs as a lightweight filler substitute for sustainable construction. LWECC is a flowable type of lightweight fiber‐reinforced concrete, which is able to illustrate strain‐hardening behaviors rather than tension softening after an initial crack and possesses a tensile strain up to 6%; however, available lightweight fillers in LWECC exhibit more brittle behavior compared with normal weight engineered cementitious composite. In this study, three different types of HGMs are used as lightweight fillers with 0.25, 0.40, and 0.60 g/cm3 densities, and their effects on fresh and mechanical properties of LWECC have been investigated. HGMs fillers are replaced at 40 and 60% weight of fly ash in the control mix. To evaluate the strength of the LWECC, samples were cured for periods of 7 and 28 days and then tested for mechanical properties by compression test and three‐point bending. Furthermore, the scanning electron microscopy, energy dispersive X‐ray spectroscopy and morphological observations to confirm the dispersion of the lightweight filler have been captured. [ABSTRACT FROM AUTHOR]